Biomedical subjects

C Kayser

Publications and source records attributed to C Kayser.

At least 37 records · Page 2Linked to original sources

PubMed1996

Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings.

OBJECTIVE: To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells. METHODS: Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation. T cell receptor (TCR) beta-chain sequences were amplified by reverse transcriptase-polymerase chain reaction, using TCR BV and BJ gene segment-specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product. RESULTS: All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (P < 0.0001) and in patients with psoriatic arthritis (P = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (P = 0.005 and P = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules. CONCLUSION: RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cells specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.

Adult↗

PubMed1996

Growth hormone-binding protein in the goat: characterization, evolution under exogenous growth hormone treatment, and correlation with liver growth hormone receptor levels.

This report describes the identification and characterization of a specific, high-affinity growth hormone-binding protein (GHBP) in lactating goat serum. Serum samples were incubated with [125I]human GH as ligand and in the absence or in the presence of bovine GH as competitor. GH-GHBP complex formation was performed by high-performance liquid chromatography, and the radioactivity was recorded on-line with a Berthold LB detector connected to a computer. The results showed that a serum protein was able to bind specifically to human GH and bovine GH but not to ovine prolactin. Scatchard plots indicated an affinity constant of 4.5 x 10(8) M-1 and a maximum binding capacity of 4.8 x 10(-10) mol/l. In addition, we conducted a 4-wk study to determine the effects of recombinant bovine GH administration on milk production in lactating goats. The effects of recombinant bovine GH treatment on milk production and on the regulation of GHBP and hepatic GH receptor levels were studied. As expected, recombinant bovine GH injected daily increased yields of milk, fat, protein (40, 61, and 40%, respectively), and circulating insulin-like growth factor 1 concentrations compared with controls. During the pretreatment and treatment periods, the control goats exhibited a constant amount of GHBP in serum. No consistent effect of GH treatment on GHBP level was observed. The binding of [125I]bovine GH to hepatic microsomal membranes of GH-treated goats was significantly decreased compared with that of control goats. After MgCl2 desaturation of membranes, the results demonstrated that the down-regulation of GH hepatic receptors, observed for the treated goat group, was induced by receptor occupancy without modification of binding affinity. The GH receptor gene expression, analyzed by slot blot and hybridization with an [alpha-32P]GH receptor cDNA probe, was not modified by the GH treatment. In lactating goats, the galactopoietic effect of exogenous GH involved a hepatic receptor occupancy. The individual concentration of GHBP in serum cannot explain the individual variations of responses to GH treatment in goats.

Animals↗

PubMed1996

Differential activation of Stat3 and Stat5 by distinct regions of the growth hormone receptor.

The GH receptor (GHR) is a member of the cytokine receptor superfamily; its signaling involves the activation of Janus tyrosine kinases (JAK2) and Stat (signal transducers and activators of transcription) transcription factors. Using truncated and tyrosine mutants of the receptor, we show that different receptor domains are essential for the activation of Stat3 and Stat5. GH-dependent phosphorylation of JAK2, Stat3, and Stat5, as well as transactivation studies with reporter genes containing Stat3 and Stat5 DNA-binding elements, was performed in cells expressing the various GHR mutants. The membrane-proximal region of the receptor necessary for JAK2 activation is sufficient for Stat3 activation. In contrast, C-terminal tyrosine residues of GHR are absolutely required for Stat5 activation. The same residues are also involved in the regulation of JAK2 dephosphorylation, possibly through the activation of a phosphatase. Using in vitro experiments with glutathione-S-transferase fusion proteins, we demonstrate that the SH2 domain of Stat5 binds to the carboxy-terminal tyrosine-phosphorylated residues of GHR. Our results show that a cytokine receptor can mediate differently the activation of distinct Stat proteins that could be involved in cytokine-specific effects.

Animals↗

PubMed1996

Clinical course of hypophosphatemic rickets in 23 adults.

