Comparison of the effects of pentagastrin and meal-stimulated gastrin on plasma calcitonin in normal man. We compared the effects of exogenous pentagastrin and meal-stimulated gastrin on plasma immunoreactive calcitonin (iCT) in various studies of 13 normal adult men. Bolus intravenous injection of pentagastrin (0.5 microgram/kg) produced increases of iCT in 8 of 9 men. There was a linearly increasing response of iCT concentrations to increasing doses of pentagastrin (0.0625, 0.125, 0.25, and 0.5 microgram/kg) and to achieved serum immunoreactive pentagastrin concentrations (r = 0.72, P less than 0.01). To determine the effects of endogenous gastrin upon peripheral iCT concentrations, we measured serum immunoreactive gastrin (iG) and plasma iCT in four men at frequent intervals for 240 min after ingestion of low- (100 mg) and high- (400 mg) calcium meals. Serum iG increased in all subjects, with a peak at approximately 30 min. However, plasma iCT levels were unchanged from basal throughout the study. The increase of pentagastrin (0.3 pmol/ml) which caused a barely detectable increase of iCT was five- to tenfold greater than the mean maximal increases of gastrin after low- and high-calcium meals (0.04 and 0.06 pmol/ml, respectively). These results suggest that increases of plasma iCT concentrations after administration of pentagastrin in man reflect pharmacologic phenomena and that postprandial gastrin secretion may be insufficient to affect peripheral iCT concentrations.


Deposition of circulating antigen--antibody complexes in the gastrointestinal tract of rabbits with chronic serum sickness. The possible role of circulating immune complexes (IC) in the production gastrointestinal lesions was studied in rabbits with chronic serum sickness (CSS) induced by multiple daily injections of bovine serum albumin (BSA). All rabbits generating a marked antibody response developed IC glomerulonephritis. In approximately 50% of these rabbits granular deposits of BSA, rabbit IgG, and C3 were also found in the gastrointestinal tract. The immune deposits in the gastrointestinal tract were mainly present in the vessel walls, close to the intestinal glands and the surface epithelium, and between the smooth muscle cells. This was accompanied by slight to moderate edema of the mucosa and the submucosa and mild infiltration of inflammatory cells. Electron-densedeposits were found in a pattern corresponding to that observed for BSA, rabbit IgG, and C3. Degranulated neutrophils, basophils, and mast cells were noticed in the interstitium. The presence in the same areas of granular deposits of BSA, IgG, and C3, corresponding to electron-dense deposits, suggests that the deposits contain BSA-anti-BSA complexes. These findings show that in rabbits with CSS circulating IC may localize and induce injury in the gastrointestinal tract.


A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma. Ninety-nine patients suspected of having pancreatic carcinoma were studied prospectively for carbohydrate tolerance. Thirty-two patients were proven subsequently to have pancreatic carcinoma; the remainder served as a control group. There was an increased incidence of carbohydrate intolerance in patients with pancreatic carcinoma compared to the control group. Insulin and C-peptide measurements during glucose tolerance tests suggest abnormal beta cell function and possibly insulin resistance as causes for this abnormality. Although factors related to malignancy in general could partly account for the results, a specific factor occurring in patients with pancreatic carcinoma must also be considered as it could serve as a marker for the early detection of this disease.


B-cell leukemia-lymphoma with striking resemblance to Burkitt lymphoma in a 70-year-old woman. A 70-year-old woman developed acute leukemia and a serum IgM spike. She entered complete remission with an adriamycin, vincristine, cytosine arabinoside, and prednisone combination. Bone marrow remission was maintained with intermittent cytosine arabinoside; however, she developed large skin nodules which partly remitted following adriamycin, vincristine, cyclophosphamide, and prednisone combination. They very rapidly recurred, and she died soon after. Autopsy revealed extensive tumor in the abdomen, pelvis, and thoracic cavity, but no bone marrow involvement. Histology revealed a "starry sky" appearance. Cytology showed undifferentiated cells with vacuolated cytoplasm resembling Burkitt lymphoma cells. Peroxidase and esterase stains were negative. There was strong pyroninophilia and the periodic acid-Schiff reaction showed granular activity in the cytoplasm. Electron microscopic appearances also resembled Burkitt lymphoma. Cytogenetic studies were normal, with no Ph1 chromosome. Immunofluorescence demonstrated surface IgM and a little IgA. 3H-thymidine incorporation was high, indicating rapid growth. Dibutyral cyclic adenosine monophosphate (cAMP) stimulated growth, which was further evidence of the lymphoid origin of the tumor. The close resemblance of this tumor to Burkitt lymphoma emphasizes the difficulties in systematically classifying the lymphomas.


Rare variants, private polymorphisms, and locus heterozygosity in Amerindian populations. The results of 21,103 electrophoretic typings distributed across 28 polypeptides in members of 12 Amerindian tribes are reported, and the accumulated results of electrophoretic studies on these same polypeptides in 21 Amerindian tribes are then analyzed. Thus far 11 'private' polymorphisms have been identified in these tribes. When the tribal samples are combined and traits achieving polymorphic proportions in the total sample excluded from consideration, the average frequency of rare variants is 2.8 per 1,000 determinations. For a subset of 23 of these polypeptides also studied in Caucasians and Japanese, variant frequencies per 1,000 determinations are: Indians, 2.2; Caucasians (British), 1.6; and Japanese, 1.5. Average locus heterogeneity for these polypeptides (based on rare variants plus polymorphisms) is: Indians, .049; Caucasians, .078; and Japanese, .077. A higher proportion of loci are monomorphic within tribes than within civilized urban populations. It is argued that for inferences concerning the forces maintaining genetic variability within populations, studies on samples from tribespeople are much more appropriate than studies on samples from civilized urban populations.


Technique of surgical sex reassignment for micropenis and allied conditions. Although the etiology of micropenis is diverse, individuals who have in common a penile length of 2 cm. or less at birth do not function well as men. For this reason, during the last 18 years, 10 individuals with this problem were selected for surgical sex reassignment. The technique of the surgical procedure is described. The immediate results are considered to be cosmetically satisfactory, and the long-term results, as judged by two individuals who have been observed for 18 plus years seem to indicate that surgical sex reassignment is a useful procedure in selected patients with this disorder.


Reappraisals of J. Marion Sims.

Reappraisals of J. Marion Sims. Sims' development of repair for vesicovaginal fistula introduced the present epoch of gynecology. He remained professionally active for 30 years thereafter and achieved national and international reputation. He continued to contribute medically until his death. Sims was extravagantly eulogized. Now, 90 years later, he is being roundly denounced for using slaves as experimental subjects and for doing multiple procedures on hapless women. One must however be skeptical of judging 1850 decisions by 1975 norms. Sims undoubtedly exploited the misery of his patients but their abject state must be remembered. Sims was insensitive to the status and needs of women, but in that he was a product of his era. His medical achievements have borne up well in the test of time.


Combined clinical and laboratory studies with carbenicillin and ticarcillin: use in infections involving anaerobic bacteria. Eleven patients with serious infections involving anaerobic bacteria were treated with carbenicillin (four patients) or ticarcillin (seven patients). All patients were cured clinically and bacteriologically of their infections. An in vitro study testing 157 recently isolated anaerobic organisms against 11 antibiotics showed chloramphenicol, carbenicillin, and ticarcillin at blood level concentrations to be inhibitory to more anaerobic strains than the other eight antibiotics tested. Ticarcillin and carbenicillin appear to be safe and effective and deserve further consideration for use in the therapy of anaerobic infections.


Localization of group B beta-hemolytic streptococci in the female urogenital tract. Isolation rates of group B streptococci were determined for various sites in 100 women attending a Special Urology (VD) Clinic. Standard procedures were used for the collection of specimens, all of which were processed using a selective medium. Specimens from the urethra and lower vagina yielded significantly higher percentages of isolations than those collected from the cervix, upper vagina, and rectum. Although lower vaginal cultures yielded more positive results than urethral cultures, the difference was not significant.


Gonadotropin profiles in fed and fasted obese women. Five obese women were studied before and at the end of a prolonged fast to determine the effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and on the response to luteinizing hormone--releasing factor (LRF). Although baseline serum LH values declined from a mean value of 9.1 to 6.5 m.I.U. per milliliter measured at the end of the fast, these changes in mean serum level were not statistically significant. However, the integrated LH secretion did decline when measured at the end of the fasts (p less than 0.05). FSH secretion did not change. LRF-stimulated LH and FSH values showed augmented stimulation at the end of the fast. Pulsatile gonadotropin secretion patterns remained normal. Prolonged fasting appears to alter the baseline LH secretion and the pituitary response to exogenous LRF.


Some rationalizations on chronic open-angle glaucoma. In this study I dealt with two principal aspects of the seemingly irrational subject of chronic open-angle glaucoma: surgery for chronic open-angle glaucoma, and the unique pattern of damage encountered in chronic open-angle glaucoma. Available surgical procedures were treated as a continuous series, depending on the amount of pressure-lowering expected. Vascular interaction was hypothesized to explain the typical pattern of damage.


A comparison of penetrating keratoplasty and lamellar keratoplasty in the surgical management of keratoconus. A retrospective study of patients who underwent keratoplasty for keratoconus was done in 100 consecutive cases, of which 50 were penetrating keratoplasty procedures, and 50 were lamellar keratoplasty procedures. Each case was done by the same surgeon in both series. Criteria for patient selection were essentially the same. Postoperative care differed primarily in the time before suture removal, being an average of ten months in the penetrating keratoplasty group and three months in the lamellar keratoplasty group. Of those patients who underwent penetrating keratoplasty, the mean best-corrected visual acuity was 6/6 (20/20-) and the average corneal astigmatism was + 5.00 diopters. Of those patients who received lamellar keratoplasty, the mean best-corrected visual acuity was 6/9 (20/30-), and the average corneal astigmatism was +3.25 diopters. The most frequent complications of both techniques were wound separations that responded well to resuturing.


Micropithecus clarki, a small ape from the Miocene of Uganda. Micropithecus clarki, from Miocene sediments of Napak, Uganda, is the smallest known hominoid primate, living or fossil. In facial morphology it is very similar to extant gibbons. Dentally, it is most similar to the small apes from the Miocene of Kenya, Dendropithecus and Limnopithecus. All of the apes from the early Miocene of East Africa seem to represent a single phyletic group that could be easily derived from the Oligocene apes known from the Fayum of Egypt. Pliopithecus from the Miocene of Europe is more closely allied with the Oligocene radiation than with the later East African radiation.


