Effect of ionic strength, serum albumin and other macromolecules on the maintenance of motility and the surface of mammalian spermatozoa in a simple medium. The seminal plasma in sperm suspensions from boar, bull, rabbit, ram and stallion was replaced with simple defined media as completely as possible by a combination of centrifugation through Ficoll and dilution. After this process, motility declined and the cells showed a tendency to agglutinate and/or stick to glass. Varying the ionic strength of the medium had little effect upon these parameters but sperm motility was preserved better in the presence of serum albumin. When a number of purified proteins and other macromolecules were tested individually in this way for their motility-preserving ability, bovine or human serum albumin was consistently the most effective. Defatting the albumin or altering its nature by mild reduction, oxidation or alkylation had little detectable effect on its motility-preserving ability; the protein did not appear to be acting as a chelator of metal ions, for it could not be replaced by EDTA. The response of the spermatozoa to replacemrnt of seminal plasma varied between species: bull spermatozoa were particularly sensitive and serum albumin had little effect upon their subsequent motility.


Ovarian responses and serum LH levels after retraction or removal of the oviduct in Japanese quail. The effects of oviduct removal, oviduct displacement or sham-operation were studied in Japanese quail (Coturnix coturnix japonica). No significant differences were observed between the treatments for body weight, number of follicles larger than or equal to 6 mm diam., or number of ruptured follicles. Retraction or removal of the oviduct resulted in similar significant increases (P less than 0.05) in ovarian weight, diameter of the largest follicle, and serum LH levels when compared with the controls. Injection of yolk into normal hens did not cause any change. It is suggested that the oviduct normally exerts an inhibitory control on ovary growth without appreciable effect on ovulation rate.


A seasonal difference in ovine peripheral plasma prolactin and progesterone concentrations in early pregnancy and in the relationship between the two hormones. In the first 11 days of pregnancy, progesterone and prolactin levels were significantly correlated (P less than 0.05), positively in December-mated animals (r = 0.889) and negatively in those mated in March (r = 0.865).


Demonstration that progesterone 'blocks' uterine activity in the ewe in vivo by a direct action on the myometrium. Intrauterine pressure was monitored in vivo in oestrogen-treated ovariectomized ewes before, during and after treatment with progesterone (50 mg s.c./day for 3 days). Progesterone reversibly reduced the frequency and amplitude of myometrial activity and abolished uterine reactivity to oxytocin (i.v.) and PGF-2alpha (intrauterine infusion). The rate of rise of intrauterine pressure during active pressure cycles was significantly reduced. These results confirm that the action of progesterone on the ovine myometrium is comparable to the classic progesterone 'block'. The intrauterine infusion of PGF-2alpha (10 microgram/min), which elicited a marked mechanical response in the control animals, failed to stimulate the progesterone-'blocked' uterus, suggesting that the inhibition produced by progesterone is due to a direct action of the hormone on the uterine muscle and not to an indirect mechanism operating through endometrial prostaglandin output.


Serum oestrogen, progesterone and prolactin concentrations in cyclic, pregnant and lactating beagle dogs. No correlations between the three hormones measured were found in any of the reproductive states examined. In 2 out of 8 dogs a negative correlation between serum progesterone and prolactin levels was found at Day 11 and Day 15, respectively (Day 0 = first day of copulation). In all of the 8 animals in which the progesterone and prolactin concentrations were measured in the same samples in late pregnancy, a negatively correlated overall pattern was obtained between both hormonal profiles. No correlation between serum oestrogen and prolactin levels was found. It is concluded that the proliferative mammary gland changes which are induced in female dogs during long-term toxicity testing with progestagens are unlikely to be related to prolactin or oestrogen synthesis and/or secretion.


Evidence that a humoral factor possessing relaxin-like activity is responsible for uterine quiescence in the late pregnant rat. When post-partum ovariectomized rats were linked to 21-day-pregnant rats by a cross-circulation system their myometrial activity was almost completely inhibited. No reduction in activity was induced by cross-circulation with other post-partum rats, or with rats in which myometrial activity had been suppressed with oestrogen. Changes in uterine activity could not be correlated with alterations in arterial blood pressure occurring during the experiments. Uteri rendered inactive by cross-circulation were found to be responsive to oxytocin. It is concluded that a humoral myometrial inhibitor is present in late pregnancy in rat blood and the possibility that it is relaxin is discussed.


Ultrasound in obstetrics and gynecology. Ultrasound is the imaging method of choice for evaluating the pregnant abdomen. It appears to be free of any deleterious biologic effects. The fetus and other structures within the uterus can be imaged in great detail, and abnormalities in growth and development of these structures can be demonstrated. Ultrasound has a far less specific role in the evaluation of gynecologic abnormalities. The normal uterus and, less frequently, the normal ovaries can be imaged. Masses arising in these strucutres can often be conclusively demonstrated by ultrasound when physical examination is inconclusive. The ultrasonic texture of these masses, whether they be solid, cystic or complex, can be determined accurately. However, the determination of whether these masses are benign or malignant cannot be made by ultrasound criteria. Ultrasound has also proven useful in evaluating patients with ambiguous genitalia, amenorrhea and suspected PID and also is an effective means of localizing intrauterine contraceptive devices.


The spectrum of alleged rape.

The spectrum of alleged rape. A prospective series of 110 alleged rape victims from July through November 1974 at Denver General Hospital is presented. The victims and assailants are characterized. The laboratory established proof of recent coitus in 68%. Four-fifths of the victims presented within 12 hours of the alleged incident. The analysis of ABO vaginal antigens appears to be promising for assailant identification. Follow-up by appointment in this group was successful in only 5%. Only a minority of cases led to arrest and criminal proceedings. Suggestions are made for alternative approaches to victims based on new developments in forensic laboratory procedures.


[1-Deaminopenicillamine,4-threonine]oxytocin, a potent inhibitor of oxytocin. [1-Deaminopenicillamine,4-threonine]oxytocin was prepared in duplicate from S-benzyl-3-mercapto-3,3-dimethylpropanoyl-Tyr(Bzl)-Ile-Thr(Bzl)-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 (I) by removal of the Bzl-protecting groups with Na-NH3, followed by cyclization of the resulting disulfhydryl compound with K3Fo(CN)6. The analogue was purified by desalting on Sephadex G-15 in 50% acetic acid and gel filtration of Sephadex G-15. The protected peptide I was synthesized (a) by the solid-phase method and (b) by a combination of solid-phase synthesis and an [8 + 1] coupling in solution. The analogue has no detectable agonist activity in rat vasopressor or isolated rat uterus assays. It has an antivasopressor pA2 of 6.67 +/- 0.09. It is a potent inhibitor of the in vitro oxytocic response to oxytocin and has a pA2 value of 7.46 +/- 0.04. (Material from the repeat synthesis has a pA2 value of 7.59 +/- 0.08.) Thus the substitution of threonine for glutamine in the antagonist [1-deaminopenicilliamine]oxytocin (pA2, 7.14 +/- 0.05) has effected a twofold increase in inhibitory potency. [1-deaminopenicillamine,4-threonine]oxytocin is one of the most potent inhibitors of oxytocin known to date.


Linked Aryl Aryloxypropanolamines as a new class of lipid catabolis agents. The synthesis of a series of stilbene, biaryl, tolane, diaryl ether, sulfide, sulfoxide, and sulfone oxypropanolamines as potential antiobesity agents is described. These compounds were evaluated in a mouse lipid catabolism screen, and the more active members of the series, 4, 57, and 58, were further investigated in rats and dogs. 1-(2,6-Ditert-butyl-4-trans-styrylphenoxy)-3-isopropylamino-2-propanol (4) possessed considerable lipid catabolic activity in mice and caused a significant reduction in the body weight of rats after 5 weeks and of dogs after 6 weeks. Only hematological irregularities in a chronic toxicity study precluded further development of this compound as an alternative antiobesity treatment.


Studies on anticoccidial agents. 12. Synthesis and anticoccidial activity of methyl-2(6)-nitro- and -3(5)-nitropyridinecarboxamides. A number of methyl-2- and 3-nitropyridinecarboxamides have been synthesized. It has been established that the presence of at least one hydrogen atom, adjacent to the NO2 function, is important for anticoccidial activity and introduction of a methyl group to the adjacent position of the CONH2 function sometimes confers enhanced activity. Among the compounds herein, 5- and 6-methyl-2-nitropyridine-4-carboxamides possess optimal anticoccidial activity, being as potent as the parent compound.


Antileukemic activity of ungeremine and related compounds. Preparation of analogues of ungeremine by a practical photochemical reaction. A number of alkoxypyrrolophenanthridinium salts and their analogues related to the antileukemic alkaloid ungeremine were prepared by a practical photochemical cyclization. The importance of the quaternary nitrogen atom and of alkoxy groups, the planarity of a molecule, and steric considerations relative to antileukemic activity are discussed.


Synthesis and antitumor activity of preactivated isophosphamide analogues bearing modified alkylating functionalities. In search of cancer chemotherapeutic agents with greater efficacy than cyclophosphamide, 4-hydroperoxyisophosphamide analogues bearing modified alkylating functionalities such as 2-bromoethyl, 2-iodoethyl, 2-methyl-sulfonyloxyethyl, and 2-ethylsulfonyloxyethyl groups were prepared by ozonolytic cyclization reaction of N,N'-substituted 3-butenyl phosphorodiamidates. Comparative cytotoxicity against L1210 cells and antileukemic life-span activity against L1210 implanted BDF1 mice of the newly synthesized compounds were tabulated. The 4-hydroperoxyisophosphamide analogues which have different alkylating groups in a molecule showed slightly greater cytoxicity in vitro than those with the same alkylating groups. Most of the compounds having different alkylating groups also showed high antileukemic activity in vivo. Among them, the highest efficacy was found for 2-[N-methyl-n-(2-chlorethyl)]amino-3-(2-methylsulfonyloxyethyl)-4-hydroperoxy-1,3,2-oxazaphosphorinane 2-xoide (NSC 280122D) whos life-span activity was also greater than that of 4-hydroperoxyisophosphamide, cyclophosphamide, and isoposphamide. The superiority of this compound was especially apparent by oral administration.


