Bactericidal and opsonic activity of cirrhotic ascites and nonascitic peritoneal fluid.

BA and OA of sera and uninfected ascitic fluid from patients with alcoholic cirrhosis were assayed against gram-negative enteric bacilli. This was compared with BA and OA in normal serum and in peritoneal fluid obtained at laparoscopy or laparotomy from noncirrhotic patients. Cirrhotic sera showed significantly reduced BA and OA against one of the organisms tested, Serratia marcescens. It had reduced OA but normal BA against E. coli. Ascitic fluid was markedly deficient in BA and OA against all strains tested when compared to both cirrhotic sera and nonascitic peritoneal fluid. Immunoglobulin and complement concentrations in cirrhotic ascites were reduced. Ascites did not inhibit the BA or OA of normal serum. However, replacement experiments suggested that the diminished activity of ascites was largely the result of its reduced complement concentration. The demonstrated deficit in both BA and OA of ascites may be a factor in the frequency of spontaneous enteric bacillary peritonitis in the cirrhotic patient.


Stimulatory and inhibitory effects of ovarian steroids on gonadotrophin secretion in ovariectomized rats after anterior hypothalamic deafferentation.

The effect of frontal hypothalamic deafferentation on the release of LH and FSH was studied in ovariectomized rats. Frontal cuts were placed just in front of the arcuate nucleus, at the posterior border of the optic chiasma (RCS), at the level of the anterior commissure (POS) and in front of the optic chiasma (PCS). Animals with RCS and POS cuts showed vaginal smears with persistent cornification; the other groups had irregular cycles. The concentrations of LH and FSH in the serum increased after ovariectomy in deafferentated animals, but after 4 weeks the levels were lower than in the animals without hypothalamic lesions except for the PCS group. The more caudally that the cuts were located, the lower were the concentrations of hormones in the serum. The injection of repeated doses of oestradiol benzoate resulted in a decrease in serum gonadotrophin of both rats without hypothalamic lesions and RCS rats. Although a greater decrease was observed in the lesioned than in the intact rats, it is believed that such an effect does not indicate an increased sensitivity of deafferentated animals to this steroid. The stimulatory effect of progesterone on LH and FSH release was studied in ovariectomized rats primed with oestradiol benzoate. The responses were unchanged in PCS animals but failed to occur in POS and RCS rats. Measurement of the level of gonadotrophin-releasing hormone in frontal hypothalamic slices from RCS animals showed a decreased level behind the cut and an increased one in front of it, suggesting that perikarya located in front of the section were sending their axons to the mediobasal hypothalamus. It is believed that the blockade of the stimulatory effect on gonadotrophins by frontal hypothalamic deafferentation is due to the transection of these axons. Cuts placed immediately in front of the arcuate nucleus, however, permitted progesterone-induced gonadotrophin release because of incoming neurones containing gonadotrophin-releasing hormone, which end in structures immediately rostral to the cut. The results indicate that effects of both inhibitory and stimulatory ovarian steroid feedback are impaired by frontal hypothalamic deafferentation.


Changes in the ovaries of rats after immunization against luteinizing hormone releasing hormone.

Rats were immunized against luteinizing hormone releasing hormone (LH-RH) and ovulation and follicular development were studied 12, 24 and 48 weeks later. The abolition of regular cyclic patterns of vaginal smears and the absence of luteal tissue in all but one of 32 rats showed that the immunization was effective in blocking ovulation. Follicular growth varied between rats and appeared to be dependent on whether the inhibition of LH-RH had been sufficient to affect the secretion of basal levels of gonadotrophins. Low levels of gonadotrophins were associated with poor follicular development, uterine atrophy and leucocytic vaginal smears, whereas levels of gonadotrophins similar to those in the dioestrous controls led to adequate follicular growth in the absence of ovulation, the production of cystic follicles, uterine stimulation and persistent vaginal oestrus. A group of rats was ovariectomized 12 weeks after immunization against LH-RH; animals with low antibody titres and large follicles responded with increases in the levels of LH and FSH in the blood, whereas in those with high antibody titres and little follicular development the concentrations of gonadotrophins remained low. The reproductive capacity of rats immunized against LH-RH was tested by caging them with normal male rats from 3 weeks after immunization. Although mating occurred in three rats during the first month, no offspring were produced. No matings occurred in the remaining 41 weeks.


The use of epidemiologic methods in family practice.

Epidemiologic methods of research can be readily used in family practice. Since the 19th century, family physicians have used epidemiologic methods in making important contributions to the understanding of disease. Using these methods requires an organized practice including patient registers, encounter data, and detailed records. Descriptive studies can define certain characteristics that are related to disease. Case-control and cohort studies can provide evidence for the association of risk factors and disease. A stepwise outline for carrying out a study is presented.


Hamster sperm cross react with antiactin.

Hamster sperm extracts contain a polypeptide which comigrates with muscle action on polyacrylamide gel electrophoresis. On double diffusion precipitation plates, sperm extracts form a single precipitin band with an antibody to muscle actin (antiactin) and show a reaction of identity with muscle actin. Indirect immunofluorescent microscopy revealed that antiactin binds along the concave margin and equatorial segment in the acrosomal region, in the connecting piece of the neck, and in the principal piece of the tail. These results are evidence that hamster sperm contain actin. The possible significance of these observations in fertilization is considered.


Quantitative behavioral studies of misdirected responses in skin-grafted Rana pipiens.

The experiments reported here describe quantitatively wiping responses elicited from three equal body sections of adult Rana pipiens having had one of two types of skin-graft operations as tadpoles. These experiments assessed the development of aberrant wiping responses in individuals and populations of grafted animals. Grafting parameters critical for the development of aberrant wiping responses were also determined. These studies indicated that the phenomenon of "misdirected responses" and the extent of these responses is highly variable among grafted individuals and between different populations of grafted animals. In addition, the development of "misdirected responses" is independent of premetamorphic stimulation and of a critical grafting period. The proportion of "misdirected responses" elicited upon cutaneous stimulation of individuals appears to be stable and predictable after metamorphosis. "Misdirected responses" could be elicited from animals with grafts including over 40% of the trunk skin. Wiping responses and grafting parameters of skin-grafted R. pipiens in other studies are also presented and possible sources of interstudy variation discussed.


Fine structure, physiology and biochemistry of arthrospore germination in Streptomyces antibioticus.

During germination, Streptomyces antibioticus arthrospores passed through stages: darkening, swelling and germ tube emergence. The first stage, darkening, whose main features were a decrease in absorbance and a loss of refractility, only required exogenous divalent cations (Ca2+, Mg2+ or Fe2+) and energy that can be obtained from the spore reserves. This stage was blocked by agents that inhibit ATP formation but not by antibiotics that inhibit macromolecular synthesis. The second stage, swelling, needed an exogenous carbon source and was not blocked by mitomycin C. In this stage, the spores exhibited the highest cytochrome oxidase and catalase activities and respiratory quotient. The last stage, germ tube emergence, required additional carbon and nitrogen sources. Ammonium compounds were superior to nitrate. Dry weight remained constant during the stages of darkening and swelling, with a rapid increase from the moment of germ tube emergence. Optimum pH and temperature for germination were 8.0 and 45 degrees C, respectively. Heat treatment (55 degrees C for 10 min) had no effect on germination. The fine structure of the spore underwent important changes during germination. The wall of the swollen spore became stratified and the inner layer was continuous with the germ tube wall. Macromolecular synthesis occurred in the sequence RNA, protein and then DNA. Rifampicin, streptomycin and mitomycin C prevented synthesis when added at the start of incubation. The same effect was obtained if the addition was made during germination, except with mitomycin C which inhibited DNA, but not RNA and protein synthesis.


Stopped-flow spectrophotometric assay of glycerol permeation in Escherichia coli: applicability and limitations.

The passive permeation and facilitated diffusion of glycerol in various strains of Escherichia coli have been studied by stopped-flow spectrophotometry. Contrary to the prediction for glycerol entry by simple diffusion, the reciprocal relaxation time (1/tau, s-1) for the passive permeation of glycerol in cells grown in the presence of glucose was not constant but decreased as the glycerol concentration increased above 100 mM. This anomaly was not due to refractive index differences or to the presence of residual levels of the glycerol facilitator protein in non-induced cells. Although reciprocal relaxation times for glycerol-induced E. coli exhibited the expected elevation relative to non-induced cells, a similar anomalous decrease 1/tar (s-1) with increasing glycerol concentration was observed. In addition, at early times after suspension in dilute buffer, the 1/tau (s-1) values obtained for induced or non-induced E. coli swelling in glycerol were considerably greater than for organisms incubated in dilute buffer for longer times. We concluded that either this spectrophotometric technique was not monitoring solely the permeation of glycerol into E. coli, or concentrations of glycerol above 100 mM significantly perturbed the structure of the E. coli cell envelope.


Molecular properties of transmissible R factors of Haemophilus influenzae determing tetracycline resistance.

The tetracycline-resistant Haemophilus influenzae strains LU121 and FR16017, recently isolated in West Germany, each harbour a plasmid; that of the former (pLU12U) has a mol. wt of 31.5 X 10(6) and that of the latter (pFR16017) has a mol. wt of 33 X 10(6). Conjugation and DNA-DNA hybridization studies have shown that both plasmids are self-transmissible and carry tetracycline-resistance genes. The purified plasmid DNA of H. influenzae strain LU121 transformed a sensitive Escherichia coli strain to tetracycline resistance. The two R factors are closely related to the H. influenzae plasmid specifying ampicillin resistance (pKRE5367). Electron microscope DNA heteroduplex analysis indicated that pLU121 and pFR15017 probably carry the tetracycline-resistance transposon TnD and that pKRE5367 probably carries the ampicillin-resistance transposon TnA. There is more than one integration site for the insertion which probably represents TnD in pFR15017. All three plasmids have a similar plasmid core and could have a common evolutionary origin.


Agglutination of blastospores of Candida albicans by concanavalin A and its relationship with the distribution of mannan polymers and the ultrastructure of the cell wall.

