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Biomedical subjects

H Kolb

Publications and source records attributed to H Kolb.

At least 235 records · Page 13Linked to original sources
PubMed1990

Development of morphological types and distribution patterns of amacrine cells immunoreactive to tyrosine hydroxylase in the cat retina.

Using an antibody against tyrosine hydroxylase on newborn to 30-day kitten retinas, we have been able to follow the development of the dopaminergic amacrine cells of the cat retina by light-microscopical investigations of retinal wholemounts. The Type 1 or large Toh+ amacrine cells described by others (Oyster et al., 1985; Törk & Stone, 1979) and named A18 from a Golgi study (Kolb et al., 1981), is at birth (P1) an immature neuron with a small cell body and two or three simple thick radiating dendrites stratifying in stratum 1 with many of the dendrites ending in enlarged growth cones. With increasing postnatal age, the cell body size increases from 12.5 microns diameter to reach 15.5 microns diameter at P30. The dendritic fields also increase in size and complexity. At P1, cells of the central area exhibit dendritic appendages which then develop progressively until at P13 (after eye opening) they are part of rudimentary rings and by P30 the dendritic plexus of Toh+ dendrites and rings in stratum 1, typical of the adult cells, are complete. Toh+ stained processes with growth cones that run deep in stratum 5 of the inner plexiform layer and processes passing to the outer plexiform layer first become apparent at P1 in cells of central inferior retina but not till after P13 are these processes clearly expressed. At P1, the total number of Toh+ Type 1 cells is approximately 4000 and this number remains unchanged to the adult retina. However, the retina increases in size over the P1-P30 stage and thus the mean density of Type 1 Toh+ cells decreases from 30/mm2 at P1 to 18/mm2 at P30. The maximum density of Type 1 Toh+ cells occurs in central retina 2-4 mm superior temporal to the area centralis, corresponding to the maximum rod photoreceptor concentration. A second type of small Toh+ amacrine cell can be visualized at P1. This Type 2 cell is characterized by a much smaller cell body than Type 1 cells (9 microns diameter), and with faintly stained dendrites located in stratum 3 of the inner plexiform layer. During later postnatal days, Type 2 cells gradually become unstainable and only few are still seen in far peripheral retina by P23. Type 2 Toh+ cells from a total population of 40,000 cells at P1 with their highest density occurring in peripheral retina. By P13, they cannot be seen in central retina and are reduced to a total population of cells staining for the antibody of 7400 cells in far peripheral retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG)

This retrospective survey of the EBMT Leukaemia Working Party describes 78 patients with myelodysplasia (MDS) or secondary acute myelogenous leukaemia (sAML) who received an allogeneic bone marrow transplant (BMT). The status of underlying disease at the time of transplantation was prognostic for the 2-year disease-free survival. Thirty-four patients received intensive chemotherapy prior to the conditioning for BMT. The 2-year disease-free survival was 60% for the 16 patients transplanted in complete remission. The results were significantly less favourable for those with more advanced disease who only partially responded to prior intensive chemotherapy (2-year disease-free survival: 18%) while none of those who either relapsed or were resistant to chemotherapy survived BMT for 2 years. Forty-four patients had not received any prior intensive chemotherapy. The disease-free survival at 2 years after BMT was 58 +/- 19% when a patient was transplanted for refractory anaemia (RA(S], 74 +/- 14% for refractory anaemia with excess of blasts (RAEB), 50 +/- 16% for RAEB in transformation (RAEBt), and 18 +/- 11% for secondary AML. Allogeneic BMT can therefore be considered as curative treatment for patients with MDS. Patients with sAML who have a histocompatible donor should be given chemotherapy intensive enough to induce complete remission. If this is achieved these individuals have a prognosis comparable to those with de novo AML in first remission after BMT.

Adolescent↗
PubMed1990

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes.

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.

Adult↗
PubMed1990

Effects of radical scavengers on the development of experimental diabetes.

The possible value of radical scavengers in the prevention of beta cell destruction was studied in two animal models of type I diabetes. Eight compounds were tested alone or in combinations. In the low-dose streptozotocin model treatment started 24 hr after the last injection of the beta cell toxin, in the BB rat daily administration was started at 50 days of age (i.e., 20-70 days before diabetes onset). No effect was seen in the low-dose streptozotocin model for 3-aminobenzamide, N-acetyl-DL-homocysteine thiolactone, ebselen, and butylated hydroxyanisole whereas partial suppression of hyperglycaemia was seen in mice receiving cysteamine. In BB rats diabetes development was delayed and partially suppressed by administration of ebselen plus vitamin E plus MaxEPA (fish lipid concentrate), but not when ebselen was replaced by nicotinamide. We conclude that the disease process is not readily modifiable by treatment with exogenous radical scavengers.

Aging↗
PubMed1990

Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats.