Relationship of molecular structure to in vivo scintigraphic distribution of carbon-11-labeled compounds. 4. Carbon-11-labeled mandelonitriles, Mandelic acids, and their esters. 11C-Labeled HCN was collected in water containing carrier KCN following bombardment of 99% N2-1% H2 with 22 MeV protons. 11C-Labeled mandelonitrile and p-methoxy-, p-hydroxy-, and 3,4-dihydroxymandelonitrile were synthesized from K11CN and the corresponding benzaldehyde. The initial distribution of 11C activity of these nitriles in dogs was primarily in the region of the heart, liver, and kidneys followed by rapid redistribution to the parotids and stomach with [11C]hydroxymandelonitriles. 11C-Labeled mandelic acid and m-methyl-, o-chloro-, and p-chloromandelic acid were synthesized from the corresponding [11C]mandelonitrile. Serial scintigraphy of 11C activity of these mandelic acids in dogs showed progressive renal excretion with accumulation of activity in the bladder. 11C-Labeled ethyl and benzyl mandelate were synthesized from [11CA]mandelic acid. These esters showed initial accumulation of activity in the lungs with eventual excretion by the kidneys.


Relationship between structure and antineoplastic activity of arylsulfonylhydrazones of 2-formylprydine N-oxide. The effects of various structural modifications on the antineoplastic activity of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide have been ascertained in mice bearing either Sarcoma 180 or leukemia L1210. To accomplish this a variety of derivatives substituted at the aldehyde proton, the aryl ring, and the 4 position of the pyridine nucleus were synthesized. Antineoplastic activity was retained when nitro, amino, chloro, bromo, fluoro, and methoxy groups were introduced into either the meta or para positions of the phenyl ring of the parent compound. In addition, substitution of the terminal phenyl group by a pyridine ring or by a bulky aromatic  ring such as alpha-naphthyl, beta-naphthyl, or fluorenyl did not abolish the marked antitumor activity expressed by this class of agents. Insertion of a nitro function or a morpholino group in the 4 position of the pyridine nucleus of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide resulted in two potent anticancer agents, while the introduction of a chloro function in the 4 position led to a pronounced decrease in biological activity. Furthermore, the essentiality of the aldehydic proton for tumor-inhibitor activity was demonstrated by the inactivity of two derivatives in which the aldehydic proton was replaced by a methyl group or by an oxygen atom.


Chemical modification of 1,4-diamino-1,4-dideoxy-3-O-(4-deoxy-4-propionamido-alpha-D-glucopyranosyl)-D-glucitol. Chemical modification of the 4'-N position of 1,4-diamino-1,4-dideoxy-3-O-(4-deoxy-4-propionamido-alpha-D-glucopyranosyl)-D-glucitol (GlA1) in the form of 4'-N-acyl analogues, e.g., 3, led to no significant potency enhancement. The n-propylamino analogue 4 was more active against gram-positive bacteria but was less act vs. gram-negative bacteria. The intrinsic activity of the 6'-chloro analogue 15 like the antibiotic GlA1 was not high, but the antibacterial spectrum was broad with moderate activity against most resistant organisms.


Dehydrative metabolites of 1-(3-chlorophenyl)-1methyl-2-phenyl-2-(2-pyridine)ethanol as potential hypocholesteremic agents. The E and Z isomers of 2-[2-(3-chlorophenyl)-1-phenyl-1-propenyl]pyridine (2a,b) and 2-[2-(3-chlorophenyl)-1-(4-hydroxyphenyl)-1-propenyl]pyridine (4a,b) were synthesized and separated as possible metabolites of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1a). Following administration of 1a to rats, a HPLC system was used to examine urine and serum specimens for the less polar metabolites of 1a. Isomers 2a and 2b were not detected but their hydroxylated derivatives 4a and 4b were observed as minor metabolites. Compounds 2a,b and 4a,b exhibited hypocholesteremic activity in rats; compounds 4a and 4b are of special interest because they possessed relatively low estrogenicity.


Conformations of selected 3-substituted 4-hydroxycoumarins in solution by nuclear magnetic resonance. Warfarin and phenprocoumon. The chemical shift position of the benzylic proton, Hx, has been found to be diagnostic in indicating the preferred conformations of selected 3-substituted 4-hydroxycoumarins. In general, the nonrigid open-chain compounds, e.g., to open-chain tautomer of warfarin and phenprocoumon, are found to exist in equal populations of the two conformations in which the benzylic proton is in the plane of the coumarin ring and is either cis or trans to the 3,4 double bond. The cyclic compounds, e.g., cyclocumoral, are constrained to two limiting conformations defined as axial2 or trans or intermediate conformations between these limits. Evidence is presented that suggests that the antivitamin K activity of warfarin is due to its open side-chain tautomeric form.


Methyl 6-(phenylsulfinyl)imidazo[1,2-a]pyridine-2-carbamate, a potent, new anthelmintic. A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.


Assessment of orthoses by means of speed and heart rate. Energy expenditure is an important parameter in the assessment of gait and orthotic treatment of heavily handicapped patients, since any orthosis which increases the effort required is likely to be discarded with consequently disturbing implications. Heart rate has been shown to be a reliable monitor of energy expenditure and is convenient because ECG can be telemetered by a miniature radio transmitter. Using a transmitter causes minimal interference with the patient, but care must be employed to obtain ECG signals free of artefact from subjects who are exercising. Means of reducing artefact are discussed, as are ways in which heart rate monitoring by radio telemetry is being used in the routine assessment of orthotic treatment of paediatric patients and the development of new orthotic devices.


Community services: technological aids for the general practitioner. This paper deals with the problem of an overworked National Health Service. It tries to show how increased services at community level could lessen the burden of the hospital services. It outlines the part played by technological aids with the history of some, and stresses the need not only for medically trained ancillary help, but also for the involvement of other trained disciplines and lawmen. It mentions present day technological aids and discusses how they might be improved. It hints that all are capable of making an emphatic contribution, however small, to those in need.


Human infections with thymine-requiring bacteria. Clinical details are presented of 16 patients from whom thymine-requiring (thy-) mutants of pathogenic organisms were isolated; all had been treated with co-trimoxazole. The urine of six patients infected with thy- mutants contained levels of a thymine-like compound sufficient to support their growth. This might be the result either of the breakdown of pus cells or of thymine production by living bacteria that persist in stones or scar tissue, a suggestion supported by the observation of mutant growth "in satellitism" in vitro. Since 1975 we have isolated mutants from patients who have had short courses of co-trimoxazole, in contrast to those we reported upon previously, all except one of whom had had long courses. We are now isolating thy- mutants more frequently than hitherto. Secondary mutations to a low thymine requirement may now be occurring more rapidly, thereby allowing more mutant organisms to survive. The clinical significance of infection with thy- mutants is not yet clear, but evidence is accumulating that they are pathogenic. Alternative chemotherapy is suggested for patients from whom such mutants have been isolated.


The dependence of some strains of Mycobacterium avium on mycobactin for initial and subsequent growth. This paper demonstrates that various degrees of mycobactin dependence exist within the M. avium group of mycobacteria and that this characteristic is not confined to M. paratuberculosis. The strains employed came from a wide range of animal species and all were virulent for chickens. Mycobactin dependence was observed in the M. avium serotypes 1, 2 and 3. The importance of employing a medium containing mycobactin for primary isolations observation may be of interest in relation to the primary isolation of other species of mycobacteria.


Detoxification of staphylococcal alpha toxin by hydrocortisone and methylprednisolone. The effects of hydrocortisone (HC) and methylprednisolone (MP) on the biological activities of staphylococcol alpha toxin were studied. Incubation of either HC or MP at concentrations of 4-8 mg per ml with purified alpha toxin (690 HU per ml) reduced or eliminated haemolytic activity for rabbit red cells, intraperitoneal lethality for mice, and dermonecrotic activity for rabbits. Detoxification was related to the dose of steroid, and MP was slightly more active than HC. The mechanism of detoxification apparently involves a direct molecular interaction between alpha toxin and steroid, and pretreatment of animals with HC or MP did not enhance their resistance to the subsequent effect of toxin.


Nitrosamine formation in human saliva.

Nitrosamine formation in human saliva. Nitrosamines formed when secondary amines were added to normal human saliva. Fractionation of saliva into cells and supernatant showed that factors that accelerated and retarded the nitrosation reaction were both present. Acidification of saliva greatly increased the nitrosamine yield, but differences in nitrosamine yield among saliva fractions were still observable.


Kinetic response to cultured human lymphoid cells to rubidazone. Analysis of rubidazone, the benzoylhydrazone derivative of daunorubicin, for its effects on cell cycle progression of a human lymphoid cell line showed a kinetic response pattern similar to that of adriamycin. Thus rubidazone induced a G2-block, the magnitude and duration of which were dependent on concentration and incubation time. However, in contrast to adriamycin, a marked phase-dependent sensitivity for the induction of G2-accumulation was observed; cells treated in early and mid-S-phase were most sensitive. This age-dependent kinetic response may account for the smaller G2-accumulation in asynchronous cultures and the closer correlation of the magnitude of this kinetic effect with concentration and duration of rubidazone treatment. Prolonged exposure to high concentrations of rubidazone also delayed the traverse through G1 and/or the G1-S transition, whereas the S-phase transit was not impaired. Interference with cell cycle progression through G1 into S-phase caused a stepwise accumulation of cells in G2-phase.


Proliferative changes in the epithelium of the human lithiasic gallabladder. Surgical specimens from 9 normal human gallbladders and from 9 lithiasic gallbladders were incubated in vitro with [3H]thymidine. Autoradiography was used to observe the cells in DNA synthesis in the mucosal epithelium. The percentages of labeled cells (labeling index) and of mitotic figures (mitotic index) were estimated. In the normal gallbladder, the labeling index was low and mitotic figures were exceptional; the labeled cells in the epithelium were observed against the basal membrane. In the lithiasic gallbladder, the labeling index was 23 times higher (P less than 0.01) and a definite number of mitotic figures was seen; the uptake of [3H]thymidine was not restricted to basal epithelial cells and occurred at any level of the mucosa. Our data showed that the proliferative activity was increased in the mucosa of the human lithiasic gallbladder. To the extent that the labelled cells against the basal membrane in the normal gallbladder represent the epithelial progenitors, our results also indicated modifications in the spatial distribution of labeled cells in the lithiasic gallbladder mucosa. Such concomitant quantitative and qualitative changes in cell kinetics could have a parallel in known precancerous conditions in the digestive tract.