Blastospores of Candida albicans were readily agglutinated by Concanavalin A (Con A) owing to the specific binding of this lectin to the mannan receptors of the cell surface. When mannan was extracted from the cell wall by neutral buffers, alkali and acid, the agglutination was decreased or lost depending on the degree of extraction. A relatively mild alkali treatment was sufficient to derange the multilayered wall organization and transform it into a uniform, medium-density structure having about the same thickness as the untreated wall. After a more drastic extraction, all the electron-dense components of the wall were lost, the residual, alkali-insoluble wall fabric being completely electron-transparent and of about the same thickness as the inner wall region of untreated cells. Thiol-reducing agents like mercaptoethanol or dithiothreitol also extracted wall materials, an effect which was enhanced by pronase. After dithiothreitol-pronase treatment, the outer wall layers were removed but the inner wall region was not apparently damaged and some electron-dense components remained. None of these treatments significantly affected blastospore agglutination by Con A--this was reduced (but not abolished) only by the sequential action of pronase and helicase, which led to sphaeroplast formation. These sphaeroplasts showed a varied amount of residual wall consisting of evenly distributed, fibrogranular components. Two main conclusions were drawn from these results: (i) mannan polymers extend throughout the wall of the blastospore of C. albicans; (ii) the layering of the wall, as seen by ordinary fixation and staining for electron microscopy, essentially reflects the distribution of the various alkali-soluble complexes, at different levels, both over and in the rigid, glucan-chitin matrix.


Dimethyl sulphoxide reduction by micro-organisms.

Dimethyl sulphoxide (DMSO) was reduced to dimethyl sulphide by a wide variety of micro-organism, including prokaryotes and eukaryotes, aerobes and anaerobes. Dimethyl sulphone was not reduced by any of the organisms tested. Cell-free extracts of Escherichia coli reduced DMSO using reduced pyridine nucleotides as electron donors. Activity was greater in anaerobically grown cells than in those grown aerobically. Two other sulphoxides, methionine sulphoxide and tetramethylene sulphoxide, substantially inhibited DMSO reduction by extracts. Mutants of E. coli, which were unable to reduce biotin sulphoxide to biotin, were tested for their ability to reduce DMSO in whole cells and extracts. These mutants were in four different gene loci, bisA to bisD. DMSO reductase activity of the mutants was generally less than that of the wild-type strain, and activity depended upon the gene locus involved, the growth medium and the growth conditions. Only the bisA mutant had very low activity under all conditions. All of the bis mutants were able to grow using methionine sulphoxide as a sulphur source, indicating that biotin sulphoxide and methionine sulphoxide are reduced by different enzyme systems. DMSO may be reduced by both of these enzyme systems.


Pharmacologic effects of polyinosinic-polycytidylic acid in man.

Twenty-four patients with cancer and concomitant infections with either herpes virus hominis or varicella zoster virus were treated with polyinosinic-polycytidylic acid (rIn.rCn) to determine: 1) the reliability of rIn.rCn to induce interferon production, and 2) the toxicity of the drug. Seven additional patients with herpes zoster were observed as controls. Two lots of rIn.rCn were used; Lot 1 was consistently effective in stimulating serum interferon at doses of 9 and 12 mg/kg, whereas Lot 2 was effective at doses of 3-12 mg/kg. There was no correlation between rIn.rCn doses within these ranges and the resultant interferon levels. Generally, peak serum interferon occurred within the first day. Toxicity to rIn.rCn consisted of fever in 21/24 patients, mild elevation of liver enzymes in 8/24 patients, and laboratory abnormalities of coagulation in 9 patients. The coagulation abnormalities appeared linearly related to the dose of rIn.rCn used. All these abnormalities were reversible, and none were considered severe of life-threatening. Since rIn.rCn was effective in stimulating interferon and since toxicity was considered acceptable, a randomized double-blind study was initiated to determine whether rIn.rCn is effective in the treatment of herpes zoster.


Some aspects of the historical development of the autonomic nervous system.

On the occasion of the twentieth anniversary of the death of Albert Kuntz (1879--1957), it is fitting that his great accomplishments be remembered. Present knowledge of the autonomic nervous system has been acquired and recorded over a long period of time. The contributions have been made by many investigators, from the crude observations of the early workers to the refinements and techniques of modern day scientists. Professor Kuntz was one of the great contributors to our present knowledge of the automatic nervous system; this paper is a small tribute in memory of his many accomplishments.


Fracture of the anterior superior iliac spine following anterior cervical fusion using iliac crest. Case report.

A case is presented in which fracture of the right anterior superior iliac spine occurred 2 weeks after the right iliac crest had been used as the donor site for a two-level anterior disectomy and fusion.


An unusual late complication of Gasserian ganglion cecompression surgery. Case report.

The authors report an unusual complication following sugery for decompression of the Gasserian ganglion. Eight years postoperatively this patient developed a left temporal lobe granuloma caused by a piece of wood used to plug the foramen spinosum at surgery. The patient's clinical and radiological findings were suggestive of a glioma involving the temporal lobe.


Hemophilus influenzae type b disease in a day-care center. Report of an outbreak.

Four episodes of serious Hemophilus influenzae type b infection occurred in three children attending a day-care center. This was 100 times the expected annual total. The pharyngeal carriage rate of Hib was 60% for siblings of patients, 20% for adult household contacts, and 5% for well children at the center. No carriers were found in control populations. Escherichia coli K100, which cross-reacts serologically with Hib, was found in rectal swabs of 20% of family contacts of patients and 3.5% of well children at the center. It was recovered from two of seven persons who carried Hib in the pharynx and two of 75 who did not (P = 0.035), suggesting that carriage of one organism may facilitate carriage of the other. In a randomized prospective trial with 85 patient contact, Hib carriage was eradicated in all of four carriers given ampicillin and in all of three given rifampin. There were no statistically significant differences in the rate of adverse reactions in the two treatment groups. No further cases were reported.


Synthesis and biological activities of 10-substituted benzo[b][1,5]naphthyridines.

Eight 10-substituted benzo[b][1,5]naphthyridine derivatives containing N-(pyrrolidino)alkylamines, methanesulfonanilides, and aminoacetanilides were prepared, and their binding with DNA was studied by (a) Tm measurements and (b) the effect on DNA-dependent RNA polymerase in vitro. In addition, they were evaluated as antineoplastic agents in the P-388 test. None of the compounds exhibited anti-cancer activity.


Amino acid analogs IV:4-fluoroisoleucine.

4-Fluoroisoleucine was produced by ammonolysis of 2-bromo-4-fluoro-3-methylpentanoic acid, which resulted from the bromofluorination of 4-methyl-2-pentenoic acid. It did not inhibit Plasmodium berghei in mice at 640 mg/kg and was not toxic to the animals. The fluoroamino acid inhibited Aspergillus niger, Trichoderma viride, Myrothecium verrucaria, Trichophyton mentagrophytes, and Mucor mucedo in Czapek solution agar at a concentration  between 10(4) and 10(3) microgram/ml. Growth of Escherichia coli was inhibited 25% at 900 microgram/ml in a defined medium.


Structure--activity studies on mutagenicity of nitrosamines using molecular connectivity.

The structure--activity relationship of a series of nitrosamines was evaluated for mutagenic potency as measured in the Ames test. The structural description was made using molecular connectivity. A good correlation was found.


Effects of divalent cations, lanthanum, cation chelators and an ionophore on acetylcholine antinociception.

The antinociceptive effect of intracerebroventricularly administered acetylcholine as measured in the mouse tail-flick test was reduced by intracerebroventricularly injected calcium, magnesium and manganese. Maximum antagonism of acetylcholine-induced antinociception was observed with a 1-hour calcium pretreatment. Significant reduction existed at 2- but not 4-hour pretreatment. Barium and strontium were inactive. The antinociceptive effect of acetylcholine was potentiated by lanthanum and ethylene glycol tetraacetic acid but not by ethylenediamine tetraacetic acid. The ionophore A23187 was shown to increase greatly the antagonistic effect of a low dose of calcium. The ionophore alone did not significantly alter the effect of acetylcholine. Thus, it appears that calcium must penetrate cell membranes to reduce the effect of acetylcholine. In addition to acetylcholine, it was found that the antinociceptive effects of oxotremorine and physostigmine could also be reduced by calcium. These data indicate that alterations in intracellular calcium are involved in cholinergically induced antinociception.


Targets of octopamine action in the lobster: cyclic nucleotide changes and physiological effects in hemolymph, heart and exoskeletal muscle.

We have examined three potential targets of octopamine action of the lobster--hemolymph, heart and exoskeletal muscle--and found that each tissue responds to the amine with increases in cyclic adenosine 3': 5'-monophosphate (cAMP) and changes in measurable physiological phenomena. A highly specific octopamine-stimulated increase in cAMP is observed in hemolymph, and this effect is probably due to the presence of a unique octopamine receptor on hematocytes. Pharmacological studies show that synephrine is a potent agonist of the hemolymph receptor for octopamine and that the alpha adrenergic receptor blockers phentolamine and dibenamine and the dopamine receptor blocker, chlorpromazine, are antagonists. Addition of octopamine to lobster hemolymph increases the rate of changes the nature of the clotting reaction. AMP levels in lobster heart are elevated by both octopamine and serotonin. Both amines also increase the rate and the amplitude of the heart beat. Octopamine, serotonin and dopamine all increase cAMP levels in lobster exoskeletal muscle preparations, and each amine causes changes in muscle tension and the strength of nerve evoked contractions. In none of the tissues studied have we been able to establish a direct relationship between amine-stimulated increases in cAMP levels and the physiological responses.


The Thompson dowel-rest system modified for chrome-cobalt removable partial denture frameworks.

This article has described the minimum laboratory and mouth procedures needed for fabrication of the Thompson dowel-rest removable partial denture using the modifications of (1) preconstructed dies for the dowel-rests, (2) a chrome-cobalt framework, and (3) a ball clasp retention device.


Retention of endodontic dowels: effects of cement, dowel length, diameter, and design.

