Contraluminal sulfate transport in the proximal tubule of the rat kidney

In order to study contraluminal sulfate transport the influx rate of³⁵SO ₄ ^2– from the interstitium into cortical tubular cells has been determined. Preloading of the rat with sulfate augmented contraluminal³⁵SO ₄ ^2– influx; preperfusion with sulfate-free solutions diminished it. The contraluminal³⁵SO ₄ ^2– influx in sulfate-loaded animals followed two parameter kinetics (K _m 1.4 mmol/l,J _max 1.2 pmol·s^–1·cm^–1). The contraluminal³⁵SO ₄ ^2– influx (starting concentration 10 mol/l) did not change when the K⁺ concentration was varied between 4 and 40 mmol/l and the Ca²⁺ concentration from zero to 3 mmol/l. Omission of Na⁺ from the perfusates augmented contraluminal³⁵SO ₄ ^2– influx markedly. The increase is larger at pH 6 than at pH 7.4. Changes of pH affect contraluminal³⁵SO ₄ ^2– influx only when the solutions are Na⁺- and K⁺-free. Under these conditions the³⁵SO ₄ ^2– influx decreased when the ambient pH was raised from pH 6.0 to pH 8.0. Thiosulfate, selenate, molybdate, oxalate, phosphate, arsenate, and bicarbonate exerted competitive inhibition, while formate, 2-oxoglutarate and paraaminohippurate showed a biphasic response: inhibition at 50 mmol/l, no inhibition at 150 mmol/l. Chloride and bicarbonate inhibited³⁵SO ₄ ^2– influx at 10 mol/l³⁵SO ₄ ^2– , but augmented sulfate influx at 5 mmol/l³⁵SO ₄ ^2– concentration in rats not preloaded with sulfate. The data indicate the presence of a contraluminal sulfate transport system which is shared by a variety of inorganic and organic anions. The biphasic behaviour of some anions suggests parallel pathways leading to a cis-inhibition at small and trans-stimulation at high anion concentrations. Na⁺ and H⁺ may be cotransported or interact with the transport system at a modifier site.     

Pharmakologische und therapeutische (p-Chlorphenylalanin) Studien über das Carcinoidsyndrom bei 11 Fällen

Zusammenfassung Von 11 Carcinoidpatienten mit vermehrter Serotonin-Synthese hatten 10 Patienten Diarrhöe, 9 Patienten nachweisbare Lebermetastasen und 7 Patienten zeigten eine Kardiopathie. Sieben Patienten hatten spontane Flushanfälle. Bei diesen Patienten konnte ein Flush auch durch intravenöse Injektion von Aminen oder Bradykinin hervorgerufen werden. Bei 3 Patienten ohne Spontanflush in der Anamnese konnte ein Flush durch Provokation nicht ausgelöst werden. Der durch Amine provozierte Flush wurde von allen Patienten als dem Spontanflush gleich empfunden. Nur die Hälfte der Patienten empfanden den Bradykinin induzierten Flush gleich dem Spontanflush. Regitinbehandlung verhindert den durch Amine provozierten Flush und verminderte die Anzahl der spontanen Flushanfälle.Die Behandlung mit p-Chlorphenylalanin (PCP) in einer Dosierung bis zu 3 g täglich resultierte bei allen Patienten in einer Verminderung der 5-Hydroxyindolessigsäure-Ausscheidung und der Diarrhöe. Bei 3 Patienten mit vermehrter 5-Hydroxytryptophan-Ausscheidung wurde diese durch PCP vermindert, was darauf hindeutet, daß die Tryptophanhydroxylase durch PCP gehemmt wird. Die PCP-Behandlung, die bis zu einer Dauer von 120 Tagen durchgeführt wurde, zeigte bei den Patienten keine Nebenwirkungen.Mit Unterstützung der Schwedischen Cancer-Gesellschaft.     

Genetic diversity of intimin genes of attaching and effacing Escherichia coli strains

In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-eta (eta), eae-iota (iota), and eae-kappa (kappa). The fourth was identical to the recently described eae-zeta (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-alpha, intimin-beta, intimin-gamma1, intimin-gamma2, intimin- epsilon, and intimin-theta alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3' region (starting at bp 2,112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: alpha and zeta; beta and kappa; gamma1 and gamma2/theta; and epsilon and eta. Calculation of homoplasy ratios of sequences of the 5' region of eae (positions 1 to 2,111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.     

Alternative splicing of IL-24 in melanocytes by deletion of exons 3 and 5

Two novel interleukin-24 (IL-24) splice variants were identified in normal human melanocytes by sequencing cloned polymerase chain reaction (PCR) products that are not expressed in metastatic melanoma. These gene products have been generated by differential skipping of exons 3 (IL-24 delE3) and 5 (IL-24 delE5). IL-24 delE3 has limited sequence identity to the IL-24-interacting protein mda-7s, and IL-24 delE5 is homologous to IL-24.     

