Spectral changes of the fluorescent acriflavine--(Feulgen) DNA dye complex at different temperatures: application of a new cryostat for measurements in reflected and transmitted light.

The fluorometric behaviour of cellular objects is influenced during excitation by two nearly independent phenomena: (1) by the photochemical reaction of the DNA/AF dye complex, and (2) by the energy transfer among several DNA/AF dye complexes. Both processes show a distinct temperature-dependent behaviour and can therefore be characterized by the analysis of the fluorescence spectra at different temperatures. All microfluorometric measurements were performed with a self-constructed cooling device. The cryostat permits measurements of the cellular fluorescence within a range of temperatures between 4 K and 300 K. The cooling unit operates in accordance with the 'Continuous Flow Principle' and allows the application of objectives up to a numerical aperture of 0.6.


Synthesis of amino acyl adenylates using the tert-butoxycarbonyl protecting group.

Alayl, [ 14c]-alanyl, phenylalanyl, and methionyl adenylates have been synthesized in high yields and relatively good purities. Elemental analysis 1H nmr and ir spectra have been utilized for the characterization of these extremely labile compounds. The present synthesis, which uses readily available N-tert-butoxycarbonyl amino acids, is compared with previous methods.


Inadequacy of prebiotic synthesis as origin of proteinous amino acids.

The production of some nonproteinous, and lack of production of other proteinous, amino acids in model prebiotic synthesis, along with the instability of glutamine and asparagine, suggest that not all of the 20 present day proteinous amino acids gained entry into proteins directly from the primordial soup. Instead, a process of active co-evolution of the genetic code and its constituent amino acids would have to precede the final selection of these proteinous amono acids.


A graph theoretic approach to the development of minimal phylogenetic trees.

The problem of determining the minimal phylogenetic tree is discussed in relation to graph theory. It is shown that this problem is an example of the Steiner problem in graphs which is to connect a set of points by a minimal length network where new points can be added. There is no reported method of solving realistically-sized Steiner problems in reasonable computing time. A heuristic method of approaching the phylogenetic problem is presented, together with a worked example with 7 mammalian cytochrome c sequences. It is shown in this case that the method develops a phylogenetic tree that has the smallest possible number of amino acid replacements. The potential and limitations of the method are discussed. It is stressed that objective methods must be used for comparing different trees. In particular it should be determined how close a given tree is to a mathematically determined lower bound. A theorem is proved which is used to establish a lower bound on the lenghtof any tree and if a tree is found with a length equal to the lower bound, then no shorter tree can exist.


A proposal concerning the origin of life on the planet earth.

The widely accepted Oparin thesis for the origin and early evolution of life seems sufficiently far from the true state of affairs as to be considered incorrect. It is proposed that life on earth actually arose in the planet's atmosphere, however an atmosphere very different from the present one. Because of an extremely warm surface, the early earth may have possessed no liquid surface water, its water being partitioned between a motten crust and a fairly dense atmosphere. Early preliving systems are taken to arise in the droplet phase in such an atmosphere. The early earth, which resembled Venus then and to some extent now, underwent a transition to its present condition largely as a result of the evolution of methanogenic metabolism.


Induction of glucagon synthesis in diabetic CBA mice bearing mammary aplastic carcinomas.

Passaging of the mammary aplastic carcinoma several times in diabetic CBA mice induced an extrapancreatic secretion of glucagon. Consequently, the concentration of immunoreactive glucagon was higher in plasma and the tumor tissue extract. After the injection of alloxan, attempts to reduce the level of this hormone in the diabetic mice were unsuccessful. The tumor cells could have been responsible for the secretion of glucagon.


Qualitative changes in the biologic characteristics of cultured fetal rat keratinizing epidermal cells during the process of malignant transformation after benzo[a]pyrene treatment.

In vitro malignant transformation of fetal rat keratinizing epidermal cells from inbred SD rats after benzo[a]pyrene (BP) treatment was analyzed from various biologic viewpoints. BP treatment directly and indirectly effected changes in cell growth characteristics, i.e., temperature dependence for growth, in vitro keratinization, chromosome structure, and the ability to form colonies on plastic substrate, on 0.57% agar medium layer, and in 0.33% soft agar medium. BP-treated cells at 30 degrees C remained in the premalignant stages and showed shifts in chromosome structure toward the hypodiploid range and parakeratotic changes in their keratinization process. However, the cells failed to form colonies even on a plastic substrate. BP-treated cell lines that adapted to temperatures of 35 and 37.5 degrees C remained in the premalignant stages; however, they acquired the ability to form colonies on plastic substrates during subcultivation. Malignantly transformed colonies appeared in these cell lines. In vitro keratinization processes were classified into nearly normal (diffuse lamellar, focal lamellar, and parakeratotic), intermediate, and atypical subtypes (columnar, spherical, and single-cell type). Cells of atypical keratinization subtypes and some of the intermediate subtypes formed squamous cell carcinomas in syngeneic hosts. Malignantly transformed cells showed shifts in chromosome structure toward the hypotetraploid range and colony formation on the 0.57% agar medium layer. However, they failed to form colonies in 0.33% soft agar medium. With the use of changes in biologic characteristics of the cells as indicators, fetal rat keratinizing epidermal cells in culture were classified into five stages. The appearance of stage III cells seemed to be the first key step in their malignant transformation.


Rapid in vivo assay of mouse natural killer cell activity.

A rapid elimination of tumor cells from some organs was detected in mice following iv injection of tumor cells labeld in vitro with [125I]5-iodo-2'-deoxyuridine. Recovery of radioactivity in different organs (spleen, liver, and lungs) was reduced in mice with high natural killer (NK) cell reactivity in their spleens, as measured in vitro by concomitant short-term 51Cr release assay. Considerable parallelism between in vitro and in vivo reactivities against two mouse lymphomas and a human myeloid cell line was found in mice of different strains and ages. Similarly, various immunophamacologic treatments had comparable effects on in vitro and in vivo reactivities. These findings are consistent with the hypothesis that rapid cytolysis of tumor cells occurred in vivo and that NK cells played a major role in their elimination.


Enhancement of experimental tumors in mice by treatment with concanavalin A.

Weanling BALB/c mice given injections of 300 micrograms concanavalin A (Con A) prior to and at frequent intervals after challenge with Moloney murine sarcoma virus (M-MuSV), 3-methylcholanthrene (MCA), or TEPC-15 plasmacytoma cells showed an enhancement of tumor induction or development. With the M-MuSV and MCA systems, this enhancement was evidenced by larger tumors and, in the MCA system, by more devastating tumors. Regression of the M-MuSV-induced tumors was more prolonged in Con A-treated mice. With the TEPC-15 system, enhancement was evidenced by a more rapid mortality rate in treated animals.


Synergism of diethylstilbestrol and radiation in mammary carcinogenesis in female F344 rats.

One compressed 20-mg pellet containing cholesterol only or cholesterol mixed with 0.98, 1.6, 2.6, or 3.9 mg of diethylstilbestrol (DES) was implanted into each of 203 female F344 rats. Two days later, half the animals in each group were exposed to 150 R of X-rays, and the other half were sham irradiated. The rats were maintained until 350 days post implantation. Mortality increased with the higher doses of DES, with or without X-rays. DES at all dose levels, with or without X-rays, produced pituitary tumors and pyometritis. Only rats that received both DES and X-rays had mammary adenocarcinomas (AC). A synergistic AC response was found in the group that received 2.6 mg DES plus X-rays. Synergism was defined as a significantly greater incidence of rats with mammary neoplasia resulting from DES plus X-ray treatment when compared to the summed incidence from comparable individual treatments. For all other groups of rats that received both treatments, synergism was detected only when their data were combined. Synergism was not detected among rats that had fibroadenomas (FA). Both types of neoplasms were independent phenomena because no significant relationship was found between the incidences of FA and AC.


Treatment of young investigators in the National Cancer Program.

To ascertain whether young investigators (those 35 years of age and under) receive equitable treatment in the National Cancer Institute's (NCI) peer review process, we analyzed recommendation and award rates for new traditional grant applicants for 3 fiscal years (nine cycles of review). The more than 4,500 applications studied showed markedly higher recommendation and award rates for younger investigators than for senior scientists; a peak award rate differential of 15% was reached. The study also revealed that young scientists submitted just one-fourth of all the traditional grant applications sent to NCI and received less than one-third of the funds awarded. These results were consistent throughout the National Institutes of Health. As a follow-up, survey results are reported that assess researchers' attitudes and perceptions of the young scientist's role in the current biomedical review system.


Promotional effect of sodium barbiturate on intestinal tumors induced in rats by dimethylhydrazine.

Noninbred Sprague-Dawley rats were administered 1,2-dimethylhydrazine hydrochloride (DMH) by gavage or methylazoxymethanol acetate by sc inoculation. Thereafter, one group was given water to which 0.1% sodium barbiturate was added, and the other was given drug-free water. They were examined 20 weeks after onset of the experiments. A direct relationship was noted between dosage of DMH and numbers of intestinal tumors induced in the rats. The rats provided with sodium barbiturate-supplemented water developed more intestinal tumors than did those that drank drug-free water.


Human colon adenocarcinoma cells. III. In vitro organoid expression and carcinoembryonic antigen kinetics in hollow fiber culture.

Cell line LS174T was established in our laboratory from a primary human colon adenocarcinoma and was serially cultured for 4 years. Following 1 month of culture in perfused hollow fiber matrices, organoid growth reminiscent of the patient's original tumor was observed. The cellular organization was predominantly glandular with mucin located within gland lumina and cells. Glands had irregular brush borders, well-developed junctional complexes, and intracytoplasmic lumina lined with microvilli, features found in adenocarcinoma tissue. Alternate-day determinations of carcinoembryonic antigen (CEA) revealed biphasic kinetics in the extracapillary fluids of the hollow fiber system but not in identically treated monolayer cultures. The initial rate of CEA release was similar to that of monolayer cultures. A significantly accelerated secondary CEA release phase was observed in 10,000- and 50,000-molecular weight (MW)-exclusion fiber cultures (P less than or equal to 0.001 and P = 0.05, respectively). Totals of 43.8 micrograms and 112.6 micrograms CEA were released into the extracapillary fluids of 10,000- and 50,000-MW-exclusion fiber cultures, respectively, which were onefold and 2.3-fold increases, respectively, over monolayer supernatant yields. Most CEA was released during the final days of the secondary phase. In monolayer cultures, maximum CEA release occurred during the stationary phase of growth.


Hereditary retinoblastoma: host resistance and age at onset.