Twenty-three adult patients (19 females, 4 males) with x-linked hypophosphatemic rickets (HPR) underwent a retrospective evaluation of the clinical course and a clinical examination by a nephrologist, orthopedic surgeon and dentist. Blood and urine analysis, bone density measurements with QCT and DEXA, ultrasonic examination of the kidneys were performed and the patients were asked to fill in a standardized questionnaire on pain and psychosocial rehabilitation. Mean final height was 152.4 cm +/- 8.5 SD in females and 157.3 cm +/- 8.9 SD in males. Decreased joint mobility was seen in all patients, deviations of the normal leg axis in 18/23 patients in spite of 69 correcting osteotomies in the past. Dental (n = 14) and psychosocial problems were associated with inability to work (n = 8). There was a trend that patients with a very low Tp/GFR had a more severe course of the disease. Early therapy with vitamin D metabolites and phosphate had a beneficial effect on growth, bone density and deformations. Eight patients had nephrocalcinosis due to vitamin D and phosphate therapy and had normal kidney function. Four patients had urinary tract abnormalities. We conclude that patients with HPR should receive continuous interdisciplinary care given by nephrologists, orthopedic surgeons, physiotherapists and dentists not only during childhood but also as adults.

Adult↗

PubMed1996

Application of attributed graphs in diagnostic pathology.

OBJECTIVE: To compute attributed graphs based upon calculation of the minimum spanning tree (MST) for various applications in diagnostic lung pathology. STUDY DESIGN: The study design included assistance in histologic diagnosis, confirmation of the diagnosis in single cases, measurement of texture alterations after induction chemotherapy, estimation of prognosis of operated-on lung cancer patients and analysis of lung cancer cells in association with differentiation markers. The histologic slides were Feulgen stained, and features of the integrated optical density (IOD) were associated with the nodes of the MST. The same procedure was applied to immunohistochemically and ligand histochemically stained slides by calculation of the mean staining intensity of the cytoplasm of tumor cells. A measure for structural entropy was introduced by computing the relative differences in distance and IOD between neighboring tumor cells in a 1/r2 field of force. In addition, the current of entropy was computed. RESULTS: Structural entropy reflects alterations in regular textures; the current of entropy is an especially good prognostic parameter in lung cancer. In immunochemistry and ligand histochemistry, construction of the attributed MST permits detailed insight into locally different staining behavior of tumor cells and immunocompetent cells. CONCLUSION: Attributed graphs contain important information that can be used for the estimation of survival or for confirmation of diagnostic entities, such as tumor cell types.

Adolescent↗

PubMed1994

Pulse amplitude and frequency modulation of parathyroid hormone in early postmenopausal women before and on hormone replacement therapy.

Although the pathophysiology of postmenopausal osteoporosis has been investigated extensively, it is still not established in what respect PTH is related to the events. Recently, consistent data on the pulsatile secretion of PTH in man have been published. In this study intact PTH was measured in six early postmenopausal women before and after 6 months of hormone replacement therapy (HRT; 0.6 mg conjugated estrogens and 5 mg medrogestone). In addition to parameters of calcium metabolism and bone mass and to control HRT, intact PTH was measured in blood drawn over 6 h every 2 min. With HRT there was a 30% reduction in PTH secretion. Both the amount secreted per pulse (baseline, 26.8 +/- 6.9 ng/L; HRT, 21.4 +/- 7.6 ng/L; P < 0.05) as well as the basal secretion (baseline, 232.6 +/- 117.6 ng/L.h; HRT, 145.5 +/- 80.0 ng/L.h; P < 0.01) were reduced, whereas the pulse count per h remained constant (baseline, 5.1 +/- 2.2; HRT, 5.1 +/- 1.3). Power spectrum analysis showed a shift in spectral maxima consistent with these findings. Ionized and total calcium were slightly, but nonsignificantly, reduced with treatment. In summary we conclude that in early postmenopausal women, HRT reduces the secretion of PTH by reducing both the basal secretion and the amount secreted per pulse. It is conceivable that some of the known effects of HRT on bone metabolism might be mediated by the modulation of PTH secretion.

