Hybrid tryptophan synthase beta 2 proteins: apparent conservation of the beta-beta binding region of the beta monomer among enteric bacteria.

Purified borohydride-reduced tryptophan synthase beta 2 protein (EC 4.2.1.20) from Escherichia coli and purified native beta 2 protein from Serratia marcescens were mixed and dissociated in urea. Removal of the urea resulted in random reassociation of the reduced and native beta monomers, forming interspecies hybrid beta 2 molecules. Interspecies hybrid beta 2 protein molecules of the reciprocal composition were also formed. Interspecies hybrid reconstituted molecules were formed with approximately the same efficiency as intraspecies reconstituted molecules (reduced and native monomers from the same species) indicating no particular preference for reassembly. The data provide evidence that the structural region of interaction between the beta monomers necessary for dimerization is highly conserved in the enzymes from the two organisms examined.


Influence of molecular size and osmolarity of sugars and dextrans on the synthesis of outer membrane proteins O-8 and O-9 of Escherichia coli K-12.

Supplementation of the growth medium with high concentrations of sugars or low-molecular-weight dextrans results in a drastic change in the ratio of outer membrane proteins O-8 and O-9, due to induction of O-8 synthesis and suppression of O-9 synthesis. Sugars and dextrans of molecular weights greater than 600 to 700 switched the synthesis of O-9 to that of O-8 more effectively than those of lower molecular weight, although the effect was almost the same within each of the two groups irrespective of the differences in molecular weight within the group. Proteins O-8 or O-9, or both, are responsible for the formation of pores that allow the passive diffusion of hydrophilic molecules whose molecular weights are smaller than about 600 (T. Nakae, Biochem. Biophys. Res. Commun. 71:877-884, 1976). The results indicate that substances that cannot pass through the outer membrane switch the synthesis of O-9 to that of O-8 more effectively than those that can penetrate this membrane with the aid of O-8, O-9, or both. It is suggested that the osmotic pressure exerted on the outer membrane plays an important role in the regulation of synthesis of the two proteins.


Escherichia coli mutants incapable of supporting replication of F-like plasmids at high temperature: isolation and characterization of mafA and mafB mutants.

Mutants of Escherichia coli K-12 defective in replication of F-like plasmids at a high temperature (42 degrees C) were found among threonine-independent (Thr+) revertants of a threonine-requiring F' stain after localized mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Transduction experiments with phage P1 permitted us to divide these mutations into two classes with respect to man location; some mutations were located between thr and ara at about 0.8 min, very close to maf-1 reported previously (Wada et al., J. Mol. Biol. 108:25-41, 1976 and the others probably were located between leu and azi at about 1.8 min. The former class of mutants designated mafA exhibited the same plasmid specificity as maf-1; replication of plasmids F and ColVB trp, but not R386 or R222, were affected at a high temperature. By contrast, the latter mutants designated mafB were defective in replication of nay of these plasmids at a high temperature. When a culture of mafA mutants carrying an F' plasmid was transferred from 30 to 42 degrees C, the plasmid replication as determined by incorporation of [3H]thymidine into covalently closed circular F DNA was markedly inhibited. Under certain conditions, the temperature shift-up caused severe growth inhibition of the mutant cells. Examination of merodiploids (mafA/FmafA+) for plasmid maintenance suggested that the two mafA mutations tested (mafA23 and mafA36) were both dominant, at least partially, over the wild-type mafA+ allele. These properties of the mafA mutants, manifested at the restrictive temperature, are similar to those previously reported for the maf-1 mutant. Taken together with other evidence it is likely that these mutations affect either the same gene (mafA) or a set of closely linked genes, playing a specific role in autonomous plasmid replication in E. coli.


Regulation of activity and synthesis of N-acetylglutamate synthase from Saccharomyces cerevisiae.

Feedback inhibition of N-acetylgutamate synthase in a particulate fraction from Saccharomyces cerevisiae by L-arginine was synergistically enhanced by N-actylglutamate, whereas coenzyme A let to an additive enhancement of arginine inhibition. N-acetylglutamate synthase was not inhibited by polyamines, nor was the enzyme inactivated by incubation in the presence of coenzyme A and zinc ions. Evidence was obtained for the involvement of at least three different regulatory mechanisms in the expression of N-acetylglutamate synthase: arginine-specific repression, glucose repression and general amino acid control. The combined action of these control mechanisms led to a 90-fold variation in the specific activity of the enzyme.


Binding of yeast killer toxin to a cell wall receptor on sensitive Saccharomyces cerevisiae.

35S-labeled killer toxin protein bound to cells of sensitive Saccharomyces  cerevisiae S14a. Strains that were resistant to toxin through mutation in the nuclear genes kre1 kre2 bound toxin only weakly. Non-radioactive toxin competed effectively with 35S-labeled toxin for binding to S14a, but did not compete significantly in the binding to mutant kre1-1. This implied that binding to kre1-1 was nonspecific. A Scatchard analysis of the specific binding to S14a gave a linear plot, with an association constant of 2.9 x 10(6) M-1 and a receptor number of 1.1 x 10(7) per cell. Killer toxin receptors were solubilized from the cell wall by zymolyase digestion. Soluble, non-dialyzable cell wall digest from S14a competed with sensitive yeast cells for 35S-labeled toxin binding and reduced toxin-dependent killing of a sensitive strain. Wall digest from kre1-1 competed only weakly for toxin binding with sensitive cells and caused little reduction of toxin-dependent killing. Although the abundant (1.1 x 10(7) per cell) receptor appeared necessary for toxin action, as few as 2.8 x 10(4) toxin molecules were necessary to kill a sensitive cell of S14a. The kinetics killing of S14a suggested that some component was saturated with toxin at a concentration 50-fold lower than that needed to saturate the wall receptor.


Spontaneous mutational specificity of drug resistance plasmid pKM101 in Escherichia coli.

Plasmid pKM101 enhances the frequency of spontaneous and ultraviolet light-induced mutations in Escherichia coli and protects the cells against the lethal effects of ultraviolet irradiation. By analyzing reversion patterns of defined trpA alleles, we showed that pKM101 caused all types of spontaneous base-pair substitution mutations with the possible exception of guanine . cytosine leads to adenine. thymine transitions. Neither insertion nor deletion frameshift mutations were enhanced. Transversions were more strongly enhanced than transitions, and adenine . thymine base pairs appeared more susceptible to pKM101 mutator activity than guanine . cytosine base pairs. In addition, there were effects from neighboring base pairs and genetic background that influenced the mutator activity of pKM101.


Escherichia coli mutants tolerant to beta-lactam antibiotics.

Two types of Escherichia coli mutants tolerant to beta-lactam antibiotics were isolated. One is E. coli chi2452, which showed a tolerant response against beta-lactam antibiotics when grown at 42 degrees C, and the others are the mutants C-80 and C-254, selected from mutagenized E. coli chi1776 by cycles of exposure to ampicillin, cephaloridine, and starvation of the nutritionally required diaminopimelic acid. Beta-lactam antibiotics caused rapid loss of viability and lysis in cultures of chi1776 or in chi2452 grown at 32 degrees C. In contrast, the same antibiotics caused only a reversible inhibition of growth in mutants C-80 and C-254 or in cultures of chi2452 grown at 42 degrees C. Beta-lactam antibiotics that show high affinity for penicillin-binding proteins 2 or 3 (mecillinam and cephalexin, respectively) induced similar morphological effects (ovoid cell formation and filament formation) in both parent and mutant strains. In contrast, beta-lactam antibiotics which have a high affinity for penicillin-binding protein 1 (e.g., cephaloridine or cefoxitin), which cause rapid lysis in the parental strains, caused cell elongation in the tolerant bacteria. In contrast to the parental cells, autolytic cell wall degradation was not triggered by beta-lactam treatment of chi2452 cells grown at 42 degrees C or in mutants C-80 and C-254. The total autolytic activity of mutants C-80 and C-254 was less than 30% that of the parent strain. However, virtually identical autolytic activities were found in cells of chi2452 grown either at 42 or 32 degrees C. Possible mechanisms for the penicillin tolerance of E. coli are considered on the basis of these findings.


AMP deaminase from baker's yeast. Kinetic and molecular properties.

The kinetic and molecular properties of AMP deaminase [AMP aminohydrolase, EC 3.5.4.6] purified from baker's yeast (saccharomyces cerevisiae) were investigated. The enzyme was activated by ATP and dATP, but inhibited by Pi and GTP in an allosteric manner. Alkali metal ions and alkaline earth metal ions activated the enzyme to various extent. Kinetic negative cooperativity was observed in the binding of nucleoside triphosphates. Kinetic analysis showed that the number of interaction sites for AMP (substrate) and Pi (inhibitor) is two each per enzyme molecule. The molecular weight of the native enzyme was estimated to be 360,000 by sedimentation equilibrium studies. On polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the enzyme gave a single polypeptide band with a molecular weight of 83,000, suggesting that the native enzyme has a tetrameric structure. Baker's yeast AMP deaminase was concluded to consist of two "promoter" units which each consist of two polypeptide chains with identical molecular weight.


Equilibrium and kinetics of the thermal unfolding of yeast 5S ribosomal RNA.

The equilibrium and kinetics of thermal unfolding of yeast 5S ribosomal RNA have been studied by optical methods, in a low ionic strength environment without Mg2+, to follow the disruption of the secondary structure base pairs in the molecule. The equilibrium results demonstrated that all of the helical regions melted simultaneously, and the kinetics of the thermal unfolding were first order. These findings suggest the validity of the two-state approximation for the unfolding reaction under the present conditions. The total number of secondary structure base pairs estimated from our experiment was consistent with that contained in the conformational model based on the Raman spectrum rather than that in the one derived by the enzymic digestion method. Taking our results on the kinetic behavior of the thermal unfolding overall, we propose that the 5S RNA has a partly melted secondary structure under the solvent conditions used.