Estrogen, progesterone, and androgen receptors in breast cancer in the Japanese: brief communication. Estrogen, progesterone, and androgen receptors (ER, PgR, and AR, respectively) were determined by dextran-coated charcoal assay analyzed with Scatchard plots in cytosols from 81 Japanese patients with breast cancer. For the estimations of PgR and AR, the following compounds were used: a synthetic progestin, [3H]R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), not bound by corticosteroid-binding globulin; and a synthetic androgen, [3H]R1881 (17beta-hydroxy-17-methylestra-4,9,11-trien-3-one), not bound by human sex steroid plasma-binding protein. Forty-two of 81 of the cancers revealed measurable amounts of ER (greater than 2 fmoles/mg cytosol protein), whereas the rates of measurable amounts of PgR (greater than 5) and AR (greater than 5) were 27% (18/67) and 36% (17/47), respectively. PgR were found in 45% of cancer patients with ER, but in only 9% of the cancer patients without ER. AR were found in 50% of the cancer patients with ER, but in only 22% of the cancer patients without ER. These results are consistent with those reported by Western investigators.


Lung cancer in coastal Georgia: a death certificate analysis of occupation: brief communication. A comparison of death certificate statements on occupation for 858 white males who lived in coastal Georgia counties and who died of lung cancer during 1961--74, and for 858 controls who were of the same age and county of residence revealed a twofold excess risk of lung cancer associated with the construction industry. No elevated risk of lung cancer was found for workers in the wood and paper industries in the urban areas of Savannah, Brunswick, or Waycross, but a threefold increase was uncovered for the remaining coastal counties where the wood and paper industry was the largest employer.


Continuous production of carcinoembryonic antigen in hollow fiber cell culture units: brief communication. A line of cultured cells derived from a primary human adenocarcinoma of the colon was grown in the extracapillary spaces of hollow fiber tissue culture units in the absence of serum components of high molecular weight (greater than 10,000). The cells were capable of producing more than 30 microgram of carcinoembryonic antigen (CEA) per day, provided that the extracapillary fluid was changed frequently. The concanavalin-A binding and molecular sieve chromatography properties of the tissue culture-derived CEA were similar to those of CEA isolated from metastatic colon cancer tissue.


Effects of diethyl maleate on aryl hydrocarbon hydroxylase and on 3-methyl-cholanthrene-induced skin tumorigenesis in rats and mice. Topical administration of diethyl maleate (DEM) and L-methionine sulfoximine (MS) reduced the L-glutathione (GSH) levels in kidneys, livers, and skin of inbred BALB/c mice. Topical administration of DEM to BALB/c mice also increased the latency period before development of skin tumors that were induced by 3-methylcholanthrene painting. Similar treatment with MS also increased the latency period, though the delay was not as striking as that observed after DEM administration. Furthermore, DEM, which was believed to be specific in its action in reducing tissue GSH, was also capable of inhibiting aryl hydrocarbon hydroxylase (AHH) both in vitro and in vivo. Cyclohexene sulfide, another "specific" inhibitor of GSH transferase, inhibited AHH activity as well. Accordingly, the blockade of AHH by DEM may have been partly responsible for the increased latency time in the skin tumorigenesis experiments.


Histologic and histochemical preneoplastic changes in the bladder mucosae of dogs given 2-naphthylamine. So that the earliest morphologic changes produced in dog bladders by a bladder carcinogen could be detected, 25 mg 2-naphthylamine/kg was given daily to dogs for 1, 6, and 36 weeks. Among early changes observed in some, but not all, dogs at 1 and 6 weeks were a loss of the bladder luminal membrane, hyperplasia of the epithelium, and lymphocytic infiltration of the submucosa. These changes were also present, to a more severe degree, in all dogs at 36 weeks. A more advanced preneoplastic change observed only at 36 weeks was a scalloped appearance of the normally straight basal cell line due to the beginning of nodule formation of the hyperplastic epithelial cells (von Brunn's epithelial nests). Histochemically, the alkaline phosphatase activity was altered from the normally regular, dense staining of the basal cell layer to a weaker, intermittent staining. No tumors were observed. Of the dogs given the same dose of 2-naphthylamine for 26 weeks and then kept for 3 years before being killed, 2 dogs had normal bladders but the other 2 had epithelial carcinomas.


Chemotherapeutic activity of new 2-chloroethylnitrosoureas in rat L5222 leukemia: comparison of bifunctional and water-soluble derivatives with 1,3-bis(2-chloroethyl)-1-nitrosourea. The chemotherapeutic activity of eight nitrosourea derivatives was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in transplantable rat leukemia L5222 cells. Bifunctional 1,1'-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas effected cure rates between 30 and 75% in single equitoxic doses in the therapy of advanced ip implanted L5222 [staging of L5222 leukemia development (hr before median day of death in controls): early = greater than 120; advanced = 120--61; late = 60--25; and preterminal = 24--0]. Of three water-soluble monofunctional alkylating 1-(omega-hydroxyalkyl)-3-nitrosoureas, 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea yielded more cures (90%) than did BCNU (cure rate, 70%) and was also superior to the other substances. Against preterminal ip implanted and late intracerebrally implanted L5222, the hydroxyethyl compound was significantly superior to BCNU.


Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies. Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.


Spontaneous regression of syngeneic transplanted tumors in rats pretreated with the antileukemia drug busulfan. Lethal growth of a syngeneic transplanted tumor (KMT-17) was inhibited in WKA rats pretreated with the antileukemia drug busulfan. The effect of busulfan was short-lasting, and administration of the drug after tumor challenge had little effect on the lethal growth of the tumor. After spontaneous regression of the tumor in rats pretreated with busulfan, specific transplantation resistance to identical tumor was acquired. Busulfan did not exhibit its effect in rats irradiated before tumor challenge. As shown by the Winn test, spleen cells from rats immunized with inactivated tumor cells after busulfan treatment inhibited growth of admixed tumor cells more strongly than did spleen cells from rats immunized without busulfan treatment. Enhancement of immune response to tumor cells rather than tumoricidal activity by busulfan was suggested.


Lack of susceptibility of F344 rats to mammary tumor induction by topically applied fluorenylacetohydroxamic acids and their acetates. Carcinogenicity of N-hydroxy-N-3-fluorenylacetamide for the mammary glands of female inbred F344 rats was examined after systemic and topical administration. The compound given ip produced a 60% mammary tumor incidence but was only marginally active after topical application. Female F344 rats did not develop mammary tumors after topical application of N-hydroxy-N-2-fluorenylacetamide, N-acetoxy-N-2-fluorenylacetamide, or N-acetoxy-N-3-fluorenylacetamide. These results contrasted with those reported earlier for female Sprague-Dawley rats and indicated differences in susceptibility of the mammary glands of these rat strains to tumor induction by these carcinogens.


Failure of immunotherapy with neuraminidase-treated tumor cell vaccine in mice bearing established 3-methylcholanthrene-induced sarcomas. C3H/HeJ mice bearing MC-80 fibrosarcomas were given immunotherapy consisting of multiple injections of a Vibrio cholerae neuraminidase (VCN)-treated tumor cell vaccine at a site remote from the established tumor. In five separate experiments we were unable to show either partial or complete tumor regression or prolongation of survival for vaccine-treated mice compared to appropriate controls. Further, the use of BCG in addition to VCN-treated tumor cells failed to show any therapeutic efficacy. We could not confirm the successful immunotherapy results reported by others despite multiple efforts of reproduce the immunotherapy model as carefully and precisely as possible.


A procedure for culture of cells from mouse tail biopsies: brief communication. A simple technique was developed for production of cell cultures from mouse tails. The use of mouse tail tissue for biopsies made repeated sampling of animals possible without their health or breeding performance being jeopardized. The procedure proved to be particularly useful in studies of murine leukemia viruses, because it allowed virus induction and Fv-1 gene-typing tests to the done on biopsy tissue from adult animals.


Penetrating wounds of the neck and upper thorax. During the past decade, a method utilizing individual case assessment has been employed in the treatment of 51 patients with penetrating wounds of the neck and upper thorax. Only those wounds penetrating the platysma are included. Thirty-five patients (68.6%) underwent neck exploration; 16 patients (31.4%) were managed nonoperatively. Overall, five patients died, four patients following operative treatment and one treated nonoperatively, for a mortality rate of 9.8%. In the nonoperative group, a mortality of 6.2% (one death) compares favorably with an operative mortality of 11.4% (four deaths). Ten patients (29%) in the neck exploration group exhibited significant later morbidity compared to seven patients (44%) in the patients not explored. Therefore the morbidity from a negative neck exploration was only 2% (one of 20 patients). The techniques for exploring the neck are discussed. Adequate surgical exposure is largely dependent on the possibility of vascular injury, the most common cause of death in this series.


Free fatty acid and arterial oxygen changes following major injury: a correlation between hypoxemia and increased free fatty acid levels. In a study of uncomplicated patients following major long-bone fracture, plasma free fatty acid levels were found to be statistically significantly higher in those with multiple injury within 12 hours of injury. Arterial oxygen tension was significantly lower in these patients 12 and 24 hours postinjury. A strong  positive correlation was found between high FFA and low arterial oxygen tensions in all cases up to 24 hours after injury. The implications of these findings in relation to fat embolism (or post-traumatic) syndrome are discussed.


Effect of glucagon on hepatic lymph (tissue) PO2 after ligation of the hepatic artery: an experimental study. In 17 greyhound dogs, hepatic oxygenation was examined after hepatic artery ligation (HAL) and subsequent administration of pharmacologic dosages of glucagon during various hemodynamic maneuvers at different per cents of oxygen in the inspired air. Measurements included arterial and portal pressure, PO2 and O2 content of arterial, portal and hepatic venous blood, and hepatic lymph (tissue) PO2. The following were observed: 1) an increase in FIO2 progressively raised hepatic lymph (tissue) PO2; 2) distal HAL decreased hepatic oxygenation; 3) a decrease in portal oxygen delivery by cross-clamping the superior mesenteric artery (X-SMA) aggravated hepatic deoxygenation induced by HAL; 4) with normovolemia and HAL, glucagon increased portal O2 delivery and hepatic venous blood O2 content, but either failed to raise hepatic lymph PO2 (FIO2 of 21% or 40%) or did so transiently (FIO-100%); 5) with an FIO2 of 100%, induced hemorrhage or X-SMA in conjunction with HAL blocked a rise in hepatic lymph PO2 after glucagon. It is concluded that administration of glucagon after HAL increases hepatic O2 delivery via the portal system, but nonetheless has minimal overall effect on hepatic tissue PO2. Accordingly, use of this agent after HAL in patients is probably of limited practical value in raising hepatic tissue PO2.