The retentive capacity of three preformed endodontic dowel designs was compared at two lengths and two diameters, with three different cements. The greatest single factor influencing retention of these devices was the design used. Of the types tested in this study, the most retentive were threaded, parallel-sided dowels screwed into tapped channels. Serrated, parallel-sided dowels cemented in matched cylindrical channels provided intermediate retention, and smooth-sided tapered posts were the least retentive. Another major factor in retention was the length of imbedment into dentin. An increase in dowel imbedment depth usually corresponded to increased retention. The effect of cement type was significant only with tapered dowels. Zinc phosphate cement was most retentive, carboxylate cement exhibited intermediate retention, and the epoxy cement was least retentive. For the other post designs, cement type had no significant effect on retentive capacity. Finally, variations in dowel diameter had no significant effect on retentive ability.


Interim complete immediate dentures for a patient wearing removable partial dentures.

This article describes a technique used for fabricating temporary (interim) complete dentures for a patient who had been wearing removable partial dentures and whose remaining teeth were to be extracted. Rather than attempt to incorporate the existing removable partial dentures into the interim complete dentures, the dentist used the existing dentures to fabricate acrylic resin teeth for the interim prosthesis.


Age-dependent changes in the hypothalamo-pituitary-ovarian axis of the laying hen.

The functional integrity of the components of the hypothalamo-pituitary-ovarian axis was examined in young and old laying hens. Ovarian function was tested by measuring the amount of progesterone released in response to an injection of LH, and pituitary function was investigated by measuring the increase in the plasma LH level after an injection of LH-RH. There were no differences between young and old birds in the response of the pituitary gland or the ovary to these stimuli. Hypothalamic function was investigated by studying the positive feedback action of a standard dose of progesterone on LH release; the positive feedback response was smaller (P less than 0.05) in old hens. It is suggested that the fall in the rate of lay in hens towards the end of their laying year is caused partly by a decrease in the response of the LH-positive feedback mechanism to progesterone.


The temporal relationship between plasma levels of FSH and LH in the ram.

Blood samples were collected from adult Soay rams at frequent intervals during the regressed, developing and active phases of the sexual cycle, or after i.v. injections of synthetic LH-RH or standard preparations of ovine FSH and LH, and were assayed for FSH, LH and testosterone. The highest FSH and LH levels occurred during the developing stage of the cycle, and the highest testosterone levels during the active stage. At each phase there were conspicuous short-term fluctuations in the concentrations of all three hormones, and episodic peaks of plasma LH were associated with increases in both FSH and testosterone. Synthetic LH-RH (5 microgram) induced a rise in the plasma values of FSH and LH at all stages and the magnitude and duration of the response could be predicted from a knowledge of the endogenous short-term fluctuations. When 50--250 ng LH-RH were given i.v. plasma LH increased in a way similar to that occurring spontaneously. The ratio of FSH:LH released after LH-RH changed with the stage of the sexual cycle, but the clearance rate of the two hormones was not affected. These findings are consistent with the control of FSH and LH by a single releasing hormone which is secreted in pulses. The different temporal patterns in the circulating FSH and LH result from differences in secretion and clearance.


Experience with modern inert IUDs to date: a review and comments.

A review of data from various large-scale studies reveals as much variation between studies as between devices. Many factors clearly unrelated to the IUD design undoubtedly influence their efficacy and continued use. Thus, the conclusions of the 1968 FDA report on effectiveness and utility still appear valid at this time. They are: A. "The Committee finds adequate scientific data attesting to the effectiveness and utility of the intrauterine devices." B. "The intrauterine devices are highly effective in preventing pregnancy, although they are not quite as reliable as the hormonal contraceptives if the latter are taken according to instructions." C. "The rate of continuation of use is similar to that of the oral contraceptives and is far higher than that of traditional methods, at least among the socially and economically deprived."


Pregnancy and the IUD.

Intrauterine devices are an effective method of birth control. Their use has resulted in pregnancy in a small number of women. If the device is left in situ after conception occurs, the pregnancy is often associated with infection and bleeding. The device apparently exerts its major effect on the uterus and offers little contraceptive protection to the fallopian tube and ovaries.


Pelvic pain and the IUD.

One of the most significant factors necessitating IUD removal is pelvic pain, which includes insertional pain, intermenstrual cramps, often associated with spotting and bleeding, and increased dysmenorrhea. The larger and stiffer devices and those whose shape does not conform to that of the endometrial cavity produce localized endometrial ulceration and inflammation, which contribute to these symptoms. Endometrial prostaglandin release secondary to the presence of an intrauterine foreign body may also play an important role. In patients who have pelvic pain with an IUD it is of utmost importance to completely evaluate them and exclude other causes of pain, such as pelvic inflammatory disease, with and without abscess formation, and ectopic gestation.


Intracranial histiocytic lymphoma with rheumatoid arthritis.

A patient with classical rheumatoid arthritis presented with a primary intracranial histiocytic lymphoma. He had not received cytotoxic drugs and had no evidence for Sjögren's syndrome or immunodeficiency. Previous radiation therapy to the shoulders is regarded as a possible, though unlikely, risk factor.


Radiation damage relative to transmission electron microscopy of biological specimens at low temperature: a review.

When biological specimens are irradiated by the electron beam in the electron microscope, the specimen structure is damaged as a result of molecular excitation, ionization, and subsequent chemical reactions. The radiation damage that occurs in the normal process of electron microscopy is known to present severe limitations for imaging high resolution detail in biological specimens. The question of radiation damage at low temperatures has therefore been investigated with the view in mind of reducing somewhat the rate at which damage occurs. The radiation damage protection found for small molecule (anhydrous) organic compounds is generally rather limited or even non-existent. However, large molecular, hydrated materials show as much as a 10-fold reduction at low temperature in the rate at which radiation damage occurs, relative to the damage rate at room temperature. In the case of hydrated specimens, therefore, low temperature electron microscopy offers an important advantage as part of the overall effort required in obtaining high resolution images of complex biological structures.


Cryofracture of paraffin-embedded heart muscle cells.

A comparative study of internal cellular structures of the sheep ventricular myocardium has been conducted by scanning electron microscopy (SEM) and by transmission electron microscopy (TEM). Access to the cell interior for three-dimensional studies was obtained by cryofracturing paraffin-embedded tissue frozen in liquid nitrogen. For accurate localization of structures of special interest thick paraffin sections were examined in the light microscope (LM). Based on the information gained, it was possible to fracture the block in a desired plane. The fracturing was carried out by a light blow to a precooled scalpel held against the surface of the block, which was immersed in liquid nitrogen. After thawing and deparaffinizing at room temperature in several baths of xylene, the tissue pieces were critical point dried using CO2. As xylene was found to be miscible with CO2, it also served as an intermediate fluid. This method resulted in good preservation fo the myofibrils, mitochondria, sarcoplasmic reticulum and transverse tubules (T-tubules), which was confirmed by TEM studies of conventionally prepared tissue and of tissue originally prepared for SEM.


A device for the rapid freezing of biological specimens under precisely controlled and reproducible conditions.

The construction and preliminary testing of a device is described which can be used to freeze biological specimens in any cryogenic liquid at temperatures down to the nitrogen freezing point (63 K) and which can operate in the pressure range 1.3 kNm-2 to 1 MNm-2. Ultra-rapid freezing can be carried out in a subcooled cryogenic liquid either hyperbarically or at atmospheric pressure. Slow freezing rates can be achieved by cooling the specimens in a controlled manner in the vapour phase above the liquid bath.


Low temperature scanning electron microscopy: a review.

Low temperature scanning electron microscopy is useful for morphological and analytical studies both in situations where low temperature techniques are used during specimen preparation and where low temperature stages are used for specimen examination and analysis. Examples are given of different low temperature specimen preparation techniques and how they may be applied to different types of specimen. There are still a number of problems associated with morphological identification in fully frozen-hydrated samples and it is important to carry out parallel studies using more conventional transmission electron microscopy and light microscopy preparation techniques. A number of criteria are presented, some or all of which may be used to establish the existence of the frozen-hydrated state.


Preparation of biological material for X-ray microanalysis of diffusible elements. I. Rapid freezing of biological tissue in nitrogen slush and preparation of ultrathin frozen sections in the absence of trough liquid.

Any method used for the analysis of diffusible elements within a cell should involve conditions which eliminate the redistribution of those elements. Redistribution of diffusible substances is caused by (a) ice damage during freezing, (b) thawing during sectioning, and (c) thawing during handling of sections. To eliminate this sections were cut (a) in the 5-8 micrometer ice crystal free surface layer obtained by freezing in melting nitrogen, (b) at a specimen temperature of 133 K and a knife temperature of 173 K to 153 K, and the temperature of the chamber was kept low by evaporating nitrogen from an extra reservoir inside the chamber, by regulating the output of a foil heater. A grid carrier was designed to simplify the section collection and the sections were affixed on to the grid in a press assembly. The sections were hard and translucent, and showed faint interference colours.


A method for the study of internal spaces in hard tissue matrices by SEM, with special reference to dentine.

Infiltration of a porous hard tissue with methyl methacrylate, followed by dissolution of the tissue provides a three-dimensional methacrylate cast of spaces within the tissue. Examination of such a cast by scanning electron microscopy provides information on the nature and extent of the pore system to a degree that cannot readily be visualized by the direct examination of fractured surfaces. The findings described concern human dentine but the technique may have a wider application in studies on the internal structure of other hard tissues.


Metallic deposition in specimens presenting cavities using the sputter coater.

Local charging effects in small biological cavities during SEM observation are apparent, even after sputter coating. Using an experimental model, the thickness of metallic coating at the bottom of cylindrical cavities has been measured and found to be less than 50% the thickness on the surface, depending on the relation of diameter to depth of the cylinder.


Competing-risk analysis of leukemia and nonleukemia mortality in X-irradiated, male RF mice.