Epidemiological Investigation of Vaginal Saccharomyces cerevisiae Isolates by a Genotypic Method

Saccharomyces cerevisiae is a ubiquitous, ascomycetous yeast, and vaginitis caused by this organism has been reported only very rarely. The aim of the present investigation was to assess the epidemiological relatedness of a group of vaginal and commercial S. cerevisiae isolates by a previously reported genetic typing method, which divided the isolates into two broad groups with numerous subtypes. Nineteen S. cerevisiae isolates obtained from patients suffering from vaginitis and four isolates from commercial products in the same city were analyzed. The cellular DNA from each isolate was digested with the restriction endonuclease EcoRI, and restriction fragment length polymorphisms were generated by horizontal gel electrophoresis. The results showed that although vaginal isolates did not cluster in any particular genetic subtype, multiple patients were infected with indistinguishable strains (there were nine distinct strains among 23 isolates). For two of three patients, all three with two episodes of S. cerevisiae vaginitis, different strains were isolated during the recurrence of this disease. Three other patients with indistinguishable isolates were epidemiologically related in that two were practitioners in the same clinic and the third was a patient at this clinic. We also found that one commercial strain was indistinguishable from the strain isolated from three different women at the time that they were suffering from vaginitis. The findings of the present study suggest that some S. cerevisiae strains may possess properties permitting persistence in the human host. Furthermore, person-to-person contact and the proliferation of the use of S. cerevisiae as a health-food product, in home baking, and in home brewing may be a contributing factor in human colonization and infection with this organism.     

Expression of growth associated protein 43 and neural cell adhesion molecule in congenital fibre type disproportion with interstitial myositis

We report on the expression of growth associated protein (GAP)43 and neural cell adhesion molecule (NCAM) in congenital fibre type disproportion (CFTD) with myopathological additional signs of interstitial myositis. We assume that sarcolemmal GAP43 in developmental disordered myocytes plays a role in maintenance of growth morphology. In muscular dystrophy light microscopical evaluation reveals no GAP43 immunoreactivity in regenerating fibres. The expression of GAP43 seems to be a characteristic feature of CFTD. The expression of NCAM, particularly in the sarcolemma of small muscle fibres of CFTD, indicates a functional state of permanent partial denervation. Whether the steroid-responsive interstitial myositis is pathogenetically related to CFTD or a coincidental inflammation is not known. Because of the clinical and myopathological data the differential diagnosis of Emery-Dreifuss muscular dystrophy is considered.     

Heterogeneity of histamine H2-receptor mediated responses in the rabbit aorta

Distribution and properties of histamine H₂-receptor mediated responses in segments of rabbit aorta was studied with histamine and H₂-receptor stimulating drugs, dimaprit and impromidine. All agonists produced concentration-dependent tonus decreased in precontracted vascular strips, which were antagonised by selective H₂-receptor antagonists, cimetidine and oxmetidine. Activities of the agonists were segment-dependent, and increased caudally along the aorta. A nonspecific smooth muscle relaxant, papaverine had homogeneous activity along the vessel, suggesting receptor specific nature of the observed heterogeneity.     

Class II (DR) antigen expression on CD8+ lymphocyte subsets in acquired immune deficiency syndrome (AIDS)

In a selected group of human immunodeficiency virus (HIV)-infected patients we confirm the expansion of a CD8⁺ T-lymphocyte subset, i.e., the CD8⁺/Leu7⁺ cells, which account for 30% of the lymphocytes, compared to 3% in the control donors. In addition, a CD8⁺ T-lymphocyte subset that coexpresses class II (DR) antigens, i.e., CD8⁺/DR⁺ cells, is also increased from 1.5% in controls to 27% in the HIV-infected patients. Using three-color immunofluorescence and flow cytometry we can demonstrate that the CD8⁺/Leu7⁺ and the CD8⁺/class II⁺ cells are not distinct but overlapping subsets. In the HIV-infected patients 42% of the CD8⁺/Leu7⁺ cells were strongly positive for class II and these CD8⁺/Leu7⁺/class II⁺ cells accounted for 13% of all lymphocytes. These findings indicate that the expanded CD8⁺/Leu7⁺ cells are activated and hence might be actively involved in immune defense in acquired immune deficiency syndrome (AIDS).     

Functional reactivation of the deafferented hippocampus by embryonic septal grafts as assessed by measurements of local glucose utilization

Summary Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic innervation in the inititally denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (¹⁴C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region. Six months after unilateral fimbriafornix transection the rate of glucose utilization was reduced markedly throughout the ipsilateral hippocampus when compared to the intact contralateral side, while in the neocortex only the cingulate cortex showed long-lasting reductions in glucose use. Rats that received a transplant of fetal septal-diagonal band tissue at the time of fimbria-fornix transection, and were sacrificed 6 months later, displayed significantly greater glucose utilization in the ipsilateral hippocampus and cingulate cortex than was measured in these areas in rats with lesion alone. The recovery in glucose use was paralleled by a significant increase in acetylcholinesterase (AChE) staining in several areas of the ipsilateral hippocampal formation and cingulate cortex. This index of graft-induced cholinergic reinnervation was, moreover, significantly correlated with the rate of glucose use. Thus, in the fimbria-fornix transected animals the magnitude of glucose depression correlated with the extent of reduction in AChE staining, and in the grafted animals the degree of normalization of glucose use was correlated with the graft-induced increase in AChE-staining density. These results thus indicate that the 2-DG autoradiographic technique can provide a unique opportunity to map both altered functional activity in localized areas of the brain following specific lesions and the extent to which transplant-derived reinnervation of the host may induce a return to normal functional levels in the target site.ETP and Royal Society (London) visiting fellow     

Assignment of gene coding for cell surface glycoprotein with a molecular weight of 75,000 to human chromosome 11

The gene for a cell surface glycoprotein recognized by a mouse monoclonal antibody (Mab 4), has been assigned to human chromosome 11 by the study of mouse-human lymphocyte hybrids. The antigen is present on all human peripheral blood leukocytes, on human fibroblasts, and on human lymphoid and erythroid cell lines, but not on erythrocytes. Immunoprecipitation and polyacrylamide slab gel electrophoresis of both human cells and mouse-human hybrid clones carrying human chromosome 11 show that the apparent molecular weight of this glycoprotein is 75,000.