Decreased activity of NADPH oxidase in alveolar macrophages as a result of traumatic shock. NADPH oxidase activity is significantly decreased in alveolar macrophages isolated from rabbits subjected to traumatic shock. In vitro studies indicate that activity of the enzyme is depressed in subcellular fractions of both resting and phagocytosing macrophages from shocked animals. Phagocytosis stimulates a twofold increase in NADPH oxidation in control alveolar macrophages, whereas NADPH oxidase activity is stimulated to a much lesser degree in macrophages from shocked animals. Results of this study suggest that the decreased activity of NADPH oxidase in alveolar macrophages from shocked animals may be associated with decreased bactericidal ability of the cells which was reported in a previous study (9).


Buckshot wounds.

Buckshot wounds. The differences between wounds due to conventional shotgun (shot) injuries and those inflicted by buckshot are inadequately appreciated by most clinicians. Cadaver extremities were used as targets for 12-gauge loads of No. 6 shot and 00 Buckshot to portray some of the "wounding" characteristics of these popular shotgun loads. "Wounds" so produced were consistent with expected ballistic performance of these projectiles. The lethality of buckshot wounds is discussed, four clinical cases are described, and the wounding mechanisms are briefly outlined.


Autosterilization in low-velocity bullets. Following a previous study (1) in which contaminated low-velocity bullets were discharged into sterile gelatin blocks with resultant growth of organisms along projectile tracts, the authors fired bullets coated with 1 drop of Staph. aureus-contaminated medium and bullets under sterile conditions into sterilized sand. Each contaminated projectile and its gun barrel were culture positive after firing. Therefore bullets should not be ruled out as possible sources of infection.


Bilateral perilunate dislocations: case report with review of literature and anatomic study. A 33-year-old man suffered bilateral perilunate dislocations with concomitant rotary subluxations of the navicular treated with open reduction and internal fixation. Anatomic studies revealed a thick V-shaped volar radio-carpal ligament one portion of which tethers the lunate to the radius in a sling with the volar ulna-carpal ligament, and the other portion with a variable insertion on either the navicular waist or the capitate, which may account for the variety of the carpus injuries that have been reported.


Chip fracture through the superior articular facet with compressive cervical radiculopathy. Four patients with cervical radiculopathy secondary to a chip fracture through the superior articular facet have been treated in the past 2 years. These small-element fractures may occasionally pass unrecognized. Although oblique X-rays are helpful, lateral tomography has provided the most precise detail. The pathological process is a compressive radiculopathy, explicable on the basis of the foraminal anatomy. The authors feel myelography is not essential. The preferred surgical approach is posterior: the results have been excellent.


Hemorrhage from open pelvic fracture controlled intraoperatively with balloon catheter. In the case reported, many techniques for controlling bleeding from an open pelvic fracture were employed without success. With arteriographic identification of a precise arterial bleeding point, control of hemorrhage was accomplished by proximal hypogastric artery ligation with distal intraarterial placement of a balloon catheter.


Pulmonary edema in cervical spinal cord injury. A 15-year-old patient with acute cervical spine injury (C5) and pulmonary edema is presented. There was no craniocerebral injury. Causes other than the injury are excluded. Acute cervical spine injury appears to be another cause of noncardiogenic pulmonary edema.


Mechanism for control of synthesis of Semliki Forest virus 26S and 42s RNA. When cells infected with the Semliki Forest virus (SFV) mutant ts-4 were shifted to the nonpermissive temperature, synthesis of 26S RNA ceased, whereas synthesis of 42S RNA continued normally. These two single-stranded SFV RNAs are synthesized in two types of replicative intermediate (RI), 26S RNA in RI(b) and 42S RNA in RI(a). Cessation of 26S RNA synthesis after shift up in temperature was accompanied by loss of RI(b). When infected cells were shifted back down to 27 degrees C, 26S RNA synthesis resumed, coincident with the reappearance of RI(b). In both types of RI, the 42S minus-strand RNA is template for synthesis of plus-strand RNA. In pulse-chase experiments, we obtained RIs labeled only in their minus-strand RNA, and thus could follow the fate of RIs assembled at 27 degrees C when they were shifted to 39 degrees C. Our results show that, after shift up to 39 degrees C, there was a quantitative conversion of RIs in which 26S RNA had been synthesized to RIs in which 42S RNA was synthesized. This conversion of RI(b) to RI(a) was reversible, since RIs in which 26S RNA was synthesized reappeared when the infected cultures were shifted back down to 27 degrees C. We propose that, associated with RI(b), in which 26S RNA is synthesized, there is a virus-specific protein that functions to promote initiation of 26S RNA transcription at an internal site on the 42S minus-strand RNA and to block transcription on the minus strand in this region by the SFV RNA polymerase that had bound and was copying the minus-strand RNA from its 3' end. A ribonuclease-sensitive region would thus result in the sequence adjacent to the one that was complementary to 26S RNA. This virus-specific protein is not a component of the SFV RNA polymerase that continues to transcribe 42S RNA, and it is temperature sensitive in ts-4 mutant-infected cells. When this virus-specific protein is not present on RIs, the SFV polymerase transcribes the whole 42S minus-strand RNA and yields 42S plus-strand RNA.


Replication process of the parvovirus H-1. X. Isolation of a mutant defective in replicative-form DNA replication. A temperature-sensitive mutant of H-1, ts14, that is partially defective in replicative-form (RF) DNA synthesis has been isolated. ts14 H-1 is characterized by a decrease in plaque-forming ability and production of infectious virus at the restrictive temperature of 39.5 degrees C. RF DNA synthesis of ts14 is reduced to 3 to 7% of that of wild-type H-1 at either the restrictive or the permissive temperature. A complementation analysis of RF synthesis of ts14 and a viable defective H-1 virus, DI-1, or wild-type H-3 indicates that the defective RF DNA synthesis of ts14 is cis-acting. ts14, unlike wild-type H-1, causes a multiplicity-dependent inhibition of DI-1 or H-3, but not LuIII, RF DNA synthesis. Mixed infections of cells with two parvoviruses also exhibited a cross-interference for viral protein synthesis that was multiplicity dependent, ts14 inhibited infectious virus production of H-1 or H-3, but not LuIII. LuIII-or H-3-pseudotype particles were produced by coinfection with H-1. H-3 and H-1 showed similar interactions with ts14, and H-3 DNA was more homologous to H-1 than was LuIII by comparative physical mapping studies. The results suggest that ts14 is a mutant with a defect in a regulatory sequence of its DNA that influence RF DNA replication.


Intracellular synthesis of measles virus-specified polypeptides. The intracellular synthesis of measles-specified polypeptides was examined by means of polyacrylamide gel electrophoresis of cell extracts. Since measles virus does not efficiently shut off host-cell protein synthesis, high multiplicities of infection were used to enable viral polypeptides to be detected against the high background of cellular protein synthesis. The cytoplasm of infected cells contained viral structural polypeptides with estimated molecular weights of 200,000, 80,000, 70,000, 60,000, 41,000, and 37,000. All of these structural polypeptides, with the exception of P1, the only virion glycoprotein (molecular weight congruent to 80,000), were also found in the nuclei. In addition, two nonstructural polypeptides with estimated molecular weights of 74,000 and 72,000 were also present in the cytoplasm of infected cells. The initial synthesis of the smaller, nonstructural polypeptide began later in infection than the structural polypeptides. Pulse-chase experiments failed to detect any precursor-product relationships. The intracellular glycosylation and phosphorylation of the viral polypeptides were found to be similar to those found in purified virions.


Common sequence at the 5' ends of the segmented RNA genomes of influenza A and B viruses. Guanylyl- and methyltransferases, isolated from purified vaccinia virus, were used to specifically label the 5' ends of the genome RNAs of influenza A and B viruses. All eight segments were labeled with [alpha-(32)P]guanosine 5'-triphosphate or S-adenosyl[methyl-(3)H]methionine to form "cap" structures of the type m(7)G(5')pppN(m)-, of which unmethylated (p)ppN- represents the original 5' end. Further analyses indicated that m(7)G(5')pppA(m), m(7)G(5')pppA(m)pGp, and m(7)G(5')pppA(m)pGpUp were released from total and individual labeled RNA segments by digestion with nuclease P1, RNase T1, and RNase A, respectively. Consequently, the 5'-terminal sequences of most or all individual genome RNAs of influenza A and B viruses were deduced to be (p)ppApGpUp. The presence of identical sequences at the ends of RNA segments of both types of influenza viruses indicates that they have been specifically conserved during evolution.


Characterization of adenovirus-associated virus-induced polypeptides in KB cells. Electrophoretic analysis of KB cells coinfected with adenovirus-associated virus (AAV) type 2, a defective parvovirus, and adenovirus type 5 (as helper) have revealed the synthesis in vivo of at least five AAV-specific polypeptides. The three largest polypeptides, with molecular weights of 90,700, 71,600, and 60,000 comigrated in polyacrylamide gels with the three AAV structural polypeptides. The remaining two polypeptides had molecular weights of 24,900 and 15,800. The concentrations of the AAV-induced polypeptides relative to one another remained approximately constant during the infectious cycle, and the structural components were present in proportions similar to those found in purified virions. As determined by pulse-chase experiments, all polypeptides were generated at the level of protein synthesis and not by posttranslational proteolytic processing. Although inhibitors of proteolytic enzymes failed to influence the pattern of AAV-induced polypeptides, and amino acid analog, L-canavanine, blocked the appearances of both the major structural polypeptide (60,000 daltons) and the larger nonstructural polypeptide (24,900 daltons). Taken in conjunction with pulse-chase data, this result supports a model whereby the major virion polypeptide is produced by proteolytic cleavage of the nascent polypeptide chain.


Synthesis of polynucleotide 5'-triphosphatase in vaccinia virus-infected HeLa cells. Synthesis of polynucleotide 5'-triphosphatase, which is presumably involved in the initial modification in the series of reactions by which 5'-termini of vaccinia mRNA become capped and methylated, has been demonstrated in vaccinia virus infected HeLa cells. Synthesis of the enzyme is prevented by actinomycin D and cycloheximide, suggesting that both de novo DNA-dependent RNA and protein syntheses are required. On the other hand, cytosine arabinoside, an inhibitor of viral DNA replication, does not prevent induction of the enzyme. The latter observation, together with the kinetics of synthesis of the enzyme in vaccinia virus-infected HeLa cells, suggests that polynucleotide 5'-triphosphatase is an "early" or prereplicative viral protein. Immunologlobulin produced against the purified virion-associated polynucleotide 5'-triphosphatase as antigen neutralized the activity of the induced polynucleotide 5'-triphosphatase, thus indicating the identity of the two enzymes.