Age-specific incidence data from 244 bilateral and 31 familial unlateral cases of retinoblastoma were analyzed. In the bilateral cases, a high intraclass correlation between ages of the patients at diagnosis in the right and left eyes was noted, even after removal of the bias due to the fact that the diagnosis for each eye is never independent. This finding indicated strongly that the age at onset was largely determined by host factors common to both eyes. The mean ages of the patients at diagnosis of the inherited cases among the bilateral or unilateral group varied consistently with parental phenotype. This finding implied that inherited host resistance played an important role in the latency period for the gene carriers. The fraction of cases not yet diagnosed fit well to a negative exponential distribution, and in the less susceptible group with hereditary unilateral cases, tumor formation may have been suppressed about twice that in the most susceptible group with bilateral cases. It was argued that the presumed second hit initiating tumor formation in the gene carriers was not a mutational process, but probably an error in the process of differentiation that could be suppressed completely in the most resistant group who could remain unaffected, but that could not be suppressed completely in the less resistant group.


Case-control study of hair dye use by patients with breast cancer and endometrial cancer.

A case-control study was undertaken of use of permanent and semipermanent hair dyes by women with cancers of several sites, including breast and endometrium. In London, Ontario, 50 cases of of breast cancer and in Toronto 35 cases of breast cancer and 36 cases of endometrial cancer were identified in cancer treatment centers. In London, controls were selected from hospitalized women with diseases other than cancer; in Toronto, controls were selected from women living in the same neighborhood as the patients with cancer. The results did not suggest an increased risk of either breast or endometrial cancer in users of permanent or permanent and semipermanent dyes combined. Although the numbers of cases and controls were small, the consistency of the results for both sites, in both study centers, and the absence of any clear positive relationship between various measures of intensity of use and risk of cancer provided evidence that a large increase in risk was not missed.


Intake of volatile nitrosamines from consumption of alcohols.

Volatile nitrosamines were determined in alcoholic drinks during epidemiologic studies on the relationship between esophageal cancer incidence and alcohol consumption in Normandy, France. Nitrosodimethylamine (NDMA) was found commonly in most alcoholic drinks tested, with the exception of wine. The average level, about 2 micrograms/liter in beers, was higher than that for other drinks; the range was 0.2--8.6 micrograms/liter. Traces of nitrosodiethylamine (NDEA) were also detected in spirits and ciders. No significant increases in levels were found after nitrosation. Calculation of daily intake in the study region showed that the main intake of volatile nitrosamine is from NDMA in beer. The intake of NDEA through consumption of cider is about one-third that of NDMA from all sources.


Premalignant lesions of the cervix in women of Cali, Colombia.

A detailed histologic study was made of uterine cervices from 441 autopsy specimens from the population of Cali, Colombia. Women in this city have one of the highest registered incidence rates of cancer of the uterine cervix. The following prevalence (in percent) of lesions in adult women was found: cervicitis, 79; reserve cell hyperplasia, 14; squamous metaplasia, 41; dysplasia, 9. Contrary to expectations, no increase in prevalence of these lesions was found with age, lower socioeconomic status, or number of pregnancies. A similar study of a sample of hysterectomies performed for uterine prolapse showed approximately the same results. The findings suggest that promotional factors are more important than initiator factors in uterine cervical carcinogenesis.


Development of Leydig cell tumors and onset of changes in the reproductive and endocrine systems of aging F344 rats.

The age-dependent onset of spontaneous testicular interstitial cell tumors was examined in F344 male rats. Light microscopy of testes established that nodular interstitial cell hyperplasia was evident in 3 of 5 12-month-old rats and in 5 of 5 rats at 15, 18, 21, and 24 months of age. Involution of the seminiferous epithelium was evident in all testes exhibiting extensive interstitial cell proliferation. Striking increments in serum prolactin and estradiol levels were noted with advancing age, whereas serum levels of follicle-stimulating hormone were unequivocally lower at 21 and 24 months than at 6 months of age. No measurable changes were detected in serum testosterone concentrations between 6 and 18 months of age, but marked increments in this androgen, without any measurable change in circulating luteinizing hormone titers, were apparent in 21- and 24-month-old rats. These findings point to a dynamic relationship between testicular interstitial cell tumorigenesis and age-related changes in the synthesis and/or secretion of gonadal and adenohypophyseal hormones.


Induction of tumors by direct injection of N-ethyl-N-nitrosourea into the amniotic space of the mouse fetus.

An N-ethyl-N-nitrosourea (ENU) solution was injected into the amniotic space of Swiss mouse fetuses. Embryos 9 days old were exposed to 2 and 4 micrograms ENU and died within the first 4 weeks of life. Injection of 4 micrograms ENU into 11-day-old fetuses induced a 10% lung tumor incidence, whereas 16 micrograms injected at 12, 15, or 16 days resulted in lung tumor incidences of 42, 100, and 84%, respectively. A mortality rate of 50% and a lung tumor incidence of 89% in survivors resulted after exposure of 16-day-old fetuses to 64 micrograms ENU. Histologic examination revealed that the tumors were alveologenic adenomas 1--7 mm in diameter. Two saline-treated control groups had no tumors. The possible utilization of this biologic model in testing chemical alkylating agents similar to ENU is discussed.


Histoplasmosis: clinical syndromes and management.

The fungus Histoplasma capsulatum produces a spectrum of disease forms ranging from a benign self-limited illness to progressive disseminated disease with a 50 percent mortality rate. The drug of choice, amphotericin B, must be given intravenously over a prolonged course and carries a high incidence of toxicity. Thus, optimal managment of serious forms of histoplasmosis requires considerable clinical judgment.


Analysis of the medical records in a pediatric emergency room.

A prospective evaluation of Pediatric Emergency Room records permitted analysis of major errors and of factors contributing to them. All records from July 1973 to June 1975 were reviewed daily by a board certified pediatrician using a previously established protocol. Patients had been seen by pediatric house staff from 4 PM to 8 AM on weekdays and from 8 AM to 8 AM on weekends and 25,907 records were reviewed. Errors were detected in 9.5 percent of these. The most common was an incomplete set of vital signs which accounts for 68 percent of all errors. Failure to arrange for appropriate follow-up care occurred in 16 percent of cases. Other errors ranged from two to four percent and included inadequate use of laboratory, incomplete physical examination, inappropriate diagnosis or therapy. Major omissions in the history were uncommon (1.3 percent). The frequency of errors was significantly greater at the start of each academic year (July to October), and at the start of each month (P<0.001). The errors occurred significantly more often at the first year level than the second year level (P<0.01). This study suggests a means of improving record keeping and house staff education, ie, attending-level supervision should be emphasized at the start of each month and academic year. Daily reviews of errors with the house staff as well as modification of chart design may bring about more complete patient evaluation and detailed recording of findings, diagnosis, and disposition.


A case of ovarian pregnancy.

Ovarian pregnancy is an uncommon event, the cause of which is unknown. The use of the intrauterine device (IUD) has increased the incidence of ovarian pregnancy. This is due to the decreasing contraceptive effect of the IUD on the fallopian tube and the ovary. This case satisfies the four criteria of Spiegelberg. It also demonstrates the advantages of laparoscopy and ultrasonography in patients with obscure pelvic pain.


Primary malignant melanoma of the bronchus.

A case is presented of a 55-year-old woman with fever, cough, chest pain, and hemoptysis. A chest x-ray showed a large mass in the right upper lobe of the lung. Bronchoscopy and bronchial biopsies revealed malignant melanoma of the bronchus. Careful search of all common sites for melanoma and the histological examinations of the two skin lesions failed to substantiate the possibility of an extrapulmonary origin and, thus, by deduction it can be assumed with some certainty that this lesion is primary bronchial melanoma.Total pneumonectomy, when there is no evidence of extrapulmonary extension, coupled with adjuvant chemotherapy seem to offer a chance of cure.The patient presented is the first reported case of primary malignant melanoma of the bronchus from the University College Hospital, Ibadan, and perhaps the first reported case in a Nigerian.


Pattern of hemoglobin concentration in untreated Burkitt lymphoma patients in Ibadan.

Hemoglobin concentration is studied in 128 untreated Burkitt lymphoma patients in Ibadan. While there is no significant diagnostic pattern in hemoglobin concentration, Burkitt lymphoma patients show marked anemia as compared with healthy adult Nigerians. The degree of involvement of malarial parasitemia in producing anemia in Burkitt lymphoma patients has yet to be determined.


Acute management of the sexual assault victim.

Sexual assault victims usually seek emergency medical care at urban hospitals. The incidence of over 52,000 cases a year reported by the FBI does not include instances in which the victim died, cases of statutory rape (victim below the age of consent), or cases not confirmed by the police. It is well known that sexual assault is one of the most unreported crimes. The incidence of this crime in affluent communities is unknown. Rape occurs in any community but nonhospital professional services may be more easily available in some.The office practitioner may feel ill-equipped to deal with this kind of problem because such patients seldom come to a private office; although in a survey done in 1976, 33 percent of family practitioners stated that they see several rape victims each year. (1) The practitioner may be hesitant about getting involved in litigation. Experience indicates that by following the approach described and documenting facts clearly, physicians will prevent disruption of their busy schedules by unfamiliar court routines, and at the same time provide what society, the victim, and the alleged assailant expect of him as a member of the health care team.


Eugenic sterilization: medico-legal and sociological aspects.

The court-ordered sterilization of a normal 18-year-old black female in North Carolina focused attention on the unfortunate impact of eugenic statutes that allow sterilization as a method of social control. The existence of these laws in many states allows misapplication and abuse of authority which, not infrequently, is directed liberally to blacks and other minority groups.Eugenic sterilization is, at this time, a legally accepted form of "medical treatment." The justification of such sterilization is the vague concept that the presumed "mentally deficient" individual is probably a potential parent of socially inadequate offspring who would likewise be socially inadequate.Since there never has been factual substantiation of whether the sterilization of these individuals will diminish the incidence of mental retardation, it is necessary to focus attention on the concept of eugenic sterilization and point out its many fallacies.


Roots: its impact and implications.

What is contained in Roots, the 587-page narrative that captured an entire world population? The answer is not simple, nor is it overly complex, but rather an admixture of significant psychological, sociological, and timing factors that served to ignite the fuse of human fascination for the unknown, the hidden truths, the obscure, and the forbidden. This paper analyzes the impact and implications of Roots on many facets of American society.


Suppressive effect of dipyridamole on the proteinuria of aminonucleoside nephrosis in rat.