Histological enamel indicator of childhood stress in prehistoric skeletal samples. Although previous paleopathological studies have used disturbances in enamel formation as indicators of childhood stress, the full potential of this technique has not been realized. This paper presents a test case which demonstrates that the frequency of disturbed enamel formation (i.e., Wilson bands) is associated with other stress indicators (i.e., probability of dying and infectious lesions) in three prehistoric skeletal samples representing the Middle Woodland (10.3%), Mississippian Acculturated Late Woodland (21.4%), and the Middle Mississippian (40.0%). Additionally, the mean ages at death of individuals with at least one Wilson band are lower than those without bands. These results suggest that Wilson bands are an indicator of the relative proportion of individuals who are high susceptibles in prehistoric populations. The data also corroborate the hypothesis that the adoption of maize agriculture in the prehistoric American Midwest is associated with increased stress.


Paleopathologic evidence for the evolution of rheumatoid arthritis. A human skeleton recovered from a Sicilian archaeological site and dating from the Hellenistic period (330-210 B.C.) presents a pathological pattern suggesting a transition between ankylosing spondylitis and rheumatoid arthritis, providing evidence in support of the hypothesis that rheumatoid arthritis may have recently evolved out of ankylosing spondylitis.


Renal potassium transport: contributions of individual nephron segments and populations. General features of the processes that contribute to renal potassium excretion are understood from clearance, stop-flow, micropuncture, and in vitro microperfusion experiments. However, the complex architecture of the kidney has made it difficult to examine individual nephron segments in all parts of the kidney. Accordingly, the extent to which distinguishable nephron populations, such as superficial and deep, may differ in their contributions to overall potassium excretion are not known. Also, the nature of transport processes across the successive segments of the nephrons (including not only the underlying cellular mechanisms, but even the direction of transport) is not known for all segments in any one nephron population. Excreted potassium is derived both from filtered potassium that escapes reabsorption and from secreted potassium. The filtered portion is large in amphibians and may be larger than generally recognized in mammals. The remainder is secreted primarily by distal nephron segments (distal tubule and cortical collecting duct). Potassium is also secreted into descending limbs of Henle loops; apparently this fraction is recycled from collecting ducts, and so does not represent an additional quantity of potassium transferred from blood to tubule fluid. Systemic factors that affect potassium excretion (potassium intake, sodium chloride intake, mineralocorticoid hormone levels, acid-base balance, and diuretic treatments) do so by modifying the net uptake of potassium from blood to cell and by altering the rate of fluid flow through the distal nephron. Under most circumstances, the distal nephron in the cortex appears to secrete potassium and the medullary collecting duct reabsorbs potassium. Although it is clear that successive nephron segments transport potassium in different ways, evidence to date does not indicate that potassium is handled differently by superficial nephrons compared to nephrons whose glomeruli lie in the deeper levels of the cortex.


Short-term dynamic psychotherapy.

Short-term dynamic psychotherapy. Short-term dynamic psychotherapy is rooted in psychoanalytic theory. The author traces the historical background of brief psychotherapy, focusing on the contributions of Freud, Ferenczi, Rank, and Alexander and French, and then presents a synthesis of contemporary views. Selection criteria for patients who can benefit from short-term therapy, and the techniques used, are discussed. Similarities to and differences from crisis intervention techniques are pointed out. The trend of the future can be expected to be toward shorter-term therapies, but given the present state of psychiatric knowledge, long-term therapy will still be necessary for many patients.


Mental health services for Medicaid enrollees in a prepaid group practice plan. The authors present the patterns of utilization of mental health services of a low-income population in a prepaid group practice setting, the Health Insurance Plan of Greater New York (HIP). Over a 6-year period, utilization rates for psychiatric consultations and mental health services by Medicaid enrollees rose to equal or exceed utilization by employed groups. The authors also provide evidence that psychiatric treatment reduces the use of other physician services, especially X-ray and laboratory services.


The impact of political process on hospital psychiatry. Political forces motivated the New York State Department of Health to withhold payment for Medicaid-financed inpatients on therapeutic passes. The elimination of therapeutic passes had many negative effects on patient care. The authors believe this experience demonstrates that political factors can overwhelm standard clinical practice and reasoned health planning to force irrational change on health care delivery.


Use of ambulatory health services by the near poor. Individuals in the gray area between Medicaid eligibility and sufficient income to meet the costs of health care, the near poor, utilize health services less than other groups. As part of a study of health care behavior in an inner-city area based on a household survey of three distinct populations (HMO) members, public housing project residents, and a defined geographical area), we examined this question more thoroughly. Survey results show that the near poor had lower levels of use than Medicaid recipients when other factors were controlled. Particularly among those classified as in poor health, the near poor were more likely to be non-users and less likely to make multiple visits. However, differences in use between the near poor and the Medicaid recipients are substantially and consistently smaller for the HMO users (whose costs were covered by a special contract) than for users of a hospital outpatient department. The patterns persist for regular care received for a chronic condition but not for care sought for episodes of illness. These findings point to the special disadvantage faced by low income individuals who are not receiving Medicaid.


Alcoholic liver disease: the problem of diagnosis. The objective of this article is to draw attention to the serious lack of correlation that exists between the detection and specific diagnosis of liver disease in alcoholic patients, based on clinical findings and investigations other than liver biopsy and histologic diagnosis established by that technique.


The prevention of alcoholism: an empirical report on the effects of outlet availability. Recent studies suggest that alcohol availability as measured by outlet rates is unrelated to per capita consumption or rates of alcoholism in the United States. Drawing from the same data bases, this article assesses the effects of outlet rates while controlling for the effects of per capita income, urbanism, and limitations by population on the number of sales outlets. The analysis discloses strong effects of outlet availability on per capita consumption and alcoholism rates in states that do not have restrictions on the number of outlets per unit of population.


Impact of alcohol misuse on family life. The shame that surrounds problem drinking contributes to delay or failure of remedy; the family tries to hide the drinking of its member from neighbors and even from the doctors. All parties to the illness choose to ignore the alcoholism and its implication for the patient.


Beginnings of the Navy program.

Beginnings of the Navy program. Problems encountered in attempting to treat alcoholism in the United States Navy are discussed. The estimation of incidence, early results of treatment, and the Navy-wide growth of the program are examined.


Physicians' attitudinal changes in alcoholism. A man is the sum of all the moments of his life, and his attitudes are the product of repeated experience. A physician's attitude toward alcoholics is a product of all of his alcohol-related experiences, including family and societal feelings assimilated in childhood and lessons, impressions, and experiences acquired during medical training and practice.


The minor alcoholics and their treatment. The codiscoverer of disulfiram's usefulness for alcoholics reports on the development of Denmark's present system of alcoholism treatment and the treatment facilities.


Potentiation of lithium toxicity by ethanol in rats and mice. The effects of ethanol treatments, both acute (single, intraperitoneal) and chronic (forced drinking of ethanol for 10 mo), on the distribution, excretion of lithium and urine output were studied in rats. Retention of lithium induced by ethanol appeared to be responsible for the potentiation of lithium toxicity. The potential hazard in the interaction between lithium and ethanol is discussed.


The surfactant system of human fetal lung organotypic cultures: ultrastructural preservation by a lipid-carbohydrate retention method. Human fetal lung organotypic cultures consisted of epithelial elements (congruent to 40- 100 micrometer in diameter) formed by the reaggregation of single cells from a monodisperse suspension of enzymatically dissociated fetal lung. These elements, termed alveolar-like structures, were composed primarily of type II alveolar epithelial cells whose apical surfaces bordered the central lumen of the alveolar-like structure. Pulmonary surfactant secreted by the type II cells was retained within the lumen and accumulated in close association with the epithelium. These characteristics made this culture system an advantageous model for the morphological study of human pulmonary surfactant in vitro. A lipid-carbohydrate retention procedure which reduced the extraction of tissue components and thus provided improved preservation of multilamellar bodies and tubular myelin surfactant was used in an ultrastructural study of organotypically cultured surfactant. Human surfactant was observed for the first time with most of its structural components intact. In vitro human surfactant was found to be similar to in vivo rodent and non-human primate surfactant, but with certain differences. Long surfactant tubules were not observed. There were more transformed multilamellar bodies present with more foci undergoing transformation. Each focus contained fewer layers of tubular myelin surfactant than occurs in rodent surfactant. No epiphase-hypophase areas were observed, only tubular myelin surfactant. In addition, a previously unreported intrasurfactant matrix material was observed.


Lack of mutagenicity of two possible metabolites of halothane. 1,1-Difluoro-2-bromo-2-chloroethylene, a probable metabolite of halothane, was purified by preparative gas chromatography and tested for mutagenicity in the Salmonella/mammalian liver system developed by Ames and colleagues. 1,1,1-Trifluoro-2-chloroethane which had been isolated from the breath or rabbits anesthetized with halothane was also tested for mutagenicity in a similar manner. Both compounds were found to be nonmutagenic in this bacterial system. Although neither this study nor any other has yet been able to demonstrate that halothane or any of its metabolites is genetically active, nevertheless, unnecessary occupational exposure to the drug should be avoided due to the possibility that future studies could reveal adverse effects secondary to halothane.


[Simultaneous estimation of phenobarbitone and valproic acid in the plasma by high performance liquid chromatography (author's transl)]. The authors describe a method of simultaneous estimation of phenobarbitone and valproic acid in the blood. After extraction with ether, these substances were estimated by high performance liquid chromatography. They were separated on a mu Bondapack C18 column. The detection involved a colorimetric procedure based on variation in colour of a solution of bromocresol purple. The technic used is simple, its reproducibility is satisfactory (coefficients of variation of 7.6% for phenobarbitone and 2.3% for valproic acid). The sensitivity was 13.8 mumol/l for phenobarbitone and 11.1 mumol/l for valproic acid. Parallel estimations by gas chromatography led to comparable results. This method is of interest in the supervision of anticonvulsant treatments, especially in pediatrics.