Inhibition of maturation of Rauscher leukemia virus by amino acid analogs. Synthesis of primary precursor polyproteins of Rauscher leukemia virus (RLV) core and envelope proteins occurs in the presence of amino acid analogs canavanine and p-fluorophenylalanine, but cleavage of these precursors is severely inhibited or slowed down. After treatment with these agents, the release of characteristic virus or stable virus-like particles is greatly depressed.


Rauscher leukemia virus populations enriched for "immature" virions contain increased amounts of P70, the gag gene product. Preparations of Rauscher leukemia virus (RLV) that had relatively low, intermediate, or high levels of P70 (the gag gene product) on sodium dodecyl sulfatepolyacrylamide gel electrophoresis were examined by thin-section electron microscopy. A direct correlation was found between the number of immature virions in the RLV preparation and the amount of P70. The immature core subparticles isolated from these RLV preparations could themselves be further subdivided into two categories, based on their P70 content and negative stain morphology. Those immature cores containing a high P70/p30 ratio predominantly (85%) exhibited a highly coiled internal structure; those with a relatively low level of P70 exhibited less of an internal coiled structure.


Reversible inhibition of Sindbis virus penetration in hypertonic medium. Under hypertonic conditions, the penetration of baby hamster kidney cells by Sindbis virus was inhibited. Virus became cell associated, but remained susceptible to neutralization by specific antiserum and to removal by elution. When cells were returned to isotonicity, inhibition was reversed.


Revised location of the rIII gene on the genetic map of bacteriophage T4. Two- and three-factor crosses showed that the T4 rIII gene is located between genes 31 and 30 rather than between genes 31 and 63.


Procedure for purification of intact DNA from vaccinia virus. A procedure for the isolation of intact vaccinia DNA molecules by chromatography on hydroxyapatite in the presence of 6 M urea is described. When lysates of virions containing 0.5 to 10 microgram of DNA were employed, over 95% of the viral DNA could be recovered free of poteins. Vaccinia DNA molecules isolated in this manner sedimented at 68S in neutral sucrose gradients and had an average contour length of 62.3 micrometer when examined in an electron microscope, and the DNA could be cleaved with the restriction endonuclease EcoRI and BamHI. The results of these analyses showed that intact vaccinia DNA molecules of 120 X 10(6) to 130 X 10(6) molecular weight could be obtained by the procedures described.


Effect of protein synthesis inhibitors on viral mRNA's synthesized early in adenovirus type 2 infection. Viral mRNA species synthesized early in adenovirus type 2 infection in the presence of cycloheximide were compared with those synthesized in the absence of drug or in the presence of the DNA synthesis inhibitor 1-beta-D-arabinofuranosylcytosine. Cycloheximide caused approximately a 10-fold stimulation in the accumulation of [3H]uridine into early viral mRNA species. The only exception was a 24s mRNA transcribed from the transforming end of the genome; in the presence of cycloheximide, accumulation of this mRNA species was stimulated no more than 2-fold. Treatment with cycloheximide also resulted in the accumulation of polyadenylated RNAs transcribed from EcoRI-C that are heterogeneous and smaller than the 20S mRNA. Other translation inhibitors were shown to have similar effects, suggesting that inhibition of protein synthesis early after infection induces alterations in the metabolism of specific RNA sequences.


Mutator and antimutator phenotypes of suppressed amber mutants in genes 32, 41, 44, 45, and 62 in bacteriophage T4. Bacteriophage T4 genes 32, 41, 44, 45, 56, and 62 are essential to DNA replication. Amber mutants (suppressed by su+1, su+2, or su+3 bacteria) in these genes were examined for any mutator or antimutator effects on the reversion of a transition mutation. In every case except for mutations in gene 56, elevated or lowered error frequencies were observed. These results indicate the importance of all of the replicative proteins in the determination of error frequency.


In vitro translation of the Two RNAs of Nodamura virus, a novel mammalian virus with a divided genome. Nodamura virus is a small ribovirus containing two RNA molecules. Both RNAs were found to be active messengers for protein synthesis in cell-free extracts prepared from wheat embryo or HeLa cells. RNA 2 directed synthesis of a 43,000-dalton product, p43, whose tryptic fingerprint was similar to that of the major viral coat protein, vp40 (molecular weight, 40,000). Though p43 appears to be a precursor of vp40, processing did not occur in the cell-free extracts. RNA 1 directed synthesis of a 105,000-dalton protein, p105. Its tryptic fingerprint revealed no evidence of coat protein sequences. Hence, the two RNAs represent genes with few, if any, redundant coding sequences.


Adenovirus type 2 mRNA in transformed cells: map positions and difference in transport time. Adenovirus type 2 rat transformed cells produced two polyadenylic acid-terminated mRNA's with approximate coordinates 1.5-4.4 and 4.4-11.0 on the physical map of the adenovirus type 2 genome. These mRNA's were also formed early during lytic infection in addition to one or more smaller mRNA's from the 4.4-11.0 region. In transformed cells, the 1.5-4.4 mRNA appeared in the cell cytoplasm without detectable lag, whereas the 4.4-11.0 mRNA required at least 20 to 30 min for the maximal rate of accumulation.


Chyluria: result of surgical treatment in 50 cases. We treated 50 patients with chyluria by stripping the renal pedicle. Until further studies reveal the etiology of chyluria ligation and stripping of the pedicle remain the treatment of choice and this fact has been borne out by our long-term results.


A laboratory evaluation of a new hydraulic incontinence device. A new hydraulic incontinence device is described. The device is physiologic because it can be deflated to allow resistance-free voiding and it is designed to respond instantaneously to fluctuations in intra-abdominal pressure, irrespective of whether the bulb is placed at the level of the bulbous urethra or the bladder neck. The device is simple, consisting only of a urethral cuff, an abdominal reservoir and 1 pump containing a single valve.


Surgical judgment in the management of vesicoureteral reflux. The varying pathological anatomy of the vesicoureteral junction in cases of vesicoureteral reflux requires the use of intraoperative judgment in the proper management of individual cases. A rigidly standardized operative technique should not be followed. Modification of the Politano-Leadbetter procedure, using various forms of ureteral advancement, is beneficial in selected cases.


Followup of cutaneous ureterostomy in children. Thirty-two children with cutaneous ureterostomies are reviewed, of whom 27 were evaluated with an average followup of 3 years 8 months. Of these 27 patients 26 had successful stabilization of the upper tracts as determined by gross radiographic and renal function parameters. The incidence of stomal stenosis and revisions is no worse than the reported rates in cases of ileal conduits followed for a comparable length of time. Proper patient selection and careful long-term followup are mandatory for the successful application of this procedure in children.


Cutaneous vesicostomy for temporary urinary diversion in infants with neurogenic bladder dysfunction. Cutaneous vesicostomy was used for temporary urinary diversion in 12 infants with neurogenic vesical dysfunction. Hydronephrosis, azotemia and clinical urinary infection were resolved in all patients. Postoperative complications consisted of diaper dermatitis in 42 per cent and vesical prolapse in 25 per cent.


Extended application of Nesbit ellipses in the correction of childhood penile curvature. The Nesbit procedure of excision of ellipses of tunica albuginea to correct distal hypospadias has been applied to more extensive penile curvature in children. The technique and a favorable experience with 8 patients so treated are describe.


Asymptomatic bilateral hypernephroma: an autopsy case report wtih discussion of possible etiologic factors. The first case of asymptomatic bilateral synchronous hypernephroma is described in a 52-year-old man who had a long history of alcoholic cirrhosis and died of uncontrollable gastrointestinal bleeding. The literature is reviewed briefly and relevant etiologic factors are discussed.


Squamous cell carcinoma of the renal pelvis presenting with hypercalcemia. A case of hypercalcemia associated with documented squamous cell carcinoma of the renal pelvis without bony metastasis is reported. Pseudohyperparathyroidism was suspected strongly because of the radioimmunoassay values of parathormone. This was confirmed by the prompt decrease of serum calcium after removal of the neoplasm. The radiologic findings were non-specific.


Upper urinary tract air: a benign finding indicating presence and degree of ureteral reflux. Two cases are reported in which air refluxed from the bladder to the pelviocaliceal systems after voiding cystourethrography. We stress that this is a benign condition, which can indicate the presence and degree of ureteral reflux.


Aspermia owing to obstruction of distal ejaculatory duct and treatment by transurethral resection. A case of a young aspermic male patient with bilateral atresia of the terminal ejaculatory duct is reported. He was treated successfully by transurethral resection of the prostate gland in the area of the ejaculatory ducts.


Bilateral nephrectomy for hypertension in patients with chronic renal failure on a dialysis program. During the last 6 years 33 bilateral nephrectomies have been performed for severe hypertension in patients with chronic renal failure on a dialysis program. Nephrectomy resulted in a prompt and sustained reduction in blood pressure, an improved sense of well-being and a gain of weight. Despite the fact that the mean hematocrit decreased from 25 to 18 per cent all patients thrived. The nephrectomy group showed an 85 per cent 5-year cumulative survival rate compared to 55 per cent in the non-nephrectomy group. There was 1 mortality and low morbidity. Simultaneous nephrectomy by 2 teams, using a posterior approach, proved more satisfactory than an anterior or bilateral flank apprach. The indications for and arguments against bilateral nephrectomy are discussed.


Bilateral renal cell carcinoma.

Bilateral renal cell carcinoma. Bilateral renal cell carcinoma was diagnosed simultaneously in 6 patients and sequentially in 4 patients, 3 to 14 years after the first tumor had been removed by nephrectomy. Four patients treated conservatively with incomplete excision of the malignant disease are alive 18 months to 14 years after diagnosis. Oue experience suggests that a radical excision, requiring renal dialysis or transplantation, is seldom warranted.


Isotope loopography, a new test: comparison with standard loopography and its relationship to renal function in patients with ileal conduit urinary diversion. Reflux associated with the classic ileal conduit has been implicated as possibly contributing to long-term renal deterioration. When demonstrated on a standard loopogram reflux occurs under highly non-physiologic conditions. A new method of radioisotope loopography performed under physiologic conditions was devised and compared to the standard loopogram. The standard loopogram is more of an indicator for the capacity for reflux. The isotope loopogram is a more specific indicator for reflux that is potentially detrimental to renal function. Approximately 50 per cent of ureteroileal anastomoses that permit reflux with conventional loopography do not do so under the physiologic conditions of the isotope loopogram.