[Stimulating effect of partial cystectomy on regeneration of rat bladder urothelium and its significance for carcinogenesis (author's transl)].

Cell proliferation kinetics of the urinary bladder urothelium have been analyzed in a total of 218 female Wistar rats after partial cystectomy. After one-third resection of the bladder DNA synthesis started 15 h postoperatively in the bladder stump and reached its maximum at 25 h with a mean 3H-TdR index of 10.1%. In the area of resection the proliferative activity increased after 20 h and the highest 3H-TdR index was found to be 24.7% after 45 h. In the case of hemicystectomy the labeling index in the stump increased 15 h postoperatively and the highest 3H-T-dR index was determined at 20 h with 16.6%. The urothelial cells in the area of resection began to proliferate synchronously with those in the stump and the maximum of DNA synthesis was measured 35 h postoperatively with an 3H-TdR index of 24.2%. After 2 weeks the proliferative activity within the stump and operative region corresponded to that of the control urothelium. The basal cells showed absolutely the highest proliferative activity, the suprabasal cells exhibited on the other side the highest regenerative potential compared with the control urothelium. Partial cystectomy might possibly serve as an experimental model for testing low potential carcinogens, in the case where carcinogenic effects would be initiated, potentiated and accelerated via stimulation of the DNA synthesis.


Biochemical analysis of ligand-induced receptor patching and capping using a novel immunolactoperoxidase iodination technique.

A novel approach for the analysis of membrane proteins involved in ligand-induced surface receptor patching and capping is described. The technique is based on the use of immunolactoperoxidase (immuno-LPO) conjugates which catalyze the iodination of those surface proteins with available tyrosine groups that are located in the immediate vicinity of the patch or cap of a particular antigen. We have used the patching and capping of the H-2 (histocompatibility) antigen on mouse thymocytes to illustrate this method. However, this technique should be generally applicable to any cell surface proteins which can be induced to form patches or caps by a specific ligand. Cytochemical analysis indicates that the immuno-LPO conjugates induce the same patching and capping of the H-2 antigen as does the unconjugated antibody. Biochemical analysis of the 125I-labeled proteins by SDS polyacrylamide gel electrophoresis indicates that a large membrane protein (mol wt of approximately 200,000 daltons) is closely associated with H-2 patches and caps. Since a number of other prominent membrane proteins are not labeled by this procedure, selective redistribution of certain surface proteins must be occurring during H-2 antibody-induced patching and capping.


Granulocyte migration through endothelium in culture.

Using a model system with which we have previously investigated the adhesion of granulocytes to cultured endothelium, we have now shown that adherent granulocytes migrate through cultured endothelium in a manner closely resembling that found during the acute inflammatory response in vivo. The migration of granulocytes was markedly enhanced in the presence of erythrocytes, whereas blood platelets did not affect migration. Several test agents, including Paroven and some prostaglandins, had different effects upon migration and adhesion. We conclude that the adhesion of granulocytes to endothelium and their migration through it are responses that are, at least in part, separately controlled, and that migration does not depend exclusively upon extravascular stimuli.


Observation of cultured embryonic epithelial cells in side view.

Epithelial cells from the early chick embryo were explanted and grown on a strip of coverglass which was positioned in a culture chamber in such a way that the cells could be filmed in side view. Ruffling of the cells at the leading edge of the sheet (marginal cells) appeared similar to the ruffles at the leading lamella of fibroblasts. The ruffles of the sub-marginal cells showed different characteristics, being longer and not propagated successively as were the marginal ruffles. Superimposition of cells was always the result of the active movement of a non-yolky cytoplasmic process underneath a yolky process (i.e. underlapping). The non-yolky processes appeared to be strongly adherent to the substrate in comparison with the yolky processes, which were easily displaced. Active movement of cells or lamellae on the dorsal surface of the sheet was never observed. Preliminary ultrastructural evidence is presented which suggests that the strongly adherent non-yolky processes possess well-defined microfilament tracts associated with the ventral plasma membrane, while the poorly adherent processes do not possess such tracts.


Simplification of methods for the production and storage of specimens to be tested for heat-stable enterotoxin of Escherichia coli.

Experiments with the infant mouse test demonstrated that there is no need of shaking for heat-stable Escherichia coli enterotoxin production when low volume of medium per volume of flask ratios are used in stationary cultures. Centrifugation and filtration of the cultures to be tested are not necessary either, and Merthiolate (1:10,000) used as preservative has no deleterious effect on heat-stable enterotoxin activity. Based upon these findings, some modifications of the procedures for production and storage of heat-stable enterotoxin preparations are suggested. Standardized pieces of filter papers are wetted with Merthiolated stationary cultures which are to be assayed for heat-stable enterotoxin activity by the infant mouse test. From dried filter papers, heat-stable enterotoxin can be eulted unaltered up to 2 months after specimen preparation. With the proposed modifications, even modestly equipped laboratories will be able to carry out the infant mouse test or at least to prepare specimens to be assayed by more specialized laboratories.


Evaluation of a ganglioside immunosorbent assay for detection of Escherichia coli heat-labile enterotoxin.

The GM1  ganglioside enzyme-linked immunosorbent assay (GM1-ELISA), an immunological method for detection of Escherichia coli heat-labile enterotoxin (LT), was quantitatively and qualitatively compared with the conventional adrenal cell test for the identification of LT-producing strains. A micromodification model of the assay was developed. Enterotoxin preparations from 120 E. coli isolates from individuals with diarrhea, which had been previously shown to be enterotoxigenic by the adrenal cell test, and from 44 control strains of E. coli were compared in parallel by the two methods. Quantitatively the covariation of the enterotoxin titers was highly significant (RS = 0.98, P less than 0.001), the GM1-ELISA being somewhat more sensitive than the adrenal cell test. The methodological error was less than 5% in both tests. Qualitatively the overall agreement for positive and negative reactions for the two methods was 89%. The GM1-ELISA is practical for routine use in the diagnosis of enterotoxigenic E. coli, especially in laboratories without facilities for cell culture.


Serology of Legionnaires disease: comparison of indirect fluorescent antibody, immune adherence hemagglutination, and indirect hemagglutination tests.

An immune adherence hemagglutination (IAHA) test for the measurement of antibodies to Legionella pneumophila was developed and evaluated for the diagnosis of Legionnaires disease. Its sensitivity was compared to that of the indirect fluorescent antibody (IFA) test and a recently developed indirect hemagglutination (IHA) test. The sensitivity of the three tests appeared to be similar, with the IFA test giving slightly higher titers. Both the IHA and IAHA tests appear useful for the serodiagnosis of Legionnaires disease; the IAHA test has the advantage that it can be used with many other serological antigens.


Ureolytic Escherichia coli of human origin: serological, epidemiological, and genetic analysis.

Forty-five strains of ureolytic Escherichia coli of human origin, isolated in the United States between 1956 and 1977, were characterized by geographical distribution, site of infection, serotype, resistance to antibiotics, and biochemical reactions. All strains were studied for the ability to generate clones of nonureolytic E. coli (segregants), and a subset of these were selected for plasmid analysis and a variety of bacterial matings. There did not appear to be a common geographical distribution, serotype, antibiogram, or other aberrant biochemical reactions other than the hydrolysis of urea among these strains. The predominance of urinary tract isolates (46.7% total) may reflect a relationship between urea hydrolysis and pathogenesis at this site. Ten of the strains (22.2%) did segregate nonureolytic E. coli colonies, and all possessed at least one common plasmid species with a molecular weight of about 65 X 10(6). Only strain 1138-77 serotype O16:H6 conjugally transfered the ability to hydrolyze urea, ferment sucrose, and resist inhibition by sulfadiazide simultaneously. The resulting, recombination-deficient E. coli K-12 tranconjugant was found to possess a plasmid with a molecular weight of about 80 X 10(6) to 90 X 10(6).


Detection of oral anaerobic spirochetes in dental plaque by the indirect fluorescent-antibody technique.

The indirect fluorescent-antibody technique was found to be a rapid and sensitive tool for the detection of oral anaerobic spirochetes in dental plaque.


Testicular cultivation of Treponema pallidum (Nichols strains) facilitated by sustained-release steroid administration.

Treponema pallidum cultivation is facilitated by substitution of methylprednisolone acetate suspension for hydrocortisone administration during rabbit testicular infection. Methylprednisolone suspension reduces testicular mononuclear cell infiltration and should benefit future studies of virulent T. pallidum.


Aerobically incubated medium for decarboxylase testing of Enterobacteriaceae by replica-plating methods.

An aerobically incubated, agar-based medium was developed for amino acid decarboxylase testing of Enterobacteriaceae family members by replica-plating methods. Results with the new medium agreed 97 to 99% with the reference broth method of Moeller, and no false-positive reactions were encountered.


Evaluation of bacteriological swabs and transport media in the recovery of group B streptococci on laboratory media.

The survival of group B streptococci on a variety of swabs, held either in their containers or in transport media for periods of up to 48 hours, at room temperature and at 4 degrees C, has been assessed. Results indicated that holding swabs in transport media did not favour prolonged survival of the streptococci and that the yield of organisms was much greater from swabs held in their ordinary plastic tubes. A holding temperature of 4 degrees C rather than room temperature is recommended if any delay in plating out swabs is anticipated.


Understanding death, dying, and the critically ill: a concern for speech-language pathologists.

The purpose of this article is to familiarize the speech-language pathologist with the behaviors that critically and terminally ill persons demonstrate. To work effectively with these groups of individuals, it appears essential that the clinician know the dynamics of the psychological stages associated with physical crisis, disability, death, and dying. This information is becoming more relevant to the speech-language pathologist, particularly as his/her role as a member of a rehabilitation team providing direct services to the aged expands.


Motivational factors in aphasia therapy: research suggestions.