The suppressive effect of dipyridamole on the proteinuria of aminonucleoside nephrosis and protamine-induced proteinuria, was investigated. Male Wistar rats were given puromycin aminonucleoside (80 mg/kg s.c.) or protamine sulfate (20 mg/kg i.v.), and the urine was collected in metabolic cages. The content of proteins in the urine was determined by using a continuous gradient microgel electrophoresis procedure. Dipyridamole (20 mg/kg p.o.) suppressed the excretion of albumin and proteins larger than albumin (HMP) in aminonucleoside nephrosis. But the excertion of proteins smaller than albumin (LMP) was not affected by dipyridamole. Dipyridamole also suppressed the excertion of HMP in protamine-induced proteinuria, though the excretion of albumin and LMP was not affected. Puromycin aminonucleoside and protamine sulfate were known to cause renal glomerular epithelial changes referred to as "fusion" of foot processes. Since dipyridamole was effective in suppressing the both types of proteinuria, this drug was considered to improve the damaged renal glomerular barrier for plasma proteins.


Interaction of zinc and other metal on the activity of erythrocyte delta-aminolevulinic acid dehydratase in vitro.

The interaction of zinc and other metal such as lead, mercury (II), cadmium, silver (II) on the activity of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) was investigated in vitro. At the concentrations ranging from 0.01 to 1.0 mmol/l, lead, mercury (II), cadmium and silver (II) strikingly inhibited the erythrocyte ALA-D activity. The in vitro addition of zinc having an activating effect for the erythrocyte ALA-D, was observed to eliminate the lead-induced inhibition of the erythrocyte ALA-D activity. And the degree of the elimination seemed to depend on the molar ratio (Zn/Pb) of both metal concentrations in the ALA-D assay. However, the inhibition of erythrocyte ALA-D activity caused by mercury (II), cadmium and silver (II) was not removed by the in vitro addition of zinc.


Effect of aflatoxin B1 on the ultrastructural and biochemical development of chick embryo liver during organ culture.

When liver fragments from eleven-day chick embryos were maintained on Eagle's minimal essential medium by the established method of organ culture, they developed ultrastructural features similar to liver cells in vivo, except that they had small amounts of smooth endoplasmic reticulum and little glycogen. The cultured liver cells synthesized DNA, RNA and protein. The addition of aflatoxin B1 to the medium inhibited the synthesis of nucleic acid. Aflatoxin B1 also produced the segregation of granular and fibrillar components in nucleoli and the disarrangement of ribosomes attached to endoplasmic reticulum. Since these results were consistent with the known effects of the toxin in animals, we concluded that organ culture of chick embryo liver could be a useful technique for other studies.


Histopathological study on effects of potassium aspartate on the hypothalamus of rats.

Rats of various ages were treated orally or intraperitoneally with potassium aspartate. The dose required to induce hypothalamic lesion varied considerably by the age of animals and route of administration. Additional experiment, in which the animals were orally treated three times a day with potassium aspartate in dose levels between the maximum safety dose and minimum lesion-producing dose in the preceding single dose study, revealed no hypothalamic lesion at all in any animals of each age group. In this condition, the maximum safety dose was 3--5 times as large as that in single dosage administration experiment. Regarding the safety evaluation of potassium aspartate preparations, brief discussions on some points in extrapolation of the results of the present experimental study to the clinical use were made.


Reproduction study of carteolol hydrochloride in mice. Part I. Fertility and reproductive performance.

Carteolol was administered orally by gastric intubation at 3, 15, 75 or 150 mg/kg/day to ICR-JCL mice of both sexes prior to mating and to females during early stage of pregnancy to determine its effects on the entire reproductive process and fetal development. Following results were obtained: 1) The decrease of spontaneous motor activity was observed in all treatment groups, and some animals in the 75 mg/kg and 150 mg/kg groups pressed the chest or abdomen against the cage wall. 2) The incidence of early resorptions in the 75 mg/kg and 150 mg/kg groups was significantly higher than that in controls.3) The ossification of the talus and calcaneus was significantly retarded in the 75 mg/kg and 150 mg/kg groups. The maximum non-effective dose on fertility and reproduction for carteolol was estimated to be 15 mg/kg/day, although the incidence of early resorptions was slightly elevated with this dose.


Reproduction study of carteolol hydrochloride in mice. Part 2. Peri -and postnatal toxicity.

Carteolol was orally administered to mice once a day at doses of 3, 30 and 150 mg/kg/day during the perinatal and lactation periods and evaluated on its adverse effects on pregnant animals and their offspring. No appreciably abnormal findings related to the drug administration were revealed. Therefore, it was concluded that carteolol have no serious toxic potential on parturition and lactation by mother animals, no adverse effects on growth and development, and behavioral and reproductive performance of offspring and no carcinogenic action through placental and milk transfer.


[Ectopic ureter ending in the seminal vesicle in adults. Apropos of a case and review of the literature].

The authors report a 38 years old patient in whom an intravenous pyelogram was performed for moderate arterial hypertension. This showed a large filling defect in the right lower part of the bladder without renal function on that side. Endoscopic separation of the jet coming from the right half of the trigone showed a liquid containing numerous spermatozoa. A cystogram opacified by reflux a cavity in the genital system via this, the right ureter. With the diagnosis of ectopic ureter ending in the genital system, a nephro-ureterectomy demonstrated the attachment of the ureter into a pouch which communicated with the bladder and the seminal vesicle. A view of the normal embryology insists on the fact that contrary to the classic view, the pronephros disappears entirely and that the metanephros is at the origin of the Woffian canal which opens on the posterior wall of the urogenital sinus at the 28th day when the ureter springs from a ureteral bud. Since 1960 this would be the 34th case in the literature, seminal ectopia (24%) coming after ectopia in the prostatic urethra (54%). Epididymitis is a frequent presenting symptom (44%). The workup shows: absence of renal function (100%), raising of the ipsilateral trigone by a cystic swelling (76%), absence of the meatus on that side on endoscopy, presence of an ipsilateral mass above the prostate on rectal examination (30%). The diagnosis is confirmed by vasography where the ureter is opacified by the seminal vesicle or by systography after endoscopic incision of the mass. Excision of the seminal vesicle was done in conjunction with total nephroureterectomy in 17% of cases.


[Surgical treatment of bladder exstrophy by functional reconstruction by stages (author's transl)].

A brief summary is given of the clinical statistical findings in 37 patients with exstrophy of the bladder, most of the whom have been reported in a previous paper. Four cases are presented for whom the method of operating by stages was applied. They have now been followed up for 17, 10, 8 and 6 years respectively and a very satisfactory functional result was obtained. The experience gained from the use of such a method clearly indicates that treatment should be carried out, whenever possible, by a one-stage operation, or by two stages within a short period of time, and at an early age. Two cases operated upon by this latter method of total primary functional reconstruction, with very encouraging morphological results, are reported.


[Replacement of the lower third of the ureter via the bladder (author's transl)].

The author suggests a special incision in the bladder permitting the formation of a tube using a strip of bladder long enough to permit an anti-reflux vesico ureteral reimplantation. The method is a combination of the Boari and the transverse bipartition described by Turner Warwick. Extraperitonealization of the hemi-bladder opposite to the diseased ureter and section of the umbilical artery. Transverse anterior cystostomy at mid height of the bladder. The mobilized dome of the bladder is stitched up to the psoas muscle above the iliac vessels. Creation of a rectangular flat, the anterior limit of which is the superior margin of the transverse cystostomy, of which the upper part is a split which cuts the dome of the bladder from front to back, of which the posterior limit is a split on the posterior wall of the bladder, parallel to the anterior incision. The length must not be larger than one and one half the width of the flap. Reimplantation of the ureter, creation of the tube and closure of the bladder is done without difficulty. Drawings illustrate the technic. Four cases are reported with three successes.


In vitro translation of adenovirus type 12-specific mRNA isolated from infected and transformed cells.

The early and late gene products of human adenovirus type 12 (Ad12), as well as the viral proteins synthesized in an Ad12-transformed cell line, were identified by translation of viral mRNA in an in vitro protein-synthesizing system. Cytoplasmic RNA was isolated from permissive KB or nonpermissive BHK cells infected with Ad12 and from Ad12-transformed HA12/7 cells. Virus-specific RNA was selected by hybridization to Ad12 DNA covalently bound to cellulose. Viral RNA was then translated in a fractionated rabbit reticulocyte cell-free system or in wheat germ S-30 extracts. The proteins synthesized were characterized by immunoprecipitation and subsequent electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. RNA prepared from KB cells late after infection with Ad12 elicited the synthesis of most of the structural polypeptides of the virion and at least two presumably nonstructural Ad12 proteins. When viral RNA isolated early after infection of KB cells with Ad12 was translated in vitro, 10 polypeptides were observed: E-68K, E-50K, E-42K, E-39K, E-34K, E-21K, E-19K, E-13K, E-12K, and E-10K. Ad12-specific RNA was also isolated from the Ad12-transformed hamster cell line HA12/7, which contains several copies of the Ad12 genome integrated in the host genome. The RNA codes for at least seven polypeptides with molecular weights very similar to those of the early viral proteins.


Adenovirus type 2 early polypeptides immunoprecipitated by antisera to five lines of adenovirus-transformed rat cells.

We have identified adenovirus type 2 (Ad2)-induced early polypeptides (EPs) and have attempted to determine which EPs are coded by each of the four early gene blocks. [35S]methionine-labeled EPs were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cycloheximide pretreatment followed by labeling in hypertonic medium (210 to 250 mM NaCl) facilitated the detection of EPs. Seven major (reproducible bands in autoradiograms) EPs were detected with molecular weights of 74,000 (74K), 21K, 19K, 15K, 13.5K, 11.5K, and 11K. Minor (weaker bands) EPs of 55K, 52K, 42K, 18K, 12K, 8.8K, and 8.3K were also often seen. To identify and map the genes for virus-coded EPs, we prepared antisera against five lines of adenovirus-transformed cells that retain different fractions of the viral genome. The lines were F17, 8617, F4, and T2C4 transformed by Ad2 virions and 5RK (clone I) transformed by transfection with the Ad5 HsuI-G fragment (map position 0 to 8). The early gene blocks retained and expressed (in part) as RNA in these cells were as follows: 5RK(I), block 1 (70% of left 8% of genome); F17, block 1; 8617, blocks 1 and 4; F4 blocks 1, 2, and 4; T2C4, blocks 1, 2, 3, and 4. The following major EPs were immunoprecipitated: 15K by all antisera; 53K and 14.5K by F17, T2C4, 8617, and F4 antisera; 11.5K by T2C4, 8617, and F4 antisera; 44K, 42K, 19K, and 13.5K by T2C4 antisera; 11K by 8617 antisera. Minor EPs of 28K, 18K, and 12K were precipitated by all antisera except 5RK(I). The 53K and 15K EPs were precipitated also from Ad2 early infected monkey cells by the F17 antiserum and by sera from hamsters bearing tumors induced by Ad1-simian virus 40. The relationships between some of the immunoprecipitated EPs were investigated by the partial proteolysis procedure. All 53K EPs are the "same" (i.e., highly related), all 15K EPs are the "same," and all 11.5K EPs are the "same." The 15K EP is highly related to the 14.5 K EP. Although less certain, all 28K EPs appeared related, as did all 18K EPs. The T2C4-specific 44K EP is probably a dimer of the 21K glycopolypeptide. The T2C4-specific 13.5K EP and the 8617-specific 11K EP appear unrelated to any other polypeptides. These immunoprecipitation data provide evidence that early gene block I (map position 1 to 11) may encode major 53K, 15K, and 14.5K polypeptides, and minor 28K, 18K, and 12K polypeptides, and that all or some of the gene for 15K and 14.5K lies within map position 1 to 8. The surprisingly complex pattern of polypeptides coded by early gene block I raises the possibility that some polypeptides may be coded by overlapping "spliced" mRNA's. The possible block locations of the genes for the 21K, 13.5K, and 11.5K polypeptides are discussed.


