The relation of blood-flow to metabolism in the submaxillary gland.
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Biomedical subjects
Publications and source records attributed to F Müller.
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Serum samples from 247 patients with positive HIV-1 IgG serology were investigated for specific IgM antibodies. We found that 109 also reacted positively with a least one antigen in an HIV-1 IgM Western Blot and only 31 in an HIV-1 IgM enzyme-linked immunosorbent assay (ELISA). It was shown that in some of the persons, specific IgM antibodies against the gp160/120, p66, p55, gp41, p24, and p17 antigens of the virus are synthesized at some time after infection. IgM antibodies to the endonuclease-related p31 antigen were observed in one serum only. IgM antibodies against the gp160/120, p66, gp41, and p17 antigens seemed to disappear early after infection. Those against the p55 and the p24 antigens were found in 62% and 75% of investigated cases, respectively. A direct correlation between the Western Blot patterns and the IgM ELISA results was not found.
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The relationships between serum levels of soluble tumor necrosis factor receptors (sTNFRs) and other prognostic and immunological parameters in different immunological subgroups of 64 HIV-1 infected patients were studied. In the patient group as a whole, the raised serum levels of sTNFRs were significantly inversely correlated to the numbers of CD4+ and CD8+ lymphocytes and significantly positively correlated with serum levels of neopterin, HIV-1 p24 antigen and the soluble CD8/CD8+ lymphocyte ratio. However, when the patients were classified into three separate immunological subgroups according to the numbers of CD4+ lymphocytes, only serum levels of neopterin were significantly correlated to levels of sTNFRs in all the defined immunological subgroups. These results indicate that HIV-1 infection is associated with a persistent and chronic immune activation in the TNF system manifested by raised serum levels of sTNFRs, which may reflect sustained activation of the immune system particularly in monocytes/macrophages. Further, these results confirm that, when comparing immunological and virological parameters in HIV-1 infection, different results may be obtained in different immunological subgroups of patients.
OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. The present paper describes the localization of GABAA receptors in the rat retina as revealed by in situ hybridization and immunocytochemistry. In situ hybridization with probes against various alpha subunits revealed a marked differential expression pattern. The alpha 1 subunit gene is expressed mainly in the bipolar and horizontal cell layer, the alpha 2 gene in the amacrine and ganglion cell layer, and the alpha 4 gene in a subpopulation of amacrine cells. beta subunit mRNA is present diffusely throughout the entire inner nuclear layer and in the ganglion cell layer. The monoclonal antibody bd 17 (against beta 2/beta 3 subunits) stained subpopulations of GABAergic and glycinergic amacrine cells as well as some ganglion cells and bipolar cells. Immunoreactivity was not restricted to synaptic input sites. In the outer plexiform layer bipolar cell dendrites were immunoreactive; in the inner plexiform layer mainly amacrine and ganglion cell processes were labeled, and bipolar cell axons appeared unstained. The results demonstrate a strong heterogeneity of GABAA receptors in the retina.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. We tested the actions of iontophoretically applied GABAergic ligands on the spontaneous and stimulus-evoked activity of retinal ganglion cells recorded extracellularly in the in vivo cat eye. GABA as well as GABAA receptor agonists inhibited all brisk ganglion cell types. This action was antagonized by bicuculline. Bicuculline on its own increased the activity of ON-ganglion cells but suppressed OFF-ganglion cells. This suppression effect was abolished during the blockade of glycinergic transmission by strychnine. The GABAB receptor agonist baclofen inhibited OFF-ganglion cells whereas the activity of ON-ganglion cells was either increased or decreased depending on the stimulus contrast. The antagonists, phaclofen and 2-hydroxy saclofen, produced opposite effects to baclofen and antagonized its action. The present study demonstrates that both GABAA and GABAB receptors modulate the activity of ON- and OFF-ganglion cells in the cat retina.