[Enzyme multiplied immunoassay technic (EMIT) (author's transl)]. In 1960, Yalow and Berson opened the route to radioimmunoassay. Now the technic of radioimmunoassay requires apart from the use of artificial radioisotopes, a compulsory stage of separation of free and linked phases. The author has developed a technic in homogeneous phase "EMIT" which avoids the intermediate stage of separation. He gives here the principle, studies the various parameters of the method, shows the advantages and disadvantages and compares it with other technics and finally mentions future prospects.


[Enzyme-linked immunosorbent assay (ELISA) (author's transl)]. The development of enzymo-immunological technics and the synthesis of efficacious immuno-adsorbants has given rise to several immuno-enzymometric methods of which one, ELISA (enzyme-linked immunosorbent assay) has proved particularly practical and sensitive for the estimation of antibodies.


Topographical ventilation and perfusion distribution during IPPB in the lateral posture. We measured topographical ventilation and perfusion distribution in the gravity field using 133Xe in 5 normal subjects either during natural breathing or during intermittent positive pressure ventilation (IPPB) in the lateral decubitus posture. The ratio of ventilation of upper regions to that of lower regions increased from 0.61 +/- 0.10 (mean +/- SE) during natural breathing to 0.95 +/- 0.08 during IPPB. In contrast, the ratio of regional perfusion was unchanged in the 2 conditions. Consequently, distribution of regional ventilation-perfusion ratios became less homogeneous during IPPB. Whereas during natural breathing the ratio of ventilation-perfusion of upper regions to that of lower regions was 1.09 +/- 0.18, during IPPB this ratio was 1.52 +/- 0.14. Despite the differences in regional ventilation distribution between natural breathing and IPPB, analysis of multiple-breath 133Xe washouts measured at the mouth did not reveal any difference. The results are consistent with the hypothesis that the magnitude of diaphragmatic tension is the main determinant of topographical ventilation distribution in the lateral posture.


The effects of smoked marijuana on metabolism and respiratory control. Marijuana is a sedative, and most sedatives are respiratory depressants. However, the ventilatory effects of marijuana are unknown. In a placebo-controlled study of 8 subjects, smoking marijuana significantly increased ventilation and hypercapnic ventilatory response. Peak effects occurred 15 min after smoking, when ventilation increased from 7.4 +/- 0.39 (mean +/- SE) to 10.4 +/- 1.41 liter per min (P less than 0.01), whereas hypercapnic ventilatory response, measured as the slope of the relationship of ventilation to CO2, increased from 2.7 +/- 0.28 to 5.4 +/- 1.02 liter per min per mm Hg (P less than 0.05). Blood pH, PCO2, and ventilatory response to hypoxia were unchanged. Changes in ventilation usually parallel changes in metabolic rate. Smoked marijuana caused an increase in metabolic rate that also peaked after 15 min. Pretreatment with propranolol completely abolished the increase in hypercapnic ventilatory response, but did not affect the other changes. Thus, smoked marijuana had stimulatory effects on metabolic rate, ventilation, and the ventilatory response to CO2. The latter appears to be mediated by the beta sympathetic nervous system.


Pharmacological control of surgical scar tissue. Pharmacological control of unwanted scar tissue theoretically is possible in human beings and has been proven to be practical and effective treatment in laboratory animals. The most advanced research involves prevention of the development of helical structure and transport of collagen by administration of proline analogues and controlled induction of lathyrism by administration of Beta-aminopropionitrile. The toxicity of proline analogues has prevented human testing; BAPN presently is being tested or has been tested in patients with scleroderma, flexor tendon adhesions, posterior urethral strictures, and surface keloids. At this time, highly purified BAPN appears generally non-toxic and is capable of exerting a higly selective and significant lathyrogenic effect on the healing wound. The combination of BAPN and other drugs, such as Colchicine, which increases collagenolytic activity, probably will make safe control of clinical properties of scar tissue possible within the next 24 months.


Heparin utilization during arterial revascularization. These studies demonstrate that therapeutic levels of heparin are achieved when either 100 u/kg or 150 u/kg are administered prior to arterial or aortic cross clamping during peripheral vascular reconstructive procedures. They further demonstrate that adequate levels of heparin are maintained for at least one hour even with the lower dosage. If heparin effect is not reversed, many patients will be returned to the recovery ward with therapeutic levels of heparin. This is undesirable and can be averted by administering appropriate doses of protamine sulfate. Excesses of protamine sulfate should be avoided since unbound protamine sulfate has anticoagulant as well as cardiovascular effects.


Effect of hyaluronidase on the incidence of cystoid macular edema. A prospective double-blind study of the effect of hyaluronidase on aphakic cystoid macular edema (CME) was performed. A 25% incidence of CME was encountered in patients receiving hyaluronidase admixed with the local anesthetic while no cases were diagnosed in the group not receiving hyaluronidase. The role of hyaluronidase in the pathogenesis of aphakic cystoid macular edema is discussed.


Treatment of herpes simplex keratitis with idoxuridine and vidarabine: a double-blind study. A double controlled clinical study comparing idoxuridine (IDU) and vidarabine (ara-A) in the treatment of uncomplicated herpes simplex keratitis was carried out with 10 patients. No statistically significant differences occurred in the healing time between IDU (6.8 days) and ara-A (8.0 days). Two moderately adverse reactions to IDU were observed, but no demonstrable ocular toxicity was noted with ara-A.


Spontaneous extrusion of intraocular foreign body after 11 years. A case of spontaneous extrusion of intraocular foreign body after 11 years is presented. Despite being magnetic and containing mostly iron the foreign body could not be removed in repeated magnet trials. It was retained in the ciliary body region for a very long time without causing siderosis. The foreign body was spontaneously extruded without any signs of intraocular inflammation.


Facial nerve repair in cerebellopontine angle surgery. Facial nerve continuity was restored during cerebellopontine angle tumor removal in nine cases. The distal facial nerve was rerouted from the stylomastoid foramen into the cerebellopontine angle. Direct suture was accomplished in seven cases while two required interposition of a greater auricular nerve graft. There was excellent return of facial function in eight of the nine cases. Overall results are superior to nerve substitution techniques. The facial nerve should be inspected for continuity following tumor removal. If one is not certain the nerve is intact, the proximal facial stump should be identified at the brain stem and facial nerve continuity reestablished. A nerve substitution procedure should be resorted to a later time only when the proximal facial stump is not identifiable.


Cross-power spectral density analysis of pursuit tracking. Evaluation of central and peripheral pathology. Twenty-one normal subjects were evaluated for pursuit tracking performance at frequencies of .2, .4, .8, 1.2 and 1.6 Hz. Measures of phase (lead or lag of target), gain (amplitude of response) and spectral purity (distortion of smooth tracking) were obtained by a cross-power spectrum analysis of the stimulus input and the eye movement output. It was determined that normal subjects could quite adequately track a target moving at .4 Hz. After establishing this parameter for normals, 43 patients with central and peripheral pathology related to the vestibulo-oculomotor system were tested at this frequency. Data revealed that not only central lesions but also peripheral labyrinthine impairment could cause a marked decrement in pursuit tracking ability. Also, marked changes in tracking were evident following both central and peripheral surgical procedures.


Computerized screening of the human vestibulospinal system. The vestibular nerve projects rostrally via the ascending medial longitudinal fasiculus (MLF) to eventually supply the ocular muscles and also projects caudally via the descending MLF to eventually supply the spinal and limb musculature. Electronystagmographic techniques are designed to evaluate only portions of the vestibulo-ocular and oculomotor systems. Vestibular lesions affecting only the caudal vestibular nerve distributions or lesions affecting both neural distributions, therefore, cannot be objectively assessed except for the vestibulo-ocular component. A promising recording technique for the evaluation of the vestibulospinal system has been developed and tested in the Raymond E. Jordan Human Vestibular Systems Laboratory. A comparison of two data analysis techniques in normal subjects, unilateral vestibular lesion patients and patients with unilateral lesions of the cerebellar hemispheres have provided pilot data which indicate that the vestibulospinal stability test technique holds considerable promise for both research and clinical evaluation of the human vestibulospinal system.


Enzyme multiplied immunoassay of phenytoin and carbamazepine using the Centrifichem analyser. Procedures for the enzyme multiplied immunoassay of phenytoin and carbamazepine using the Centrifichem centrifugal analyser are described. Within-batch, between-batch, and between-day precision are reported. Accuracy is assessed by recovery experiments. The technique is compared with gas-liquid chromatography in the analysis of a number of human serum samples containing a range of concentrations of the drugs.


[Andrews' pustular bacterids of hands and feet; Sachs' acrodermatitis pustulosa perstans. Histological study (author's transl)]. Pustulosis palmaris et plantaris chronica et recidivans (pustular bacterid of Andrews) is not an exceptional disease. Its characteristic histological structure is to be considered as a major element of the diagnosis. The fully developed pustule is an oval cavity with transverse long axis, entirely situated within a loca-ly hyperplastic epidermis. Its formation goes through several stages. The first one is spongiosis appearing in the epidermis above the top of a dermal papilla. This gives rise to a vesicle filled with fluid and mononuclear leucocytes. In the next stage, the roof consisting of the malpighian layers is disrupted, and the vesicular fluid comes into contact with the horny layer. There is massive invasion of the cavity by polymorphonuclear leucocytes which penetrate into the intercellular spaces of the vesicle wall, where pictures of spongiform pustules are seen. The initial vesicle, and the late, secundary appearance of the spongiform aspects demonstrate that the mechanism of formation of the lesion of pustulosis palmaris et plantaris chronica et recidivans is different from the one of psoriasis pustulosa palmo-plantaris and that, consequently, these are two different diseases.


[Cutaneous symptoms of ulcero-haemorragic rectocolitis and of Crohn's disease (author's transl)]. The association between ulcerative colitis, Crohn's disease and various abnormalities of the skin is reviewed. Erythema nodosum and pyoderma gangrenosum are the most specific external manifestations and thereby the ones of greatest diagnostic value. Erythema multiforme is probably a manifestation of drug hypersensitivity. Many other dermatosis have been observed in association with these gastrointestinal disorders. However, these associations are not statistically significant. A specific "aphtous colitis" may be observed in the course of Behçet's disease.