Post-translational modification of Rauscher leukemia virus precursor polyproteins encoded by the gag gene.

Post-translational modifications of retrovirus gag gene-encoded polyproteins include proteolytic cleavage, phosphorylation, and glycosylation. To study the sequence of these events, we labeled JLS-V9 cells chronically infected with Rauscher murine leukemia virus in pulse-chase experiments with the radioactive precursors [35S]methionine, [14C]mannose, [3H]glucosamine, and [32P]phosphate. Newly synthesized gag polyproteins which incorporated label, and the modified products derived from them, were identified by immunoprecipitation of cell lysates with anti-p30 rabbit serum, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Pulse-chase experiments were carried out in the presence as well as in the absence of tunicamycin, an inhibitor of glycosylation. Among the three major polyproteins synthesized in the absence of tunicamycin, two were found to be glycosylated but not phosphorylated. These were designated gPr80gag and gP94gag. Both shared identical [35S]methionine peptides with Pr65gag and p30. Of the two nonglycosylated precursors, Pr65gag and Pr75gag, only Pr65gag was found to be detectably phosphorylated, and Pr75gag could be readily identified only when glycosylation was inhibited. On the basis of these results, a scheme for the post-translational modification of gag polyproteins is proposed. According to this scheme the gag gene-encoded polyproteins are processed from a common precursor, Pr75gag, by two divergent pathways: one leading through the intermediate Pr65gag to internal virion components via cleavage and phosphorylation and the other via tunicamycin-sensitive mannosylation to the intermediate gPr80gag, which is further glycosylated to yield cell surface polyprotein gP94gag.


Gene 24-controlled osmotic shock resistance in bacteriophage T4: probable multiple gene functions.

By use of mixed infections with conditional lethal mutations in the head genes and an osmotic shock-resistant mutant we have demonstrated that osmotic shock resistance is controlled by gene 24. Using acrylamide gel electrophoresis combined with the "immune replicate" technique, we confirmed the positions of gene products 24 and 24* (P24 and P24*). In this paper we have still used the notation "P24," etc., for designating the product of gene 23, etc., although we prefer and use in general the designation "gp23" as introduced by Casjens and King (Annu. Rev. Biochem. 44:585, 1975). The reason for using the old notation is because the illustrations were prepared several years ago.) P24 ts showed a significantly slower mobility. Both osmotic shock-resistant and -sensitive mature phages contain 24*. Giants constructed with the Osr phage showed the same surface lattice as normal phage. Through temperature-shift experiments with 24(tsL90) alone and in combinations, we studied the phages which are matured after the shift to permissive temperature in the absence of new protein synthesis. Our results strongly suggest that only a fraction of the total phage complement of gene 24-controlled proteins is involved in determining the phenotype of shock resistance, and the remainder is necessary to mature the head.


Intermolecular duplexes formed from polyadenylylated vaccinia virus RNA.

Approximately 15% of the polyadenylic acid-containing cytoplasmic RNA labeled from 5 to 7 h after vaccinia virus infection formed intermolecular duplex structures characterized as double-stranded RNA by RNase resistance, density in Cs2SO4, base composition, chromatography on cellulose, and ability to inhibit reticulocyte cell-free protein synthesis. Both sucrose gradient sedimentation and electron microscopic analysis indicated that the double-stranded regions were several hundred to more than a thousand nucleotide base pairs long. The double-stranded RNA, after denaturation, hybridized to approximately 25% of the vaccinia virus genome, whereas total late RNA hybridized to 42%. The finding that the duplex RNA, after denaturation, hybridized to most HindIII restriction endonuclease fragments of vaccinia virus DNA indicated that symmetrical transcription is not confined to the terminal inverted repeat sequence or to one contiguous region of the genome. Although relatively little labeled, early, polyadenylic acid-containing RNA formed RNase-resistant hybrids upon self-annealing, the percentage increased upon addition of unlabeled late RNA, indicating that the latter contains "anti-early" sequences.


Generation of defective interfering particles of Semliki Forest virus in a clone of Aedes albopictus (mosquito) cells.

Serial undiluted passage of Semliki Forest virus in a clone of Aedes albopictus cells resulted in a marked decrease in infectious virus yields due to the generation and accumulation of defective interfering particles. Virus from the third passage had a high particle/infectivity ratio and interfered specifically with homologous but not heterologous standard virus replication. Two RNA species of molecular weights 0.78 X 10(6) and 0.61 X 10(6) were the major RNA components of purified passage 4 virus. These RNA species were also the predominant virus RNA species detected in cells infected with passage 3 virus. Synthesis of standard virus RNA and virus-specified protein was much reduced in passage 3 virus-infected cells. Interference with standard virus replication and the synthesis of large amounts of defective interfering RNA were also observed in chicken embryo cells infected with passage 3 virus from mosquito cells.


JC human papovavirus replication in human amnion cells.

JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological methods as JC virus. By restriction endonuclease analysis of the viral DNA, the fragments observed were identical to those previously reported for the prototype strain.


Early events in parvovirus replication: lack of integration by minute virus of mice into host cell DNA.

Viral DNA sequences were not detected in high-molecular-weight host DNA until well after the onset of viral DNA replication.


Heterologous interference in Aedes albopictus cells infected with alphaviruses.

Maximum amounts of 42S and 26S single-stranded viral RNA and viral structural proteins were synthesized in Aedes albopictus cells at 24 h after Sindbis virus infection. Thereafter, viral RNA and protein syntheses were inhibited. By 3 days postinfection, only small quantities of 42S RNA and no detectable 26S RNA or structural proteins were synthesized in infected cells. Superinfection of A. albopictus cells 3 days after Sindbis virus infection with Sindbis, Semliki Forest, Una, or Chikungunya alphavirus did not lead to the synthesis of intracellular 26S viral RNA. In contrast, infection with snowshoe hare virus, a bunyavirus, induced the synthesis of snowshoe hare virus RNA in both A. Ablpictus cells 3 days after Sindbis virus infection and previously uninfected mosquito cells. These results suggested that at 3 days after infection with Sindbis virus, mosquito cells restricted the replication of both homologous and heterologous alphaviruses but remained susceptible to infection with a bunyavirus. In superinfection experiments the the alphaviruses were differentiated on the basis of plaque morphology and the electrophoretic mobility of their intracellular 26S viral RNA species. Thus, it was shown that within 1 h after infection with eigher Sindbis or Chikungunya virus, A. albopictus cells were resistant to superinfection with Sindbis, Chikungunya, Una, and Semliki Forest viruses. Infected cultures were resistant to superinfection with the homologous virus indefinitely, but maximum resistance to superinfection with heterologous alphaviruses lasted for approximately 8 days. After that time, infected cultures supported the replication of heterologous alphaviruses to the same extent as did persistently infected cultures established months previously. However, the titer of heterologous alphavirus produced after superinfection of persistently infected cultures was 10- to 50-fold less than that produced by an equal number of previously uninfected A. albopictus cells. Only a small proportion (8 to 10%) of the cells in a persistently infected culture was capable of supporting the replication of a heterologous alphavirus.


Role of virus variants and cells in maintenance of persistent infection by measles virus.

Hamster embryo fibroblasts persistently infected with a derivative of the Schwarz vaccine strain of measles virus spontaneously released virus particles with an average buoyant density considerably lower than that of the parental virus. The released virus contained all of the measles virus structural proteins and interfered with replication of standard virus. All of the virus structural proteins were associated with a membrane-free cytoplasmic extract from the persistently infected cells. Membrane-free cytoplasmic extracts prepared from Vero cells lytically infected with Schwarz strain measles contained little or no virus envelope structural protein. Maintenance of persistent infection may involve both the presence of virus variants and a defect in the ability of the infected cell to replicate the virus efficiently.


Insensitivity of a ricin-resistant mutant of Chinese hamster ovary cells to fusion induced by Newcastle disease virus.

The role of membrane components in the interaction of cells with Newcastle disease virus (NDV) was studied using a ricin-resistant mutant of Chinese hamster ovary cells (CHO-15B), in which there is a deficiency in distal saccharides at the plasma membrane. Compared to the parental wild type, the mutant was shown to be 4- to 10-fold less sensitive to either fusion from without or fusion from within induced by NDV. The mutant and wild type were nearly indistinguishable with respect to other interactions with NDV. Viral attachment was investigated with 125I-labeled NDV and found to be comparable in both lines. Functionally equivalent amounts of hemagglutinin were produced, as measured by the fraction of cells positive for hemadsorption, or by the number of erythrocytes adsorbed per cell. No significant differences in the morphogenesis or yield of progeny virus were seen. The ability of the mutant to produce a fusion factor was measured by transfer of infected cells to uninfected monolayers. Infected CHO-15B cells were capable of inducing fusion normally in the indicator wild-type monolayers, but were incapable of inducing fusion in mutant monolayers. These results suggest that the insensitivity of the CHO-15B mutants to fusion may be due to inhibition of an early virus-cell interaction subsequent to viral attachment, whereas other events in infection appear to be unaffected by the cell surface mutation.


Multiple integration sites for Moloney murine leukemia virus in productively infected mouse fibroblasts.