Three approaches to study the function of mammalian rod bipolar cells are described. Extracellular recordings from the intact cat eye under light- and dark-adapted conditions showed that in dark-adapted retina all light responses can be blocked by 2-amino-4-phosphonobutyrate (APB). Immunocytochemical staining with an antibody against protein kinase C (PKC) labeled rod bipolar cells in all mammalian retinae tested. When rat retinae were dissociated, PKC immunoreactivity was also found in isolated bipolar cells and could be used for their identification as rod bipolars. Patch-clamp recordings were performed from such dissociated rod bipolar cells and their responses to APB were measured. APB closed a nonselective cation channel in the cell membrane. The actions of GABA and glycine were also tested and both opened chloride channels in dissociated rod bipolar cells. These results suggest that rod bipolar cells are depolarized by a light stimulus and that GABA as well as glycine modulate their light responses.
In the mammalian retina, neuronal nitric oxide synthase (NOS) is mainly localized in subpopulations of amacrine cells. One function of nitric oxide (NO) is to stimulate soluble guanylate cyclases which in turn synthesize cGMP. We used an antibody specific for cGMP to demonstrate cGMP-like immunoreactivity (cG-IR) in bovine, rat, and rabbit retinae and investigated the effects on cGMP levels of both exogenously applied NO and of endogenously released NO. We found that cGMP levels in inner and outer retina were controlled in opposite ways. In the presence of the NO-donors SNP, SIN-1 or SNAP, cG-IR was prominent in neurons of the inner retina, mainly in cone bipolar cells, some amacrine and ganglion cells. Retinae incubated in IBMX showed weak cG-IR in bipolar cells. Glutamate increased cG-IR in the inner retina, presumably by stimulating endogenous NO release, whereas NOS inhibitors or GABA and glycine decreased cG-IR in bipolar cells by reducing NO release. In somata, inner segments and spherules of rod photoreceptors the situation was reversed. cG-IR was undetectable in the presence of NO-donors or glutamate, was moderate in IBMX-treated retinae, but increased strongly in the presence of NOS inhibitors or GABA/glycine. We conclude that NO is released endogenously in the retina. In the presence of NO, cGMP levels are increased in neurons of the inner retina, but are decreased in rods.
Using the Treponema Pallidum Haemagglutination Assay (TPHA) for the demonstration of treponema-specific antibodies, 444 children in age groups between 5 months and 10 years from different parts of Mali (Africa) were investigated for endemic treponematoses. The rate of seroreactivity (1,85%) in the age groups under four years (n = 270) indicates a low incidence of treponemal infections. From these observations it can be concluded that treponemal infections in infants are not caused by suckling of the babies on infectious nipples of their mothers. The high rate of TPHA-reactive children (17,8%) in the age groups between 5 and 10 years (n = 174) can be explained by the assumption of nonvenereal transmission of the disease. Furthermore, 101 mothers from Bamako and their newborn babies, were investigated serologically. In 17 mothers (17%) the TPHA was reactive. Treponema-specific antibodies were transmitted to the children in all cases and with nearly identical antibody titres.
Cryptococcosis is an important cause of lymphocytic meningitis, especially but not necessarily in immunocompromised patients. We present the case of a 23-year-old man with a severe and rapid course of a cryptococcal meningoencephalitis, which led to visual and hearing loss, psychotic illness and radiculopathy. There was no evidence of immunodeficiency. Treatment with amphotericin B and flucytosine led to improvement of the symptoms but did not eradicate the micro-organisms from the cerebrospinal fluid (CSF). Maintenance therapy with fluconazole was necessary and led to improvement of the CSF pathology.