Following Wepman (1953), the process of recovery from aphasia is seen as involving stimulation, motivation, and facilitation. The most adequate studies of aphasia therapy outcome focus on facilitation to the virtual exclusion of stimulation and motivation, although clinical experience suggests their importance. Motivation includes both the subjective and experiential aspects of the patient's response to aphasic disablement (anxiety, feelings of inadequacy) and the quality of the speech-therapist/patient alliance during the treatment. Retrospective studies utilizing sufficiently improved aphasics and ratings of the patient-therapist alliance are suggested as preliminary means of defining "motivation" in this context more accurately. Research approaches are also outlined which would assess the importance of and interaction between the three factors implicated in recovery for therapeutic outcome.


Projections of lamprey spinal neurons determined by the retrograde axonal transport of horseradish peroxidase.

The spinal cords of larval sea lampreys (Petromyzon marinus) and adult river lampreys (Ichthyomyzon unicuspis) were injected with horseradish peroxidase through a transection 1 cm caudal to the last gill. Some animals also had a spinal hemisection 1 cm caudal to the injection. After recovery periods of 1 to 52 days, the spinal cords were treated with diaminobenzidene and hydrogen peroxide, and the projections of various cell types determined in wholemount slides. From these observations the following conclusions were drawn. Most dorsal cells (primary sensory cells) are bipolar with a long rostral projection and a short caudal projection of no more than 5-10 mm. Both processes travel in the ipsilateral dorsal column. Their peripheral processes enter the dorsal roots as branches of their central axons. Some dorsal cells send processes out three or more dorsal roots both rostral and caudal to the cell body. Myotomal motoneurons have characteristic locations in the medial gray column and send prominent transversely oriented dendrites into the lateral columns. A few motoneurons are unusually large. In addition to giant interneurons the majority of smaller rostrally projecting interneurons also have decussating axons. A recently described cell type, the oblique bipolar cell, appears to have an exclusively crossed rostral projection. Although most edge cells project rostrally, as many as 20% may have a caudal projection or both rostral and caudal projections. Edge cells project equally to the ipsilateral and contralateral spinal hemicord, but their processes do not extend more than about 18 mm in sea lamprey larvae and 37 mm in adult river lampreys. Lateral cells project exclusively to the ipsilateral caudal hemicord. A few cells which resemble lateral cells in location and in possessing large lateral dendrites, project rostrally. However, these have atypical morphologic features which probably distinguish them from true lateral cells. Thus far, regardless of cell type, all decussating axons seem to pass ventral to the central canal, while decussating medial dendrites pass dorsally.


Congenital nevocytic nevi and malignant melanomas.

The subject of the relationship between congenital nevocytic nevi and malignant melanomas has many controversial aspects. Data are insufficient to come to firm conclusions concerning how often melanomas supervene in such nevi and to determine the prognosis of those melanomas. What data are available indicate that malignant melanomas develop in a substantial percentage of large (giant) nevocytic nevi. This lends support to those who recommend surgical excision of such large lesions, when feasible. On the other hand, the information currently available concerning the association of malignant melanomas with medium- and small-sized congenital nevocytic nevi (i.e., those less than 20 cm in larges diameter) is scanty. Because of this lack of data on congenital nevocytic nevi, our current approach is to take into consideration the probability of cosmetic improvement by surgical removal in conjunction with education of the patient and/or family that malignant melanomas have been known to occur in congenital nevocytic nevi but are probably rare except in nevi of large size. Such information provided to the patient and/or family will often help in making the decision for removal or continued observation. A Congenital Nevocytic Nevus Registry has been established in the Oncology Section of the Skin and Cancer Unit at New York University Medical Center in the attempt to begin a long-term prospective study which might eventually provide some meaningful information concerning the natural history of such lesions, including the incidence of malignant melanomas.


Use and abuse of systemic corticosteroid therapy.

Steroid-responsive acute dermatoses should be treated with a single morning dose of prednisone for approximately 2 weeks. It is necessary to "taper" a short course of oral prednisone given by this method. Chronic dermatoses should be treated whenever possible with prednisone used in the morning and on alternate days. This method is effective, is free of most side effects, and suppresses the HPA axis minimally. There are few real advantages in using intramuscular corticosteroids. TAC is an unusually strong suppressor of the HPA axis. For chronic dermatoses, a less suppressive preparation might best be chosen if the physician feels that the intramuscular route is the most reasonable one. In any event TAC should never be used more often than every two months. Finally, the time-course of HPA recovery following short courses of steroids is presently unknown. Nonetheless, some astute critics of steroid metabolism have felt obliged to advise us that individuals who have received from 1 to 4 weeks of suppressive steroid treatment should be suspect as to the integrity of their HPA axis in stressful situations for up to one year. The withdrawal from, as well as the use of, systemic corticosteroids requires a creative and critical physician.


The treatment of ulcers on legs with split-thickness skin grafts: report of a simple technique.

The placing of split-thickness skin grafts on chronic ulcers on legs in the usual way is tedious and time consuming. An effective technique that is simply and quickly done is described and illustrated herein. At least two weeks of hospitalization is required to insure complete healing.


Treatment of ulcers on legs from venous hypertension by split-thickness skin grafts.

Chronic ulcers on legs resulting from venous hypertension can be successfully managed by split-thickness skin grafts. Special attention must be paid to preliminary preparation of ulcers and to the period after grafting. Technical details of grafting are described and the results in 12 patients are recounted.


Differential ventilation in unilateral lung disease: effects on respiratory mechanics and gas exchange.

Conventional PEEP ventilation has been recently reported to be deleterious in some cases of ARF with unilateral pneumonia. In such respect, two cases of unilateral bacterial pneumonia were intubated with a Carlens tracheal tube. Measurement of tidal volume, static compliance, and functional residual capacity of each lung showed marked inequality. Subsequently, both patients were ventilated with a selective distribution circuit, allowing the introduction of a PEEP valve in the expiratory line of the diseased lung. Evident improvement in blood gases was obtained within 24 hours, as tidal volume, static compliance, and FRC of the diseased lung were markedly improved. In one case equalisation of V/Q ratio was documented using the 81m Kr method. Final recovery was obtained in one case.


Management of the low myopia pediatric patient.

A review of the literature on myopia etiology indicates that environmental factors, particularly those related to nearpoint use of the eyes, appear to play a significant role. A regimen is described for control of environmental factors producing myopic progression, including use of bifocal lenses to reduce accomodative demand, visual hygiene to foster accommodative relaxation, and vision training to develop adequate accommodative skills and freedom of action between accommodative and convergence systems.


Public choice in health: problems, politics and perspectives on formulating national health policy.

Development of health policy goals necessitates a choice among normative premises--an accommodation of conflicting values. Any debate that does not identify underlying assumptions or link policy prescriptions to a theoretical perspective is destined to degenerate into uncommunicative and unproductive rhetorical posturing. A sensible approach toward formulating national health policy requires that competing values be identified and discussed explicitly. This article will examine the effect that selection of different theoretical perspectives can have on the identification of problems and on the formulation of prescriptive policies in the health field. It will also focus on the different values that are promoted by different policy perspectives and consider alternative models for implementing value choices.


The design of failure: health policy and the structure of federalism.

This paper explores the impact of the federal structure of American government on health policy through the examination of three case studies of unsatisfactory policy: Medicaid cutbacks; provider licensure; and health planning under P.L. 93-641. Problems arise in three areas because of a disjunction between administrative or regulatory responsibilities and financial accountability. How the division of responsibilities among different levels of government might be managed better is examined briefly, in the context of possible state roles under a system of national health insurance.


Kallikrein localization in rodent salivary glands and kidney with the immunoglobulin-enzyme bridge technique.

Kallikrein has been localized in rodent kidney and salivary glands by means of an immunoglobulin-enzyme bridge technique. In sections of kidney, anti-kallikrein antibodies bound to the apical region of certain distal tubule segments in the cortex, to reabsorption droplets of proximal convoluted tubules, and to certain duct segments in the papilla. In salivary glands of both male and female rats and mice, and apical rim of most striated duct cells of submandibular, parotid and sublingual glands and granular tubules of submandibular glands exhibited immunoreactivity. Granular intercalated duct cells in female submandibular glands also displayed immunostaining for kallikrein. Phenylephrine administration resulted in loss of immunoreactive granules from the granular convoluted tubule cells of male mouse submandibular gland. This response was paralleled by a biochemically demonstrable decrease in kallikrein-like tosylarginine methyl ester (TAME) esterase activity.


Effect of colchicine on the immunohistochemical localization of somatostatin in the rat brain: light and electron microscopic studies.

Somatostatin (SRIF), the hypothalmic hormone which inhibits the secretion of growth hormone by the pituitary, has been localized immunohistochemically in the rat hypothalamus after intracerebral injection of colchicine. The number of cell bodies staining for SRIF was increased in the periventricular nucleus while the number of nerve fibers was decreased in the median eminence after treatment. The number of secretory granules containing SRIF in the nerve cell bodies was increased in the treated animals, suggesting a correlation between the number of specific secretory granules and intensity of the immunohistochemical reaction. These observations are in agreement with the hypothesis that SRIF cell bodies in the periventricular nucleus send their axons into the median eminence.


Skeletin immunoreactivity in heart Purkinje fibers from several species.

Ever since its discovery, the identification of the specialized conducting system of the heart has been a matter of debate. In some species, a main distinguishing feature under the electron microscope, as compared with ordinary myocytes, is the presence of large pools of juxtanuclear filaments, so called intermediate or skeletin filaments. In the present study, we have adopted the indirect immunofluorescence method and anti-skeletin antisera for the identification of the ventricular conducting system in several species. It was found that anti-skeletin reactivity generally exceeded that of ordinary myocytes. The degree of immunofluorescence could be related to a previous classification model of the differentiation of the conducting cells. It is suggested that skeletin is highly conserved throughout phylogeny and that anti-skeletin may serve as an additional tool for the identification of conducting cells at the light microscopic level.