The theory of competing risks, extended by the addition of several newly defined estimators, was applied to the analysis of mortality data for acutely X-irradiated, male RF mice, in which the cause of each death was assigned to one of four categories: myeloid leukemia (M), thymic lymphoma (T), lymphosarcoma and reticulum cell sarcoma (L), and all remaining causes (R), Doses from 0 to 450 rads were delivered within two age ranges: A) 5-6 weeks and B) 9-10 weeks, to give 11 treatment groups totaling 2,073 mice. The data were analyzed in terms of: 1) the nonparametric, Kaplan-Meier (K-M) adjusted survival function; 2) its logarithmic transform, the cumulative force of mortality (cumFM) function; 3) a disease model called "early terminating," applied to causes M and T; and 4) a "late-terminating" model, applied to causes L and R. For any given cause and group, two estimators were used, which measured, respectively: a) the relative lateness of the corrected (or adjusted) time course and b) the relative corrected incidence. For causes M and T, these were: a) the mean age of the force of mortality distribution (MAF), or corrected mean latent period; and b) the final cumFM. For causes L and R, the estimators were: a) the adjusted mean age at death (adjMAD), given an upper limit (as %) of adjusted mortality (adjMAD, 50% for L; adjMAD, 100%--the K-M estimator--for R) and b) the cumFM at a cutoff time of 640 days. For causes M and T, the MAF values showed highly significant decreases of the latent periods with dose, through 300 rads. The final cumFM data showed a marked increase of corrected incidence with dose, for both M and T. In addition, the data for cause M were consistent with a three-parameter, leukemogenic cell model that incorporated two opposing radiation effects: leukemogenic cell potentiation and cell killing. For cause R, the adjMAD, 100% data showed a general decrease with dose and considerable scatter. For cause L, the adjMAD, 50% values showed: for treatment A, a gradual decrease with dose through 300 rads; for treatment B, a highly significant drop for 150 rads, with little change for higher doses. The cumFM, 640-day values for both L and R showed a general increase of corrected incidence with dose. The mortality curves for all causes combined showed the expected life shortening, i.e., decreases of the mean age at death with dose, in the 0- to 300-rad range. In addition, the standard deviations of the mortality curves were significantly less for animals irradiated at age range B than at age range A, for each of the doses--150, 300, and 450 rads.


Prospective trials of dexamethasone and aerosolized gentamicin in the treatment of inhalation injury in the burned patient.

The addition of an inhalation injury to a cutaneous burn results in a significant increase in patient mortality rates, both from early pulmonary edema and, later, Gram-negative pneumonitis. Steroids have been shown to decrease mortality in an inhalation injury model. Aerosolization of gentamicin has been used successfully to treat severe bronchial infections. Therefore, a prospective, randomized trial was undertaken to evaluate both these drugs. Sixty burned patients, with inhalation injury confirmed by bronchoscopy and 133Xenon scan, were studied: 30 patients received either dexamethasone or saline placebo for 3 days; serial pulmonary functions were measured on those able to cooperate; another 30 patients received either aerosolized gentamicin or placebo for 10 days. Both drug-treated groups were comparable to their controls in age and mean burn size. Results of the steroid trial showed no major differences in mortality, pulmonary complications, or changes in pulmonary functions. Results of the gentamicin trial showed no major differences in mortality, time of death, or pulmonary and septic complications between treated and control groups.


The variable effect of PEEP in acute respiratory failure associated with multiple trauma.

Both short and longterm effects of positive end-expiratory pressure (PEEP) on oxygenating capacity (OC) were investigated in three groups of patients with acute respiratory failure following multiple trauma (MT). Group A consisted of six patients with "uncomplicated" MT; Group B, eight patients with MT and generalized sepsis; Group C, nine patients with MT and lung contusion. OC was evaluated in terms of PaO2/FIO2 and P(A-a)DO2 on FIO 2 = 1.0. OC was markedly and equally reduced in the three patient groups before use of PEEP. The use of a mean PEEP of 6-7 cm H2O resulted in an initial improvement in mean PaO2/FIO2 of 152.5, 36.1, and 59.2 mm Hg, and an overall improvement of 196.8, 57.5, and 107.0 mm Hg in Groups A, B, and C, respectively. There was a similar improvement in both the initial and the overall effect of PEEP on P(A-a)DO2 in the three groups. The difference in the improvement in OC due to PEEP was statistically significant between Groups A and B. It is concluded that acute respiratory failure following MT includes a wide spectrum of clinical syndromes, and that the improvement in OCT due to PEEP depends on the clinical sydrome that is responsible for the respiratory failure associated with MT.


The use of microfibrillar collagen hemostat for control of renal bleeding.

Microfibrillar collagen hemostat was used in 23 patients with renal injuries owing to multiple causes in an attempt to control small vessel bleeding from raw renal surface areas. Minimal complications have occurred with the use of this substance. Control of bleeding has been prompt and no late bleeding has occurred.


A technique for correction of ileocutaneous stomal stenosis.

A technique for the revision of the ileal stoma is described. The technique is based on the skin flap interposition procedure reported by Smith for the prevention of stomal stenosis.


Levamisole in the treatment of non-invasive and invasive bladder cancer: a preliminary report.

We have done a double-blind, randomized, controlled study on 37 patients with transitional cell carcinoma in which levamisole was used as an immune adjuvant in addition to the standard therapy for non-invasive and invasive bladder cancer. Levamisole is administered easily and is well tolerated, especially when compared to other immune adjuvants, such as bacillus Calmette-Guérin or Corynecbacterium parvum. Recall antigens, dinitrochlorobenzene reactivity and total lymphocyte count demonstrated little correlation to the initial stage of disease. Monocyte chemotaxis was increased significantly in patients receiving levamisole. Since our study is ongoing on data exist as yet to make any statement regarding the efficacy of levamisole in the treatment of bladder cancer.


Revascularization of totally occluded renal arteries.

Two cases of total renal artery occlusion are presented. The clinical durations of occlusion were 10 days and 6 months. Revascularization procedures were successful in both patients, resulting in return of renal function and alleviation of hypertension. Our 2 cases and a review of 30 other cases demonstrate that the maximum duration of main renal artery occlusion with subsequent return of renal function is unknown.


Studies of immunoglobulin M and malarial antibodies in Nigerians.

Measurements of immunoglobulin M, in 111 healthy adult Nigerians have been presented. IgM values ranged between 10 and 518 mg per 100 ml with a mean of 213.2 mg per 100 ml. Using the indirect immunofluorescent antibody test, 53.7 per cent of the 111 symptomless subjects in the study had demonstrable malarial antibodies of titres greater than 10,000. The implications of the observations in a holoendemic malarial zone are briefly discussed.


High- and low-potency neuroleptics in elderly psychiatric patients.

The efficacy and side effects of a low-potency neuroleptic, thioridazine hydrochloride, and those of a high-potency neuroleptic, fluphenazine hydrochloride, were compared in 30 elderly chronic schizophrenic patients. Through a crossover design, each patient received both drugs with an intervening washout period. Although both drugs produced a similar degree of improvement, their side effects differed. Fluphenazine caused slightly more extrapyramidal effects than thioridazine, though few occurred with use of either drug. Thioridazine caused weight gain, blood pressure decreases, and ECG changes. High-potency neuroleptic agents appear to be the drugs of choice for elderly schizophrenic patients.


Double-blind evaluation of deanol in tardive dyskinesia.

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.


Quality of life for long-term survivors of end-stage renal disease.

Eighteen children and adolescents who survived two years or longer in an attempt to manage their end-stage renal failure by transplantation were studied. The psychological adaptation of the young person to this form of management of renal disease was assessed by a semistructured interview of the patient and his parents. Fifty percent of the patients functioned at school or on the job and did not have depression. The remaining half did less well. In our institution a satisfactory quality of life required a successful transplant.


[Pharmacological action on the thrombocyte link in hemostasis in the treatment of ischemic heart disease].

The expediency of using agents inhibiting the functional property of blood platelets for the treatment and prevention of thrombus formation in the system of arteries is substantiated theoretically and by the findings of experimental and clinical study. Data are cited on the clinical use of acetylsalicylic acid, dipyridamole, clofibrat, and also of such preparations as pyridinol carbamate, nonachlasine, pentoxyphylline, cetedil, heparin, streptokinase and anti-vitamins K for the treatment of patients with ischemic heart disease. The correlations of the clinical effect and the influence of these drugs on various aspects of the functional blood platelet activity is analysed.


[Indications for the use of inosine in myocardial infarct (a clinical and experimental study)].

The effect of the nucleoside Inosie-F (inosin) on the intracardiac hemodynamics and the contraction and relaxation of a diseased myocardium was studied in the clinic and in experiments. An examination was made of 102 patients with macrofocal myocardial infarction (22 received inosin by intravenous drip in a single dose of 200 mg in the acute stage of infarction; 60 patients were given inosin pills in a daily dose of 800 mg in the restoration period for one month, and 20 patients were given placebo). Comparative appraisal of treatment in the period of rehabilitation showed prevailing improvement in the condition of individuals treated with inosin, positive ECG dynamics, increase of cardiac output and decrease of peripheral resistance. In experiments on 28 dogs with a model of acute myocardial ischemia a noticeable improvement in myocardial contraction and relaxation in the absence of negative ECG dynamics was recorded after intravenous infusion of inosin. Inosin achieves maximum effect by 60-90 mins after the beginning of infusion.


[Evaluation of the efficacy of xavin treatment  of ischemic heart disease].

The results of ksavin treatment of 90 patients suffering from ischemic heart disease are discussed. Ksavin was given in a daily dose of 450-1,200 mg for 3 weeks. The clinical efficacy of the treatment was correlated with the risk factors and the indices of the ECG, centra hemodynamics and spiroergometry. The effect was good in 55% of the patients and satisfactory in 30%. No effect was produced in 15% of the patients. The best results were observed in younger patients with disease of short duration and no concomitant arterial hypertension. A favourable effect of ksavin on lipid metabolism and blood coagulation was noted. The study showed ksavin to be an effective measure in the treatment of ischemic heart disease.


[Dynamics of the amount of fluid in the chest cavity and lower extremities in cardiac insufficiency under the influence of strophanthin and lasix].

The effect of lasix (in 51 patients) and strophanthin (in 16 patients) on the dynamics of changes in the amount of fluid in the chest and leg in cardiac insufficiency was studied by impedance plethysmography. It was established that in isolated insufficiency of only the left parts of the heart, parenteral administration of 20 mg of lasix led almost in all cases to a decrease in the total amount of fluid in the chest and its organs by 14% on the average; the decrease in the volume of fluid in pulmonary edema, cardiac asthma, and insufficiency of the left parts of the heart without acute manifestations is practically the same and amounts to 17, 14, and 12% on the average, respectively. In isolated hypervolemia of the pulmonary circulation, lasix causes a decrease in the amount of fluid in the leg also, by 7% on the average, in three fourths of cases. In total cardiac insufficiency, lasix reduces the volume of fluid in the chest and leg to a similar degree (by 13 and 16% on the average) practically in all cases.