The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), has been shown to induce monocyte-to-macrophage maturation in vitro as well as monocytic differentiation of bone marrow precursors and monocytic leukaemic cell lines. In this study we assessed whether 1,25D could improve the maturation defect we have previously demonstrated in monocytes from AIDS patients. In vitro growth and maturation of monocytes from 10 controls, 15 asymptomatic HIV positives (CDC group II or III) and 13 symptomatic HIV positives (CDC group IV) was examined by assessing cellular morphology, differentiation, adherence and protein content. Cells were cultured for 10 days with or without addition of 1,25D at a concentration of 100 pg/ml. In addition, patients were monitored clinically and by immunological parameters and HIV p24 antigen in serum. The present study showed that addition of 1,25D significantly improved the growth and maturation in both patient and control groups. There was a significant negative correlation between response to 1,25D and CD4+ lymphocyte count in blood in HIV-infected patients. A greater response to 1,25D was seen in monocytes from patients with advanced immunodeficiency and symptomatic disease than in monocytes from asymptomatic patients. However, in the most advanced cases of HIV infection with serious ongoing opportunistic infections the response to 1,25D was very poor, possibly reflecting profound and incorrigible dysfunction of monocytes.
Platelet monoamine oxidase B (MAO-B) activity has been found to increase significantly in demented patients. For the first time, a 4-year follow-up of platelet MAO-B activity and Mini-Mental State (MMS) was performed in patients with probable dementia of the Alzheimer type (DAT) and age-matched controls. MAO-B activity of DAT patients increased significantly 2 years after the beginning of the study as compared with controls and remained significantly higher for the entire period of the examinations (p < 0.0001). The decrease of the MMS scores did not correlate with the time course of the increase of platelet MAO-B activity (Spearman rank correlation test). The decline of the MMS scores of DAT patients preceded the elevation of MAO-B activity. Since degenerative processes in brain areas which are responsible for cognitive function and are reflected by the MMS scores rather affect cerebral cholinergic than monoaminergic neurotransmitter systems, degeneration of the latter at late stages of DAT might be reflected by increased platelet MAO-B activity.
We previously provided evidence that atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and angiotensin II-stimulated aldosterone production by isolated adrenal cells. To examine the importance of these effects in vivo, synthetic ANF (auriculin A) was administered intravenously (2 micrograms/kg bolus followed by 0.3 microgram/kg/min constant infusion) to conscious, unrestrained two-kidney, one-clip and one-kidney, one-clip rats on normal sodium intake and their sham-operated controls. The one-kidney, one-clip rats also were studied on a sodium-deficient diet. Mean blood pressure, plasma renin activity, and plasma aldosterone levels were measured before and after 60-minute infusion. In saralasin-responsive two-kidney, one-clip rats (n = 10), ANF administration reduced blood pressure (from 187 +/- 11 [SE] to 153 +/- 11 mm Hg; p less than 0.001) and plasma aldosterone levels (from 182 +/- 61 to 125 +/- 60 ng/dl; p less than 0.05), while plasma renin activity increased (from 59 +/- 16 to 82 +/- 20 ng/ml/hr; p less than 0.05). Lesser changes in blood pressure occurred in saralasin-nonresponsive two-kidney, one-clip rats (149 +/- 10 to 143 +/- 8 mm Hg; n = 5), sodium-replete one-kidney, one-clip rats (183 +/- 9 to 170 +/- 11 mm Hg; n = 9), two-kidney sham-operated rats (122 +/- 3 to 115 +/- 4 mm Hg; n = 8), and one-kidney sham-operated rats (117 +/- 3 to 112 +/- 3 mm Hg; n = 7). Control plasma renin and aldosterone levels were not elevated in these latter groups and did not change significantly with ANF administration. In sodium-depleted one-kidney, one-clip rats, which became saralasin responsive, ANF administration significantly reduced blood pressure (from 184 +/- 11 to 156 +/- 12 mm Hg; n = 8), plasma aldosterone levels (from 286 +/- 41 to 179 +/- 36 ng/dl), and plasma renin activity (from 69 +/- 19 to 44 +/- 13 ng/ml/hr).(ABSTRACT TRUNCATED AT 250 WORDS)
The early development of the digestive and respiratory systems is summarized in relation to embryonic staging. It has frequently been emphasized that the digestive and respiratory tubes do not arise from a common chamber, that they pursue separate courses as soon as the lung bud appears, that a mesenchymal septum comes to intervene between them, and that the two tubes rapidly acquire independent outer coats. Some commonly held views such as the supposed caudorostral separation of the trachea from the esophagus, have been shown to be incorrect. These ideas often arose from the use of unstable landmarks during development. It is pointed out that, for 3 weeks after its appearance, the tracheoesophageal separation point remains at a constant level, whereas the tracheal bifurcation descends. The application of valid embryological data to the interpretation of several congenital anomalies has been shown to be of value. Although the modes of origin in some instances are still obscure, considerable advance has been made in understanding the timing of the relevant events.