Long-term treatment with recombinant interleukin-2 (IL-2) of diabetes-prone BB rats had contrasting effects in two different BB rat sublines. Diabetes development was enhanced in the subline with a low intrinsic diabetes risk and suppressed in the subline with a high diabetes risk. IL-2 treatment started between 35 and 42 days of age and lasted for 3 months. In subline 1, diabetes incidence increased from 23% to 53% (P less than 0.01), in subline 2 it decreased from 73% to 32% (P less than 0.01). The two sublines differed in serum levels of factors controlling IL-2 synthesis and activity. Mean IL-2 inhibitory activity was higher in subline 2 (between 140% and 290% of levels in subline 1, P less than 0.01). Conversely, mean concentrations of thymosin alpha 1 and beta 4 were higher in subline 1 (between 140% and 200% of levels in subline 2, P less than 0.01). Thus the two sublines differ in their response to exogenous IL-2 and also in serum levels of mediators affecting availability of IL-2. We conclude that an internal network of hormonal factors, including IL-2, contributes to the control of diabetes development in the BB rat.

Animals↗
PubMed1989

Morphology and distribution of neurons immunoreactive for substance P in the turtle retina.

Immunocytochemical staining procedures with the HRP-complexed antibody to substance P have been carried out on the turtle retina. Examination by light microscopy of wholemount retinas has allowed us to evaluate the morphology and distribution of the substance P immunoreactive cell types. Two amacrine cell types and two or more ganglion cell types are stained in our hands. Type A amacrines are tri-stratified wide-field amacrines. They have their major dendrites in S1 and S3 of the inner plexiform layer and they emit fine dendrites from the major dendrites that end in varicose boutons in S5 on and around cell bodies in the ganglion cell layer. Some of the dendrites in S1 radiate out in axon-like fashion for 1 mm across the retina. The type B amacrine cells are small to medium-field in dendritic extent. They have smaller cell bodies than type A and a single or, at most, two primary dendrites that pass directly to S3 before branching profusely into an intricate net-like dendritic field. The ganglion cells that are stained with substance P antibodies appear to be of several types but their exact morphologies are in doubt because only portions of their major dendrites are stained. Substance P immunoreactive axons are clearly seen to project from the cell bodies to the optic nerve head and axons are stained in the optic nerve itself. The substance P-stained ganglion cells occur in an irregular distribution that reaches a peak density in an elongated band parallel to and 1 mm below the visual streak. The type B amacrine cells reach a maximum density in the visual streak and are distributed in a highly regular mosaic decreasing in density in elliptical isodensity contours from the visual streak. In contrast the type A amacrine cells are rare or absent in the streak, being located in an irregular mosaic in peripheral retina.

Animals↗
PubMed1989

Spontaneous cytotoxicity of macrophages against pancreatic islet cells.

Activated peritoneal macrophages were found to lyse syngeneic [3H]leucine-labeled pancreatic islet cells or rat insulinoma cells after 15 h of coculture at 37 degrees C. Lysis was verified by electron microscopic analysis. Islet cell lysis was dependent on the T:E ratio and was comparable with P815 and L929 tumor cells used as targets. The cytotoxic activity was localized in the adherent fraction of Corynebacterium parvum activated peritoneal cells and was destroyed by incubation of cells with macrophage-toxic silica particles. Syngeneic thyrocytes and hepatocytes were found to be resistant to the cytolytic action of activated macrophages. It has been shown previously that macrophages contribute to pancreatic islet inflammation. The present in vitro analysis demonstrates that macrophages can function as effector cells in islet destruction.

Animals↗
PubMed1989

Nonenzymatically glycated serum albumin: interaction with galactose-specific liver lectins.

The possible interaction of galactose/glucose-specific liver lectins with nonenzymatically glycated human serum albumin was analyzed. The binding activity of the asialoglycoprotein receptor on hepatocytes and of the corresponding lectin on Kupffer cells was determined using freshly isolated liver cells from Wistar rats. Nonenzymatically glucosylated or galactosylated human serum albumin (HSA) did not inhibit lectin binding in a competitive adhesion assay (less than 15% inhibition). In contrast, lactosylated HSA strongly interacted with the two liver lectins (more than 80% inhibition). Lectin binding increased with lactosylation reaching a maximum at 44-49 mol D-galactose bound per mol HSA. In conclusion, at least in certain cases, nonenzymatically glycated proteins may interact with endogenous lectins.

Animals↗
PubMed1989

Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus.

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1 degree Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1 degree Rel vs 0.4% of controls (P less than 0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1 degree Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1 degree Rel vs 1.4% of controls (P less than 0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3 -DR1,4, or -DR3,4 (16.5%, P less than 0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P less than 0.01). In brothers the prevalence of IgG-IAA is higher than in other 1 degree Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n = 810) tested for both antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Modulation of low-dose streptozotocin-induced diabetes in mice by administration of antibodies to I-A, I-E and I-J determinants.