Comparison between peroxidase-conjugated antigen or antibody and peroxidase-anti-peroxidase complex in a postembedding procedure.

The staining efficiency of peroxidase labeled immunoglobulin conjugate, used either as antigen or as antibody, has been compared with that of peroxidase-anti-peroxidase complex (PAP) on ultrathin sections of araldite embedded material. The conjugate gave positive results in a two layer method as well as in a three layer method when used as antibody. No staining was observed when it was used as antigen. The conjugation seemed to impair the antigenic reactivity of immunoglobulin. The conjugate when used as antibody in the three layer method gave approximately the same staining efficiency as PAP.


Fluorescent DNA probes for flow cytometry. Considerations and prospects.

Techniques employing base specific deoxyribonucleic acid (DNA)-binding fluorochromes and flow cytometry (FCM) are potentially useful for obtaining information of the compositional features of chromatin or chromosomes of mammalian cells. Fluorescent compounds which form complexes preferentially at the A-T rich regions (i.e., DNA-reactive Hoechst dyes) or the G-C rich regions (i.e., mithramycin, chromomycin, olivomycin) in DNA are available and compatible with current FCM technology as are other compounds (i.e., ethidium bromide, propidium iodide) which show little or no base specificity and bind by intercalation in the double stranded regions of helical DNA. Energy transfer between appropriate DNA-bound dyes is a reflection of the quantity and proximity of regions containing the respective base pair segments. Since extrinsic fluorescent probes provide only a measure of available binding sites or regions unobstructed by chromatin-associated or chromosomal-associated proteins, interpretations of fluorescence measurements need to be substantiated by adequate control measures.


Laser flow cytometry and cancer chemotherapy: detection of intracellular anthracyclines by flow cytometry.

The intracellular distribution of important chemotherapeutic antibiotics belonging to the anthracycline group (e.g. adriamycin) can be detected by laser flow cytometry. The indirect method is based on the interference of these compounds with the binding of propidium iodide to the nuclear DNA. While in the direct method, the intracellular fluorescence of these antibiotics is excited and detected with a laser beam in a flow system. The present report demonstrates the use of these two methods for intracellular detection and quantitation of a number of important anthracyclines.


A relaxation technique in the management of hypercholesterolemia.

Chronic sympathetic nervous system overactivity has been implicated as a factor capable of elevating and maintaining high serum cholesterol levels independent of dietary measures. We conducted a controlled trial to determine the effect of a relaxation technique. Transcendental Meditation, on serum cholesterol levels in hypercholesterolemic subjects. Serum cholesterol levels were measured at beginning and end of an 11-month period in 12 hypercholesterolemic subjects who regularly practiced meditation. Eleven hypercholesterolemic controls who did not practice the technique were similarly followed up for 13 months. Paired comparisons showed a significant (p less than 0.005) reduction in fasting serum cholesterol levels of those subjects who practiced meditation. These results suggest that the regular practice of a relaxation technique may contribute, most likely through a reduction in adrenergic activity, to the amelioration of hypercholesterolemia in certain subjects.


Radiocarbon (14C) migration and metabolism kinetics (a review).

Radiocarbon (14C) introduced into the biosphere as a result of nuclear explosions and operation of nuclear power stations has upset the equilibrium existing in nature. The increase in 14C concentration in the biosphere is a problem of considerable hygienic and social importance, since 14C affects all living organism in the world. This paper presents data on 14C migration and metabolism kinetics. Radiocarbon metabolism kinetics depends on the form of the chemical compound metabolized. Inorganic 14C compounds are metabolized relatively fast. Organic 14C compounds (carbohydrates, fats and proteins) are retained longer in the body. Differences in the metabolism kinetics of differents 14C compounds lead to the formation of unequal irradiation doses in various organs and tissues. In establishing standards for admissible 14C intake, one should take into consideration the kind of chemical compound in which the element is incorporated.


Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials.

The results of three serologically controlled double blind field trials in army units are presented. The evaluation of results according to morbidity, regardless of aetiology, showed a significant reduction in acute respiratory diseases (ARD) after administration of Impulsin. In the 1973 trial (901 volunteers), 22.7% of ARD cases were found in the Impulsin group contrary to 34.4% in the placebo group (P less than 0.0002). The relevant values in the 1974 trial (610 volunteers) were 19.7% and 40.7% (P less than 0.002) and in the 1975 trial (353 volunteers) 10.6% and 28.8% (P less than 0.004). The study of the immunological background in representative sets of volunteers allowed determination of the aetiology, the proportion of asymptomatic infections and possible deformation of results due to preexisting protective antibodies. Manifestation rate (MR) expressing the proportion of sick persons out of all sensitive subjects with serologically proved infection was found useful. This indicator is relatively independent of randomization and is more sensitive as compared to the incidence rate. In the 1973 trial, influenza A 2 England was prevalent, the MR of infection being 15.4% in the Impulsin group and 44.9% in the placebo group (P less than 0.0002). After elimination of persons with preinfection antibodies greater than or equal to 1:256 the corresponding values of MR were 17.6% and 46.6% (P less than 0.005), reflecting the "relatively clean effect" of Impulsin. In the 1974 trial, where influenza B Hong-Kong was prevalent, MR was 14.3% and 57.1%, respectively (P less than 0.001). Preinfection antibodies were negligible. The preliminary prophylactic index of the drug seemed to be 4.3 for combined adenoviral infections (trials 1973 and 1974 taken together). In the 1975 trial, the results of serological examination were unsatisfactory. Antibodies vs. influenza A Port Chalmers were found in 24.5% of ARD only. The differnce is aetiologically unclarified ARD was statistically significant. Although displaying a significant limitation of clinical infections, the administration of Impulsin did not seem to have any influence on the formation of antibodies.


Indication of antigens and antibodies using the reaction of compound immune adsorption and reactivation of the phage.

A method of determining antibodies by their adsorption on large-pore or surface immunosorbents with subsequent treatment of the carrier with anti-immunoglobulin serum and antiphage serum isologous to the antibodies and then with the bacteriophage has been presented. The adsorbed virions are split off by means of papain-induced hydrolysis of the antibody complex. The antigens are determined by the reaction of phage fixing inhibition. The method permits to determine small amounts of antibodies to proteins, haptenes and cells with objective calculation of results.


Role of bacteria in human carcinogenesis.

The bacterial hydrolysis of conjugated carcinogens, production of potential carcinogens from amino acid metabolism, formation of N-nitroso-compounds, and production of carcinogens from bile salt metabolism are discussed. The limited evidence implicating these compounds in the causation of bowel, gastric, bladder, biliary tract and cervical cancer is presented. Although there is no example of a proven role for bacteria in the causation of any human cancer, there are many leads currently under investigation. They have exciting implications for prevention.


Thermal characteristics of microtitre plates used in immunological assays.

Thermal studies of various types of microtitre plate have shown that wells at the edges of a plate have different thermal characteristics from those in the centre. This may contribute to the 'edge effect' observed when such plates are used as solid supports for protein immunobilisation in immunoassays.


Automation of enzyme-linked immunosorbent assay (ELISA).

A prototype of automatized enzyme-linked immunosorbent assay (ELISA) in tubes is described, using a commercially available basic material, easily modified. Nine hundred samples could be completely studied in a day by only one person. The different steps of the automatized ELISA were systematically studied to obtain the best performance. Its application is described in toxoplasmosis serodiagnosis.


A rapid, semi-automated procedure for the evaluation of leukocyte locomotion in the micropore filter assay.

A commerically available bacterial colony counter has been modified to allow rapid, accurate, semi-automated evaluation of cell numbers in the micropore filter assay for chemotaxis. The method is valuable for objective, rapid evaluation of cell counts at various levels through the filter, as well as counts on the distal surface of the filter. Coupled with a programmable calculator, this instrument had made feasible a new method of assessing random migration by the regression line analysis, which discriminates between migration rate and mass migration of cells. This combination of equipment may thus serve as a considerable time saving accessory to laboratories engaged in cell locomotion research, but also will allow more rigorous assessment of differences among specific populations of cells.


A technical improvement for crossed immunoelectrophoresis.

A simple antibody overlay technique for crossed immunoelectrophoresis is described. After the initial electrophoresis of antigens, the gel is overlaid with antibody-impregnated filter paper. This makes it necessary to pour only one gel, simplifying technique as compared with the conventional method.


Role of the H-2 complex in the homing affinity of injected lymphoid cells to the host's lymph nodes.

The role of H-2 and non-H-2 gene products was studied in a model of non-immune cell-cell interactions which underlie the homing affinity to lymph nodes of injected 51Cr-labelled lymph node cells. The effect of various donor-recipient combinations was tested by comparing the allogeneic/syngeneic ratio of radioactivity recovered from the lymph nodes. The homing affinity was reduced to about 50% when the donor-recipient incompatibility extended over the whole H-2 chromosome. When confined to a single region (H-2K, I or D) H-2 incompatibility caused no significant allogeneic inhibition of the homing affinity. The cumulative effect of two partial incompatibilities (K + I or D + I) was, however, reflected in a significant allogeneic inhibition. Non-H-2 incompatibilities had, as a rule, a weak effect; the non-H-2 gene products may not be directly involved in the cell interactions under test.


[Some studies on the ability appreciation of dental handpieces (author's transl)].

Dental handpieces are usually used for cutting teeth instruments of dental treatments. But as ability appreciation of cutting instruments are widely influenced with cutting tools and then these studies have scarcely been reported until now. This paper shows the one method of the ability appreciation of handpieces which are used for test bur as the cutting tools. Test apparatus used for ability appreciation are manufactured for trial as the same way as the dental treatments and experiments of handpiece are carried out. Handpiece test specimens are standard type (air bearing type) made by own country as basic characteristics and then compering with the ability of the type differences, standard, miniature, supertorque and air bearing type made by foreign country are experimented. These results of tests are examined the influence of service air pressure and load speed to be bases on the relation between push load revolution of test burs. And then equivalent efficiency of the works of handpieces are discussed for the experimental results of these characteristics.