[Digestive symptoms of scleroderma (author's transl)]. The authors successively study the oral, peri-oral, esophageal, intestinal and anal manifestations of systemic scleroderma. They point out that dental, salivary, and esophageal involvement is of great interest for diagnosis and prognosis. They particularly describe the malabsorption syndrome including anatomical and ultrastructural lesions of the smooth muscle fibers. They present an original study of arrector pili in clinically and histologically non-involved skin of patients undergoing scleroderma. Finally they state that any suspected or diagnosed scleroderma needs a digestive check-up as follows: radiologic examination of the teeth, biopsy of the minor salivary glands of the lower lip, radiologic study of esophageal motility and radioactive C 14 glycocholate test.


Bioavailability and effect of food on the gastrointestinal absorption of two erythromycin derivatives. The concentrations of erythromycin in the serum were comparable after a single 500 mg oral dose of two brands of erythromycin stearate (Resibion and Erythrocin) in six healthy fasting volunteers. There was no significant difference in their pharmacokinetics. Over a period of 24 hours, 4 and 5% of the 500 mg dose of each preparations was excreted in the urine. Analysis of serum erythromycin concentration data were performed according to a one-compartment open model. The short half-life in the serum (1.43-1.78 hours), small portion of the dose excreted in the urine (4-5%), and the low renal clearance value (0.43-0.51 ml/min/kg) indicate that the majority of erythromycin is extensively cleared by extrarenal mechanisms. In addition, serum concentrations of erythromycin were measured during continuous treatment (250 mg base every 6th hour) with erythromycin stearate (Resibion) or enteric-coated erythromycin base (Etromycin) in ten healthy volunteers, in both fasting and non-fasting conditions. Again in the fasting state the serum levels were comparable and those from both the stearate and base were markedly reduced by food.


Clinical use of pseudorandom binary sequence white noise in assessment of the human vestibulo-ocular system. White noise rotational stimulation has been used to evaluate the human vestibulo-ocular response for 30 normal subjects over the frequency range from 0.02 to 1.6 Hz and is being extended to characterize response of patients having documented abnormalities. For clinical use, the white noise stimulus has the advantages of shortening the test time by presenting all stimulus frequencies simultaneously, and being well-tolerated by both normal subjects and patients alike. Cross spectral calculations which compare the computer reconstructed slow phase eye velocity response to the pseudorandom acceleration stimulus yield a set of linear and nonlinear estimates of the vestibulo-ocular response. Pilot data indicate that a classification of the disease state can be made using this set of estimates. This classification will be presented and discussed.


The excretion of urinary N-acetyl-beta-glucosaminidase and beta-glucuronidase as a sign of impending rejection of kidney transplants. An evaluation was made of the assay of two urinary lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta-glucuronidase, in the diagnosis of impending rejection of renal transplant. The output of enzymes was measured in 34 cadaver transplant recipients, 17 of whom underwent rejection episodes. The enzyme output during the 4 days preceding the definitive diagnosis was compared with the output during a non-rejection period. The mean excretion of both enzymes increased during the period before rejection. The best distinction for diagnostic purposes was obtained by comparing the pre-rejection values with baseline values separately in each case.


Characterization of antioligodendrocyte serum. An antioligodendrocyte serum (AOS) has been raised in rabbits against preparations of isolated bovine oligodendrocytes. The antibody was assayed by two techniques. By complement fixation with isolated oligodendrocytes, the titer of the antibody was 1:64 to 1:128. By indirect immunofluorescence testing of oligodendrocyte suspensions and frozen brain sections, the titer of the AOS was 1:256 to 1:512. When unabsorbed AOS was used, immunofluorescent staining proved it specific for bovine oligodendrocytes in suspension and in sections, and for human oligodendrocytes in sections. In cell suspensions, the staining was membrane related and in sections, cytoplasmic. The oligodendrocyte staining could be totally removed by absorption of AOS against oligodendrocyte suspensions, whereas absorption against bovine myelin, bovine myelin basic protein, and bovine neurons did not affect the staining reaction. AOS also stsined Schwann cells, a property possible related to antigens shared with oligodendrocytes. It is concluded that AOS is specific for oligodendrocytes and can now be applied to fundamental and disease-rel


Meningoencephalitis following enucleation for cryptococcal endophthalmitis. A man developed meningoencephalitis 9 months after enucleation of his right eye for proved cryptococcal endophthalmitis secondary to a penetrating injury. The presumed portal of entry of Cryptococcus neoformans into the central nervous system was along the optic nerve subarachnoid sheath.


[Delayed type hypersensitivity reactions to "Candida albicans" in mice (author's transl)]. Mice injected intravenously (IV) or subcutaneously (SC) with living Candida albicans developed subsequently delayed-type hypersensitivity (DTH) which was measured in vivo by the footpad test after injection of 10(6) heat killed C. albicans (HKC.a.). Compared to systemic injections, SC immunizations with living C.a. gave higher levels of DTH, and lethality was absent. Subcutaneous injections of hundred time more doses of HKC.a. were also able to produce in normal mice a DTH reaction elicited with HKC.a. or with C.a. soluble extracts, but not with candidine. Intraperitoneal injections of varying doses of HKC.a. or subcutaneous injections of varying doses of C.a. soluble extracts failed to produce significant DTH. High levels of sensitization can be induced by using cyclophosphamide or BCG or both pretreatment before immunization, which seems to indicate immunomodulating factors for induction or expression of DTH in normal mice after injections of HKC.a. Kinetics of the local reaction elicited with HKC.a. fulfull usual criteria of DTH in actively immunized mice after CY pretreatment or not, and in passively immunized mice after systemic or local transfer of spleen cells from actively immune donors. Serum from same group of donors was unable to transfer DTH.


[Effect of bacterial phospholipidic extract (EBP) on the immune response in mice toward sheep red blood cells (author's transl)]. Injection in mice of bacterial phospholipidic extract (EBP) stimulates immune responses to sheep red blood cells (SRBC). Immunostimulation was observed mostly for antibody response and to a less extent for delayed-type hypersensitivity (DTH). The adjuvant effect of EBP is dependent on several factors: dose, route and time. Maximal activity was found when mice received 100 to 200 microgram of an intravenous injection of EBP, twenty-four hours before systemic immunization with optimal doses for antibody or DTH response. Subcutaneous injection of EBP did not modify the cellular or humoral immune response to SRBC inoculated subcutaneously in the same or in a different site of EBP. Adjuvant action of EBP was different of those of endotoxin, since the later suppresses the DTH response to optimal dose of SRBC, this effect being abolished with cyclophosphamide pretreatment. EBP inoculated intravenously suppressed the local reaction of a DTH adoptively transferred with immune spleen cells. These results taking together seem to indicate a preferential role of EBP on the accessory cells in the induction or expression of the immune response to SRBC.


Improvement in the sensitivity of DNA polymerase I-deficient Escherichia coli for detecting mutagens and carcinogens. The sensitivity of a polA strain to the antibacterial activity of mutagens and carcinogens may be increased by inserting one or both of the following characteristics, a lexA mutation or the R391 bacterial plasmid. The effects of the lexA mutation and the plasmid appear to be additive. The differential sensitivity of a polA lexA (R391) strain could be adapted as a preliminary screening test for mutagens and potential carcinogens.


Simultaneous determination of the total number of aquatic bacteria and the number thereof involved in respiration. The electron transport system of respiring organisms reduces 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride (INT) to INT-formazan. Respiring bacteria deposit accumulated INT-formazan intracellularly as dark red spots. Corresponding to electron transport system activity, these deposits attain a size and a degree of optical density which allows them to be examined by light microscopy. If polycarbonate filters and epifluorescence microscopy are applied to analyze an INT-treated water sample, it is possible to differentiate between respiring and apparently nonrespiring bacteria. This differentiation, which permits determinations of the total number of bacteria and the proportion thereof involved in respiration, is realized directly within one and the same microscopic image. Initial applications of the present method for hydrobiological purposes showed that the proportion of respiring aquatic bacteria ranged between 6 to 12% (samples taken from coastal areas of the Baltic Sea) and 5 to 36% (samples taken from freshwater lakes and ponds). Cells of 1.6 to 2.4 micrometer (freshwater) and 0.4 micrometer (Baltic Sea) account for the highest proportion of respiring bacteria.


Two stomacher accessories.

Two stomacher accessories. Two useful and easily constructed accessories for the Colworth Stomacher blender are described. The first automatically opens and holds Stomacher bags above a balance of weighing in the sample. The second stores bags on the bench between manipulations and opens and holds them as required for pipetting, etc.


Coliform aerosols generated from the surface of dewatered sewage applied to a forest clearcut. Concentrations of airborne coliform bacteria as high as 1.5 X 10(4) m-3 were observed 8 cm above anaerobically digested sewage sludge applied to a forest clearcut. Dry conditions and high wind speeds tended to favor aerosol generation.


Comparative study of methods for the enumeration of total and fecal coliforms in the eastern oyster, Crassostrea virginica. Violet red bile agar and Coli-Count Sampler (Millipore Corp.) procedures were shown to be acceptable alternatives to the standard most-probable-number method for monitoring relative coliform levels in oysters.


Smouldering epidemic of Yersinia pseudotuberculosis in barn rats. Yersinia pseudotuberculosis was isolated from 8 (8 Rattus norvegicus) of 270 (259 R. norvegicus and 11 R. rattus) rats examined. Seasonal variation was not found in the incidence of isolations. The isolation occurred almost equally in both young and old rats. The isolated strains were determined as serovar IB in one rat, and serovar IVA in seven rats. The strains were isolated from the contents of the intestinal tract (the duodenum, jejunum, ileum, cecum, colon, and rectum), the spleen, liver and mesenteric lymph nodes; they were not detected in the kidneys. Agglutinin titer in the eight rats was no more than 32.