Transurethral ureteroscopy in women: a ready addition to the urological armamentarium. Ureteroscopy via the transurethral route and limited to the terminal ureter in women lends itself to inclusion in the urological armamentarium. The technique requires no equipment other than routine urological instruments and makes endoscopic inspection, biopsy and resection within the distal ureter possible. The procedure is done with the patient under anesthesia, following urethral dilation to 32F. With the aid of a small caliber cystoscope, 20F or smaller, straight Jewett sounds can be passed into the urethra alongside the cystoscope and directed under cystoscopic control into the ureteral orifice. The orifice is then dilated gently, using 12, 14 and, if necessary, 16F sounds. One of the standard pediatric cystoscopes can then be introduced easily into the orifice. Currently, the technique is being used routinely in women with transitional cell carcinoma involving the ureteral orifice or intramural ureter. In 1 patient a tumor arising from within the lower ureter was resected successfully using a pediatric resectoscope.


Radical retroperitoneal surgery: a 25-year experience. A review of 210 radical retroperitoneal excisions performed through an abdominal or flank thoracoabdominal incision showed these procedures to be relatively safe. The flank approach had less morbidity and provided better exposure of the renal hilus and suprarenal areas. Pulmonary complications in the flank thoracoabdominal incision were reduced by closing the thorax with an indwelling pleural drainage tube. The flank thoracoabdominal approach is suitable for all radical retroperitoneal excision when extensive bilateral renal exposure is not needed.


Lymphangiography in staging patients with carcinoma of the bladder. Pedal lymphangiography was used in the evaluation of 28 patients with carcinoma of the bladder. Correlation of the lymphangiogram with histologic examination of the surgically excised pelvic and para-aortic nodes was less than 50 per cent and suggests limited applicability of this diagnostic technique in staging bladder cancer.


Evaluation of bladder washing cytology for bladder cancer surveillance. Urinary cytology is almost as accurate as cystoscopy in appraising the presence or absence of visible tumor. Falsely negative results are virtually limited to low stage, low grade tumors. Urinary cytology often provides information about the neoplastic state of the epithelium not provided by cystoscopic examination. Cytology has become practical and simple to do even as an office procedure. Urinary cytology must be considered an essential part of patient management in bladder cancer surveillance.


Prognosis in early carcinoma of the bladder based on chromosomal analysis. In 53 cases of non-invasive or submucosal invasive well differentiated carcinoma of the bladder observed for 4 to 101 months cytogenetic analysis by the direct technique (non-culture) has been performed repeatedly. Markers, abnormal chromosomes, have been found in 33 patients and recurrence has developed in 32 of these 33 patients, resulting in 9 deaths. All but 1 of the 20 patients without markers have been observed for up to 8 years and have remained free of recurrence. In this 1 recurrence, 8 months post-diagnosis, the mode changed from 69 to 92, evidence of dedifferentiation and development of a new tumor in a bladder prone to neoplasia. Based on our over-all cytogenetic experience with 165 patients with carcinoma of the bladder a simplified classification is presented. This classification, built on measurable characteristics of early carcinoma, including the presence or absence of marker chromosomes, allows accurate prognostication and, thus, provides the foundation for development of standard therapy.


The cell surface antigen A, B or O(H) as an indicator of malignant potential in stage A bladder carcinoma: preliminary report. The presence or absence of cell surface antigens (A,B and H) on the cell surface of bladder tumors has been studied. The major blood group antigens A, B or O(H) are present on normal bladder epithelium but are not present on some low grade and low stage papillary transitional cell carcinomas of the bladder. We have demonstrated that of 5 stage A bladder tumors that have not recurred in at least 5 years 3 retained the cell surface antigens, while tumors that have recurred locally, invaded or metastasized had lost these cell surface antigens on the original stage A tumor.


Tissue blood-group antigens and prognosis in low stage transitional cell carcinoma of the bladder. The loss of A, B or H blood-group antigens from the surface of neoplastic epithelial cells has been correlated with aggressive tumor behavior. We examined this phenomenon in low stage transitional cell carcinoma of the bladder. In an analysis of biopsy material from 37 patients the absence of these antigens on the original or recurrent tumors correlated with the subsequent development of invasive disease (stage B or greater), while the presence of antigens correlated with failure to develop invasive disease. Analysis of transitional cell surface antigens may help improve the therapy of bladder cancer.


Segmental resection in the management of bladder carcinoma. Segmental resection for bladder carcinoma was performed on 144 patients at our medical center between 1945 and 1971. Of these 144 cases 101 had sufficient documentation to provide meaningful data for a retrospective study. The 5-year survival rates for patients with invasive bladder carcinoma, expressed as a function of the stage of disease, were stage A--79 per cent, stage B1--80 per cent, stage B2--45 per cent and stage C--6 per cent. The combined survival rates for patients with stages O, A and B1 tumors and for those with B2 and C disease were 83 and 27 per cent, respectively. A significant observation was that of the patients with stages O, A and B1 disease only 7 per cent had a history of antecedent tumor. In contrast, 59 per cent of the patients with stage B2 and C disease had antecedent tumor.


Adjuvant chemotherapy for bladder cancer with doxorubicin hydrochloride and cyclophosphamide: preliminary report. We describe 25 patients with bladder cancer who received adjuvant chemotherapy with doxorubicin hydrochloride and cyclophosphamide after radical cystectomy. Two patients had stage A disease, 3 had stage B, 3 had stage C and 17 had stage D. The 2 patients with stage A tumors have been free of disease for 12 and 15 months, respectively, and the 3 patients with stage B tumors have been free of disease for an average of 25 months. Of the 3 patients with stage C tumors 2 have been free of disease for an average of 34.5 months. Of the 17 patients with stage D tumors 10 have been free of disease for an average of 1 year (59 per cent). These preliminary results seem to indicate the value of adjuvant chemotherapy with doxorubicin hydrochloride and cyclophosphamide in cases of bladder cancer.


Urologic complications of pelvic irradiation. We evaluated 964 patients who had undergone radiation therapy for malignant disease of the pelvic viscera during a 5-year period and who ahd been followed for 5 to 10 years after completion of treatment. Therapy had been given for gynecological tumors in 493 cases, genitourinary tumors in 240 cases, bowel tumors in 172 cases and various other malignant tumors in the pelvis in 59 cases. The incidence of cystitis, hematuria, ureteral obstruction and fistula formation was determined for each group. There were 203 urological complications, an incidence of 21 per cent, but only 25 of these complication (2.5 per cent) could be ascribed to the effects of radiation alone, the remainder being associated with persistent or recurrent tumor. Approximately 20 per cent of the patients had some abnormalities detected in the pre-treatment excretory urogram. The development of urologic complications was related to the radiation dosage and previous bladder operations.


Sarcoma of the bladder and prostate.

Sarcoma of the bladder and prostate. A retrospective analysis of 30 patients with primary sarcoma of the bladder and prostate is presented. Prognosis seems to be better in adults irrespective of the type of treatment. The survival rate is poor for children with sarcoma of the prostate. Two children were cured of sarcoma of the bladder by a radical operation. Sarcomas of the bladder and prostate are more common in adults more than 50 years old. The type of treatment and the results are reviewed. The place of multimodal treatment in the management of these sarcomas is discussed.


Carcinoma in situ of the urethra associated with bladder carcinoma: the role of urethrectomy. Carcinoma in situ of the urethral margin was demonstrated in 12 men who underwent radical cystectomy for bladder cancer. Six of the 7 patients who underwent simultaneous urethrectomy are free of the tumor but 4 of the 5 who did not undergo urethrectomy died of the disease. This dismal survival rate for patients with carcinoma in situ in the retained urethra indicates the necessity for clear-cut guide lines for the performance of urethrectomy. Frozen section of the urethral margin, as well as of both distal ureters, should be obtained at the time of operation, and urethrectomy, either simultaneous or during the same hospitalization, should be considered strongly for those with carcinoma in situ of the bladder neck or of the urethra.


Restoration of fertility by vasovasostomy. Vasovasostomy was performed on 41 patients. The surgical technique is described and the results are presented. The success rate was 83 per cent for pregnancy. Reasons for failure and suggestions for improvement in results are discussed.


One-handed prostatic biopsy needle.

One-handed prostatic biopsy needle. A dependable and disposable one-handed perineal prostatic biopsy needle has been developed. The needle makes it relatively easy to obtain multiple, good cores of tissue from the desired areas of the prostate gland without contamination of the needle or field by the rectal finger or hand.


Early stage prostatic cancer investigated by pelvic lymph node biopsy and bone marrow acid phosphatase. A prospective study was done to evaluate 47 patients with early stage prostatic cancer. Pelvic lymphadenectomy was combined with bone marrow acid phosphatase determination to evaluate early metastatic disease. Thirteen patients (28 per cent) had tumor in the pelvic lymph nodes. In no instance was the bone marrow acid phosphatase elevated to more than the normal value for serum by the substrate used. Combined high grade and stage tumors seemed to have an increased incidence of metastases to pelvic lymph nodes. A surprisingly high incidence of B1 lesions (5 of 21 patients or 24 per cent) had positive lymph nodes. Generally, the nodes were moderately well or well differentiated lesions. The metastases were unilateral, frequently microscopic only and involved 1 or only a few nodes. Pelvic lymphadenectomy seems to have a well defined role in the diagnostic study of early stage prostatic cancer, while bone marrow acid phosphatase determinations were of no value.


Specialty board certification rates. A longitudinal tracking study of US medical school graduates. This study is follow-up analysis of increments in specialty board certification rates occurring between 1971 and 1976 for 2,046 physicians who graduated in 1960, 1964, and 1968. Data obtained at 8-, 12-, and 16-year intervals following graduation from medical school indicate that it is not until 12 years' following receipt of the MD degree that most physicians will have entered the certification process or be certified. An additional increment is found 16 years following graduation. At eight and 12 years following graduation, the more recent graduates showed a much higher rate of board certification than earlier graduates at a comparable interval following graduation. Of the total study population, 81% are either board certified or in the certification process. When two essentially office-based specialties are excluded, 92% of the study population have formally entered the certification process.


Tuberculoma of the brain.

Tuberculoma of the brain. Four patients with cerebral tuberculomas had presenting manifestations that included seizure disorder, exophthalmos, or extremity weakness. Although rare in this country, this diagnosis should not be overlooked in such patients, since combined surgical and medical therapy may be curative.