The laryngeal cavity was studied in eight serially sectioned embryos of stage 23 and in three early fetuses, and graphic reconstructions were prepared. After the isolation of the tracheal from the pharyngeal cavity during stages 16 through 22, a communication (not necessarily the pharyngotracheal duct) appears again during stage 23. At this time (8 postovulatory weeks) the laryngeal cavity comprises 1) the coronal and parts of the sagittal clefts of the vestibule (uniting later at the laryngeal inlet); 2) the ventricles, which are not yet completely formed; and 3) the subglottic cavity, which appeared already in earlier stages. The characteristic events of stage 23 are the dissolution of the epithelial lamina and the development of the ventricles. The disruption of the epithelial lamina is an active process that comprises rearrangement and growth, but not loss of cells. The ventricles, which begin as solid outgrowths in stage 20, do not represent fifth pharyngeal pouches. They now point toward the middle of the still paired thyroid laminae and are not at the level of the future glottis, which lies more caudally. In the absence of the median part of the soft palate, the nasopharynx communicates widely with the oral cavity. The epithelium of the respiratory tube, including the larynx, resembles that of the pharynx and esophagus in being pseudostratified columnar and showing a clear basement membrane. It is ciliated over that part of the epiglottis that surmounts the arytenoid swellings, and also over the tip and back of the latter. The transitional area between the laryngopharynx and the esophagus is already innervated by the recurrent laryngeal nerve. Nerve fibers have not yet reached the epithelium of the coronal cleft and the ventricles, but fibers are present near the sagittal cleft of the vestibule. The sensory innervation of the pharynx and larynx has been followed and plotted for the first time in an embryo, and previously unrecorded silver-impregnated receptors have been observed.
The larynx at stage 23 (about 27-32 mm C-R, 8 postovulatory weeks) is being studied in detail, and findings on the musculature and its innervation are presented here. Serial sections of six embryos all belonging to the one developmental stage were investigated and compared, and graphic reconstructions were made from five of the specimens. All the infrahyoid and most of the major laryngeal muscles are present, and their innervation follows closely the adult pattern. The ary-epiglottic and thyro-epiglottic apparently may or may not be identifiable. The vocalis is beginning to differentiate and is noted here in the embryonic period proper for the first time. The histological degree of development of the intrinsic laryngeal muscles is not as advanced as that of adjacent muscles in the neck, including the infrahyoid group. Variation within this one stage of development are small but definite. They include differences in the position, level, and shape of the skeletal components, and the precise position and extent of development of some of the muscles.
A new method has been developed for introduction of foreign genes into fish eggs. The procedure is based on the incubation of fish sperm cells suspended in dilute citrate solution with plasmid DNA, followed by application of high-field-strength electrical pulses (electroporation) to increase DNA binding., uptake, or both. Tissue homogenates and genomic DNA extracts of free swimming fry developed from eggs fertilized with treated sperm was tested to evaluate the efficiency of gene transfer. Dot blot hybridization and gene expression assay demonstrated the presence and expression of the reporter genes introduced in 2.6 to 4.2% of several hundreds of tested larvae of common carp (Cyprinus carpio L.), African catfish (Clarias gariepinus), and tilapia (Oreochromis niloticus). No transgene has been found in the fry resulting from parallel experiments without sperm electroporation. This is the first report on successful application of electroporated sperm cells for production of transgenic fish.