Ecology, serology, and enterotoxin production of Vibrio cholerae in Chesapeake Bay. A total of 65 isolates of Vibrio cholerae, serotypes other than O--1, have been recovered from water, sediment, and shellfish samples from the Chesapeake Bay. Isolations were not random, but followed a distinct pattern in which salinity appeared to be a controlling factor in V. cholerae distribution. Water salinity at stations yielding V. cholerae (13 out of 21 stations) was 4 to 17 0/00, whereas the salinity of water at stations from which V. cholerae organisms were not isolated was less than 4 or greater than 17 0/00. From results of statistical analyses, no correlation between incidence of fecal coliforms and V. cholerae could be detected, whereas incidence of Salmonella species, measured concurrently, was clearly correlated with fecal coliforms, with Salmonella isolated only in areas of high fecal coliform levels. A seasonal cycle could not be determined since strains of V. cholerae were detectable at low levels (ca. 1 to 10 cells/liter) throughout the year. Although none of the Chesapeake Bay isolates was agglutinable in V. cholerae O group 1 antiserum, the majority for Y-1 adrenal cells. Furthermore, rabbit ileal loop and mouse lethality tests were also positive for the Chesapeake Bay isolates, with average fluid accumulation in positive ileal loops ranging from 0.21 to 2.11 ml/cm. Serotypes of the strains of V. cholerae recovered from Chesapeake Bay were those of wide geographic distribution. It is concluded from the data assembled to date, that V. cholerae is an autochthonous estuarine bacterial species resident in Chesapeake Bay.


Bacteriology of chronic leg ulcers.

Bacteriology of chronic leg ulcers. The quantitative bacteriology of 13 chronic leg ulcers was sequentially assessed by both swab and biopsy culture techniques, and the effect of either a 10% benzoyl peroxide lotion or placebo lotion was evaluated. There was good correlation between the swab and biopsy culture techniques in 12 of the 17 instances where simultaneous swabs and biopsies were done. Though the benzoyl peroxide did not favorably affect the bacterial flora, ulcer healing did appear to correlate with quantitative bacterial counts. THREE of five ulcers containing fewer than 10(5) organisms per gram of tissue or per centimeter of ulcer surface area healed, while none of eight ulcers containing more than 10(5) organisms healed. Quantitative bacteriological measurements can serve as useful tools in evaluating healing of leg ulcers.


Nevus of large spindle and/or epithelioid cells (Spitz's nevus). By now it is well recognized that there is a benign melanocytic nevus, common in the young and common enough in adults, that has histological features that are confusable with those of malignant melanoma. The anomaly is usually referred to as benign juvenile melanoma, sometimes as Spitz's nevus, and, by some histopathologists, as spindle and epithelioid cell nevus. All the histological subtleties and variations of the condition are still not fully appreciated and some of them are still being misinterpreted as those of malignant melanoma. We herewith present a study designed to clarify the issue and offer firm criteria for histological differentiation of the nevus in point from malignant melanoma. We also suggest a new name for it and supporting arguments therefor.


Defective neutrophil migration in granuloma annulare, necrobiosis lipoidica, and sarcoidosis. The neutrophil mobility in patients with granuloma annulare, necrobiosis lipoidica, and sarcoidosis was tested using both in vivo and in vitro techniques. Use of a skin window chamber for measurement of chemotaxis in vivo demonstrated defective neutrophil migration in each group. This contrasted with the finding that, in vitro, chemotaxis toward casein and endotoxin-activated sera was normal. The importance of this dissociation is discussed. Abnormal neutrophil accumulation at sites of inflammation may be of importance in the pathogenesis of these granulomatous disorders.


Delayed cutaneous hypersensitivity and lymphocyte transformation: dissociation in atopic dermatitis. Studies of cell mediated immunity (CMI) in atopic dermatitis have demonstrated various defects and frequently contradictory results. The true nature of immune dysfunction remains uncertain. We approached this question by concurrently examining two aspects of CMI: delayed cutaneous hypersensitivity and in vitro lymphocyte transformation. Responses were tested using the antigens Candida albicans and streptokinase-streptodornase (SKSD). Mean lymphocyte transformation was equal in atopic patients and controls, although a subgroup of severely dermatitic patients showed depressed responses. Cutaneous anergy was the rule in atopic patients (96% to candidin and 84% to SKSD). Although normal subjects showed good correlation between in vitro and cutaneous responses, atopic patients showed a significant lack of correlation. Many patients manifested cutaneous anergy in the face of normal lymphocyte transformation re sponses.


Vitamin A deficiency following small-bowel bypass surgery for obesity. Side effects are common in individuals who have undergone small-bowel bypass surgery for morbid obesity. Most of these side effects subside after a few months. More serious complications may require reestablishment of the bypassed loop. Rarely have vitamin deficiencies been observed. Development of vitamin A deficiency in a patient was characterized by phrynoderma and night blindness. This was promptly reversed by oral treatment with vitamin A. There was no improvement in low to subnormal serum levels of fat-soluble vitamins after a course of tetracycline hydrochloride. Studies suggested presence of a malabsorption state probably due to rapid transit time through the small bowel and reduced absorptive surface.


[Problems of distinction of normal, artificial, and pathological structures in mature human placental villi. II. Morphometrical studies on the influence of the mode of fixation (author's transl)]. Morphometrical relations of human placental villi from 14 normal placentas of the 38th to 42nd week of pregnancy terminated by Cesarean section were examined in relation to the method of fixation. Villous tissue was obtained from central areas of the in situ placenta with intact maternal circulation by means of puncture aspiration and punch biopsy. Further punch biopsies were performed 2, 5, 10 and 20 min after manual removal of the placenta. Semithin sections of these villi were photographed and examined morphometrically. The findings demonstrate clear effects on quantitative data as a result of the period of ischemia between manual removal and fixation of tissue. Significant changes of several parameters (mean trophoblastic volume, size of epithelial plates, volume of connective tissue, volume of fetal vessel lumina, etc.) occur as early as 2 min after separation of the placenta from the maternal circulation. They are mostly related to a collapse of intravillous vessels. The villous branches may be classified according to structure and morphometry, if they have been obtained under optimal conditions of fixation and prior to any vascular collapse.


A prospective randomized study of three expanded polytetrafluoroethylene (PTFE) grafts as small arterial substitutes. A prospective, double-blind, randomized study was performed to determine the relative patency rate of polytetrafluoroethylene (PTFE) grafts, Gore-Tex, Impra, and a Surgikos prototype PTFE graft. The 48 grafts (40 x 4 mm) replaced excised segments of femoral arteries in adult mongrel dogs, whose mean weight was 20.6 +/- 0.9 kg; the grafts were removed after 12 weeks. Sterile technique and antibiotic therapy were included in the study. Anticoagulation was not employed. Anastomoses were performed with 6 = 0 polypropylene. Angiographic assessment of each anastomosis was made at surgery and prior to sacrifice. Patency was assessed daily by palpation and Doppler flow signals, as well as angiographically, prior to sacrifice. The overall patency rate was 62.5%. There were no statistically significant differences in patency rates among the three groups (Gore-Tex, 56%; Impra, 75%, Surgikos, 56%). Histologic evaluation revealed incomplete neointima formation and significant pannus formation in all three types of grafts without any significant discernible difference among them. The results suggest that further experimental evaluation of PTFE, as a small vessel substitute, is indicated prior to its use clinically in preference to autogenous vein.


In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi. The toxic effect of lapachol, beta-lapachone and several 1,2-naphthoquinone derivatives on the growth, viability and infectivity of Trypanosoma cruzi were compared. beta-lapachone was the most active compound in vitro. No inhibition was observed in suspensions which contained inactivated foetal calf serum or rabbit haemoglobin solution. The infectivity of trypomastigotes in mice was not affected when cells were previously incubated with beta-lapachone or one of several other naphthoquinone derivatives in vitro in the presence of blood. It is suggested that beta-lapachone and the other compounds can be inactivated either by reduction in the presence of oxyhaemoglobin or by interaction with serum proteins. A beta-lapachone derivative, allyl-beta-lapachone, was not inactivated in the presence of blood and remained effective in suppressing trypomastigote infectivity.


Loss of filarial larvae in a natural mosquito population. Analysis of log normal parasite densities of Wuchereria bancrofti in the mosquito Culex pipiens fatigans collected in the suburbs of Colombo, Sri Lanka, has shown a decreasing parasite load with age of infection. The median density of microfilarial intake in the natural population was 10.3, but this had decreased to 2.6 by the infective stage. Of the total microfilariae ingested, 51.9% were found in the thorax 12--17 hours after infection of the mosquitoes in the laboratory. Further decrease in parasite density during development could not be attributed to filarial mortality in the mosquito but could be accounted for by increasing mosquito mortality dependent on the density of parasite infection. Dissection of recently blood-fed house-resting mosquitoes gave a prevalence rate of 7% microfilarial carriers in the human population compared to a rate of 4% by routine blood-filming.


LH and FSH response to gonadotropin releasing hormone (GnRH) in normospermic, oligospermic and azoospermic men. GnRH was administered to 34 men (8 normospermic, 8 moderately oligospermic, 10 severely oligospermic and 8 azoospermic) and the responsiveness of serum LH and FSH determined. For LH, basal levels were not different among each group, nor was there any difference in response to GnRH at any point in time after injection; however, there was a trend for the azoospermic group to respond more briskly. For FSH, basal levels also did not differ among the groups, but both the azoospermic and severely oligospermic groups showed a hyperresponsiveness that differed significantly from the response elicited by the normospermic group. It is concluded that oligo-azoospermia results from a pantesticular defect involving both seminiferous tubules and Leydig cells and that latent pituitary insufficiency is rarely a cause of subfertility in men.


Effect of LH-RH loading in subfertile men. Thirty-two infertility patients were studied to evaluate the response of plasma FSH and LH to intravenous injection of 100 microgram synthetic LH-RH. Initial LH and FSH levels were taken into consideration in evaluating the responses. While the LH response was usually more pronounced, it seemed more valuable, from the prognostic point of view, to examine the FSH changes because of their applications to the diagnostic and prognostic processes.


Experimental orchitis induced in rats by passive transfer of an antiserum to seminiferous tubule basement membrane. A multifocal damage of the testis was obtained when rats were injected intravenously or under the tunica albuginea of the testis with a rabbit antiseminiferous tubule basement membrane serum. The damage was characterized by foci of perivascular and peritubular infiltrates of mononuclear round cells, infolding, thickening, and rupture of the seminiferous tubular wall and different degrees of injury of the germinal epithelium such as, cell disorganization, cell sloughing, and atrophy. Delamination and thickening of seminiferous tubule basement membrane and vacuolization of the Sertoli cell cytoplasm was often observed by electron microscopy. A linear deposit of rabbit gamma-globulin was detected by immunohistochemical techniques along the basement membranes of the seminiferous tubules and vessels. Testicular damage was not detected in rats injected with normal rabbit serum, used as control. In the kidneys of rats injected intravenously with the immune serum, a deposit of rabbit gamma-globulin was detected along glomerular basement membrane. Focal areas of mononuclear cell infiltrates, hypercellularity of glomeruli and thickening of glomerular capillary walls and Bowman's capsule were also observed.