Ultrasonic evaluation of pulsatile abdominal masses. Gray scale ultrasound B-mode scanning provides a rapid and safe method for evaluating the origin of a pulsatile midline abdominal mass. In those patients who do not have an aortic aneurysm, ultrasound will frequently provide another explanation. Tortuous aortas, pancreatic pseudocysts, metastatic cancers, lymphomas, and low-lying livers may all present as pulsatile masses clinically mimicking an aortic aneurysm. Visualization of the para-aortic soft tissues as well as the aorta allows these conditions to be distinguished by abdominal ultrasound.


Delayed hemolytic transfusion reactions. An often-missed entity. Delayed hemolytic transfusion reactions in eight persons were manifested solely or primarily by an apparently unexplained posttransfusion decrease in the hematocrit value. Alloantibodies were eventually found in all eight patients, but were sometimes undetectable for as long as 72 hours after the reaction. This did not preclude the occurrence of a new, acute hemolytic reaction. There were three instances of reversible renal failure complicating the reaction. In two patients, some or all of the antibodies became undetectable after four and nine months. In a third, the indirect antiglobulin reactions became considerably weaker after 12 months. Patients previously sensitized to RBC antigens should have available records inspected and a warning device (wristband or wallet card) provided to help prevent reactions caused by an anamnestic antibody rise.


Platelet aggregation. Adult-onset diabetes mellitus and coronary artery disease. Using a turbidimetric technique, we determined 1.7 micrometer adenosine diphosphate--induced platelet aggregation and disaggregation at 37 degrees C in the platelet-rich plasmas of two groups of men with coronary artery disease. Eleven men were nondiabetic and 11 had adult-onset diabetes mellitus without retinopathy. There were no significant differences (P greater than .05) between diabetics and nondiabetics of the following variables: age, platelet count in platelet-rich plasma, first and second phases of platelet aggregation, maximum extent of aggregation, and percent disaggregation at three minutes after maximum aggregation occurred. Although the mean adenosine diphosphate--induced platelet aggregation in the platelet-rich plasmas of adult-onset diabetic men with coronary artery disease and no retinopathy was not enhanced, and the mean rate of disaggregation was not reduced, when compared with nondiabetic men with coronary artery disease or with healthy men; a slow rate of platelet disaggregation (less than 10%) occurred more frequently in the platelet-rich plasmas of men with coronary artery disease.


Discontinuing anticoagulant therapy in surgical patients with cardiac valve prostheses. Observations in 180 operations. Between 1962 and 1975, a total of 159 patients with previously implanted man-made cardiac valve prostheses underwent 180 subsequent noncardiac operations at Mayo Clinic. All of these patients were receiving anticoagulants. The overall incidence of their documentable thromboembolic complications was approximately 10%. None of the postoperative complications occurred while the patient was in hospital, with the earliest such complication seen two years later. Patients receiving anticoagulants on a long-term basis did, however, have a 13% incidence of various difficulties with hemostasis during and following the later operations. We conclude that there is minimal risk to patients with cardiac valve prostheses who are receiving anticoagulants when the drug regimen is stopped for one to three days preoperatively and one to seven days postoperatively.


Precursor lesions in familial melanoma. A new genetic preneoplastic syndrome. In seven consecutive melanoma-prone families, pigmented lesions with distinctive clinical and histologic characteristics occurred in 18 of 20 melanoma patients (90%) and 24 of 43 first-degree relatives (56%). Recognition of these lesions led to the detection of early-stage melanoma in six family members. This syndrome appears to represent an autosomal dominant trait and may serve as a cutaneous marker to identify persons at high risk for melanoma.


[Combined action of weightlessness and ionizing radiation on the body of rats (based on data from morphological studies)]. The combined effect of weightlessness and ionizing radiation (24 hour exposure to Cs-137 at a total dose of 800 rad) was investigated morphologically in Cosmos-690 flight, synchronous and vivarium rats. Irradiation-induced lesions prevailed in both groups of rats. Comparative study of changes in flight and control rats showed that weightlessness and other space flight factors did not induce any new, previously unknown effects as compared with the exposure on the Earth; they did not exert a significantly aggravating effect on the development of radiation-induced lesions.


[Provision of radiation safety for the crew of the 2d Saliut-4 expedition]. The paper describes the radiation environment in the compartments of the orbital station Salyut-4 and in its flight orbit. It also discusses the measures taken to provide radiation safety of the crewmembers and the main results of radiation monitoring. During the flight the dose received by the crew was 1400 mrem.


[Lactate dehydrogenase isoenzymatic makeup of the skeletal muscles of rats after a flight on the Kosmos-690 biosatellite]. The isoenzyme composition of lactate dehydrogenase in the soleus and plantaris muscles of rats which had flown for 20.5 days onboard the biosatellite Cosmos-690 equipped with a radiation source was studied. Difference in the isoenzyme composition of lactate dehydrogenase in flight and synchronous rats disappeared 27 days after the experiments; however, some changes persisted as compared with vivarium controls. The data obtained give evidence that irradiation-induced effects in skeletal muscles manifested themselves at a far later stage than weightlessness-induced changes.


[Harmful action of radiations with different linear energy losses on the nerve cells of the rat cerebellum]. The damaging effect of 25 and 50 Mev protons, X-rays and Co60 gamma-rays on the cerebellar cells of rats of early postnatal period was studied. Radiosensitivity of neurons of different compartments of the cerebellar cortex varied significantly. Radiosensitivity of the inner and outer granular layers of the cerebellum to irradiation with 25 Mev protons was similar.


[Biological effects in the partial irradiation of dogs with high-energy protons]. Biological effects of irradiation of the head, chest and stomach of dogs with 250 Mev protons at a dose of 600 rad were investigated. Due to irradiation all the animals developed radiation sickness of moderate severity. A comparative study of the peripheral blood and immunobiological reactivity of the dogs showed that an exposure of the head exerted the least effect; an exposure of the chest and stomach had a very similar effect.


[Effect of space flight and of the accompanying radiation on amino acid metabolism in the skeletal muscle of rats]. It was demonstrated that a combined effect of 20.5-day space flight and gamma-irradiation reduced the content of biologically important amino acids (methionine, phenylalanine, serine, aspartic and glutamic acids) and inhibited the activity of aspartate aminotransferase of sarcoplasmatic proteins in the quadriceps muscle of rats. Comparison of these data with the Cosmos-605 results and literature reports suggested that gamma-irradiation inhibited the synthetic processes in the skeletal muscle.


[Functional activity of the testes of dogs exposed to chronic gamma irradiation over a 3-year course]. During three years 36 male dogs were exposed to chronic irradiation with a total dose of 21, 62 and 125 rad per year. tin addition to this irradiation at a dose rate of 62 rad per year, some dogs were also exposed to acute irradiations three times a year with a dose of 42, 8 and 8 rad and 42, 42 and 42 rad (at the combined irradiation the total doses were 120 and 190 rad per year). The study of the functional activity of testes gave the following results. The males that were chronically irradiated with a total dose of 125 rad per year showed hypospermia after 8-10 months of the experiment. The dogs that were exposed to combined irradiation displayed oligospermia after 5-7 months of the experiment which persisted throughout the period of 3 years. These effects depended on the dose rate, total dose and scheme of irradiation.


[Mammalian cell culture reaction to the action of a constant magnetic field of 1000 and 3000 Oe intensity]. The effect of a constant magnetic field of 1000 and 3000 oersted on mammalian cell cultures was examined. The effect of prolonged (12 days with three successive subcultures) and short-term intermittent action (repeated 6 times 60 min exposures with a 60 min interval) was studied. The magnetic effect was evaluated with respect to variations in the cell population density, mitotic activity and cytogenetic parameters. The experimental findings indicated that the magnetic fields of the above strength did not change significantly the rate of cell division and cell morphology neither did alter the genetic apparatus at the chromosomal level.


[State of the temporal organization of the system of cell reproduction in rat tissues under hypokinesia]. The study of time parameters of cell kinetics in the rats exposed to 34-day hypokinesia showed that changes in cell reproduction developed in rapidly and slowly renovating cells in a different way. The DNA synthesis and mitotic division were drastically inhibited in liver cells; the duration of the premitotic period of the mitotic cycle was significantly reduced in the cryptal epithelium of the small intestine. Hypokinesia did not cause important changes in the phasic structure of diurnal rhythms of cell division in the tissues tested and, consequently, did not lead to changes in the mechanisms of time organization of the cell reproduction system. It is concluded that the state of motor activity of animals is not the major time cue for cell division processes.


[Mathematical model of the postradiation recovery of the hematopoietic system]. The paper describes a mathematical model of hemopoiesis that takes into consideration postradiation arrest of mitoses and the stimulatory effect of a lack of functional cells on the yield of dividing cells into the maturing pool. Computer-aided modelling shows good agreement with the experimental data.


Stereomicroscopic and ultrastructural characterization of propionitrile-induced duodenal ulcer in the rat. Acute duodenal ulcer produced by subcutaneous injection of propionitrile in rats was studied by stereo, light, and electron microscopy in order to gain insight into the localization and mechanism of initial cell injury. Stereomicroscopy revealed an initial fissuring and splitting of the tips of the villus folds within 4 hours after two injections of propionitrile. This was followed by sloughing of the epithelium, shortening and effacement of the villus folds, and within 24 hours the appearance of discrete ulcers in the mucosa of the proximal duodenum. In most of the rats, two ulcers developed: the first and larger ulcer was on the antimesenteric side of the duodenum, and the other, a small and more superficial one, was on the opposite wall. Ultrastructural lesions appeared in the absorptive epithelial cells of the proximal duodenum within 5 hours following a single dose of propionitrile. The cytoplasmic changes of cellular injury were preceded and/or accompanied by beading and loss of microvilli. The initiation of propionitrile-induced alterations at the tip of the villi in the proximal duodenum suggests that the ulcerogenic agent acts from the luminal side of the duodenum and probably originates from the stomach.


The effects of leukocyte depletion on corneal neovascularization. The role of leukocytic infiltration in the initiation and maintenance of corneal neovascularization was studied in rats. Vascular ingrowth was induced by central cauterization of the cornea with silver nitrate and assessed after intraarterial perfusion of colloidal carbon. In normal rats, the mean vascular length was 0.33 mm. at 3 days and 0.63 mm. at 4 days. Whole-body x-irradiation with 800 rads depressed peripheral blood leukocyte counts to 1% of normal, prevented infiltration of monocytes, and reduced infiltration of neutrophils, but did not alter the neovascular response at 4 days. Combined treatment with radiation (800 rads) and repeated injections of antineutrophil serum (ANS) reduced peripheral leukocyte counts to nearly zero and eliminated infiltration of both monocytes and neutrophils. Despite the absence of leukocytes, neovascularization occurred in all corneas. However, the mean vascular length was reduced to 67% of control at 3 days and to 33% at 4 days. The results indicate that vascular growth can be initiated in the absence of leukocytic infiltration. The reduced neovascularization in totally leukopenic animals might be due to either the ability of neutrophils to facilitate or augment vascular growth or the nonspecific effects of treatment with radiation and antineutrophil serum.