Calcium↗

PubMed1994

Pulse amplitude and frequency modulation of parathyroid hormone in primary hyperparathyroidism.

Pulsatile secretion of PTH in human subjects has been described recently. However, the pattern of PTH secretion in primary hyperparathyroidism (pHPT) remains to be characterized. In this study intact PTH was measured in 9 female patients with pHPT. As a control group we present data from 10 postmenopausal women. In addition to parameters of calcium metabolism and bone mass, PTH was measured in samples drawn over 4 or 6 h every 2 min by central venous blood sampling. The mean intact PTH concentration was 39.0 +/- 20.3 ng/L in healthy women and 193.2 +/- 127.9 ng/L in female patients with pHPT (P < 0.01). Pulse rhythm analysis showed significant differences between both groups for total PTH secretion per h (patients, 1196.4 +/- 485.3 ng/L; control group, 271.7 +/- 132.2 ng/L), basal PTH secretion per h (patients, 852.4 +/- 459.1 ng/L; control group, 185.6 +/- 126.1 ng/L), and average PTH secretion per pulse (patients, 112.6 +/- 54.8 ng/L; control group, 23.2 +/- 7.1 ng/L). Both patients and control subjects had, on an average, five pulses per h, and the pulsatile secretion accounted for about 50% of the total secretion. Differences in power spectrum analysis were consistent with these findings. The cross-correlation of PTH and calcium indicates an impaired feedback regulation in pHPT. PTH secretion in female patients with pHPT results from both an increased basal secretion and an increased amplitude of PTH pulses. Other features of secretion are the same as those in normal women. Feedback regulation of PTH and calcium is impaired in pHPT.

Aged↗

PubMed1993

Alteration of human lung parenchyma associated with primary biliary cirrhosis.

The clinical history, radiological and histomorphological alterations of the lung parenchyma in a patient suffering from primary biliary cirrhosis are described. The 70-year-old woman had developed a primary biliary cirrhosis, verified by serological abnormalities (AMA positivity, elevated IgM levels) and by liver biopsy. The lung parenchyma displayed immature epithelioid granulomas and characteristics of a chronic organizing pneumonia. Lung function revealed moderate restrictive changes; chest radiographs revealed bilateral, diffuse, patchy infiltrates in the basal lobes. Application of immunohistology detected antigens in liver cells reactive with anti-IgD and anti-IgG, in pneumocytes those reactive with anti-IgD. Presence of macrophage migration inhibitory factor (MIF) by application of its antibody and of the ligand sarcolectin as well as expression of binding capacities to MIF could not be demonstrated in the liver and lung parenchyma. Neoglycoproteins exposing fucose, N-acetyl-D-glucosamine, lactose and mannose residues did not bind to both the liver and lung tissue. The data indicate that at least some patients with primary biliary cirrhosis may develop or suffer from immunological abnormalities, affecting the lung.

Aged↗

PubMed1991

Identification of prolactin and growth hormone binding proteins in rabbit milk.

Two distinct soluble proteins that specifically bind 125I-labeled human growth hormone (GH) are identified in the supernatant of ultracentrifuged rabbit milk, using HPLC gel filtration. The higher molecular weight proteins is GH specific, whereas the other one is specific for prolactin (PRL). The PRL-binding protein has a very high affinity for the hormone, almost 10 times higher than the affinity of the mammary gland membrane receptor. The PRL-binding protein is immunoprecipitated by a monoclonal antibody against the PRL receptor; another monoclonal antibody, which inhibits the PRL binding to mammary gland membranes, is a poor competitor for the PRL binding to the milk protein. These findings suggest that the milk PRL-binding protein corresponds to the binding domain of the receptor, but also that the conformation of the receptor and of the binding protein might differ. The milk and the plasma GH-binding proteins have a similar binding affinity. In cross-linking experiments using 125I-labeled human GH, the Mr of the GH-binding protein and of the PRL-binding protein were estimated to be 51,000 and 33,000, respectively. The binding proteins identified in the present work are probably responsible for the transport of their specific ligands in the milk. It is also conceivable that they have a role in the effects of GH and PRL in the mammary gland and/or the intestine of the young.