Rubella antibodies and adverse events late after renal transplantation. Rubella antibody titers were determined pretransplant and then serially posttransplantation in 52 consecutive patients whose renal allografts survived at least three months. Group A patients (18) had antibody titers greater than or equal to 1:128 in the posttransplant period. Group B (24) had intermediate antibody titers that never rose higher than 1:64. Group C (10) consistently had antibody titers less than 1:8. Group A did not differ from groups B and C with respect to age, race, sex, type of transplant, underlying renal disease, or maximum complement fixation antibody titers posttransplant to cytomegalovirus or herpes simplex virus, type 1. Group A did differ from groups B and C in its frequency of hepatitis, chronic liver disease, episodes of late rejection (greater than or equal to 21 days after transplant), transplant nephrectomy required for rejection, infections whose defense involves intact cell-mediated immunity, and the number of late rejection episodes per patient. Mechanisms underlying these associations are not known but apparently are not related to HLA phenotype.


[Contribution to the morphology and biochemistry of mustelide blood. 1. Blood specimen collection in various mustelides with special reference to the use of the tissue adhesive "Fimomed"]. An account is given of various techniques of blood sampling in the context of certain mustelids, including cardiopuncture, amputation of tail tip, talon cutting, incision of the ear vein, puncture of the jugular or femoral vein, and catheterisation of the abdominal aorta. Reference is made to details of use of all techniques, characteristics, advantages and potential setbacks, and preferable use of some of the tested methods to collect blood from mustela and martes species. Blood collection from the abdominal aorta may be helpful in obtaining no-haemolysis and no-additive plasma for biochemical multi-screening. Biochemical, pharmacological, and toxicological follow-up checks may be feasible under certain conditions following surgical exposure of the external jugular vein. The use of "Fimomed" (n-butylcyano-acrylate), a tissue adhesive, may help to reduce effort in terms of time and material and consequently, rationalise veterinary hygiene action as a whole, provided that the conditions for its application are observed. The skin adhesive is properly applicable to skin lesions of mustelids. A combination of suturing with adhesive should be used to close laparotomy wounds for better mechanical strength of the abdominal wall. Possible applications of "Fimomed" should be tested with other species as well.


[The effect of various organochlorine pesticides on the immunologic reactivity of the white rat]. Wistar rats, aged 30 and 90 days, received Aldrin and Lindan treatment (8 ppm or 11 ppm) over 60 days, followed by inoculation of E. coli. The capacity of antibody formation was changed but not inhibited. Functional disorders occurred in the thymus (decline of nucleic acids), adrenal gland (decline of Vitamin C), and in the protein synthesis. The toxicity of even smaller Aldrin doses obviously was stronger than that of Lindan. The toxicity of either substance to younger animals was stronger than to individuals in more advanced age.


Visual input: its importance in the control of postural sway. A new and measurable parameter in the study of static equilibrium is described. Using a minicomputer, the locus of postural sway was measured during 1 minute periods in 144 volunteer subjects, including 105 control subjects and 39 persons with above-knee amputations. It was hypothesized that the above-knee amputee group had lost a relatively predictable degree of proprioception and kinesthetic sense. Vestibular mechanisms were normal and, therefore, constant in both groups. Using a simple arithmetic formula, the effect of such loss of proprioception was estimated by comparing the amputee group with the nonamputee group, while the contribution of visual input was estimated by comparing both groups with their eyes open and closed. Using this parameter, no clear age dependency was demonstrated. The mean locus of sway for the amputee group was the same as the nonamputee group with the eyes open. However, a comparison of the eyes open/eyes closed ratio in both groups demonstrated a significantly greater increase for the amputee group than for control subjects (p less than 0.001). In the future, mean locus of sway might provide a useful clinical method of measurement and the eyes open/eyes closed ratio might provide a simple and useful method to communicate the dependency upon vision in individual patients.


Limbic lobe involvement in presenile dementia. Limbic lobe involvement in presenile dementia was studied from a neuropathological and neuropsychiatric viewpoint. The material consisted of seven cases of Alzheimer's disease, four cases of Pick's disease, and four cases of Jacob-Creutzfeldt's disease. These three groups showed different patterns of distribution of the degeneration characteristic for each group, in particular for the first two. Among the groups, these patterns differed with regard to involvement both of nonlimbic and limbic areas. Thus the Alzheimer group had a mainly temporoparieto-occipital and posterior cingulate gyrus involvement. The Pick group in many respects showed an inverse distribution with frontotemporal and anterior cingulate gyrus accentuation of the damage. Basal temporal limbic areas were involved in both groups. The Jacob-Creutzfeldt group had a less schematic lesion pattern, without involvement of limbic areas. From a neuropsychiatric aspect, these differences were reflected in symptoms that could be referred both to areas spared and those more pronouncedly destroyed by the degenerative process. Thus the Alzheimer group long retained emotional qualities that were lost early in the Pick group. The possible relationship between neurotransmitters and regional accentuation of the degeneration is discussed.


Evaluation of criteria for discontinuing mechanical ventilatory support. Thirty-three patients who required short-term postoperative mechanical ventilatory support were studied to compare different criteria established to initiate weaning from mechanical ventilation. Intermittent mandatory ventilation criteria (i.e., decreasing mechanical respirator rate as long as the arterial (pHa) remains above 7.35) and conventional criteria (ie, vital capacity greater than 15 ml/kg and peak negative pressure greater than 20 cm H2O) were compared to determine which would more rapidly predict a patient's ability to sustain total spontaneous respiration. All patients were eventually weaned from mechanical ventilation and had their tracheas extubated. Twenty-one patients maintained a pHa of greater than 7.35 during total spontaneous ventilation before they would, or could, meet conventional criteria for initiating a trial of spontaneous respiration (P less than .001). Seven patients simultaneously met both criteria for maintaining total spontaneous ventilation and the remaining five patients met conventional criteria before intermittent mandatory ventilation criteria. In the latter group, the pHa decreased below 7.35 during spontaneous respiration but in only one patient did it fall below 7.30. Our findings suggest that a patient's ability to maintain a pHa of greater than 7.35 while decreasing the frequency of mechanical ventilator breaths is more accurate than peak negative pressure and vital capacity for predicting ability to sustan adequate spontaneous respiration.


[Urinary infections in children].

[Urinary infections in children]. The E. Coli antibody response was studied in 81 infants and children with urinary tract infection. An haemagglutination technique was used. The antigen used was the bacteria present in urine. The correlation between the site of infection and response of haemagglutinating antibodies was statistically demonstrated. In some cases, the antibody titers were followed for several weeks, allowing an appreciation on the effectiveness of treatment. On the other hand, the correlation between serology and some of the results emphasize the interest of these tests in the general investigation of urinary tract infection in childhood.


[The investigation of lead levels in vertebra and rib samples (author's transl)]. The dithizone extraction method has been applied in the determination of lead content in human bones. The lead in 21 samples of fresh vertebrae and ribs from autopsies is compared with the lead content of historical bones of 17 skeletons from 600--800 A.D. The preparation and the direct mineralization of the bones are presented. The lead content detected in the ash of bones is to low compared with the value found by direct wet mineralization of the bones. During the dry ashing process with temperatures of 500 degrees C or higher lead may be lost. For the same person the lead content of rib is always lower than the value found in vertebra. The difference of the lead content of fresh bones and the historical bones is only small. In both groups the lead content in the bones increased with age. Compared with studies of other authors in the time of 1930--1970 the results would suggest that the present intake of lead in accidental selected bones among a population situated in an appointed area is not greater than in the past.


Napoleon Bonaparte's exposure to arsenic during 1816. Analysis of hair from Napoleon showed that he was exposed to considerable amounts of arsenic during 1816. The distribution pattern of the arsenic in the hair is similar to that found after the daily ingestion of excessive amounts of arsenic.


Comparative study by immunofluorescence of T and P antigens induced by adenovirus type 12 in permissive and nonpermissive cells. The development of adenovirus type 12 T antigen and of the complex of antigenic early proteins designated as P antigen was studied by immunofluorescence in productively infected KB cells and abortively infected RK-13 cells. T antigen is detected in both cell types very early in infection. In KB cells it presents the well known pattern of nuclear dots and flecks but in RK-13 cells at the time of maximum abundance, 18 hours p.i., T antigen forms a net of long filaments that fills the nucleus. Later, part of the filaments condense into a large aggregate that finally is apparently degraded. P antigen in infected RK-13 cells looks like T antigen in KB cells. In these cells, besides an early phase wherein P antigen is almost indistinguishable from T antigen, a late component is evident under the form of large balls and rosettes. The possible identification of this component with the DNA binding protein is discussed.


[Topological principle in the study of microcirculatory structuro-functional units]. Topological approach, suggested in the work, is a further development of methodology in studying microcirculation, especially its morphological basis. Owing to this approach, it is possible to consider spacial-time (coordinative) interrelations of different transport communications together with their histotopography. Hemato-lymphatic interrelations in the peritoneum can serve as an excellent example. Regularly repeating ansambles of transport communications (vascular and others) are interpreted as systems invariable for structural-functional units of the organ as to transport of fluid in tissues. Such complexes (modules) possess certain anatomy in hemodynamical and metabolic sense. Analysis of hemato-lymphatic interactions mediated by the interstitial space makes it possible to unite, within the module, processes of transmural, interstitial and axial (intervascular) transport. Movement of blood, interstitial fluid and lymph in tissues must be of oscillatory (discrete) character. As their trigger mechanism regulating rhythm and sequence of transport processes can serve the activity of metabolic lymphatic microvessels. Regulation of blood volume in capillaries depends on hydraulic and osmotic conditions in the interstitial space and on intensity of transmural transport. Topological approach can be effective in analyzing transport interrelations in tissues of different organs.