[Studies on the cutting ability of dental diamond points--the trial manufacture of the cutting test apparatus (author's transl)].

Diamond points and tungstencarbite burs are used as the dental cutting tools for many appliance accordingly with the many purpose of used positions. Notwithstanding that the dental cutting tools have been usually applied for many purpose of dental treatment, the paper on these studies have scarcely been reported. In this studies the test of dental cutting tools curried out using the diamond points and examined these characteristics. As the problems on the cutting tests are the push load of cutting tools and the cutting quantities. This studies tried to make the test apparatus for the cutting test of dental diamond points considering to dental treatments. The glass plates used for photograph are used for cutting materials supposing to the enamel properties of teeth and the cutting tests put into practice for the types of diamond points with different diameter. The cutting characteristics of the diamond points are examined with the using of the test results and are appreciated with the considering to the test apparatus.


[Investigation of Pd-Ag alloy for porcelain fusing. (Part 2) Thermal expansion (author's transl)].

Thermal expansion coefficient and thermal expansion hysteresis (residual expansion after thermal cycles) were measured using nine Pd-Ag alloys (In and/or Sn added) prepared in Part 1. The following results were obtained. (1) The thermal expansion coefficients were ranged 13 approximately 15 x 10(-6)/ degrees C in the temperature range of 400 to 200 degrees C. (2) The effects of the addition of indium and tin to the thermal expansion coefficient depended on the concentration of palladium and silver. (3) The thermal expansion hysteresis was ranged from 0.21 to -0.02% third thermal cycle. It was very small in comparison with that of precious alloys. (4) The thermal expansion hysteresis decreased with increase of addition of indium and tin. (5) The thermal expansion coefficient had no correlation with the bonding strength.


[Flow of molten metal in denture base in horizontal centrifugal casting procedure. (Part 2) Flow, inflow volume and casting time of molten metal passing through several sprues into model denture plate mold (author's transl)].

Two types of spruing methods were used in the casting of the denture type model pattern (thickness, 0.43 mm). Flow of molten metal in the mold was filmed by the improved system of Part 1. When three sprues were attached to the pattern vertically, molten metal passed through each sprue gate flowed being affected by the direction of gravity and revolution of casting machine, and gathered at the lower part of the mold. Next molten metal filled the mold from the lower part to the upper part. In this spruing type, molten metal turned its direction of flow several times. At the middle stage of casting, the inflow volume per unit time (inflow rate), v (mm3/10-2)s)was evaluated as v = 12.36 + 5.16A-0.16 A2 (A: total cross-sectional areas of sprues). The inflow rate increased with increase of the area of the sprues, but it saturated. When the main sprue and the subsprues were attached at the posterior border, the molten metal filled the mold from the lower part to the upper part quietly. In this spruing type, the casting mold was set facing its sprue gates downwards. The inflow rate at the middle stage of casting was evaluated as v = 21.05 + 1.79 C (C: the cross-sectional area of the main sprue). The inflow rate increased linearly with increase of the area of the main sprue.


[Studies on the performance of the dental air turbine handpieces. (Part 1). Air pressure and bur length to be influenced over the rotational performance of the air bearing type handpieces (author's transl)].

Air turbine handpieces are used as the dental cutting instruments for the clinical use and many appliances. But, there are no studies on the performance of air turbine handpieces. So, this paper shows the rotational performance of air turbine handpieces which are influenced over the supplying air pressure and cutting bur length. Experimentally used air turbine handpieces is air bearing type and it's set up air pressure to be supplied is 3.5 kg/cm2. So, in this experiments, the range of air pressure is 1.8 approximately 3.5 kg/cm2, which is established five stages. And the bur length of the rotational parts is 5 approximately 9 mm with five steps. As the results, the rotational performance of air handpieces are influenced over these factors of the air pressure and the bur length. And air pressure to be supplied are influenced to be not only over the rotational speed but the load for the putting a stop to the revolutions.


Development of a solid-phase enzyme immunoassay for ursodeoxycholic acid: application to plasma disappearance of injected ursodeoxycholic acid in the rabbit.

A bile acid disappearance test using an enzyme immunoassay for ursodeoxycholic acid (UDCA) is presented. The immunoassay employs an antiserum produced in rabbits with UDCA coupled by amide linkage to egg albumin. An antigen (UDCA)-enzyme (beta-D-galactosidase) complex was prepared by adding the N-hydroxy-succinimide ester of UDCA to beta-D-galactosidase in a molar ratio of 5000:1. The anti-UDCA serum was coupled to glass beads and a competitive reaction between bile acids and UDCA coupled to the enzyme on the glass beads was measured by determining enzyme activity. One bead was used for each test tube. Thus it was convenient to wash and transfer the bead to a fresh test tube after incubation. The procedure requires 2.5 hr at 30 degrees C for the competitive reaction and enzyme assay. Using a 1:100 dilution of anti-serum, the intensity of fluorescence of 4-methylumbelliferone produced from 4-methylumbelliferyl-beta-D-galactoside by the enzyme decreased linearly with a logarithmic increase of UDCA concentration over a range of from 0.1 to 10 pmnd taurine conjugates, and good recovery data were obtained. The development of the enzyme immunoassay using glass beads shortens analysis time; furthermore, the method makes it possible to detect obstructive jaundice in rabbits before the serum bilirubin level is elevated.


Variation in size of the 'readily releasable pool' of luteinizing hormone during the oestrous cycle of the rat.

The size of the 'readily releasable pool' of luteinizing hormone at various times of the oestrous cycle has been determined by injecting a supramaximal dose of luteinizing hormone releasing factor (LH-RF) i.v. into rats anaesthetized with sodium pentobarbitone. In an attempt to block replenishment of the 'pool' during release, cycloheximide was administered 30 min before LH-RF. A 20-fold increase in pool size occurred between the morning of dioestrus and the evening of pro-oestrus in the absence of any significant change in total pituitary content of LH. This suggests that increased responsiveness may be brought about by a change in the receptor-release apparatus and/or a transfer of LH from a 'storage pool' which leads to an apparent increase in the proportion of LH available for release.


Use of a pulsed infusion of luteinizing hormone releasing hormone to mimic seasonally induced endocrine changes in the ram.

Adult Soay rams were housed indoors under natural lighting during the spring non-mating season when gonadotrophin secretion was low. Four animals received small doses (100 ng or 500 ng) of synthetic LH releasing hormone (LH-RH) infused into the jugular vein by a mechanical device for 60 s every 2 h for 33-57 days: two other rams acted as controls. The prolonged treatment with LH-RH resulted in growth of the testes and the development of the sexual skin flush; these effects were lost when treatment stopped. The plasma concentrations of LH, FSH and testosterone were low at the beginning; each short infusion of LH-RH resulted in a transitory increase in the level of LH and testosterone while the concentration of FSH was only marginally affected. After prolonged treatment with 500 ng pulses of LH-RH the plasma concentrations of all three hormones were permanently raised. The response to the individual injections of LH-RH was also modified, the peak in LH being reduced in amplitude but more prolonged while the FSH and testosterone responses were both enhanced. When the pulsed infusion was stopped the concentration of LH and testosterone declined rapidly while the decline in FSH levels took many days. These endocrine changes induced by the pulsed infusion are comparable to those that occur naturally in the ram during testicular redevelopment before the mating season.


Cellular localization of a prolactin-like antigen in the rat brain.

The distribution of immunoreactive neurones and fibres was studied in rat brain using an antiserum to rat prolactin. Neurones containing the immunoreactive material were localized in the arcuate, ventromedial, premamillary, supraoptic and paraventricular nuclei of the hypothalamus. Immunoreactive nerve fibres were widely distributed within the brain. No differences were observed in labelling between male and female rats, or as a consequence of hypophysectomy.


Application of agarose gel electrophoresis to the characterization of plasmid DNA in drug-resistant enterobacteria.

A simple gel electrophoresis method has been described for the detection of plasmid DNA in bacteria (Meyers et al., 1976). We investigated further the problems encountered in using this method for the analysis of plasmids in wild enterobacterial strains. The migration of open circular and linear plasmid DNA was examined, since these forms sometimes caused difficulty in the interpretation of the plasmid content of uncharacterized strains. Electrophoresis at different agarose concentrations was employed to resolve clearly plasmid DNA from the chromosomal DNA fragments in the crude preparations. Dissociation of some plasmids occurs in Salmonella typhimurium, and this was detected by electrophoresis. The technique was applied to the study of drug-resistant strains of S. typhimurium phage type 208 from several Middle Eastern countries. The cultures carry a drug resistance plasmid of the FIme compatibility group, and at least two other plasmids which were detected and identified by gel electrophoresis. The studies supported and extended the genetic findings and provided information on the distribution of particular plasmids.


Peptide transport in Candida albicans.

The tripeptide L-methionyl-L-methionyl-L-[METHYL-14C]methionine was taken up into Candida albicans by a saturable system with a pH optimum of 3.5, a temperature optimum of 37 degrees C and an apparent Km of 3.3 x 10(-5) M. Metabolic inhibitors such as sodium azide and dinitrophenol completely prevented uptake. Neither methionine nor dimethionine effectively competed with trimethionine uptake. (Leu)3, Gly-Met-Gly, acetyl-(Met)3, D-Met-L-Met-L-Met and Met-Met-Ile effectively competed with (Met)3 uptake, whereas (Lys)3, L-Met-L-Met-D-Met, D-Met-D-Met-D-Met, (Met)3 methyl ester and (Ala)3 did not. Trimethionine was rapidly hydrolysed by a peptidase after entry into the cell.