[Resection of the levator muscle: contribution to the surgical technique. (author's transl)].

The levator muscle of the upper lid is resected transconjunctivally as described by Wolff in 1896, the procedure is however improved by our present knowledge of more rigorous but controlled shortening of that muscle and by the use of the present most delicate suturing procedure. The sutures remain in situ and the stay in hospital is reduced to one or two days.


[Treatment of herpes simplex keratitis with Vidarabin ointment (author's transl)].

In 20 cases of herpes simplex keratitis the efficacy of Vidarabin ointment has been tested, in 19 cases after corneal abrasion. The eyes were treated once a day and padded until the epithelial defects had closed. Thereafter the ointment was applied 4 times per day for about one week more. On the average epithelial closure had been achieved after 2.4 days, complete normalization of the epithelium after a total of 3.6 days. This therapy results in a considerable shortening of the healing process as compared to the topical use of anti-viral medication alone. From this aspect Vidarabin ointment has proved to be a valuable adjuvant.


[Possibilities of examination on soft contact lenses (author's transl)].

Choosing typical lipid deposits on hema-lenses, the possibilities of examination are demonstrated. Apart from the macroscopic examination different microscopic methods are shown, allowing an examination of lenses without producing artefacts. Sections through hema-lenses give exact information about the relation between the deposit and the lens material.


[Gonadotropin secretion after stimulation with a highly effective analog of the gonadotropin-releasing-hormone (GnRH) in normal adult human males (author's transl)].

Potent long acting anologs of GnRH are of great interest especially in view of treatment of hypothalamic hypogonadotropic hypogonadism and of cryptorchidism. To find necessary parenteral doses of such a substance immunoreactive serum LH and FSH were measured in 4 normal adult human males after s.c. injection of various doses of D-Leu6-des-Gly10-GnRH-EA. 5 microgram of the GnRH anlog were necessary to obtain increased serum gonadotropins over a period of at least 8 h. Comparable maximal levels were seen after i.v. bolus injection of 25 microgram natural GnRH a dose as used in diagnostic routine tests in 3 probands. Comparing the areas under the curves of LH secretion an over 15 times greater effectiveness of the analog was calculated.


Surface markers on peripheral blood lymphocytes of patients with follicular lymphoma suggesting a clonal origin.

PBL of 14 patients with FL were examined by membrane fluorescence using anti-Ig antibodies (mu, gamma, delta; kappa, lambda), spontaneous rosette formation with SRBC and rosette formation with SRBC coated by antibody-complement complexes (EAC). Eight of the patients were untreated. In 3 patients monoclonal Ig were detected in the serum or urine. 7 patients exhibited clonal proliferation as judged by analysis of surface Ig. In addition, normal or elevated figures for EAC rosettes were found. The strong expression of S. Ig in PBL of FL patients is in contrast to the findings in CLL and multiple meloma, the increase of EAC-rosettes is shared by myeloma patients. It follows that membrane properties of PBL as studied in this work is of value in the diagnosis of malignancies of the B-cell system.


Adaptive responses of the pulmonary macrophagic system to carbon. I. Kinetic studies.

The adaptive capacity of the lung to increase the output of alveolar macrophages is vital to its handling of foreign material, particularly in an overload situation. In previous papers we demonstrated the role of pulmonary intersititial cells in providing a pool of precursor cells that may be available for this purpose. We now extend these observations to a study of pulmonary cytodynamics in mice subjected to a single large load (4 mg.) of carbon delivered by endotracheal tube. The output of free macrophages over a period of 14 days was correlated with DNA synthesis of pulmonary cells as measured by their uptake of 3H-thymidine. The initial increase of macrophagic output, 5 times in 12 hours and 10 times in 24 hours occurred before any increase in mitotic activity or cellularity was demonstrated in the pulmonary interstitium. The high level of macrophagic cell output which was maintained over the next week was accompanied by increased thymidine uptake in the lung. Increased mitotic activity was confined to the interstitial cell population; no mitoses were observed in free macrophages. The results indicate a biphasic macrophagic response to inhaled particulates, an early phase apparently unrelated to a local cellular response and a later phase of interstitial cell proliferation which appears to be concerned with the maintenance of the high output of macrophages.


Acute hematogenous pyelonephritis in the rabbit. Electron microscopic study of Escherichia coli localization and early acute inflammation.

Injection of approximately 10(6) to 10(9) Escherichia coli into the renal arteries of rabbits resulted in retention of sufficient numbers of organisms in renal vessels to permit study of the mechanism of localization by electron microscopy. After injection of the bacterial suspension, perfusion fixation was used to maintain open vascular contours. Individual organisms were found to adhere to the endothelium of glomerular and intertubular capillaries, and ruthenium red staining demonstrated a close interaction between the largely polysaccharide bacterial microcapsule and the sialoglycoprotein endothelial surface coat. Thus, individual E. coli seem to localize in the rabbit kidney in this model by sticking to the endothelial surfact coat of the renal vessels. After localization, polymorphonuclear leukocytes and monocytes appeared in the capillaries and phagocytosed the bacteria. Phagocytosis of bacteria was evident at 10 minutes and was almost complete at 60 minutes and, although less frequent, were associated with small amounts of fibrin at 60 minutes. This acute inflammation and thrombosis may be mediated by activation of complement through the alternate pathway.


Tamm-Horsfall protein. Abnormal localization in renal disease.

Interstitial deposits of periodic acid-Schiff positive fibrillar material have been detected in a variety of diseases associated with tubulointerstitial pathology. This material has been shown to be Tamm-Horsfall protein by immunofluorescent, immunochemical, and electron microscopic studies. Prospective evaluation of 133 kidneys revealed deposits in 11 per cent. These deposits included medullary cystic disease (50 per cent), obstructive uropathy and vesicoureteral reflux (21 per cent), and tubulointerstitial disease (29 per cent). Tamm-Horsfall protein was also detected in Bowman's space in four cases of obstructive uropathy. It is proposed that these deposits result from severe tubular damage with release of Tamm-Horsfall protein from its normal intracellular and intralumenal locations into the renal interstitium. We speculate that the intersitial deposition of this sequestered protein may result in a continued inflammatory response and progressive renal damage.


Anal carcinoma: basic concepts and management.

Surgery has been the mainstay in the management of anal carcinoma. However, anal carcinomas are reasonably sensitive to ionizing radiation. By appropriate combinations of external radiation beams and interstitial implantation techniques, curative therapy with preservation of anal continence can be rendered by radiation alone. Sufficient radiation dose to the draining lymph nodes, both intraabdominal and inguinal, along with intensified dose to the primary lesions, is required for high cure and low complication rates.


Antitumor tests of amygdalin in spontaneous animal tumor systems.

In a series of 6 experiments with CD8F1 mice with spontaneous mammary adenocarcinomas Sugiura noted by macrovisual observation with some histology an overall average of 21% of mice with lung metastases when treated with 1,000--2,000 mg/kg/day of amygdalin compared with 90% of the control mice. The significance attributed to those early observations is seriously challenged by the negative findings of 3 independent investigators, by 2 out of 3 negative cooperative experiments in which Sugiura participated, and particularly by the blind experiment in which he and others under blind readings found no anticancer activity. Treatment of Swiss albino mice showed no destructive effect upon their spontaneous mammary adenocarcinomas. Of the treated mice, 22% were found by macrovisual observation to have lung metastases while 91% were noted among the controls. The results are subject to questions raised in the discussion. Amygdalin at 2,000 mg/kg/day was ineffective both in treating and preventing the development of spontaneous leukemia in AKR mice. At 1,000 mg/kg/day it was not found effective in preventing or significantly delaying the development of spontaneous mammary tumors in CD8F1 mice. In summary, we do not have evidence to support taking amygdalin to clinical trial, although other considerations may require that one be conducted.


Current expectations in cardiac transplantation.

Survival after cardiac transplantation has improved significantly over the past 3 1/2 years at our Center as compared to previous experience (Fig. 5). Currently, survival rates for 60 patients who have had heart transplantation since late in 1973 (program year mean survival +/- S.E.) are 66 percent (+/- 6.6 S.E.), 63 percent (+/- 7.0) and 58 percent (+/- 8.2) 1, 2, and 3 years after operation, respectively. In this report the major reasons for this successful trend have been summarized. These consist of transvenous endomyocardial biopsy for diagnosis and management of graft rejection, use of RATG, immunologic monitoring for early detection of impending rejection, and cardiac retransplantation in selected cases. The present expectations for survival and rehabilitation after heart transplantation are fully comparable to the current results of renal transplantation from unrelated donors. These considerations support the inclusion of cardiac transplantation as a realistic therapeutic alternative in the management of patients with advanced heart disease irremediable by standard forms of treatment.


Anesthetic experience with cardiac transplantation.

The anesthetic management of 17 patients undergoing cardiac transplantation is described. Recipients had severe biventricular failure and pulmonary hypertension. Careful administration of diazepam and morphine was the preferred induction method, and pancuronium was the favored relaxant for both intubation and maintenance. Sterile technique was used in placing endotracheal tubes. Relatively small doses of morphine and diazepam, combined with 50 percent nitrous oxide, were satisfactory for the maintenance of anesthesia. Postperfusion problems were few but included poor tolerance of hypovolemia and an exaggerated hypotensive response to protamine. Isoproterenol was required to support ventricular performance, but no other cardiac stimulants were needed. Postoperative courses were uneventful. There were no operative deaths and no recall of awareness during the operation with the described method of "light" anesthesia.


Improved survival of heart transplants. Graft and/or donor pretreatment with antilymphoblast globulin, cyclophosphamide, or methylprednisolone.

Survival of heart allografts flushed with antilymphoblast globulin (ALG) was significantly prolonged when the grafts were transplanted into minimally immunosuppressed recipients. When no immunosuppression was given, there was no prolongation of survival of ALG-flushed grafts. Donor pretreatment with cyclophosphamide, methylprednisolone, or ALG had no influence in the prolongation of survival of cardiac allografts. We do not have a clear explanation for the prolonged survival of ALG-flushed grafts transplanted into minimally immunosuppressed recipients.