[Correlative relationship between coronary arteriosclerosis and stromogenic cardiosclerosis in ischemic heart disease (stereometric study)]. Stereometric studies showed that the volumetric portion of diffuse stromagenic cardiosclerosis in the myocardium increased in parallel with the prolongation of the course of ischemic heart disease and with an increase in the average values of atherosclerotic involvement of the intima of coronary arteries and was inversely related to the index of retention of the total summary functioning lumen of the coronary arteries. There is a direct correlative relationship between the degree of narrowing of the summary functioning lumen and the intensity of stromagenic cardiosclerosis, increasing with the prolongation of the course of the disease.


[Ultrastructural basis of acute cardiac insufficiency not associated with rhythm disorders]. On the basis of the data from the literature and own studies the genesis of acute cardiac insufficiency has been shown to be directly associated with a sharp decline in the effectiveness of intracellular energy transportation. A challenging factor in the transformation of the pathological process into acute cardiac insufficiency may consist in one of the three main types of influence: (1) hypoxia of the myocardium, (2) effects causing disorders in the calcium metabolism, and (3) additional mechanical loads on the already affected myocardium. The pattern of the observed ultrastructural changes may be used to a certain extent for the judgement on the type of effect which was most important in the genesis of acute cardiac insufficiency.


[Nature of intercellular interactions at various stages of post-transplantation immunity]. The paper presents the results of studies on the nature and frequency of intercellular interactions at various stages of posttransplantation immunity done by means of the grating microscope. The study was carried out in inbred mice. The donors of the skin included CBA mice (for the syngeneic system) and BALB/c mice (for the allogeneic system), and the recipients were CBA mice. The target cells were epidermal cells of the tails of mice of the appropriate lines. The interaction of the target cells with lymphocytes, thymocytes and macrophages obtained from the animals sensitized with the appropriate transplant were examined at various intervals after transplantation. The frequency and the nature of intercellular contacts were found to vary in relation to the time after grafting and the species of the graft. Numerous arches, bridges, outgrowths and microvilli were formed both between killer cells and immunocompetent cells and between lymphoid and non-lymphoid cells.


[Relationship between mononuclear infiltration of the epidermis and its hyperplasia after auto- and allotransplantation of the full-thickness skin of mice]. Histological and histochemical studies of the back skin were carried out with morphometry on the 1st, 2nd, 3rd, 6th, and 9th days after auto- or allotransplantation of its full thickness graft in 60 lineal (C3H) and random-bred mice. In both kinds of transplantation, mononuclear infiltration of the epidermis of the graft and the surrounding skin was established. A correlation between the intensity of this infiltration and the thickness of the epidermis in the skin surrounding the grafts and in the autograft was established. In allotransplantation, there was no such correlation in the graft. No mononuclear cells were found in regeneration layers of the epidermis. It is suggested that epidermis regeneration is stimulated by autogenous lymphocytes.


[Morphological manifestations of graft functional insufficiency in the 1st 2 months after a human cadaver kidney transplant]. The autopsy and biopsy materials were used for clinico-anatomical comparisons, and three types of changes were distinguished in transplants of cadaver kidneys of man in insufficiency of the function developing in the first 2 months after transplantation: I type--necrotic changes, II--changes resembling the picture of acute renal insufficiency in circulatory shock with retention of the signs of cortical bloodflow and filtration; III--osmotic nephrosis. The nature of the initial function of the transplant reflects not only the features of the rejection reaction but also the degree of ischemia of nonimmune character suffered by the kidney which determines the rate of restoration of its function as well as sensitivity to the rejection reaction and the effect of some therapeutic factors.


[Structural foundation for the functional connections of the endocrine apparatus and nervous system of the kidneys]. Data from the current literature are used to demonstrate the structural-functional relationship of endocrine and nervous apparatuses of the kidneys which must be taken into consideration in the analysis of clinical manifestations and pathogenesis of many diseases, first of all those of the kidneys. Therefore it is recommended that in examinations of kidney biopsies the state of the endocrine apparatuses and nervous system be evaluated which requires deep kidney biopsy and special methods of morphological analysis.


[Simple method of embedding in paraffin under vacuum]. A method of embedding into paraffin under vacuum is proposed. Pieces of tissues are placed into a glass jar containing melted paraffin from which the air is pumped out. The jar is permanently placed into TC-80 thermostate. The air-removing hose is placed inside the thermostate through the opening in its upper wall meant for the control thermometer. The air is pumped out by any vacuum pump with electric drive. The proposed method is simple, provides for a good saturation with paraffin, shortens the time of tissue contact with melted paraffin, and gives thin sections of good quality.


[Status of pathological anatomy in the capitalist countries of Europe and the USA]. A review of the status and development of pathological anatomy in some European capitalist countries and in the USA is presented on the basis of the literature of recent years. The difficulties which arose in the development of this discipline are described and some comparisons of its status in these countries, the DDR, and the USSR are presented.


Charles Dickens and the ear, nose, and throat. Charles Dickens is known as a novelist, humorist, humanist, and a social reformist. One of his many abilities was an astute power of observation, and some of his writings included descriptions considered as original medical knowledge. Among the hundreds of characters portrayed by Dickens, many had depictions or diseases of interest to the otolaryngologist. Dickens described deaf children and was interested in the methods used in their teaching. He had a keen interest in children and their welfare and described his visits to the Childrens Hospital in London and to Parkins Institute at Boston. He described both temporary and permanent deafness following exposure to loud noise. Dickens was a medical critic and most of his writings on the subject were humorous, though mixed at times with a spicy element of satire.


Homografts of the middle ear. Privileged tissue or privileged site. To explain the survival and behavior of homografts, we have tried, by means of discussion and use of biological models, to resolve a problem with three unknowns, ie, the tympanic membrane, the ossicle, and the middle ear, with the notions of privileged tissue and privileged site. The tympanic membrane survives because of the relative stability of its fibers and the absence of mechanical trauma. Later, the membrane is sheathed by fibrous tissue. The ossicle is not only tolerated by the host but is also invaded and ossified.


Autografts of uncrushed and crushed bone and cartilage. Experimental observations and clinical implications. This study evaluated autografts of bone and cartilage, uncrushed and crushed, in the perichondrial space of the ear and subcutaneously in the paraspinal region in rabbits six weeks and six months after transplantation. The results support the belief that in a clinical setting it is important to preserve perichondrium because it facilitates growth of new cartilage. This study suggests that when autogenous tissue is to be used for subcutaneous augmentation, it is best to use crushed or uncrushed cartilage or uncrushed bone because they remain viable. In the perichondrial space, crushed and uncrushed cartilage grafts not only remain viable but also induce growth of new cartilage and bone. Autogenous crushed bone does not survive in the perichondrial space of the rabbit ear.


Primary reconstruction by modified cervical island skin flap following resection of oral and pharyngeal cancer. Reconstruction of the intraoral defect following cancer surgery often causes formation of fistula, impairment of lingual movement, and prolonged hospitalization by secondary reconstruction. To reduce such complications, the modified cervical island skin flap method as a one-stage intraoral reconstruction was used in 18 patients. Lateral cervical island flap was used in 15 cases and the median flap in three. This method proved to be successful for 17 patients. One patient who received a preoperative full dose of irradiation developed a fistula. There were two types of healing of the skin flap. The postoperative external appearance and function of the tongue were commendable.


The role of the overlay denture in the prevention of mandibular ridge atrophy. The overlay denture concept may be used to postpone and in some cases avoid the atrophied mandibular ridge syndrome. The co-operation of the patient is a vital factor for success and the treatment regimen is divided into a series of self-contained stages to allow the patient to demonstrate his mastery of each before proceeding to the next. Function in the edentate can be enhanced by the use of this type of denture.


Current concepts in the surgical management of the atrophic mandible. 1. For the severely atrophic mandible surgery cannot be considered as a magical panacea. 2. Retention of teeth or tooth roots is important as we are unable to predict the degree of mandibular bone resorption relating to the innate vascular pattern. 3. More emphasis should be given to mylohyoid reduction as described in this paper. 4. A gain in stability by surgery should not be at the expense of retention. 5. Mucosal grafts are more satisfactory than skin grafts. 6. Bone graft augmentation in the future must be considered with great caution. 7. When removing denture hyperplasia which involves the sulcus, every effort must be made to preserve viable mucosa in order to reconstitute a resilient border seal.


Child psychiatry: what it is all about.

Child psychiatry: what it is all about. This paper discusses the history of child psychiatry, and outlines the role and training of a child psychiatrist. Case histories are introduced as illustrations of the factors with which both therapist and patient have to contend during the course of their relationship.


Group B streptococcal infection in the perinatal period. An increasing problem in newborn care. Group B streptococcal infections in newborn infants are increasing in frequency. Infection takes two forms--early-onset, developing in the first 24 hours, and late-onset, developing after the first week. Early-onset disease, a fulminating septicaemia, has a mortality of 40-70%. Late-onset disease, usually meningitis, has a mortality of 20-30%, with a high incidence of neurological damage in survivors. Early-onset disease is acquired during delivery from organisms colonizing the vagina. Up to 25% of women are colonized in late pregnancy. So far, no effective programmes for prevention have been developed.


Immunoglobulin deposition in the kidney in pre-eclampsia: its significance. Renal biopsies from two patients with classical toxaemia of pregnancy demonstrated heavy deposition of IgG and IgA in a predominantly finely granular pattern. It is suggested that this may be a manifestation of immune complex formation and may provide further evidence for an immunological basis for the renal lesion of this poorly understood disease process.


Primary selective deficiency of immunoglobulin M. Selective deficiency of IgM as a primary disorder is seldom encountered1--3, and the syndrome remains ill-defined4. It is generally accepted that for a diagnosis to be made, the serum IgM level should be consistently below 2 SD of normal, no other immunodeficiencies are present, and it is not secondary to other disease processes4. This report of an additional case may provide further insight into this rare disease.


Lymphoblastic transformation of Ph1-positive chronic myeloid leukaemia: therapeutic implications and relevance to haemopoietic stem cell theory. A proportion of patients with blast crisis of CML have blast cells identical to those found in common non-T, non-B all, and whilst this disease is often referred to as lymphoid blast crisis (LBC), evidence is presented that it may in fact arise from a prelymphoid, pre-myeloid (pluripotential) stem cell. Recently developed membrane and enzyme markers (anti-ALL antiserum, TdT assay) have provided convenient diagnostic tests for the detection of LBC. The clinical and haematological features of LBC are reviewed: patients with LBC show a higher response rate to therapy with vincristine and prednisolone, and their survival may be significantly prolonged. The frequent occurrence of meningeal leukaemia suggests the need for prophylactic CNS therapy in LBC patients achieving remission.