The integration sites for viral DNA in cells infected with Moloney murine leukemia virus (M-MuLV) were studied by restriction endonuclease cleavage of cellular DNA followed by electrophoresis in agarose gels, blot transfer to nitrocellulose, and detection by M-MuLV-related sequences by hybridization with high-specific-activity 32P-labeled M-MuLV complementary DNA. When EcoRI was used to cleave cellular DNA, numerous DNA fragments with sequence homology to M-MuLV were detected in uninfected mouse cell DNA. These endogenous sequences are mouse specific since they are not detectable in rat cell DNA, and are related to the 38S genomic RNA of M-MuLV. Infected cells contain additional M-MuLV-specific DNA fragments which are not detected in uninfected cells. Different patterns of M-MuLV-specific DNA fragments were detected in each cloned infected line examined. These data suggest the existence of multiple sites for integration of M-MuLV DNA in infected mouse fibroblasts. Cleavage of infected cell DNA with BamHI, which cleaves M-MuLV viral DNA at least twice, released the internal BamHI B fragment from each infected line, confirming the presence of integrated M-MuLV DNA sequences in each infected cell line which retain some features of the sequence organization of unintegrated M-MuLV DNA.


Structure of the membrane protein of influenza virus. I. Isolation and characterization of cyanogen bromide cleavage products.

After cleavage of the membrane (M) protein of influenza A/WSN virus by using cyanogen bromide (CNBr), six peptide peaks representing approximate molecular weights of 6,000, 4,000, 2,200, 1,600, 1,200, and 1,000 were resolved by gel filtration on BioGel P6. Analysis by thin-layer chromatography indicates that the first, second, fourth, and fifth peaks contain single-peptide components, whereas the third and sixth peaks contain more than one peptide. By using Whatman CM52 ion-exchange chromatography in 5 M urea, four peptides were resolved from the third BioGel P6 peak. The amino acid composition of each of the purified peptides has been determined, and partial sequences were obtained for several peptides. Based on finding a blocked amino terminal residue, the 6,000-dalton fragment appears to contain the amino terminus of the M protein, whereas the carboxy terminal peptide was identified as a 2,000-dalton peptide.


M viral RNA segment of bunyaviruses codes for two glycoproteins, G1 and G2.

Tryptic peptide digests of the two viral glycoproteins (G1 and G2) of snowshow hare (SSH) virus, La Crosse, La Crosse (LAC) virus, and an SSH/LAC recombinant virus which has a large (L)/medium (M)/small (S) RNA segment genome composition of SSH/LAC/SSH were analyzed by ion-exchange column chromatography. The analyses prove that the M RNA species of bunyaviruses codes for the two viral glycoproteins.


Program of bacteriophage gh-1 DNA transcription in infected Pseudomonas putida.

The program of transcription in phage gh-1-infected Pseudomonas putida was examined. It was found that the host P. putida RNA polymerase transcribes early RNA from the L strand of gh-1 DNA during the initial stages of infection. The host RNA polymerase is also undoubtedly responsible for transcription of complementary RNA late in the infectious cycle because complementary RNA was not transcribed when rifampin was added to the infected cell culture. The gh-1-induced RNA polymerase transcribes late RNA from the L strand of gh-1 DNA late in the infectious cycle. The P. putida RNA polymerase transcribed only early RNA from primarily the L strand of gh-1 DNA in vitro when the molar ratio of enzyme to gh-1 DNA was 0.5. When the molar ratio was 50 the P. putida RNA polymerase transcribed RNA from the H strand of gh-1 DNA as well as complementary RNA. Thgh-1 RNA polymerase transcribed only the L strand of gh-1 DNA in vitro but transcribed both early and late RNA.


Reovirus serotypes 1 and 3 differ in their in vitro association with microtubules.

Utilizing negative-stain electron microscopy in which similar concentrations of reovirus types 1 and 3 are incubated with a carbon support film containing chick brain, rabbit brain, or HeLa cell microtubules, 81% of the type 1 and 56% of type 3 exhibited an association with the apparent "edge" of the microtubule. This implies that there is a high level of specific affinity for type 1 but not for type 3 to microtubules, since it has previously been determined that only 50% of randomly associated particles would be associated with the edge. The high edge binding of reovirus type 1 is virtually independent of the origin of microtubule, or of whether microtubules or virus has been initially adhered to the support film. On the other hand, reovirus type 1-specific antiserum reduced the edge binding or reovirus type 1 to 45%, whereas type 3 specific antiserum caused no less (within the variability of the assay) of the edge binding of reovirus type 1 to microtubules (76% edge bound). High edge binding of reovirus type 1 to microtubules is correlated with the presence of type 1 or sigma 1 polypeptide. This minor outer capsid polypeptide is encoded in the S1 double-stranded RNA segment and is the viral hemagglutinin and neutralization antigen. Recombinant reovirus clones containing the S1 double-stranded RNA segment of type 1 (80 and 802) show about 85% edge binding, as compared to a value of 42% for clones and the S1 gene of type 3 (204. Electron microscopy of purified reovirus types 1 and 3 by negative staining reveals that type 1 and 802 capsomers are distinctly visualized, whereas those of type 3 and 204 appear diffuse. Thus, the greater in vitro binding of type 1 to microtubules may reflect an increased accessibility of certain of its outer capsomers, and thereby, sigma 1 polypeptides to microtubules. Examination of its outer sections of reovirus type 1- and 3-infected cells at 24 to 48 h postinfection at 31 degrees C showed that about eight times as many viral factoris in type 1-infected cells exhibited an extensive association of virus particles with microtubules, as compared to viral factories of type 3-infected cells. Thus, both in vivo and in vitro there appears to be a greater specificity for the association of reovirus type 1 particles with microtubules, as compared to reovirus type 3 particles.


In vivo assembly of a biological membrane of defined size, shape, and lipid composition.

At restrictive temperature, mutant ts1 of bacteriophage PM2 makes membrane vesicles inside infected Alteromonas espejiana. A shift from restrictive to permissive temperature resulted in rapid maturation to infectious virions. The membrane vesicles were isolated from cellular membranes by sucrose density gradient centrifugation. Analysis of the unique peak at rho = 1.190 g/cm3 showed spheres of two diameters, 50 nm and 54 nm. The wild-type virus is icosahedral with an average diameter of 60 nm. Gel electrophoresis indicated the absence in the vesicles of the coat and spike proteins. sp27 and sp43, respectively, and the presence of only one viral structural protein, sp6.6. DNA was also present. The lipid in the vesicles was composed of phosphatidylglycerol and phosphatidylethanolamine in a proportion similar to that of the wild-type virus, whose ratio is nearly the inverse of that found in the host membrane. Thus, membrane vesicles made by mutant ts1 resembled the membrane of the wild-type virus in size, shape, and lipid composition, but contained only one of the four structural proteins of the virus. This hydrophobic protein, sp6.6 may be responsible for stimulating membrane morphogenesis.


Mutagenic specificity in reovirus.

Mutagenic specificity in response to chemical mutagens has been observed with certain temperature-sensitive mutants of reovirus type 3. One mutant induced by nitrous acid reverted specifically with nitrous acid. Three nitrosoguanidine-induced mutants reverted after nitrous acid treatment. These findings thus suggest that analysis of chemical induction of reversion from the temperature-sensitive phenotype may be a useful approach for studying the nature of mutation in animal viruses.


Comparison of late mRNA splicing among class B and class C adenoviruses.

Adenovirus class B (Ad3 and Ad7) and class C (Ad1, Ad5, and Ad6) late r-strand mRNA's were found to have segmented 5' leaders. These leaders were very similar among serotype within a class but differed in sequence from the leaders on late mRNA's of a different class. However, the leader components of class B viruses mapped at essentially the same map coordinates as those of class C viruses. The 5' coordinates of the main bodies of class B messages to which the tripartite leaders are attached as well as the map positions of several of their early mRNA's were very similar to those of Ad2 transcripts. Infrequent examples of late r-strand polysomal RNAs of Ad3 and Ad7 had, in addition to the three common leader segments, a fourth leader segment derived from RNA encoded at various sites between the second and third leaders. The extra components formed several distinct groups. These molecules are presumably intermediates in the splicing processes that generate mature messages.


Transcription of the bovine parvovirus genome in isolated nuclei.

Transcription of the genome of the nondefective parvovirus BPV was examined in nuclei isolated from synchronized bovine fetal spleen cells. The relative levels of total RNA polymerase and RNA polymerase I, II, and III activities in nuclei isolated from BPV-infected and mock-infected cells were found to be similar throughout the course of infection. Hybridization of RNA synthesized in isolated nuceli indicated that BPV-specific RNA synthesis began during the period of 8 to 12 h postinfection and proceeded linearly until at least 20 h postinfection. By 20 h postinfection, 5% of the total RNA synthesized in nuclei from infected cells was virus specific. BPV-specific RNA synthesis was inhibited by 95% in the presence of 0.1 microgram of alpha-amanitin per ml, suggesting that the viral genome is transcribed by cellular RNA polymerase II.


Physical map of bacteriophage BF23 DNA: restriction enzyme analysis.

Cleavage maps of bacteriophage BF23 DNA have been constructed for the restriction endonucleases SalI (3 fragments), BamHI (5 fragments), EcoRI, (8 fragments), BalI (13 fragments), and HpaI (49 fragments, 32 of which have been ordered). The maps were determined by (i) analysis of deletion mutants, (ii) digestion with two endonucleases, (iii) digestion of isolated fragments with a second enzyme, (iv) analysis of partial digests, and (v) digestion after treatment with lambda exonuclease.


Polarized injection of the bacteriophage T5 chromosome.

Examination of the first-step-transfer DNA of T5ris mutants which carry new EcoRI sites showed that the left end of the chromosome is injected first.


Functional relationship between bacteriophages G4 and phi X174.

Mutants of bacteriophage G4 were isolated and characterized, and their mutations were mapped. They constitute six different genes, namely, A, B, E, F, G, and H. The functional relationship with bacteriophage phi X174 was determined by complementation experiments using amber mutants of phi X and amber mutants of G4. Bacteriophage phi X was able to use the products of G4 genes E, F, G, and H. In bacteriophage G4, however, only the phi X gene H product was functional.


RNA-directed DNA synthesis in Moloney murine leukemia virus: interaction between the primer tRNA and the genome RNA.

Initiation of RNA-directed DNA synthesis in virions of Moloney murine leukemia virus requires a cellular tRNAPro as primer. The site(s) on the Moloney murine leukemia virus genome RNA at which functional primer molecules are bound and at which purified tRNAPro hybridizes has been located near (within 20%) the 5' end of the genome. A relatively stable duplex (temperature at which 50% dissociation has occurred, 76 degrees C) is formed between the amino acid acceptor stem of the tRNAPro and a complementary sequence in the Moloney murine leukemia virus 35S RNA. The interaction involves 19 base pairs, extending from the penultimate nucleotide at the 3' end of the tRNAPro but apparently not including the 3'-terminal adenosine residue. In most respects, the interaction between primer and template in Moloney murine leukemia virus parallels the situation in the avian leukosis-sarcoma viruses.