Alterations in total and regional myocardial blood flow during acute rejection of orthotopic canine cardiac allografts.

Using radioactive microspheres, we studied the quantitative and sequential distribution of myocardial blood flow during acute rejection of cardiac orthotopic allografts in 15 nonimmunosuppressed dogs. During rejection mean cardiac output per kilogram decreased 49 percent from control, stroke volume per kilogram decreased 40 percent, total left ventricular flow decreased 43 percent, and the subendocardial/subepicardial flow ratio (I/O) of the left ventricular free wall decreased 21 percent. Relative subendocardial hypoperfusion occurred despite an increase in the ratio of left ventricle subendocardial supply (diastolic pressure-time index) to demand (tension-time index). The data indicate that total left ventricular flow decreases severely and selective left ventricular subendocardial ischemia develops very early during acute cardiac rejection.


Pulmonary function in mitral stenosis.

The reported results of pulmonary function testing in patients with mitral stenosis are summarized, including a few studies done after operative correction of the mitral stenosis. The physiologic effects of increased pulmonary water explain most of the reversible abnormalities in pulmonary function. Fixed pathologic changes that occur with longstanding interstitial edema may account for the irreversible nature of other alterations in pulmonary function.


Development of gastrointestinal function and selected dysfunctions.

This brief review of gastrointestinal function was designed to update the reader on our current state of knowledge about development in general as well as certain specific gastrointestinal functions necessary for effective enteric feedings as the primary source of neonatal nutrition. Many more studies in humans during the perinatal period are needed. However, these studies must await before their use can be condoned in man. The development of LES and gastric emptying was discussed in the context of regurgitation, a common problem in premature infants. Factors contributing to the maturation of the intestinal surface were reviewed as a basis for considering colostral stimulation of intestinal maturation in the external environment. Finally the development of intestinal motility and anal rectal tone were considered and suggestions as to further studies needed made.


Colonization of the gastrointestinal tract.

The alimentary tract is sterile at birth but colonic colonization is relatively complete by the end of the first week of life. The upper alimentary tract is colonized by microorganisms normally inhabiting the oral cavity. The colon on the other hand appears to be colonized by microorganisms originating in the maternallower alimentary tract. The colonic flora of infants is affected by diet (breast or formula feedings). The presence of a "fecal-type" flora in the proximal small bowel should be considered abnormal. Most authors agree on the need to define the role of the microflora in health and disease.


[Comparative studies of various suture techniques in transthoracic esophagogastric anastomoses in dogs (author's transl)].

In 27 dogs esophagogastric anastomoses were performed in a single-layered end-on, a three-layered end-on and a double-layered inverting technique. The anastomoses were reinvestigated on the 2., 4., 7., 15. and 30. postoperative day. Suture line leakages were not observed. The inverted suture resulted in considerable anastomotic stenosis, ulceration of the mucosa, disordered and initially incomplete revascularisation, and widespread granulomatous inflammatory reaction. In contrast, the end-on technique led to almost no stenosis, ordered revascularisation, and narrow and delicate scar tissue formation while maintaining a normally layered structure. The single-layered methode was superior to the three-layered one. The best results were obtained by the extramucous technique.


[Traumatic hemobilia. A case report (author's transl)].

A case of traumatic hemobilia is reported. After ligation of the left hepatic artery and additional dearterialisation a third bleeding period occured due to a porto-hepatic communication, diagnosed by a transumbilical portography. A left hepatic lobectomy was finally necessary to achieve hemostasis. This case demonstrates that a selective artery ligation for the treatment of hemobilia is only successful if a complete dearterialisation is performed at the first operation. Furthermore a porto-hepatic communication may require partial hepatectomy.


Reconstruction of laryngeal function for recurrent laryngeal nerve paralysis: historical view, advancement of latest investigations and a preliminary experiment.

Historical investigations of the functional restoration for recurrent laryngeal nerve paralysis are reviewed and some advancement in recent studies are introduced. A preliminary experiment is reported in which the ansa hypoglossi and the sternothyroid muscle pedicle was implanted into the denervated posterior cricoarytenoid muscle in dogs. From these experiments we have concluded that the ansa hypoglossi and sternothyroid muscle pedicle, which has been shown to transmit efferent inspiratory bursts, is capable of restoring function to the paralyzed posterior cricoarytenoid muscle in some dogs.


[Device for measuring microconcentrations of indicator dyes in the blood].

A device operating on the principle of spectrophotometry that allows it by using an auricular sensor to continually record changes in the microconcentration (up to 1 mg/1) of dyes-indicators (ueviridin, cardiogrin, indigocarmin) that are introduced in the human blood circulation system for the purpose of diagnosing affections of the liver, kidneys and heart, is described.


[Comparison of cryogenic support systems of surgical instruments for the local destruction of large biological tissue lesions].

Of two types of systems for cryogenic support (SCS) of surgical instruments made with open and closed contours those of the discharge type meet to a greater extent basic requirements on the SCS as concerns destruction of extensive areas of the biological tissue. These SCS permit it more readily to withstand optimal conditions of cooling, can secure better reliability in performing operations, offer greater possibilities for unification of parts in packing up the set and for covering a wider range of operations. In cases when it is important to provide for self-containment and a longer period of continuous operation the application of the SCS with a closed contour is more advisable.


Non-traumatic gram-negative bacillary meningitis in the Detroit Medical Center, 1964-1974; (with special mention of cases due to Escherichia coli).

Clinical and autopsy records of eight adults with non-traumatic gram-negative bacillary meningitis who were admitted to the hospitals of the Wayne State University--Detroit Medical Center during the years 1964 to 1974 were reviewed. There were five community-acquired cases, and five patients died. Escherichia coli was the causative enteric bacillus in six cases. Community-acquired infections were due to Esch. coli in four of the patients. Each of the patients with a community-acquired infection was a chronic alcoholic. Esch. coli bronchopneumonias, urinary infections, and bacteremias seeding the meninges were usual. Shunting contaminated portal venous blood through the liver in patients with Laennec's cirrhosis, or bypassing the liver with similar infected blood from a genitourinary source by way of Batson's perivertebral plexus draining into the cerebral dural sinuses may be important in the pathogenesis of these infrequent cases of nontraumatic gram-negative bacillary meningitis. Spontaneous gram-negative bacteremias, peritonitis, bronchopneumonias, and now "meningitis" may be a constellation of special complications of the alcoholic. Mortality among 25 patients with Esch. coli meningitis reported from 1922 to 1974 is approximately 50%, and has not changed appreciably during the antibiotic era. Mortality, however, is significantly higher in nosocomially acquired cases. Early and more recent cases have had bloody, xanthochromic pleocytoses indicative of leptomeningeal arterial and venous vasculitis, and far advanced disease. Since causative/enteric bacilli have been susceptible to antimicrobial agents employed, another mode of antibacterial administration, perhaps utilizing parenteral plus intraventricular dosing, particularly for patients acquiring their infections in the hospital, may be required.


Human aeromonas infections: a review of the literature and a case report of endocarditis.

Our patient, with cirrhosis and chronic renal failure, represents an example of the susceptibility of a compromised host to Aeromonas infections. This patient, however, differs from previously reported cases in at least two important aspects. First, it is possible that her portal of entry was a fresh A-V fistula puncture site rather than an intestinal site. The temporal relationship of exposure to flood water prior to the onset of sepsis lends support to this possibility. Epidemiologic investigation of the dialysis center failed to reveal Aeromonas isolates from cultures of the water supply, machinery, or other patients. Second, this case is unique in that our patient developed a destructive aortic valve endocarditis resulting in valvular perforations and acute aortic insufficiency. Furthermore, this infection was initiated on what appears to have been a previously normal valve. Based on a review of the literature and the virulence demonstrated by A. hydrophila in our patient, we conclude that organisms of the genus Aeromonas are capable of inducing serious human infection. Such infections are more likely to occur in compromised hosts. A. hydrophila has accounted for the majority of reported infections.


Preparation and stability of mureinoplasts of Escherichia coli.

A peptidoglycan bounded form termed a mureinoplast was prepared from cells of Escherichia coli and the stability of this was examined in various suspending media. True protoplasts were subsequently formed from mureinoplasts.


Cellular elements in the resistance to candida infection in mice. I. Contribution of T lymphocytes and phagocytes at various stages of infection.

Live organisms (cfu) of Candida albicans per organ were counted 1 hr and 1 to 20 days after an intravenous inoculation into various groups of mice which had distinct levels of immunologic or non-immunologic defense mechanisms. a) The number of cfu in the liver decreased progressively in normal mice, but those in the kidney maintained a constant level during the observation period. b) The number of cfu in the liver decreased progressively also in nude mice. In their kidneys, however, cfu increased progressively at a late stage of infection. c) In lethally irradiated AKR of nude mice in which phagocyte functions were severely depressed, the number of cfu increased progressively in both liver and kidney from the initial stage of infection. d) In immunized AKR mice, growth of C. albicans was suppressed at late stages of infection. Such protective immunity could be transferred partly with immune lymphoid cells but not with hyperimmune serum in the experimental system employed. In protection against candida infection, non-immune phagocytosis and T cell-mediated immunity appear to be required at the early and late stages of infection, respectively.


The assessment of an antiarrhythmic agent, sustained-release procainamide, with the aid of Holter monitoring.

A sustained-release preparation of procainamide (PAD) was evaluated in a double-blind cross-over study. The preparation was found to reduce ventricular ectopic activity in all seven patients who completed the investigation in five patients the effectiveness reached the defined level of significance. A larger clinical trial to assess the long-term use of this preparation in terms of efficacy, safety and convenience is recommended.


The susceptibility of Candida albicans to amphotericin B, nystatin, and 5-fluorocytosine.

Sensitivity tests were performed on 332 consecutive isolates of Candida albicans. All isolates were inhibited by 0.5 microgram/ml of amphotericin B, and 6.4 microgram/ml of nystatin; and 92.5% of strains were inhibited by 25 microgram/ml of 5-fluorocytosine. Therefore, all three drugs may be employed clinically in the treatment of candidiasis with a reasonable chance of success.