Pathophysiology of platelet-vessel interactions. Thrombosis results from the interaction of a number of processes which are summarized in table I and figure 1. The predominant role of platelets in the genesis of rapid-flow, arterial thrombosis provides a rationale for the clinical trial of inhibitors of platelet functions in the management of several thrombotic disorders.


Cardiac thromboembolism: evidence for role of platelets and value of platelet suppressant therapy. Thromboembolism remains a frequent and serious problem in cardiac patients. Methods to identify the thrombosis-prone patient and the identification of safe and effective forms of treatment would be of great value. The accumulating evidence which indicates that abnormalities in platelet tests are often present in cardiac patients and may help identify those at greatest risk of thrombosis is encouraging. It suggests that patients with cardiac disease are desirable groups for investigation. It also indicates that the platelet survival test may be useful as a reference against which new and more practical tests can be compared, as well as a means to identify useful platelet suppressant drugs or to monitor the effects of these drugs.


Use of platelet inhibitor drugs in peripheral and cerebral vascular disorders. A review is given on the clinical studies performed with aspirin in patients with chronic vascular occlusions of the limbs and on studies in cerebral ischemia using aspirin and sulfinpyrazone. Aspirin reduces the risk of reocclusions in patients after vascular surgery and also reduces the risk of peripheral vascular occlusions in diabetic patients. In doses of 1.2-1.5 g/day it also reduces the frequency of transient ischemic attacks. Conclusive results of similar studies with sulfinpyrazone and dipyridamole can be expected of the ongoing studies. Aspirin has no effect on the course of glomerulonephritis in children. Warfarin plus dipyridamole seem to have some effect in patients renal allografts. Sulfinpyrazone and ASA reduced the incidence of shunt thromboses in hemodialyzed patients. Several case reports in patients with thrombocytemia or Raynaud's syndrome made it likely that treatment with antiplatelet drug reduces the incidence of vascular occlusions.


Thrombin: structural features related to specificity. A comparison of the primary structure of human thrombin with the structures of chymotrypsin, trypsin, elastase and factor Xabeta reveals several structural features which may be involved in the specificity of thrombin toward macromolecular substrates. Among the major structural differences noted in such a comparison are the insertions of five extended peptide regions in the primary structure of alpha-thrombin when compared to chymotrypsin. These insertions, which we refer to as "loops", have been designated A, B, C, D, and E. The A, B and C "loops" in human thrombin appear to be large enough to interact at or near the active active site if an alpha-thrombin-chymotrypsin three-dimensional structural homology is assumed. In beta-thrombin, the configuration of the A and B "loops" may be perturbed by proteolysis, and the ability of beta-thrombin to clot fibrinogen is thus reduced. Perturbation of the configuration of the C "loops" by proteolysis in the formation of gamma-thrombin may further reduce the ability of thrombin to bind fibrinogen.


Amino acid sequence homology and the vitamin K-dependent proteins. Examination of amino acid sequence data on bovine vitamin K-dependent clotting zymogens, using the Gibbs and McIntyre diagonal plot, leads to the conclusion that they are homologous and have evolved by a series of gene duplications. Plasminogen is also homologous but lacks the region containing glutamic acid (Glu) residues gamma-carboxylated in a vitamin K-dependent step. Both prothrombin and plasminogen show internal sequence homology resulting from partial gene duplication and quintuplication respectively; each internal homology loop in prothrombin shows significant homology with each of the five putative loops in plasminogen. Recently, Walz et al. (Proc. natn. Acad. Sci. USA 74: 1969-1972, 1977) have sequenced the non-thrombin region of human prothrombin (residues 1-273) and this has enabled identification of regions conserved in 90 million years of eutherian evolution. The relative conservatism of homology loop 1 (bovine residues  66-144) which has no known function is discussed 'gamma-Carboxyglutamic acid; (Gla) has been found in proteins unrelated to the plasma clotting factors; a bovine bone-matrix protein('osteocalcin') has been sequenced  by Price et al. (Proc. natn. Acad Sci. USA 73: 3373-3375, 1976) but it shows no homology with prothrombin or factor X.


Functional mutants of yeast alcohol dehydrogenase affecting kinetics, cellular redox balance, and electrophoretic mobility. Repeated selection of petite (respiratorily incompetent) Saccharomyces cerevisiae on medium containing allyl alcohol, both on plates and in the turbidostat, results in mutants with a remarkably similar response. Most of the mutations affect the constitutive alcohol dehydrogenase, resulting in enzymes with a cathodal shift in electrophoretic mobility, and none shows a significant anodal shift. The genetics, kinetics, and physiological effect of three of the mutants have been investigated in detail, and while all confer resistance to allyl alcohol through a shift in the NAD/NADH ratio, they do so in slightly different ways. The potential of this system for exploring the range of short-term adaptations open to this organism is discussed.


Genetic control of enzyme polymorphisms in the california vole, Microtus californicus. Inheritance of 15 polymorphic isozymes was investigated in captive Microtus californicus. Eleven of the isozymes show patterns consistent with a Mendelian model of inheritance: glycerol-3-phosphate dehydrogenase (GPD), lactate dehydrogenases A and B (LDH-A and LDH-B), malic enzyme 2 (ME-2), isocitrate dehydrogenase 1 (ICD-1), phosphogluconate dehydrogenase (PGD), glutamate-oxaloacetate transaminase 1 (GOT-1) phosphoglucomutase 2 (PGM-2), leucine aminopeptidase (LAP), glucosephosphate isomerase (GPI), and esterase 2 (ES-2, from kidney). Four of the isozymes show patterns that cannot be interpreted by a simple genetic model: esterases 1 and 4 (ES-1, ES-4, from hemolysate), esterase 3 (ES-3, from plasma), and protein 1 (PT-1). The following pairs of loci are assorting independently: LAP and PGD, LAP and PGM-2, GOT-1 and PGD, GOT-1 and GPD, LAP and GPD, GPD and PGD, GPI and PGD. Data from one test cross mating indicate that GPD and PGM-2 are loosely linked with recombination about 30%. Additional data are needed to confirm this relationship.


Purification of the hexokinases by affinity chromatography on sepharose-N-aminoacylglucosamine derivates. Design of affinity matrices from free solution kinetics. The purification is described of rat hepatic hexokinase type III and kidney hexokinase type I on a large scale by using a combination of conventional and affinity techniques similar to those previously used for the purification of rat hepatic glucokinase [Holroyde, Allen, Storer, Warsy, Chesher, Trayer, Cornish-Bowden & Walker (1976) Biochem. J. 153, 363-373] and muscle hexokinase type II [Holroyde & Trayer (1976) FEBS Lett. 62, 215-219]. The key to each purification was the use of a Sepharose-N-aminoacylglucosamine affinity matrix in which a high degree of specificity for a particular hexokinase isoenzyme could be introduced by either varying the length of the aminoacyl spacer and/or varying the ligand concentration coupled to the gel. This was predicted from a study of the free solution kinetic properties of the various N-aminoacylglucosamine derivatives used (N-aminopropionyl, N-aminobutyryl, N-aminohexanoyl and N-aminooctanoyl), synthesized as described by Holroyde, Chesher, Trayer & Walker [(1976) Biochem. J. 153, 351-361]. All derivatives were competitive inhibitors, with respect to glucose, of the hexokinase reaction, and there was a direct correlation between the Ki for a particular derivative and its ability to act as an affinity matrix when immobilized to CNBr-activated Sepharose 4B. Muscle hexokinase type II could be chromatographed on the Sepharose conjugates of all four N-aminoacylglucosamine derivatives, although the N-aminohexanoylglucosamine derivative proved best. This same derivative was readily able to bind hepatic glucokinase and hexokinase type III, but Sepharose-N-amino-octanoyl-glucosamine was better for these enzymes and was the only derivative capable of binding kidney hexokinase type I efficiently. Separate studies with yeast hexokinase showed that again only the Sepharose-N-amino-octanoylglucosamine was capable of acting as an efficient affinity matrix for this enzyme. Implications of these studies in our understanding of affinity-chromatography operation are discussed.


Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complex of Escherichia coli. The intramolecular passage of substrate between the component enzymes of the pyruvate dehydrogenase multienzyme complex of Escherichia coli was examined. A series of partly reassembled complexes, varying only in their E1 (pyruvate decarboxylase, EC 1.2.4.1) content, was incubated with pyruvate in the absence of CoA, conditions under which the lipoic acid residues covalently bound to the E2 (lipoate acetyltransferase, EC2.3.1.12) chains of the complex become reductively acetylated, and the reaction then ceases. The fraction of E2 chains thus acetylated was estimated by specific reaction of the thiol groups in the acetyl-lipoic acid moieties with N-ethyl[2,3-14C]maleimide. The simplest interpretation of the results was that a single E1 dimer is capable of catalysing the rapid acetylation of 8-12 E2 chains, in good agreement with the results of Bates, Danson, Hale, Hooper & Perham [(1977) Nature (London) 268, 313-316]. This novel functional connexion of active sites must be brought about by transacetylation reactions between lipoic acid residues of neighbouring E2 chains in the enzyme complex. There was also a slow transacylation process between the rapidly acetylated lipoic acid residues and those that did not react in the initial, faster phase. This interaction was not investigated in detail, since it is too slow to be of kinetic significance in the normal enzymic reaction.


Modification of yeast ribosomal proteins. Phosphorylation. Two-dimensional polyacrylamide-gel electrophoretic analysis of yeast ribosomal proteins labelled in vivo with 32PO43- revealed that the proteins S2 and S10 of the 40S ribosomal subunit, and the proteins L9, L30, L44 and L45 of the 60S ribosomal subunit, are phosphorylated in vivo. Most of the phosphate groups appeared to be linked to serine residues. Teh number of phosphate groups per molecule of phosphorylated protein species ranged from 0.01 to 0.79. Since most of the phosphorylated ribosomal proteins appear to associate with the pre-ribosomal particles at a very late stage of ribosome assembly, phosphorylation is more likely to play a role in the functioning of the ribosome than in its assembly.