In vivo transcription and protein synthesis capabilities of bunyaviruses: wild-type snowshoe hare virus and its temperature-sensitive group I, group II, and group I/II mutants.

The in vivo primary and secondary transcription capabilities of wild-type snowshoe hare (SSH) virus and certain of its temperature-sensitive (ts) mutants have been analyzed. The results obtained agree with in vitro studies (Bouloy et al., C.R. Acad. Sci. Paris 280:213-215, 1975; M. Bouloy and C. Hannoun, Virology 69:258-264, 1976; M. Ranki and R. Pettersson, J. Virol. 16:1420-1425, 1975) which have shown that bunyaviruses are negative-stranded RNA viruses with a virion RNA-directed RNA polymerase. The in vivo transcription studies have demonstrated that in the presence of protein synthesis inhibitors (puromycin or cycloheximide) SSH virus can synthesize viral complementary RNA (primary transcription) throughout the infection cycle. The increased levels of viral complementary RNA obtained in the absence of protein synthesis inhibitors (secondary transcription) were not markedly reduced if cells were pretreated with actinomycin D (5 mug/ml), alpha-amanitin (25 mug/ml), or rifampin (100 mug/ml), although progeny virus yields were reduced by up to 80% in the actinomycin D- and rifampin-treated cells. The in vivo transcription capabilities of SSH group I ts mutants at temperatures which were nonpermissive (40 degrees C) for virus replication gave values comparable to those obtained at permissive temperatures (33 degrees C). The SSH group I mutants appear, therefore, to be RNA-positive mutant types. When compared with their transcription capabilities at 33 degrees C, the in vivo transcription abilities of four SSH group II ts mutants (and one double group I/II ts mutant) were found to be more impaired at 40 degrees C than those of the SSH group I ts mutants or wild-type SSH virus at 40 degrees C, although the viral complementary RNA synthetic capabilities of these group II (and group I/II) mutants at 40 degrees C were significantly higher than their primary transcription capabilities (as measured at 33 degrees C in the presence of puromycin or cycloheximide). It was concluded, therefore, that these SSH group II (and double group I/II) ts mutants have an intermediate RNA phenotype. Hybridization studies using (32)P-labeled individual L, M, and S viral RNA species of SSH virus have demonstrated the presence of viral complementary RNA to all three species in extracts of cells infected with SSH ts II-30 and incubated at 33 degrees C (primary and secondary transcription) or 40 degrees C, a nonpermissive temperature for its replication. The results of pulse-labeled in vivo protein analyses indicated that greater quantities of intracellular N protein (coded for by S RNA [J. R. Gentsch and D. H. L. Bishop, J. Virol. 28:417-419, 1978]) than G1 and G2 polypeptides (coded for by M RNA [J. R. Gentsch and D. H. L. Bishop, J. Virol. 30:767-776, 1979]) were present in extracts of cells infected with wild-type SSH virus. In extracts of SSH group I, II, or I/II ts mutant-infected cells incubated at 33 degrees C, N and G1, and for the group II mutant-infected cells, G2, viral polypeptides were detected, whereas in extracts obtained from group I or II mutant virus-infected cells incubated at 40 degrees C, low levels of N and G1 polypeptides were evident.


Tubular subviral structure produced in adenovirus-infected KB cells.

At 40 to 90 h after infection with high multiplicities of adenovirus type 2, 4 to 15% of KB cells produced relatively few intranuclear virions detectable by electron microscopy. The nuclei of these cells were found to contain long tubular structures which were made up at least in part by adenovirus structural proteins. The ends of these tubular structures were frequently terminated by morphologically normal adenovirions in varying degrees of completeness. Circumstantial evidence suggests that the production of these aberrant virus structures results from the malfunction or absence of some essential host-provided function and not from a defect in the infecting virus.


Results of surgical treatment of renovascular hypertension.

We have used a comprehensive protocol to identify secondary forms of hypertension and operated upon 77 patients with functionally significant renovascular disease. The population included 52 patients with atherosclerotic renal arterial lesions (31 unilateral and 21 bilateral) and 25 patients with fibrodysplasia (19 unilateral and 6 bilateral). In the entire population there was a 90% cured-improved rate, a 5% failure rate and a 5% postoperative mortality. The cure rate was highest in the unilateral fibrodysplasia group and lowest in those with bilateral atherosclerotic disease. The choice of initial operative approach was based on an attempt to preserve renal mass; in 11 patients vascular reconstruction was attempted and these required secondary nephrectomy because of early or late failure. All 11 patients had a good result after nephrectomy. Our observations indicate that a vigorous operative approach to renovascular hypertension is beneficial once accurate demonstration of a functionally significant lesion is made.


A new catheter system for permanent percutaneous nephrostomy.

A new catheter system is described for permanent percutaneous nephrostomy. The system allows the rapid, single stage placement of a large diameter drainage catheter. The technique avoids several problems associated with previous methods of percutaneous nephrostomy.


The role of intraoperative angiography in salvaging bovine grafts for hemodialysis.

Bovine grafts used in hemodialysis frequently need declotting. Success of the declotting procedure usually is dependent upon relieving outflow obstruction. Intraoperative angiography was done during 22 declotting procedures and outflow obstructions were detected in 14 grafts. Of these 5 grafts had clinically unsuspected clots, residual to the initial declotting attempt. Four grafts had stenotic areas at the site of the venous anastomosis, which were corrected subsequently by patch grafts. Two grafts had stenotic areas in the graft owing to an infolding of the intima covered with an organized blood clot. In 2 grafts the veins draining the grafts were stenotic for a considerable length and needed revision. In 1 graft there was stenotic change at the site of the arterial anastomosis, which required revision. Of the 14 grafts 11 have remained functioning for an additional 6 to 18 months after relief of obstruction.


Determination of filtration fraction using the gamma scintillation camera.

A simple technique for determining effective renal plasma flow, filtration fraction and filtration rate is described. The determination depends upon the use of 131iodine labeled hippuran and 99mtechnetium labeled iron ascorbate or Sn diethylenetriaminepentaacetic acid. The filtration fraction is determined by dividing the corrected uptake for the technetium compound by the corrected uptake for radiohippuran. The uptake is simply determined by the 1 to 2-minute count over the kidneys with background subtraction and taking into account the amount injected. The technique is simple, quick and appears to be a useful clinical tool.


Diuretic radionuclide urography: a non-invasive method for evaluating nephroureteral dilatation.

The diuretic radionuclide urogram is a simple, rapid and non-invasive technique to determine whether true obstruction exists in dilated nephroureteral systems. The methodology, results and interpretation of 102 studies in 41 patients are presented and compared to the conventional methods of assessing hydroureteronephrosis.


Familial factors in bladder carcinoma.

Surprisingly, little is known about host factors in cases of bladder carcinoma. We investigated 2 families prone to transitional cell carcinoma of the bladder. A high degree of pathology verification of cancer of all anatomic sites and a meticulous recording of genealogy, associated diseases and environmental exposures, when known, have allowed a more cogent appraisal of cancer etiology. It is reasonable to assume that members of the subject families may be more susceptible to variable carcinogenic exposures, a concept that is in accord with a genetic-environmental interaction hypothesis for cancer etiology. In addition to increased surveillance of high risk patients for earlier detection of bladder cancer, cancer control measures also should take into consideration preventive programs directed toward the avoidance of known carcinogenic exposures, such as cigarette smoking in high risk relatives of cancer-affected probands. We propose that the etiology of familial bladder cancer may be complex, involving possible other associated malignant neoplasms and/or certain non-neoplastic disorders, in addition to specific carcinogenic exposures. There is a serious need for the detailed reporting of families prone to bladder cancer wherein all of these potentially important associated factors are considered, so that a fuller appraisal of etiology might be achieved.


The prognostic value of cell surface antigens in low grade, non-invasive, transitional cell carcinoma of the bladder.

Tumors in 23 patients who presented with a low grade, non-invasive transitional cell carcinoma of the bladder were studied for blood group antigens A, B or O on the cell surface. Of 14 patients without cell surface antigens initially 13 suffered an invasive tumor subsequently and 1 had diffuse carcinoma in situ. Of 9 patients with cell surface antigens initially 8 did not have an invasive recurrence during a 5 or more-year followup and 1 did. The presence or absence of blood group cell surface antigen on a low grade, non-invasive transitional cell carcinoma of the bladder would seem to have value in predicting future recurrence with muscle invasion.


HLA-A and HLA-B antigens in transitional cell carcinoma of the bladder.

A possible association between HLA-A and HLA-B loci alleles and bladder carcinoma has been investigated in 44 patients with biopsy proved transitional cell carcinoma of the bladder. The patients were compared to 400 healthy controls and matched for ethnic origin. Typing was done by the standard National Institutes of Health microlymphocytotoxicity technique. Comparison between the HLA-A and HLA-B series of the patients and the controls, and the different stages of disease did not yield any significant difference.


Immunological evaluation of a streptococcal preparation (OK-432) in treatment of bladder carcinoma.

When 21 patients with bladder cancer (transitional cell carcinoma) were given local and systemic injections of a streptococcal preparation, OK-432, tumor regression was observed in 3 cases (14.3%). The marked infiltration of lymphocytes observed on histological examination of regressed tumors suggested that a host-mediated action was involved in the antitumor effect of OK-432.


Bladder carcinoma treated by partial cystectomy: a review of 54 cases.

A retrospective study of 54 partial cystectomies done between 1958 and 1973 was undertaken to evaluate the proper role of the procedure in the treatment of bladder carcinoma. The operative mortality rate was 1.8% and the postoperative morbidity was low in the series. The 5-year survival rate for stages B1 (21 cases) and B2 (16 cases) lesions was 57%, with an over-all 5-year survival rate for all stages of 48%. Indications for the operation are presented and factors influencing survival are discussed.


Carcinoma of the bladder treated by segmental resection.

We herein review 45 patients with carcinoma of the bladder treated by segmental resection from 1955 to 1976. Survival rates were similar to those reported in other series and compared favorably to those found with total cystectomy. Patients with high grade (III and IV) stage A tumors experienced a 100% recurrence rate and only 40% survived more than 5 years, whereas patients with low grade (I and II) stage A tumors had a 28% recurrence rate and 86% lived 5 years or more. Therefore, it is postulated that patients with high grade lesions, even though stage A, undergo more aggressive therapy. It also was found that extensive segmental resection, even though necessitating ureteroneocystostomy, resulted in a favorable 5-year survival rate.