A trial of lactose hydrolysed milk in Australian Aboriginal children.

Weight gains in 50 young Australian Aboriginal children were studied in a blind controlled hospital trial of reconstituted, lactose hydrolysed milk powder (test) and full-cream milk powder (control). The mean weight gains (+/- SEM) were 4.80 +/- 0.80 g kg-1 day-1 for children receiving the lactose hydrolysed milk, and 2.20 +/- 0.75 g kg-1 day-1 for those receiving the normal milk P less than 0.0125). Weight gain of infants (that is, those under one year of age) in the control group was less than 10% of that in the test group (P less than 0.0025). Weight gain was higher in children fed hydrolysed milk irrespective of percentage of Standard Weight for Age or the presence or absence of recognizable symptoms of lactose intolerance. Lactose malabsorption appears to be a major factor in the growth retardation of Aboriginal children. It is recommended that lactose hydrolysed milk replace normal milk in the supplementary feeding of Aboriginal infants and children.


Does ambient ozone pose a serious public health concern as a widespread environmental mutagen?

Based on bacterial, plant, animal and human studies, it is evident that O3 is a general mutagen. However, there is still considerable uncertainty as to the extent to which O3 is a human mutagen. Attempts to develop dose-response relationships have not yielded consistent results in the several studies thus far reported. At the present time there is a complete lack of data concerning human responses from ambient exposure. In light of the extent of the photochemical oxidant problem in the U.S. and the potential genetic effects of O3, it is suggested that a major research effort be directed at both the elucidation of the potential mutagenic effects of O3 as well as the implementation of effective oxidant control strategies.


[In vitro activity of cefoxitin compared with the activity of other antibiotics and trimethoprim-sulfamethoxazole (author's transl)].

The new developed antibiotic cefoxitin has been tested in vitro on its effectiveness against bacteria isolated from human material. Pseudomonas aeruginosa and streptococci of the serological group D were not tested, because these microorganisms are not sensitive against this antibiotic. Besides cefoxitin other antibiotics (cephalothin, cephalexin, ampicillin, carbenicillin, tetracycline, gentamicin, penicillin G, oxacillin) and trimethoprim-sulfamethoxazole were also tested. As to the results cefoxitin shows the best effectiveness against all gram-positive bacteria and against gram-negative bacteria including indol-positive species of proteus, providencia, serratia marcescens and the anaerobe, gram-negative, non-spore-forming rods. There are different results with enterobacter-, citrobacter-, achromobacter- and acinetobacter-species.


Genetic map of the bacteriocinogenic plasmid CLO DF13 derived by insertion of the transposon Tn901.

An ampicillin transposon Tn901 was used as a "mutagen" to isolate insertion mutants of the bacteriocinogenic plasmid Clo DF13. By combining the obtained heteroduplex and restriction maps of the Clo DF13::Tn901 plasmids (van Emboden et al., 1977b) with their polypeptide pattern in minicells, we were able to map five genes on the Clo DF13 genome. These five genes designated A (cloacin gene), B, C, D, and G cover 55% of the coding capacity of Clo DF13 DNA. Since integration of Tn901 within these five genes did not result in a loss of the Clo DF13::Tn901 plasmids involved, it is suggested that these genes do not play an essential role in the maintenance of these plasmid insertion mutants. In addition, the described methods allowed us to indicate the initiation site of cloacin synthesis and to propose the counter-clockwise direction of transcription of the cloacin gene. The Tn901 DNA directed the synthesis of at least three polypeptides one of which is shown to be a TEM-1 beta-lactamase.


Cloning of a restriction fragment of phage mu DNA coding for early functions.

The DNA of an E. coli K12 strain harboring ten wildtype Mu prophages was restricted with endonuclease EcoRI, and the fragments ligated into the plasmid vector pMB9. Upon transformation of a strain carrying a heat inducible (Mu cts62) prophage, one temperature-resistant transformant was isolated. This transformant strain harbors the hybrid plasmid pKN001, containing the EcoRI.C fragment of Mu DNA as shown by restriction and heteroduplex analysis. Stable transformants of pKN001 are immune to superinfection with phage Mu. Transformation of Mu sensitive bacteria with pKN001 results in killing of the recipients (10(-4) surviving bacteria). The killing function is not expressed upon transformation of Mu-immune (lysogenic) bacteria.


Genetic damage during thymidylate starvation in Saccharomyces cerevisiae.

Thymidylate starvation in a yeast mutant auxotrophic for dTMP caused cell death and the induction of mutations in the mitochondrial genome. After 24 h of starvation almost all surviving cells were respiratory deficient petites. In addition, shorter episodes of dTMP starvation induced chloramphenicol and erythromycin resistant mutants, indicating the occurrence of mitochondrial point mutations. Suboptimal concentrations of exogenous thymidylate were also found to induce petites and a decline in cell viability and the magnitude of these effects was acutely dependent upon the dTMP concentration. Cesium chloride gradient analysis of DNA from cells undergoing thymineless incubation revealed a progressive loss of mitochondrial DNA, and a decrease in the molecular weight of nuclear DNA.


Haemoprotein formation in yeast. III. The role of carbon catabolite repression in the regulation of catalase A and T formation.

Catalase A and T activities were investigated in two standard strains and three catalase regulatory cgr mutants of yeast in respiratory competent and incompetent states, which were under various degrees of glucose repression. The formation of catalase A was very sensitive to glucose repression and was characterized by a long delay in derepression. Deprivation of the energy source in respiratory incompetent cells prevented the derepression of catalase A. The lack of catalase A in respiratory imcompetent cells can be overcome by growing the cells in raffinose or by the prolongation of the fermentative phase of derepression. Catalase T is under control of different regulatory systems probably common with some other haemoproteins.


Non-coordinate expression of the neighbouring genes rplL and rpoB,C of Escherichia coli.

The operon rpoB,C of Escherichia coli codes for the RNA polymerase subunits beta and beta'. rpoB procedes rpoC in the direction of transcription. The nearest characterised gene to rpoB on the chromosome is rplL, which codes for the ribosomal proteins L7/12. rplL appears to be transcribed in the same direction as rpoB,C, and it has been suggested that all three genes may lie in a single operon. The drug rifampicin induces increased production of beta and beta' in suitable strains of E. coli. We show here that alpha and sigma are also induced, whereas synthesis of L7/12 is not detectably affected.


UV-inducible repair: influence on survival, dimer excision, DNA replication and breakdown in Escherichia coli B/r Her+ cells.

Using a model of double-UV-irradiation with inducing1 (non-lethal) and lethal fluences2 we have studied involvement of UV-inducible functions in post-UV-irradiation restoration processes and survival of Escherichia coli B/r thy-trp-Hcr+. Cells irratiated with both inducing and lethal fluences differed from cells irradiated with lethal fluence in the following respects: They were more UV resistant; they did not die during postincubation with chloramphenicol3; they exhibited a significant reduction in dimer excision; they were able to resume DNA replication and produce normal-sized DNA molecules in the presence of chloramphenicol. Since induction was provoked in cell prestarved for amino acids it was not associated with damage to points active in replication. However, the inducible product was more important for repair of replicating than non-replicating cells. The data indicate that protein necessary for resumption of DNA synthesis after UV is not constitutive but inducible.


Specific localization and quantification of biotin transport components in yeast by use of a biotin-conjugated, impermeant, electron-dense label.

Two approaches are described for the localization and quantification of biotin transport components in yeast cells. One approach is based on tracing the fate of a radioactive affinity label for the biotin transport system, [14C]biotinyl-p-nitrophenyl ester (pBNP), through various stages of subcellular fractionations. A complementary method involves the use of a biotin-derivatized, impermeant, electron-dense, affinity-cytochemical label (ferritin-biotin conjugates) for subsequent visualization by electron microscopy. Values of approximately 8,000 and 4,000 sites/cell, respectively, were achieved by the two methods. Complicating factors, future perspectives and the relevance of the two methods to the isolation of transport components are discussed.


The relationship between guanosine tetraphosphate, polysomes and RNA synthesis in amino acid starved Escherichia coli.

A relA+ strain of E. coli with four amino acid requirements was starved separately for each amino acid, after which the levels of polysomes, guanosine-5'-diphosphate-3'-diphosphate and the residual net synthesis of RNA were determined. The polysome level and guanosine-5'-diphosphate-3'-diphosphate production were coordinately affected by starvation for the different amino acids, whereas no correlation was found between these two parameters and residual RNA synthesis. The main conclusion stemming from these results is that guanosine-5'-diphosphate-3'-diphosphate cannot act as the sole effector molecule in stringent control of RNA synthesis.


Differential effect of amino acid starvation on polysome decay in Escherichia coli.

In a relA+ strain of E. coli starved separately for each of four required amino acids, the intracellular concentration of polysomes decreases as a function of time in all cases: very rapidly in the absence of arginine or leucine, slowly in the absence of threonine or histidine. In a starved isogenic relA strain, the polysome level is either totally stable or else drops slowly. The decrease in the level, when it occurs, does not significantly affect the polysome size distribution. Models for polysome metabolism in amino acid starved cells are discussed.


[Immunological diagnosis of leukemias in childhood (author's transl)].

Subclassification of leukemias in childhood by cytochemical methods or blast size is arbitrary to some extent. The increased knowledge of physiological development of hematopoetic cells allows to classify these diseases according to the degree of differentiation of the cells involved. Immunological cell-membrane structures are used as for markers differentiation. In this way, 4 types of lymphoblastic leukemias and 5 types of myeloid leukemias can be diagnosed. This classification can help to answer clinical and theoretically important questions. In ALL and during the blast crisis of CML, new groups with increased risk are defined, important for the choise of initial therapy, and evaluation of therapeutic trials. The immunological markers can help to detect already small numbers of blasts at the beginning of a hematological relapse. Transformations of the blast type during the course of the disease can be explained. Experiments in animals indicate that an immunological classification of leukemias correlates with differences in pathogenesis and etiology.


R plasmid-mediated enhancement of mutagenesis in strains of Escherichia coli deficient is known repair functions.