A solid-phase immunosorbent technique for the rapid detection of rubella IgM by haemagglutination inhibition.

The rubella haemagglutination inhibition (HAI) test has been modified for the detection of rubella-specific IgM. The rubella HAI test is performed in microtitre plate wells in which IgM from patients' sera has been selectively retained by anti-human IgM bound to the polystyrene surface. The test requires only anti-human IgM-coated microtitre plates, in addition to the standard rubella HAI reagents. The results obtained in this test, a solid-phase immunosorbent technique (SPIT), are in good agreement with results obtained by the sucrose density gradient centrifugation technique (DGCT). Advantages include the essentially unrestricted number of sera which can be tested daily, the availability of results within 24 h and the lack of interference by rheumatoid factor and by rubella-specific IgG.


The sensitivity of measles virus haemolysin to acetone and the preparation of mono-specific human anti-haemolysin by absorption.

The haemolysin of measles virus, either in the virion or in infected cells, is functionally and antigenically sensitive to acetone. Absorption of human sera with acetone-treated, measles virus-infected cells removes antibodies to all measles virus structural antigens except haemolysin. The antibody titres of absorbed sera give good correlation in HLI, neutralization and fluorescent antibody staining on unfixed infected cells.


Formation of DNA-damaging and mutagenic activity in the reaction systems containing nitrite and butylated hydroxyanisole, tryptophan, or cysteine.

It was confirmed by the procedure of rec-assay that DNA-damaging activities were formed in the reaction systems containing nitrite and phenol derivatives including BHA, tryptophan or cysteine under gastric pH conditions. The mutagenic action of the nitrite-BHA, nitrite-tryptophan and nitrite-cysteine systems was also tested according to Ames' method using Salmonella typhimurium TA 1535 and TA 98. The mutagenic activity was observed in the nitrite-tryptophan and nitrite-cysteine systems, though the nitrite-BHA system did not show the activity. The DNA-damaging products were generally labile, i.e., the activity decreased significantly after 1.5 to 2 hours of the reaction, except in the case of the nitrite-BHA system. The DNA-damaging activity in the nitrite-BHA system did not decrease even after 48 hours of the reaction. Nitrosophenol derivatives themselves showed the DNA-damaging activity at pH 1. The active product in the nitrite-BHA system was isolated and the structure was determined to be 2-tert-butyl-quinone. This compound gave a positive rec-assay test, and showed no mutagenesis by Ames' method. The active product from the nitrite-cysteine system was infered to be nitrosocysteine, and the product showed both DNA-damaging and mutagenic activity.


The case for Victor A. Reko--an unrecognized pioneer writer on New World hallucinogens.

Victor A. Reko's book Magische Gifte, in which he recorded a number of original observations on New-World psychotropic drugs including the first modern recognition that teonanácatl was a mushroom and not a cactus, was well received when it first appeared in 1936. However, his contributions to the literature of this and other obscure plant hallucinogens such as ololiuqui and sinicuichi, have not received the recognition they deserve. His writings, evaluated objectively on the bases of modern scientific knowledge and historical evidence, establish Reko as an important pioneer in this field and show his accomplishments worthy of acclaim.


An ultrastructural and immunohistochemical study on the delta antigen associated with the hepatitis B virus.

Thirteen liver biopsies in which the delta antigen was detected by immunofluorescence were studied by electron microscopy and immune electron microscopy with peroxidase labelled IgG and F(ab1)2 fraction obtained from a human antiserum containing high-titre anti-delta antibodies. The findings were compared with those obtained in 11 HBcAg positive and in two HBsAg negative controls. Neither unique particulate morphology nor any HB virus ultrastructural component were visualised in the delta positive specimens; 20-23 nm naked core particles were observed in 10 of 11 biopsies displaying the HBcAg in immunofluorescence. Delta positive nuclei frequently contained dense round structures of diameter varying between 20 and 30 nm with a soft indistinct edge. These granules did not exhibit characteristic ultrastructural features which enabled them to be distinguished from other granular material observed occasionally in nuclei of normal and diseased livers. However, their association with the delta antigen has been proved by the deposition on identical structures of peroxidase labelled anti-delta antibody. These results suggest that the delta antigen is unrelated to the Dane particle, the putative HB virus. The granules observed in the delta positive nuclei are composed of an amorphous matrix, possibly insoluble aggregates of the delta antigen.


Action of gold thioglucose on pericapillary structures in the ventromedial hypothalamus.

The administration of GTG to mice leads to death of all structures in a circumscribed area of the VMH as a result of loss of blood circulation. The loss of circulation is due to damage by GTG of neural processes adjacent to some of the capillaries in this area; damage to these processes leads to abnormal capillary permeability. Pericapillary damage occurs under conditions where capillary damage and consequent necrosis are prevented. Abnormal capillary permeability appears to follow release of a vasoactive substance from the damaged neural processes. Damage to the pericapillary neural processes by GTG is insulin-dependent and is counteracted by glucocorticoids.


Mediation by serotonin of gold thioglucose-induced necrosis of the ventromedial hypothalamus.

Agents that lower serotonin levels or inhibit serotonin action prevent GTG-indurea and that such damage leads to abnormally increased capillary permeability. Since the VMH is rich in serotonin and since serotonin is a potent oedema-producing agent mice, these findings indicate that the production of necrosis by GTG is mediated by release of serotonin from the damaged pericapillary processes.


The detection of a contractile apparatus in murine multinucleate giant cells.

Cinemicrographic investigations have shown multinucleate giant cells to be motile and contractile while immunofluorescent and biochemical studies have demonstrated the presence of actin-like proteins. These contractile proteins are concentrated in the centrospheric and perinuclear regions, while a more streaky distribution is present in the more peripheral parts of the polykaryon. This distribution corresponds with that of cytoplasmic filaments measuring 6-7 nm as seen by electron microscopy. The presence of similar proteins in macrophages, the precursor cells of multinucleate giant cells, indicates that these contractile proteins continue to be produced after macrophage fusion and that they are reorganised within the structural arrangements of the syncytium.


Relationships between Hand Test variables and mental retardation: a confirmation and extension.

Eighty-one mentally retarded individuals, including a range of deficiencies (severe, moderate, and mild), were given the Hand Test in order to investigate the relationship between IQ and personality. There were significant correlations between Hand Test personality variables and IQ and different subgroup configurations were noted. Implications of the results are discussed.


Pediatric keratoplasty: problems in management.

A summary of experience in pediatric keratoplasty is given by adding ten recent cases to a previous report. A review of keratoplasty in infants and children from the literature generally recommends the procedure as safe and effective. Recent reports, however, cast some doubt on the effectiveness of the procedure for certain conditions. An update of experience is given as a focal point for a discussion of problems in clinical management of children who undergo keratoplasty. These problems are arbitrarily separated by pre-, intra-, and postoperative time frames.


Morphological characteristics of lateral rectus motoneurones shown by intracellular injection of HRP.

The morphology of identified lateral rectus motoneurones is described after staining by intracellular iontophoresis of horseradish peroxidase. Soma vary in shape and size according to the number and orientation of primary dendrites. The basic pattern of arborisation shows short primary dendrites which branch close to the soma, forming a distal ramification extending over 600 to 1,200 micrometer from the soma. Distal dendrites extend into the ipsilateral medial vestibular nucleus, the reticular formation and amongst the fibres of the medial longitudinal fasciculus. This extension is greater than that previously seen in procion yellow and Golgi stained lateral rectus motoneurones. The axon originates from the perikarya or from the base of a primary dendrite. No axon collaterals have been observed.


A randomized controlled trial of aspirin in the prevention of early mortality in myocardial infarction.

A randomized controlled trial is reported in which a single dose of aspirin (300 mg) was given to patients with myocardial infarction on first contact with a general practitioner. A total of 1,705 patients with confirmed infarction were studied, and survival ascertained. There was no evidence of benefit from the aspirin.


The evidence that inhibin must exist.

The historical development of the 'inhibin' hypothesis is restated and the recent evidence reviewed. The circumstantial evidence for inhibin now seems very strong, and it probably acts in both sexes. Active materials have been isolated from several sources but it is not clear which is the circulating form of inhibin and a reciprocal relationship between circulating inhibin and FSH levels has not yet been demonstrated. Nevertheless, it appears that we may be optimistic about the existence of inhibin though the importance of its role as a physiological feedback inhibitor is still controversial.


Inhibin production by Sertoli cells in culture.

Studies on the secretion of inhibin and its mode of action were carried out in vitro, utilizing cell cultures. Isolated rat Sertoli cells secreted an inhibin-like heat-labile, non-dialysable substance, Sertoli Cell Factor (SCF), which could selectively suppress FSH secretion by rat anterior pituitary cells. SCF selectively suppressed the basal and GnRH-stimulated FSH release as well as the de-novo synthesis of FSH by acting directly on the pituitary cells. In 1 out of 5 experiments, SCF also suppressed the synthesis of LH, possibly by affecting the overall protein synthesis. Under similar culture conditions, Sertoli cells isolated from animals between 18 and 90 days of age secreted comparable amounts of SCF. In contrast, anterior pituitary cells from adult rats (60-90 days old) were considerably more sensitive to SCF than pituitary cells obtained from younger (18-33 days old) animals, suggesting that decline in circulating FSH level, occurring at approximately 35 days of age, may result from increased pituitary sensitivity to inhibin. Besides identifying the Sertoli cells as the site of inhibin production in the testis, these studies demonstrated direct action of inhibin at the pituitary cell level, resulting in suppression of FSH synthesis and release.


Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2 alpha. An overview of 815 cases.