In male mice of strains C3H and C57BL/6 an experimental immune-mediated diabetes can be induced by multiple low doses of streptozotocin. The delay and partial suppression of hyperglycaemia after anti-I-A monoclonal antibody administration was dose dependent. Even saturation levels of anti-I-A did not cause complete protection from diabetes development. Administration of anti-I-E monoclonal antibody also significantly delayed the onset of hyperglycaemia. Surprisingly, the combined treatment with anti-I-A and anti-I-E did not result in better protection from diabetes. Thus, there is an I-A and I-E independent component of the disease. Furthermore, there is no restriction to either I-A or I-E. Anti-I-A was only effective when given at the beginning of the experiment, which implies that I-A molecules have a primary function during the induction of diabetes. The contribution of I-J to the disease process is different. Administration of a polyspecific alloantiserum to I-J almost completely prevented hyperglycaemia. Injections of monospecific antibodies to I-J determinants enhanced hyperglycaemia, especially when given after the induction of diabetes. This indicates that I-J is involved in initial as well as in later stages of the disease process.

Animals↗
PubMed1989

Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats.

We have analysed whether infiltration of macrophages and lymphocyte subtypes into pancreatic islets of diabetes prone BB rats occurs at random or whether insulitis requires a specific sequence of events. Serial sections from more than 700 islets of diabetes prone BB rats (70-150 days of age) were analysed for infiltrating immunocytes and expression of major histocompatibility complex antigens by 4-11 different monoclonal antibodies. In parallel, electron microscopy was performed in a fraction of islets. Part of the animals had been treated with macrophage toxic silica particles. A specific non-random sequence of events was identified and 4 stages of islet inflammation were recognised. Stages 1a and 1b are defined by macrophage (ED1+, W3/25+. Ox3/6/17+, ED2-) infiltration and concomitant enhanced major histocompatibility complex class I antigen expression initially at one pole or at the periphery of islets. T-, NK- and B-lymphocytes are absent (less than 1 cell per mean islet section). In stage 2, more macrophages are infiltrating and concomitantly Ox19+-T-lymphocytes and Ox8+-granular (NK-) lymphocytes are observed. In stage 3, additional massive infiltration of Ox12+-B-lymphocytes is noted. Silica treatment of BB rats largely prevented macrophage infiltration. Concomitantly islets were free of lymphocytes. Thus, macrophage infiltration clearly precedes T- and NK-lymphocyte and later B-lymphocyte infiltration. Lymphocytes do not infiltrate islets in the absence of prior macrophage invasion.

Animals↗
PubMed1989

Pathogenesis of low dose streptozotocin induced diabetes in mice: requirement for alpha 1-adrenoceptor activation and vasoactive amine release.

Pancreatic islet inflammation and subsequent diabetes was induced by multiple low doses of streptozotocin in male C57 Bl/6J mice. The development of hyperglycaemia was almost completely prevented by treating the animals with the alpha 1-adrenoceptor antagonist prazosin (20 mg.kg-1.day-1) as well as by the vasoactive amine antagonists methysergide (50 mg.kg-1.day-1), disodium cromoglycate (100 mg.kg-1.day-1), pizotifen (5 mg.kg-1.day-1) or cyproheptadine (20 mg.kg-1.day-1). Treatment with vasoactive amine antagonists largely inhibited infiltration of pancreatic islets by L3T4+-lymphocytes and to a lesser extent by Lyt2+-cells. The infiltration of macrophages was not affected except after pizotifen treatment. These results indicate that alpha 1-adrenoceptor activation is required for disease development and that vasoactive amine release is a prerequisite for lymphocytic insulitis but not for macrophage infiltration of islets.

Animals↗
PubMed1989

Signal integration at the pedicle of turtle cone photoreceptors: an anatomical and electrophysiological study.

The morphology of the axon which connects the cell body and pedicle of turtle cone photoreceptors was studied by light and electron microscopy. The axon which contains numerous synaptic vesicles, some endoplasmic reticulum, and a few cisternae is basically filled with cytoplasm. The length of the axon is related to the class of cone and varies slightly with retinal location, with axons as short as 3-6 microns found in red cones, and as long as 60 microns in cones containing colorless oil droplets. By simultaneously voltage clamping the cell body and pedicle regions of single isolated cones, we measured the longitudinal axonal resistance and the cell body and pedicle membrane resistances. For each cell studied, the axonal resistance of cones with short axons was lower than the cell and pedicle membrane resistances. Thus, the cell can be considered to be an isopotential structure. However, in some cones with long axons, the axonal, cell body, and pedicle resistances were comparable. The pedicles of these cones, therefore, could act like summing points and may provide a locus for spatial signal integration. Electrical coupling between the principal and accessory members of double cones was also studied. Electron-microscopic observation of the membrane junction between the apposed inner segments of the double cones in the intact retina show narrow segments which resemble gap junctions. However, in every double cone studied in culture, passing currents into one member of the double cone did not result in measurable current flow in the adjacent cell. Thus, the two members of the double cone, isolated from the turtle retina, are not electrically coupled.

Animals↗