The response to four mutagens (UV radiation, methyl methanesulfonate (MMS), cis-platinum dichlorodiamine (cis-PDD), and a 2-aminopurine (AP)) known to cause different types of DNA damage was investigated in the WP2 strain wild-type for DNA repair and in uvrA-, lexA-, polA-, uvrD- and recL- strains. Each strain was also tested after introduction of either the pKM101 or R648 plasmid. The number of revertants produced by a given mutagen in a given bacterial strain depended in a complex way on: (1) the nature of the mutagen and the type of lesion it created in DNA; (2) the prensence and the nature of defects in the chromosomally determined DNA-repair system; and (3) the presence and the nature of plasmids with mutator effect. The results confirm that plasmids enhance mutagenesis through an error-prone DNA-repair system, which is expressed at different levels for different plasmids. Or, alternatively, different repair mechanisms for different plasmids may exist.


Phenotypic lag and mutation to 6-thioguanine resistance in diploid human lymphoblasts.

Mutants of a diploid human lymphoblast line resistant to 6-thioguanine (6TG) appear 6--16 generations after treatment with any of a diverse group of mutagents: methylnitrosourea (MNU), methylnitrosoguanidine (MNNG), ICR-191, 5-bromodeoxyuridine (BUdR). A hypothesis is advanced that expression of the 6-thioguanine-resistant state may require the removal of essentially all pre-existing hypoxanthine--guanine phosphoribosyl transferase (HGPRT) molecules via division, dilution, and protein turnover. Design of protocols for quantitative mutation assays requires attention to this phenomenon.


Removal of pyrimidine dimers from Saccharomyces cerevisiae nuclear DNA under nongrowth conditions as detected by a sensitive, enzymatic assay.

A sensitive and quantitative procedure for the detection of pyrimidine dimers in yesast nuclear DNA is described. The assay employs dimer-specific, endonuclease activities from Micrococcus luteus together with DNA sedimentation through calibrated, alkaline sucrose gradients to detect endonuclease-induced, single-strand breaks. Breaks were induced in a dose-dependent manner from 0 to 80 J m-2 at 254 nm and in numbers equivalent to the numbers of dimers induced by similar doses (Unrau et al., Biochim. Biophys. Acta, 312 (1973) 626--632). This procedure also allows the use of [6-3H] uridine to label cellular nucleic acids, but dose not require extensive DNA purification to eliminate concomitantly labeled RNA. Endonuclease-sensitive sites in the wild-type, haploid strain S288C, after irradiation with 5 J m-2 (254 nm), were removed in less than 5 min when cells were incubated in buffer (pH 7.0) at 28 degrees C. After irradiation with doses from 30 to 100 Jm-2 site removal in S288C required longer postirradiation incubations and was about 90% complete. In a radiation-sensitive strain carrying the mutant allele rad4-3 the number of endonuclease-sensitive sites remained constant for 6 h after irradiation with 5 Jm-2. The retention of sites in this strain indicates that it is defective in the excision of pyrimidine dimers.


Sister-chromatid exchange induced by X-ray of human lymphocytes and the effect of L-cysteine.

A staining technique that detects sister-chromatid exchanges (SCEs) has been used to examine the response of human lymphocyte chromosomes to various dosages of X-irradiation. The SCE frequency was markedly increased following irradiation. However, the increase was of a significantly smaller magnitude when irradiation occurred in the presence of an antimutagenic agent. Scoring SCEs may provide a useful technique for assaying the mutagenic effects of environmental carcinogens as well as the protective effects of antimutagenic agents.


The mutagenicity of heterocyclic N-nitrosamines for Salmonella typhimurium.

14 carcinogenic and noncarcinogenic heterocyclic N-nitrosamines were evaluated for mutagenicity to Salmonella typhimurium TA-1535, which responds to mutagens inducing base-pair substitutions. Both suspension and plate tests were used, with mouse and rat liver in vitro metabolic activation systems. All carcinogenic nitrosamines showed a positive response in at least one test system, as did the noncarcinogens. In general, the mutagenic responses obtained with mouse liver were equal to, or greater than, the responses obtained with rat liver in both the suspension and plate tests. Although it is difficult to make quantitative comparisons between plate and suspension tests, both systems appeared to be responsive to the same dose ranges for the individual nitrosamines.


Genetic activity of allyl chloride.

Allyl chloride (3-chloroprene) is mutagenic for Salmonella typhimurium and it induces gene conversions in Saccharomyces cerevisiae. It also displays DNA-modifying activity for E. coli. This is in contrast to a recent study which reported its lack of genetic activity for Salmonella typhimurium.


Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation.

Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment. The second patient underwent a successful transplantation after similar preparation, except that procarbazine was omitted. At 11 and five months after transplantation both had normal hematopoiesis and no evidence of graft-versus-host disease. This treatment of the Wiskott-Aldrich syndrome may be a model for the correction of other genetically determined immune and hematologic bone-marrow disorders.


The academic medical center: a stressed American institution.

In recent years, relations between academic medical centers and the government have become increasingly adversarial. Although the centers and the government were formerly partners in a number of health ventures, to the mutual benefit of both, the climate is now too often confrontational. It is a confrontation in which there will be no winners, but the larger society may be the loser. A number of pressures on academic centers have helped to contribute to this situation. The federal sector and academic medical institutions must understand one another better and rediscover effective ways to preserve the special strengths of academic medicine in this country.


Human leukocyte interferon for the treatment of herpes zoster in patients with cancer.

We tested the effect of human leukocyte interferon on  early localized herpes zoster infections in three placebo-controlled, randomized double-blind trials involving 90 patients with cancer.  There were no significant differences in pretreatment severity of infection or nature of underlying disease in the groups. Higher dosages of more purified interferon in the second and third trials produced a significant (P less than or equal to 0.01) decrease in cutaneous dissemination. No dissemination occurred in those receiving the highest dosage (5.1 x 10(5) U per kilogram per day) (P less than or equal to 0.025). The number of days of new-vesicle formation in  the primary dermatome decreased (mean, 2.3 days, P less than or equal to 0.05) in this group. Treated patients had a trend toward less acute pain, and significantly (P less than or equal to 0.05) diminished severity of post-herpetic neuralgia,  at the two highest dosage levels. Visceral complications were six times less frequent in interferon recipients. High-dosage interferon appeared effective in limiting cutaneous dissemination, visceral complications and progression within the primary dermatome.


Induced intragenic recombination in yeast can occur during the G1 mitotic phase.

The conditional cell division cycle yeast mutants cdc have been used to demonstrate that intragenic recombination induced by ultraviolet or gamma rays occurs in diploids arrested in G1, a short time after irradiation and before the initiation of the S phase. This implies that pairing of homologous chromosomes does not require duplicated chromatids.


Mammals, resources and reproductive strategies.

The breeding systems of mammalian species are strongly influenced by the density and dispersion of their populations. These in turn are affected by variations in the distribution of resources. Through quantitative comparisons, it is possible to trace evolutionary relationships between feeding behaviour, population dispersion, breeding systems and morphology.


Cellular reaction to autologous tumor tissue followed by "skin window" technique in orofacial tumors.

In a sample of patients with pseudotumors and benign and malignant tumors of the orofacial region there has repeatedly been investigated, after radical surgery, the cell reaction to autologous tumor tissue applied at indicated time intervals on a small skin lesion. The prognostically favorable picture of a cellular-type hypersensitivity reaction with massive participation of lymphoid cells and basophil granulocytes was only found in some basaliomas and leukoplakias. Conversely, spinocellular carcinomas are, irrespective of localization, characterized by areactivity.


Antibody coating of urinary bacteria in transplanted patients.

24 patients with renal transplants were studied beyond the immediate postoperative period (greater than 8 weeks p.o.) for a period of 6 months in three weekly intervals. Quantitative bacteriology (dip slide method) and immunofluorescence microscopy (antibody coating of urinary bacteria) of the urine were regularly performed. Urinary tract infection was found in 13 of 24 patients, being permanent in 9 and episodic in 4 of the patients. There was no correlation between presence of urinary tract infection and deterioration of renal function. Mixed infection was found in 7 of the 13 patients and monoinfection in the others. In 7 out of these 13 patients, antibody coating of urinary bacteria could be demonstrated by immunofluorescence microscopy. In 3 of the 7 cases with antibody coating, this was permanently positive, in the other 4 it was intermittently positive. In only 1 case could conversion to positive antibody coating be attributed to urological complications (pyelostomy). Both IGG and IGA were demonstrable in 6 of 7 cases with positive antibody coating and IGG exclusively was demonstrable in 1 more case. IGM was questionably positive in 1 case and complement (beta1C) could not be demonstrated in any of the patients. This investigation shows that despite immunosuppression patients with renal transplants are able to mount an immune response against urinary tract infections.


Evidence for an inhibitory dopaminergic and stimulatory noradrenergic hypothalamic influence on PMS-induced ovulation in the immature rat. II. A pharmacological analysis.

Pregnant mare's serum gonadotropin (PMS; 10 IU day 30)-induced ovulation was used as a model to study the effect of drugs interfering with monoamine neuro-transmission on CNS processes controlling ovulation. The drugs were administered during the critical period on day 32 and tubal eggs were counted in the morning of day 33. When injected during the critical period, dopamine (DA) receptor agonists such as apomorphine, ET 495, ergotamine, 2-bromo-alpha-ergocryptine, lergotrile and ergocornine inhibited ovulation, an effect which was counteracted by the DA receptor blocking agent, pimozide. However, by itself pimozide had no significant effect, whereas combined noradrenaline (NA) and DA receptor blocking agents such as chlorpromazine and clozapine inhibited ovulation. alpha- and beta-adrenergic blocking agents and drugs influencing 5-hydroxytryptamine (5-HT) neurotransmission did not affect ovulation. LH-RH removed the ovulatory blockade induced by ET 495 in the same dose-range as it removed pentobarbital-induced blockade of ovulation. Furthermore, ergocornine did not black ovulation after the critical period and was less effective when given prior to the critical period. Therefore it is likely that the DA receptor agonists act via a central action. Thus, the present findings give further support for the existence of a central inhibitory DA and facilitory NA mechanism in the control of PMS-induced ovulation in the immature female rat.