The use of intramuscular (15S)-15-methyl prostaglandin F2 alpha (Prostin/15 M [The Upjohn Company, Kalamazoo, Michigan] sterile solution; carboprost tromethamine) for termination of pregnancy between six and 24 weeks' gestation was studied by 20 investigators. Of 815 women treated according to the dosage regimen described here, 78.4% had complete abortions and 18.0% incomplete abortions, for an overall success rate of 96.4%. The majority of patients had vomiting and diarrhea but usually tolerated these side effects well enough that treatment did not have to be discontinued. There were no serious adverse reactions directly attributable to the prostaglandin therapy.


Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene.

A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward S. typhimurium TA 100. The compounds prepared were 5,11-dimethylchrysene (2), 5-(hydroxymethyl)chrysene (3), 5-(acetoxymethyl)chrysene (4), 5-carbomethoxychrysene (5), 5-(hydroxymethyl)-1,2,3,4-tetrahydrochrysene (6), 5-carbomethoxy-1,2,3,4-tetrahydrochrysene (7), and 5H-chryseno[4,5-bcd]pyran-5-one (31). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3--7 were less mutagenic than 1; 31 was highly mutagenic. The mutagenicity of 1 and 2 contrasts with the low activity of 5,12-dimethylchrysene, which supports the generalization that the structural requirements favoring activity are a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The low activity of 3--7 indicates that methyl oxidation is not an important activation process for 1. This agrees with previous studies in which the major proximate mutagen and carcinogen of 1 was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene.


2-Acetylpyridine thiosemicarbazones. 2. N4,N4-Disubstituted derivatives as potential antimalarial agents.

The most effective antimalarial agents among the N4-monosubstituted 2-acetylpyridine thiosemicarbazones recently described by us have a cyclohexyl or a phenyl substituent and produce cures in Plasmodium berghei infected mice at a dose of 160 and 320 mg/kg, respectively. We report here on a related series of N4,N4-disubstituted 2-acetylpyridine thiosemicarbazones. Several members of this group bearing alkyl or cycloalkyl substituents at N4 show activity superior to the most active monosubstituted 2-acetylpyridine thiosemicarbazones. However, the greatest improvement in potency was seen when the N4-nitrogen atom was incorporated into a six- or seven-membered ring, such as the piperidine, piperazine, or azabicyclo[3.2.2]nonane systems, to give compounds with curative properties at a dose level as low as 20 mg/kg.


Increasing dose of naproxen in rheumatoid arthritis: use with and without corticosteroids.

A group of 50 patients with rheumatoid arthritis (half of whom received prednisone for 12 weeks before and then during the study) participated in a double-blind trial evaluating the efficacy and safety of 3 dosages of naproxen (125, 250, and 500 mg b.i.d.). Increasing dosages of naproxen were associated with increasing levels of therapeutic response and increasing serum levels of naproxen with no evidence of toxicity. Corticosteroid patients did not exhibit the same pattern of increasing levels of efficacy. The study demonstrates a dosage-related increasing pattern of efficacy for naproxen up to 1,000 mg/day, a pattern not yet demonstrated for the other non-steroidal antinflammatory drugs.


Cephalosporin derivatives with 2- and 4-pyridone groups at carbon-3.

Two compounds, analogues of cephalexin with 2- and 4-pyridone groups at C-3, were prepared. Biological evaluation found the compounds to exhibit activity against Gram-positive and Gram-negative organisms in vitro and in vivo. The compounds were only active in vivo on subcutaneous administration.


Results of combined amphotericin B-5-fluorcytosine therapy for prosthetic knee joint infected with Candida parapsilosis.

A prosthetic knee joint became infected with Candida parapsilosis, apparently introduced by arthrocentesis. The infection was quite indolent, present for several months before treatment. Although the joint fluid contained antibiotic concentrations in excess of the organism's minimum inhibitory concentration, medical therapy failed, and cure required removing the prosthesis and fusion of the knee.


Complement fixing antibodies to DS-DNA in systemic lupus erythematosus: a study using the immunofluorescent Crithidia luciliae method.

Crithidia luciliae, a hemoflagellate, was used in an immunofluorescent procedure to assay for antibodies to ds-DNA and their capacity to fix complement. Positive reactions with this method were limited to systemic lupus erythematosus patients, and sensitivity was comparable to the DNA binding assay. Complement fixing activity of antibodies to ds-DNA in 45 sera was determined using kinetoplast ds-DNA of Crithidia luciliae and an antiserum to C3. Complement fixing antibodies to ds-DNA were found in nearly all patients with documented active renal involvement and absent in nearly all patients with no, or inactive renal involvement.


Search for Reiter's syndrome after an outbreak of Shigella sonnei dysentery.

Forty-seven % of 4,205 individuals living in a Puerto Rican community developed Shigella sonnei dysentery. Questionnaire and, where relevant, clinical evaluation of 1,970 patients and the remaining 2,235 unaffected residents disclosed no cases of Reiter's syndrome (RS). Among the possible explanations for failure to observe any cases is the important suggestion that S. sonnei is not arthritogenic.


Estimation of tubule or cylinder LV, SV and VV on thick sections.

The estimators of tubule or cylinder LV = 2NA, SV = 2IL, and VV = PP are considered in terms of bias due to section thickness, diameter, overlap, and grazing or fuzzy profiles. The superiority in a number of cases of the indirect estimation of SV and VV as functions of LV and profile diameter is discussed. Statistical aspects are dealt with in a practical example.


Evaluation of IgG molecules, Fab' fragments and IgG-horseradish peroxidase conjugates as surface labels for freeze-etched membranes.

Sheep red blood cell (SRBC) ghosts were incubated with preparations of anti-SRBC IgG, antigen-binding fragments of IgG (Fab') or IgG coupled to horseradish peroxidase (HRPO). Frozen samples of the labelled ghosts were deep-etched and replicated with platinum-carbon to visualize their surface features in the transmission electron microscope. The surfaces of control ghosts contain a very low number of 'background' particles (42 +/- 8 particles/micron 2) that vary in size from 4.5 to 25 nm. After labelling with whole IgG the density of surface particles (average diameter 12.3 nm) increases dramatically to 480 +/- 54 per micron 2. Fab'-labelled ghosts exhibited both significantly fewer (87 +/- 14 particles/micron 2) and smaller (average diameter 9.8 nm) surface particles. Ghosts labelled with IgG-HRPO conjugates possessed 590 +/- 45 particles/micron 2 with an average diameter of 15.3 nm. When these ghosts were incubated with diaminobenzidine and hydrogen peroxide the average size but not the density of the particles increased. Based on these and other observations we conclude that an organic surface marker for freeze-etched membranes has to have a diameter of greater than 15 nm if it is to be consistently seen over extended areas and against the background granularity of the surface of a red blood cell ghost. Somewhat better resolution may be expected if markers consisting of inorganic crystals with a distinct shape and coupled to Fab' fragments can be made.


On defining the thermal history of cells during the freezing of biological materials.

An explicit numerical finite difference scheme for defining the thermal history of a cell or group of cells contained within a biological sample of prescribed shape is described. Solutions are presented for three different cases of freezing of biological materials prior to microscopic examination. It is concluded that a surface boundary condition must be specified in any experiment before cell ultrastructure or viability can be related to thermal history or cooling rate.


A new light microscopic method for the synchronous bidirectional illumination and viewing of living cells in different contrast modes, and/or at different focal levels or magnifications.

A new method of light microscopy for the analysis of the behaviour of living cells in vitro exploits two objects for simultaneous image formation, each serving the other as a condenser. Simultaneous viewing from opposite sides allows the specimen to be examined at: (a) two different magnifications, permitting the locomotion of whole cell (groups) to be studied at a low magnification and details of interaction of colliding surfaces at a high magnification; (b) two different focal levels, permitting, for example, details near the substrate surface to be recorded at the same time as information concerning the behaviour of the free, dorsal surface; and (c) two different contrast modes, such as negative and positive phase contrast, and dark and bright field illuminations. These possibilities can be combined, for example, to contrast a high magnification view in negative phase contrast at one focal level with a low magnification image in ordinary brightfield at another focal level in the same living cells.


Metabolic inhibitors and subcellular distribution of GABA.

Experimental procedures are described which are believed to yield results that reflect, within certain limits, the in vivo changes of the size of the GABA pool in nerve endings in comparison with those of all other GABA pools. Two irreversible GABA-T inhibitors, vinyl GABA and acetylenic GABA, two GAD inhibitors, 3-mercaptopropionic acid and pyridoxal phosphate glutamyl-gamma-hydrazone, and di-n propylacetate, a clinically useful anticonvulsant, have been studied to determine their effects on GABA compartmentalization in mouse brain cortex. The changes elicited by these drugs in subcellular fractions of brain cortex homogenates support the notion that measurement of amino acid concentrations in crude synaptosomal fractions and in supernatant fractions under controlled conditions allow one to draw conclusions about relative changes of pool sizes in vivo. In particular this work showed that a specific increase in the concentration of GABA within the nerve endings is more important than a large increase of total brain GABA as a means of decreasing susceptibility to a variety of chemically or physically induced seizures.


Isolation of pathogens other than Yersinia pestis during plague investigations.

From 1975 to 1978, 37 isolates of Pasteurella multocida, 1 of Salmonella enteriditis, and 5 of Francisella tularensis were recovered from 42 mammalian specimens and 1 flea pool submitted for examination for evidence of infection with Yersinia pestis. Most of the specimens were collected during investigations of either a human plague infection or a reported epizootic among rodent populations. All specimens were of species regularly or occasionally involved in plague or tularemia cycles in nature and most were collected in areas of known plague or tularemia activity.


[Methods for registration of vital parameters and longtime control in neonatologic intensive care].

The authors report about their experiences in the bed-side monitoring and registration of different vital parameters by means of apparatuses produced in GDR. The following parameters were recorded: electroencephalogram, myogram, electrocardiogram, phonocardiogram, electrocardiotachogram, respirogram, tidal volume, flow-volue and esophageal pressure. Special attention was payed to the problems of electrodes and the practical construction of the systems for the discontinuing and the continuing registration in order to realize an automatical trend-analysis and data-documentation in a neonatal ICU.