Further experience with the inflatable penile prosthesis.

Since 1974, 93 men with erectile impotence have been treated with surgical implantation of an inflatable penile prosthesis. Followup has been 6 months to 4 years. Long-term functional success was achieved in 87 patients (93%). Complications requiring 31 secondary operations occurred in 27 patients (29%).


Post-lymphangiography fine needle aspiration lymph node biopsy in staging carcinoma of the prostate: preliminary report.

Five cases of clinical stage B carcinoma of the prostate are reported. Bipedal lymphangiography showed unequivocal involvement of the pelvic nodes in 3 patients and was equivocal in the other 2. Percutaneous transabdominal fine needle aspiration biopsy of abnormal or suspicious iliac nodes was performed and a positive cytolocal diagnosis of metastasis was obtained in all 5 patients. Therefore, staging lymphadenectomy and an extensive radical operation were avoided. Percutaneous fine needle biopsy is a reliable, easy and safe technique that should be used in staging prostatic carcinoma whenever there is evidence of metastatic nodal involvement by lymphangiography.


Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase.

Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase provide a unique means for the early diagnosis and more accurate clinical staging of prostatic cancer. The combined screening technique appears to be helpful, particularly in providing a clinical assessment of the presence or absence of early, subclinical lymphatic and bone marrow metastases. Low titer elevations of bone marrow prostatic acid phosphatase by radioimmunoassay have been observed commonly in clinically understaged C prostatic cancer with normal technetium bone scans, indicating the presence of unrecognized stage D disease with bone metastases. The combined screening method also is of distinct clinical value in the early diagnosis of prostatic cancer and in monitoring the effects of specific therapy. In therapeutically responsive patients marked suppression of serum and bone marrow prostatic acid phosphatase is observed regularly with the radioimmunochemical method under study.


Continuous intercostal nerve block for pain relief after lumbar incision.

To relieve postoperative pain along a lumbar incision in 9 patients the intercostal nerves were blocked with catheters for continuous epidural anesthesia. The catheters were inserted near the intercostal nerves, above and beneath the incision, just before the wound was closed and 0.25% bupivacaine hydrochloride solution was infused periodically through the catheters. With this technique 5 of 9 patients had a satisfactory analgesic effect and could breathe deeply or cough without pain. The other 4 patients did not have satisfactory results and this was believed to be owing to inadequate insertion of the catheters. None of the patients had any complications. The technique is simple and can produce an analgesic effect repeatedly without causing pain for the patient.


Venous injury in major urological surgery.

With the increasing use of pelvic node dissection for staging and treating pelvic urological cancer injury to the common, external and internal iliac veins will occur. The sequelae of these injuries are described and the treatment is outlined. A case is described that epitomizes the problems and solutions of this condition.


Carbon dioxide uroflowmetry.

A method using pneumatic compression to determine flow rate is described. The procedure is best suited for physicians using carbon dioxide instrumentation for a urodynamic assessment of patients since the carbon dioxide cystometer is readily converted to a uroflowmeter. Values obtained with this method are similar to values reported in the literature using other techniques. When voided volumes are more than 200 ml. the values for peak flow rate are reproducible within subjects and are volume-dependent.


Pediatric urodynamics: a clinical comparison of surface versus needle pelvic floor/external sphincter electromyography.

Urodynamic evaluations were done on 37 children to diagnose voiding pattern abnormalities and/or recurrent urinary infections. Each of 25 children had 2 sets of testing to judge a practical method of urodynamic evaluation. Bipolar anal skin electrodes were compared to bipolar perianal muscle needle electrodes as a means of monitoring the urethral sphincter/pelvic floow electromyographic activity. In addition, the urethral catheter was compared to the suprapubic catheter as a means of monitoring intravesical pressure. The results were similar and statistically significant (p less than 0.001). The remaining 12 children were evaluated based only on the results of bipolar anal skin electrodes and uroflowmetry. The results of both groups clearly demonstrated that surface perianal electrodes are practical, accurate and reliable for the diagnosis and treatment of children with voiding pattern abnormalities. We recommend the use of surface electrodes and a urethral catheter as techniques for the urodynamic evaluation of voiding pattern abnormalities of children without overt neuropathology or extensive urethral operation. Preoperative surface electromyography of the urinary sphincters may prove to be a useful screening test to detect occult dyssynergia in patients who have had failed ureteral reimplants.


Increased physical growth after successful antireflux operation.

Gross vesicoureteral reflux with infection can retard renal growth. Resumption of renal growth or even accelerated growth has been reported after successful surgical repair of reflux in children. No published reports examining the effect on physical growth are available. The preoperative and postoperative physical growth curves were examined in 35 consecutive pediatric patients undergoing ureteroneocystostomy for reflux. The significant (average 81%) increase in the postoperative physical growth percentile is presented and discussed.


Bacteriuria with intestinal loop urinary diversion in children.

Bacteriuria and intestinal loop urinary diversion with open (refluxing) ureterointestinal anastomoses did not prevent normal renal and body growth in 44 children, who were followed for 55.2 months. A comparison of the long-term use of sulfamethoxazole and nitrofurantoin with no treatment showed no statistically significant changes in the stoma, loop residual, renal function, serum electrolytes and treatment or prevention of bacteriuria.


Prepubertal gonorrhea.

Two cases of gonococcal urethritis in male children are presented and the records of 45 other children with gonorrhea are reviewed. The presentation, diagnosis and treatment are discussed. Data on the mode of transmission are presented with emphasis on the high incidence of gonorrhea in family members or close contacts of infected children, or a history of sexual abuse.


Enucleative surgery for renal malignancy.

Bilateral renal cell carcinoma, malignant tumors of a solitary kidney or renal carcinoma in the presence of a contralateral kidney with compromised function may be treated by simple enucleation of the tumor, usually pseudoencapsulated, permitting relatively avascular removal. We treated 5 such patients by surgical enucleation of renal cell carcinoma who have survived for intervals of 9 months to 5 years without evidence of recurrent local or metastic disease. The simplicity of the technique offers several advantages, primarily those of applicability to lesions of any portion of the kidney and the minimal disturbance of renal hemodynamics and renal function.


Revision of ureteral reimplantation by the transverse advancement technique.

Antireflux ureteral reimplantation may be performed by a variety of techniques with consistently satisfactory results. Complications, such as persistent reflux and postoperative ureterovesical obstruction, may be encountered occasionally and, when significant, they will necessitate a revision operation. Herein 6 cases are described of failed ureteral reimplantation, which were revised successfully by performing a transverse advancement ureteral reimplantation.


Obstructive uropathy and nephrogenic diabetes insipidus in infants.

The syndrome of acute post-obstructive nephrogenic diabetes insipidus is a rare phenomenon. The lesion is acquired during the pre-diuretic phase, owing to antidiuretic hormone resistance of the distal tubule as well as a severe concentrating defect. The diuretic phase after relief of obstruction can result in a massive, sustained and life-threatening diuresis. Sodium restriction and thiazide diuretics produce a mild volume contracted state, enhancing sodium and water reabsorption, primarily in the proximal tubule and possibly in the distal tubule owing to aldosterone. The recognition and differentiation of this unique pyloric syndrome from other more common post-obstructive diuretic states are important for all urologists who are responsible for the care of children.


Retroperitoneal seminoma presenting with inferior vena caval obstruction.

A retroperitoneal seminoma in the presence of clinically normal testes can present a considerable diagnostic problem and therapeutic dilemma. We report on a patient with low back pain and inferior vena caval obstruction in whom no primary neoplasm could be detected by surgical exploration of the testes.


Computed tomography in evolution of testicular cancer during intensive chemotherapy.

The evolution of malignant testicular tumor to mature teratoma has been studied in 4 patients. Computed tomography has been helpful in early diagnosis of this biologic phenomenon in these patients receiving intensive chemotherapy for disseminated non-seminomatous testicular cancer. Although the potential significance of this conversion in terms of survival is not known its early recognition by computed tomography has been useful in selecting and monitoring the therapy of these patients.


Urogenital sinus abnormalities in the female patient.

Three patients with a urogenital sinus and 1 with a cloaca presented with complex diagnostic and therapeutic anomalies. A classification of these and other vaginal anomalies is based on the theory that they all represent an arrest in normal embryological development. Six categories are described, including vaginal agenesis, urogenital sinus, vaginal atresia, vaginal septa, vaginal stenosis and cloaca.


Paratuberculosis (Johne's disease) in bighorn sheep and a Rocky Mountain goat in Colorado.

Between May, 1972 and February, 1978, six cases of paratuberculosis (Johne's Disease) caused by Mycobacterium paratuberculosis were diagnosed in free-ranging Rocky Mountain bighorn sheep (Ovis canadensis) and one Rocky Mountain goat (Oreamnos americanus) on or near Mt. Evans in Colorado. Diagnosis of paratuberculosis was based on gross and histopathologic examination of the animals and by isolation of M. paratuberculosis from three sheep and the goat. The clinical signs and pathologic changes seen in the bighorn sheep resembled those described in cattle, while the lesions in the goat were similar to those described for domestic sheep and goats.


Mycobacterium intracellulare infection in a water monitor.

Mycobacteriosis caused by Mycobacterium intracellulare serotypes Davis (8) and Altman (18) is described in a water monitor (Varanus semiremex). Infection with this of organism has not been reported previously in reptiles in Australia.


Isolation of Aeromonas hydrophila from the American alligator, Alligator mississippiensis.

Aeromonas hydrophila was isolated from the internal organs of nine adult alligators, Alligator mississippiensis, which died without apparent cause, suggesting the bacterium may have been a factor. One hundred and twenty-three alligators ranging in age from six months to over 10 years were captured from five locations in the southeastern United States and sampled for A. hydrophila. The bacterium was isolated from the oral cavity of 85% of the animals, on the external jaw area from over 50% and from 70% of the internal tissue samples. A. hydrophila is ubiquitous with alligators in their natural habitats, but apparently does not cause clinical disease. However, stress factors such as trapping, handling, and warm water temperatures may be conducive to the rapid proliferation of the bacteria, thereby facilitating disease.


Serologic evidence of leptospirosis in woodchucks (Marmota monax) in central New York State.