The type II epithelial cells of the lung. III. Lecithin synthesis: a comparison with pulmonary macrophages. Synthesis of lecithins in isolated type II alveolar cells was compared with that in alveolar macrophages as a means of exploring the biochemical mechanisms underlying surfactant production in the lung. Counted cell populations were suspended in a simple glucose-salt solution and 14C-labeled precursors were added singly, in physiologic concentrations, to assess the potential importance of each as a substrate for lecithin synthesis. Molar incorporation of glucose, glycerol, choline, lysolecithin, acetate, palmitate, oleate, and linoleate was determined in lecithins fractionated according to degree of saturation after 1 hour of incubation. Palmitate ws the most actively utilized substrate in type II &cells. Type II cells incorporated 6 nmoles of palmitate per 10(7) cells, of which 77% was in disaturated lecithins, and 66% at the C2 position (compared to 0.8 nmoles, 47% disaturated, in macrophages). Acetate was also incorporated mainly into disaturated lecithins in type II cells; macrophages did not utilize acetate, and no precursor specifically supported disaturated lecithin synthesis in macrophages. Type II cells and macrophages synthesized similar quantities of total lecithins and disaturated lecithins from glucose and choline. Only the type II cells, however, were capable of increasing disaturated lecithin synthesis from 14C-choline when unlabeled palmitate was added to the medium. Type II cells synthesized significantly more disaturated lecithins from lysolecithin than did macrophages (451 versus 60 pmoles per 10(7) cells). Macrophages utilized glycerol in lecithin synthesis, but type II cells did not. Our data demonstrate directly for the first time that type II cells are the site of disaturated lecithin synthesis and that acyl turnover mechanisms are important in production of disaturated lecithins by the type II cell.


Rabbit bone marrow after administration of saponin. An electron microscopic study. Saponin rapidly induced injury to the wall of vascular sinuses in rabbit bone marrow so that the barrier between hematopoietic cells and the circulation became defective. This change was followed by hypocellularity and necrosis and fibrosis. Adult male rabbits received saponin intravenously (2 mg. per kg.) every 4 days for periods of up to 4 weeks; the animals were killed at varied times. In untreated animals, much of the sinus wall consisted only of endothelium. Within 2 hours after administration of saponin the endothelium was damaged and hematopoietic cells, mostly reticulocytes and normoblasts, entered the circulation. Some sinuses hemorrhaged into the hematopoietic compartment. At 4 hours, sinuses were markedly dilated and hemorrhage was extensive. By 3 days, extravasated erythrocytes, which were tending to aggregate, were unevenly distributed in the extravascular space of marrow. Damaged hematopoietic cells were dispersed among them. Regenerating blood vessels were noted and a few clusters of hematopoietic cells occurred in association with fibroblasts. At 1 week, a large portion of the marrow was either necrotic or contained large-scale diffuse or focal hemorrhage. Fibrotic areas often surrounded the arteries. After 2 to 4 weeks, myelofibrosis became pronounced. The fibrotic tissue was well vascularized and contained small clusters of hematopoietic cells and a few fat cells. Macrophages were abundant and tended to fuse, forming multinucleated giant cells surrounding pockets of degenerated fat cells.


Influence of ordered backbone structure on protein folding. A study of some simple models. Four series of model molecules, each of which contains a coil section and one or two sections of fixed ordered backbone structure, have been examined to locate their low-energy conformations in water. The four series are: helix-coil, helix-coil-helix, extended-coil, and extended-coil-extended. In each series, the length of the coil is allowed to vary from four to ten residues, while the nuclei (ordered backbone structures) are held fixed at six residues. By comparing these molecules, it is observed that the low-energy conformations of those containing two nuclei can be regarded as being derived from low-energy conformations of molecules containing one nucleus. This suggests that folding of proteins containing preformed nuclei proceeds through interactions between the nuclei and adjacent non-regular sections of the chain rather than between nuclei. It is also observed that helices are better promoters of globularity than extended strands. These results are compared with those from recent studies of various aspects of protein folding.


Echocardiographic spectrum of tricuspid atresia. Standard M-mode and contrast echocardiographic features of 35 patients with tricuspid atresia are reported. These features included a single posteriorly located atrioventricular valve with large excursion, often demonstrating the pattern of systolic prolapse, mitral semilunar valve continuity, and small right ventricular chamber. Left ventricular dimension and left ventricular posterior wall thickness were usually increased. Ventricular septal and posterior wall excursion and percent thickening of the left ventricular posterior wall were in the normal range in most cases. However, fractional shortening of the left ventricular minor diameter was below normal in most patients (26/29, 90%) regardless of the age at presentation. A characteristic and reproducible flow pattern of contrast medium was also observed. After systemic venous injection of indocyanine green, the resultant echoes initially appeared in the left atrium and subsequently, via the mitral valve funnel, appeared in the left ventricular cavity. If a small right ventricular chamber could be recorded, this chamber filled with subsequent systole except in patients with intact ventricular septum. With the use of these M-mode echographic features, along with contrast studies, diagnosis of tricuspid atresia can confidently be established at the bedside and can readily be distinguished from other cyanotic congenital defects.


Idiopathic pulmonary hemosiderosis: two cases in a family. Two patients, a mother and her son, had idiopathic pulmonary hemosiderosis. In the son, the onset was acute and he died of massive hemoptysis. The mother's disorder developed less acutely and the condition improved after temporary respiratory support and massive corticosteroid therapy. This is the first reported instance of idiopathic pulmonary hemosiderosis occurring in more than one member of the same family. The diagnosis of idiopathic pulmonary hemosiderosis depends on compatible clinical and pathologic data and on exclusion of secondary causes of intrapulmonary hemorrhage.


Size and density of fibrin fibers from turbidity. In agreement with earlier observations that the angular dependence of light scattering by fibrin gels obeys the theory for light scattering by very long and thin rigid rodlike particles (intensity proportional to the square of half the scattering angle), we find that the turbidity, tau, of the less opaque gels varies as the inverse third power of the wavelength, lambda. Mass-length ratios of the fibers calculated from these two measurements closely agree. For fibrin gels containing fibers with a very high mass-length ratio (of which we had not been able to obtain interpretable scattering data), the turbidity is found not quite to vary as 1/lambda3. For these opaque gels, the fiber diameter is no longer negligible with respect to the wavelength. It is shown how the radius of gyration of the fiber cross section (and therefore the radius of cylindrical fibers) can be obtained from the ratio of slope and intercept of a plot of 1/tau lambda3 vs. 1/lambra2. The square of the radius of the fibers is found to be proportional to the mass-length ratio. The density of the fibers is calculated to be 0.28. This corresponds to a ratio of fiber volume to volume of protein contained in the fiber of 5.0.


Contribution of the electroencephalogram in monitoring cardiac dysrhythmias. It is often difficult to distinguish between episodic cerebral symptoms resulting from primary disorders of the brain and those resulting from cardiac dysrhythmias. When patients with such symptoms are referred for electroencephalography, the electrocardiographic activity recorded concurrently can provide additional useful diagnostic information. Two cases are presented to illustrate the contribution of the electroencephalogram in the diagnosis of significant cardiac dysrhythmias.


Chronic eosinophilic pneumonia (Carrington's): a follow-up study. A follow-up study of eight Mayo Clinic patients with chronic eosinophilic pneumonia (also called Carrington's eosinophilic pneumonitis) was done in order to ascertain, if possible, the long-term prognosis of this entity, since it has not been delineated clearly in the literature. Chronic eosinophilic pneumonia is a subacute-to-chronic pulmonary disorder occurring most commonly in nonatopic women with cough, fever, dyspnea, weight loss, and night sweats. The typical chest roentgenogram shows peripheral non-migratory infiltrates, and the characteristic pulmonary histologic finding is eosinophilic infiltration of the interstitium and alveolar spaces. Peripheral eosinophilia is seen in most cases but not all. At the time of follow-up, two of eight patients were continuing to take corticosteroids after 5 1/2 and 8 years. Five patients have been able to discontinue corticosteroid treatment after an average of 4 years, and one patient never required corticosteroids. Chronic eosinophilic pneumonia is added to previous classifications of pulmonary infiltrate with eosinophilia.


Influence of water on protein structure. An analysis of the preferences of amino acid residues for the inside or outside and for specific conformations in a protein molecule. The x-ray structures of 20 proteins have been examined and each of the residues in these proteins was assigned to the inside or outside of the molecules and to a conformational state. The data obtained confirm that polar groups are generally found on the outside of proteins and nonpolar residues are generally found on the inside. Seven of the amino acids (Ala, Arg, Cys, His, Pro, Ser, Tyr) have inside/outside preferences which are not consistent with their usual assignment as either polar or nonpolar residues; explanations are given for these apparent inconsistencies. Of the three types of backbone structure considered here (extended, alpha helix, and nonregular), extended structures have the greatest preference for the inside of proteins, and nonregular structures have the greatest preference for the outside. It is suggested that differences in entropy play an important part in the inside/outside preferences of backbone structures. There are generally significant changes in the conformational preferences of the residues in going from the inside to the outside of proteins; environmental (rather than local) solute-solvent interactions seem to be the predominant cause of these changes in conformational preferences.


Visual prognosis of optic nerve sheath meningiomas producing shunt vessels on the optic disk. Nine patients--seven women and two men--had meningiomas of the optic nerve sheath. The defect was bilateral in two, in the right eye in six, and in the left eye in one. Most had edema of the disk, and all had progressive loww of vision in the affected eye owing to optic nerve atrophy. In 10 of the 11 affected eyes, opticocilliary shunt veins developed on the optic disk. Exophthalmos was mild and did not measure more than 3 mm in any patient. Ocular movement was mildly impaired in three patients. Indentation and flattening of the posterior pole of the eye were documented in five eyes. Nine of the 11 eyes progressed to blindness; 1 was worse after operation, and the outcome of the 11th is unknown because the patient was lost to follow-up. Surgical treatment has not been effective in these cases or in those reported in the literature.