[Embryonal alcohol syndrome ].

The permanent alcohol abuse of a pregnant woman is of high risk for the embryo especially during the first weeks of pregnancy. It is prerequisite to the embryonic alcohol syndrome that the ethylalcohol passes the placenta. Subsequently hypotrophic infants with multiple malformations of minor and major quality are born. Part of the malformations are characteristic, part of them are unspecific for the disease. They altogether represent the entity of the embryonic alcohol syndrome. Occurrence and intensity of the disease depend on the daily quantity of pure alcohol, especially during the first month of pregnancy, on the level of non-metabolized ethylalcohol in the mother's blood, and on the stage of the maternal alcohol disease according to Jellinek. To prevent the embryonic alcohol syndrome means to prevent the maternal chronic alcohol abuse.


[Operative treatment of spastic entropion with the A. M. Vodovozov procedure (author's transl)].

Vodovozov's operation was performed in 37 cases of spastic entropion. The functional effect was always lasting and the cosmetic outcome good. Not one relapse was seen. The operation can be used in acquired and in congenital forms of entropion.


[Development of the retrocorneal membrane following penetrating keratoplasty (author's transl)].

The results of 57 cases with retrocorneal membrane following penetrating keratoplasty are reported and discussed with regard to their clinical and histopathological pictures and pathogenesis.


[Fatal complications following the implantation of artificial lense (author's transl)].

The number of cataract operations with implantation of artificial lenses has been increasing in recent years. However, there is hardly any information available concerning possible serious consequences. While there are detailed reports on histopathological findings following conventional cataract operations, fatal complications of this technically complex intervention are only mentioned occasionally. There were 9 cases with serious complications in our polyclinic in 1976, and this report deals with the histopathological findings in 6 enucleated eyes. The authors warn against ill-considered decisions to perform a lens implantation.


[Efficacy and safety of long-term maintenance treatment with timolol ophthalmic solution in chronic open-angle glaucoma (author's transl)].

Timoptol Ophthalmic Solution (timolol maleate, MSD) is a topical beta-adrenergic receptor blokking agent which lowers elevated intraocular pressure when applied once or twice daily. It represents a major advance in topical therapy for glaucoma and elevated intraocular pressure. It is more effective in reducing elevated intraocular pressure and produces fewer side effects than pilocarpine and epinephrine. It does not alter pupil size or affect visual acuity. Timoptol maintained satisfactory reductions in intraocular pressure in long-term maintenance studies treating over 100 patients for up to 16 months. The drug was well tolerated and without serious adverse effects. In general, reductions in intraocular pressure for non-white patients (predominantly Blacks) were similar to the Whites.


[Optical properties and clinical performance of the Topcon retinal camera TRC-FET 3 (author's transl)].

A Topcon Retinal Camera TRC-FET 3 was tested for several weeks under laboratory and clinical routine conditions. The optical properties turned out as good and meet the requirements for retinal cameras in all details. Remarkable is the high speed of the imaging system, which allows working with low flash energies and with high flash frequency. The resolving power is high (8 microns at the center) and decreases slowly to the periphery. The illumination of the fundus is fairly homogeneous. Many filters of good performance are provided. There was no problem in handling the camera, and the test photographs as well as the clinical routine photographs were of high quality.


Renal transport of amino acids.

According to recent experimental data the renal transport of amino acids (AA) is characterized as follows. 1. Kinetics: Several reabsorption systems remove AA from the tubular fluid by active transport with Michaelis-Menten type kinetics. Passive diffusion does play only a relatively small role in reabsorption, but determines the pump leak steady state concentration at the end of the tubule. 2. Stereospecificity: Except for aspartate the naturally occurring L-analogs show a much larger affinity to the transport "carriers" than the D-isomers do. 3. Specificity: Separate transport mechanisms exist for a) the "acidic" AA (Glu and Asp); b) the "dibasic" AA (Arg, Lys, Orn); c) cystine/cystine; d) the "imino" acids (Pro, OH-Pro and other N-substituted AA); e) the beta- and gamma-AA (beta-Ala, GABA, Taurine); f) all other "neutral" AA. For the group (d) and maybe also for (b) and glycine additional low capacity/high affinity systems exist. 4. Localization: Except for glycine and taurine under normal conditions more than 80% of the filtered load are reabsorbed within the first third of the proximal tubule. At an elevated load the rest of the proximal tubule (including pars recta) but not the distal nephron is included into the reabsorptive process. AA are also taken up from the peritubular blood. 5. Energy sources: At least the main part of AA uptake at the brushborder membrane is dependent from a transmembranal Na+-gradient which in turn is established by the ATP driven Na+-pumps at the basolateral side of the cell (Secondary active transport or co-transport of AA). 6. Biochemistry: The biochemical nature of the AA-"carriers" is unknown. The recent hypothesis than a "gamma-glutamyl cycle" plays a major role in this context has been disproved to great extent. 7. Peptides: Oligopeptides (Angiotensin, Gluthathion) filtered at the glomerulum are hydrolyzed by brushborder peptidases within the tubule lumen. The splitting products, the free constituent amino acids, are reabsorbed subsequently by their respective transport systems.


[Role of erythropoietin deficiency in the pathogenesis of renal anemia].

A review is given of clinical studies performed by use of a highly sensitive in-vitro erythropoietin assay (fetal mouse livercell culture) in large patients' populations to clarify the controversial role of erythropoietin deficiency in the pathogenesis of renal anemia. Studies involved a.) patients with chronic renal disease and varying degree of renal insufficiency in the predialysis phase b.) non-nephrectomized and anephric patients on regular hemodialysis treatment. The data available demonstrate that the initial phase of renal anemia is accompanied by a compensatory increase of serumerythropoietin concentration and therefore erythropoietin deficiency has to be excluded as a primary cause of the anemia of renal failure; merely a relative lack of erythropoietin seems to exist. In the terminal phase of renal failure, erythropoietin deficiency becomes absolute, such in 50% of the investigated non-nephrectomized hemodialysis patients and in all anephric patients. However in individual patients even in terminal renal failure a sustained regulatory feedback mechanism between serumerythropoietin concentration and hematocrit, probably working at lower hematocrit level, could be demonstrated.


[Renal kallikrein-kinin system and control of blood pressure (author's transl)].

Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.


Salivary kallikrein excretion in hypertension.

According to immunohistochemical investigations kallikrein in the majors salivary glands is located predominantly at the apical border of the striated duct cells and as a luminal rim in the main excretory ducts. Comparatively the highest concentrations are observed in the submandibular gland of rats and cats in the cytoplasmic granules of the granular tubules. In normal humans and rats the kallikrein activity of parotid saliva is inversely related to flow rate and sodium concentration. An increased salivary kallikrein concentration is found in human essential hypertension and renoparenchymal hypertension associated with impaired kidney function. Furthermore in rats with various forms of hypertension (genetic hypertension, DOCTMA salt and renovascular hypertension) the salivary kallikrein secretion - as determined by the BAEE-esterase activity - is enhanced. In contrast to the kallikrein secretion the flow dependent sodium concentration of parotid saliva is reduced in human essential and renoparenchymal hypertension as well as in rats with various forms of experimental and genetic hypertension, which indicates an enhanced sodium reabsorption in the glandular duct system. Furthermore in most forms of hypertension, there is a tendency of higher potassium levels in the saliva. The pathogenesis of the enhanced glandular kallikrein secretion in hypertension is discussed with regard to a counterregulatory mechanism in hypertension as well as to a sympathicoadrenergic activation. The enhanced sodium reabsorption in the duct system in the various forms of hypertension could be the cause as well as a consequence of the enhanced kallikrein secretion.


[Vitamin D metabolism in kidney insufficiency: disorders of an endocrine regulatory zone].

The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss. In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3. Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients. A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3. Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for the therapeutic suppression of the parathyroids of uremic patients. Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.


Role of parathyroid hormone in the pathogenesis of the uremic manifestations.

A multitude of clinical and experimental data points toward the role of the elevated blood levels of parathyroid in the pathogenesis of the uremic syndrome. The possible pathways through which parathyroid hormone may exert its deleterious effects and evidence for its toxicity are discussed.


[Principles of epithelial transport in the kidney and intestines].

Epithelia of kidney and small intestine consist of one layer of cells which, at their luminal edge, are linked together by terminal bars. Solute transport proceeds either across the cells, which is true of all active transports, or it proceeds paracellularly through the basolateral spaces and terminal bars and is then passive. The driving force for the active transport of a substance is derived either directly from metabolism (primary active transport), or from the gradient of another solute, usually Na+, which in turn is created by primary active transport. In the latter case the transport is referred to as secondary active. The driving forces of passive transport are the electrochemical gradient of the respective substance and solvent drag. The proximal parts of the kidney as well as of the intestine are leaky so that a considerable part of net reabsorption proceeds passively. Their distal parts, however, where the transport is regulated, are tight so that large concentration differences can be created and maintained. Transcellular active transport is only possible if the cells are polar, i.e., the transport characteristics of the luminal cell membrane differ from those of the contraluminal cell membrane. By measuring the cellular electrical potential difference or by measuring transport into isolated plasma membrane vesicles from either cell side the driving forces for the two transport steps, the luminal and contraluminal, have been elucidated. Schemes for the transport steps in the proximal tubule and in the small intestine are given. They show the principal similarity of the transport of many substances in both epithelia.


Systemic involvement in tuberculoid leprosy--pathogenesis of leprosy.

Occurrence of leprous pathology/bacilli in the internal organs in cases of polar tuberculoid leprosy, support the systemic nature and haematagenous transmission and spread of the disease process. Pathogenesis of leprosy has been postulated.