Serum samples from 153 woodchucks (Marmota monax) from Tompkins County, New York, obtained in 1976 and 1977, were examined by plate agglutination tests for antibodies against five Leptospira antigens. Fourteen sera showed significant titers against either L. hardjo, L. icterohemorrhagiae and/or L. pomona. Reactions against L. hardjo were the most frequent. Woodchucks collected from two dairy farms with histories of bovine leptospirosis did not have a greater prevalence of antibodies than woodchucks collected from other locations. Each of two woodchucks experimentally-inoculated with L. hardjo developed titers to L. hardjo. Maximum titers occurred approximately 30 days post-inoculation. L. hardjo was not observed in urine specimens of these animals.


Use of Ketamine hydrochloride and xylazine hydrochloride to immobilize black bears (Ursus americanus).

Ketamine hydrochloride (KH) and xylazine hydrochloride (XH) used in combination (KH-XH) were effective immobilants for captive and wild black bears (Ursus americanus). Single intramuscular injections of 1.5-17.1 mg of KH per kg body weight combined in an approximate ratio of 2:1 with 0.9-10.0 mg of XH per kg body weight immobilized bears for 1.5-197 min. Dosages most frequently used were 4.5-9 mg KH/kg with 2-4.5 mg XH kg. Supplemental administrations maintained tractability for up to 31 h. Immobilization was characterized by smooth induction, relaxed muscles, occasional groaning and vomition, no eye closure, no defecation, and a smooth recovery phase of variable length. Male and female bears responded similarly to KH-XH. Induction times for small bears (less than or equal to 25 kg) were shorter than for larger bears.


Gastrointestinal nematodes of wild sheep (Ovis orientalis) from Iran.

A total of 250 wild sheep (Ovis orientalis) from different national parks and protected regions of Iran were examined for gastrointestinal nematodes at necropsy. Twenty five species of nematodes were found. Marshallagia marshalli, Ostertagia spp; Nematodirus spp; and Skrjabinema ovis were the most prevalent. Although all the species found are recorded from wild sheep for the first time in Iran, 88% were reported previously from domestic sheep. New host and distribution records for Nematodirus davtiani, N. gazellae and Nematodirella longissimespiculata were established during the present study.


Tick paralysis in a grey fox.

One hundred seventeen Dermacentor variabilis were removed from the head and back of a grey fox (Urocyon cinereoargenteus) showing paresis and diminished motor reflexes of the hind limbs. Rapid and total recovery led to a diagnosis of tick paralysis.


Dermacentor albipictus on moose (Alces alces) in Ontario.

Fifty-five moose (Alces alces) collected from 1963 to 1965 in the Chapleau Crown Game Preserve of northern Ontario were examined for ectoparasites. Dermacentor albipictus was the only parasite recovered. D. albipictus was absent from 15 moose examined during June, July and August; first observed on 1 or 2 moose examined in September; and present on all 38 moose collected from October to May. Ticks were not evenly distributed on the body. Infestations varied from 32 to 13,490 ticks/moose for 14 individuals. Levels of infestation observed did not have an obvious adverse effect on the health of the moose.


Tonsillar carcinoma with metastases in a captive wolf.

Gross and histopathologic findings of primary tonsillar squamous carcinoma with metastases to lymph nodes of the neck and thorax and to the lung in a captive 13-year-old male wolf are presented.


Myxosarcoma in a wapiti.

Myxosarcoma was diagnosed in an adult male wapiti (Cervus canadensis) from western Colorado. The neoplasm was located on the medial aspect of the right thigh and had extensively infiltrated adjacent soft tissue.


Experiments on direct and secondary poisoning by fluoroacetamide (1081) in wildlife and domestic carnivores.

Fluoroacetamide (1081 or F.A.A) is used in Israel for field rodent control. Experiments on direct and secondary, short and long term poisoning caused by 1081 were carried out. Mongoose (Herpestes ichneumon), hyena (Hyaena hyaena), cats and dogs were susceptible. Barn owls (Tyto alba), buzzards (Buteo buteo) and black kites (Milvus m. migrans) were markedly resistant. Barn owls tolerated total direct poisoning ranging from 6.8 to 10.9, and a final dose ranging from 0.8 to 2.0 mg/kg. In secondary poisoning, total doses ranging from 1.7 to 7.1, and final doses ranging from 0.2 to 1.3 mg/kg were tolerated. Buzzards tolerated total direct poisoning ranging from 6 to 12.0, and final doses ranging from 0.7 to 1.3 mg/kg. In secondary poisoning, doses ranging from 0.8 to 10.3 and final doses ranging from 0.2 to 2.4 mg/kg were tolerated. One black kite tolerated a total direct dose of 6.1 and final dose of 0.7 mg/kg, another survived a total dose of 2.3 and final dose of 0.2 mg/kg in secondary poisoning. A small-scale secondary poisoning experiment on two Palestine vipers (Vipera palestinae), a Syrian black snake (Coluber jugularis) and two Montpellier snakes (Malpolon monspessulanus) indicated that these species were resistant to total doses ranging from 0.1 to 3.2 and final doses of 0.1 to 0.8 mg/kg.


Prevalence of selected zoonotic diseases in vertebrates from Haiti, 1972.

Vertebrate animals collected in Haiti in 1972 were tested for selected zoonotic diseases. No rabies virus or neutralizing (N) antibody was detected in bats (Artibeus jamaicensis). However, N antibody against St. Louis encephalitis, Western equine encephalitis (WEE), and Eastern equine encephalitis were detected in resident species of birds and WEE antibody in bats. No N antibody against Venezuelan equine encephalitis was found. The possible introduction by migratory birds and local transmission of these arboviruses is discussed.


Isolation of Newcastle disease virus from teals (Anas crecca) in Iran.

Eight of 30 teals (Anas crecca) died several days following capture and Newcastle Disease Virus (NDV) was isolated from all eight. Brains from the dead birds were homogenized and inoculated into chicken embryos. The allantoic fluid from the embryos were inoculated into 10 domestic chickens susceptible to NDV and 10 chickens immunized against NDV. Eight of 10 (80%) susceptible chickens died, while the immunized chickens remained healthy. Anti-NDV serum showed complete homology against NDV and the eight isolates.


Additional data favoring use of anticoagulant therapy in myocardial infarction. A population-based study.

A community-wide study was conducted in metropolitan Baltimore in which the survival of 1,307 patients with acute myocardial infarction was examined according to use of anticoagulants. The adjusted in-hospital case-fatality rate was lower for patients receiving anticoagulants (18%) than for those not receiving this therapy (31%). This difference persisted in each period examined in the study (1966 and 1967 or 1971) and was found in 17 of 20 participating hospitals. For hospital survivors followed up for as long as ten years, a better survival was again found for those treated with anticoagulants in the acute phase compared with those not treated.


Death during jogging or running. A study of 18 cases.

We investigated the circumstances of death and the medical and activity histories of 18 individuals who died during or immediately after jogging. Thirteen men died of coronary heart disease (CHD) and four men and one woman died of other causes. Six CHD subjects had medical histories relevant to the cardiovascular system, but only one had diagnosed CHD. Six CHD subjects experienced prodromal symptoms but continued vigorous exercise programs. Two subjects had exercised less than a month, but most had trained regularly for years. The CHD risk factors for the CHD cases did not differ significantly from those for other age-matched, physically active men. Superior physical fitness does not guarantee protection against exercise deaths. Physicians and exercising adults should be aware of this fact and give appropriate attention to possible prodromal symptoms.


Family history in an oncology clinic. Implications for cancer genetics.

Detailed family histories of cancer were solicited from 200 consecutively ascertained cancer patients undergoing treatment in an oncology clinic. Approximately 18% had two or more first-degree relatives with cancer of any anatomic site. In several cases, striking familial aggregations of cancer fulfilled more rigorous criteria for hereditary cancer syndromes, including early age at onset of generally late-occurring tumors, characteristic tumor patterns, vertical transmission, and collateral family lines similarly afflicted. Review of preexisting clinic charts demonstrated that, in most cases, the family history of cancer had been either omitted altogether, reported as negative despite substantial evidence to the contrary, or, if noted as positive, not pursued or acted on. Family history can be more successfully utilized in recognition of suggestive familial cancer aggregations, ultimate identification of hereditary cancer syndromes, and control of cancer in clinical practice.


Drug-related superinfection in hospitalized patients.

In a series of 14,077 hospitalized medical patients receiving antibiotics, superinfection developed in 95 (0.7%) during drug therapy. The majority were yeast and fungal infections, and serious infections occurred with a frequency of less than one per 1,000 patients treated. Concurrent immunosuppression and impaired renal function increased the risk of new infections.


Contact dermatitis to neomycin sulfate.

The prevalence of contact allergic dermatitis and nonallergic irritant reactions to neomycin sulfate was determined in a large group of young adults who had a noteworthy exposure to topical antibiotics. Only two subjects (0.09%) had contact allergy proved by closed patch testing, while 20 (0.9%) had nonallergic irritant reactions to 20% neomycin sulfate and 17 (0.78%) had nonallergic reactions to one of the hydrophilic ointment bases. In a separate population of 653 children referred for diagnostic patch testing, only one subject had contact allergy to neomycin. All three subjects who had reactions had a history of repeated use of neomycin on chronically damaged skin. These results support the conclusion that intermittent use of neomycin on minor cuts and wounds is not associated with an excessive rate of sensitization.


Antimicrobial selection by a computer. A blinded evaluation by infectious diseases experts.

An evaluation of a computer-based consultation system called MYCIN was made. Eight independent evaluators with special expertise in the management of meningitis compared MYCIN's choice of antimicrobials with the choices of nine human prescribers for ten test cases of meningitis. MYCIN received an acceptability rating of 65% by the evaluators; the corresponding ratings for acceptability of the regimen prescribed by the five faculty specialists ranged from 42.5% to 62.5%. The system never failed to cover a treatable pathogen while demonstrating efficiency in minimizing the number of antimicrobials prescribed. The study design may be useful in assessing the performance of other computer-based clinical decision-making systems.


Reye's syndrome in nonpediatric age groups.

Reye's syndrome (encephalopathy and fatty liver) is generally considered a disease of children. Four patients, aged 16, 18, 19, and 23 years, with Reye's syndrome were initially seen by internists. A viral prodrome followed by vomiting and encephalopathy without focal neurological signs or jaundice clinically suggested Reye's syndrome. Normal findings of CSF examination (except for increased opening pressure), abnormal findings of liver function tests, and increased blood ammonia further supported the diagnosis. None was hypoglycemic. Reye's syndrome was related to influenza B virus in three patients and to Varicella in another. Three patients survived. Reye's syndrome may be seen intially by general practitioners, emergency room physicians, internists, or psychiatrists. The importance of considering this syndrome in the differential diagnosis of unexplained encephalopathy in adults is stressed.