Animals↗

PubMed1990

Increased growth hormone binding to liver membranes of obese Zucker rats.

Developmental changes in hepatic growth hormone binding sites were examined in the genetically obese male fa/fa rats and in the lean littermates. At 16 days, fa/fa pups are normoinsulinemic; the specific binding of 125I-hGH to liver membranes is comparable in the two genotypes. At 4 weeks and later on, plasma membranes and Golgi fractions of male obese Zucker rats have more GH binding sites than lean littermates. The GH pituitary content is comparable in the two genotypes from 2 to 8 weeks and in 14-week-old fa/fa rats it is half that in lean animals. In the two genotypes plasma IGFI dramatically increases during puberty. At 4 weeks, plasma IGFI level is significantly higher in fa/fa rats than in lean littermates. In this model of genetic obesity, an increased GH binding to liver membranes is observed after the third week of life, shortly after the onset of hyperinsulinemia in the fa/fa rat.

Animals↗

PubMed1990

Toxoplasmosis of the conus medullaris in a patient with hemophilia A-associated AIDS. Case report.

Toxoplasma gondii has been reported to be the most common cause of focal brain lesions in patients with acquired immunodeficiency syndrome (AIDS). A case of intramedullary toxoplasmosis of the conus medullaris is reported in a patient with hemophilia A-associated AIDS. The diagnosis is discussed, with particular emphasis on the magnetic resonance imaging appearance.

Acquired Immunodeficiency Syndrome↗

PubMed1989

The human liver growth hormone receptor.

Human livers, obtained from donors at the time of transplant, were homogenized in 0.25 M sucrose and fractionated by differential centrifugation. The specific binding of [125I] human (h) GH to total particulate fractions from 18 livers varied from 0.4-5.1% of the total radioactivity/100 micrograms protein. Binding affinity was 2.0 +/- 0.3 X 10(9) M-1, and binding capacity ranged from 14-53 fmol/mg protein. A different proportion of receptors occupied by endogenous hGH did not explain the large variation in binding. Binding sites were specific for hGH. Dissociation of the hormone-receptor complex was extremely slow. No specific binding of [125I]hPRL was observed. Specific binding of insulin was found in fractions from all livers and varied less than hGH binding. Cross-linking of [125I]hGH to plasma membrane and microsome receptors yielded two major autoradiographic bands corresponding to an estimated mol wt of 103,000 for the receptor, with a possible subunit of 54,000. Human liver primary fractions were characterized. The binding of hGH and insulin displayed a nucleo-microsomal distribution pattern in the primary fractions; 54.2% and 27.9% of the hGH-binding activity were found in the microsomes and the nuclear fraction, respectively, whereas insulin binds equally to nuclear and microsomal elements. Our findings suggest that hGH-binding sites are present in the plasma membrane and also in one or more intracellular compartments, whereas a high proportion of insulin receptors is associated with the plasma membrane.

Binding Sites↗

PubMed1989

In-vivo uptake of human growth hormone in male rat liver.

125I-Labelled human GH (hGH) was injected i.v. to male rats and its subcellular distribution in the hepatocyte was examined using fractionation techniques. Uptake into liver homogenates was maximal by 15 min after injection and represented 24% of the injected radioactivity; it was markedly inhibited by coinjection of native hGH. 125I-Labelled hGH taken up by the liver underwent a time-dependent translocation process. The peak of specific labelling of plasma membranes occurred at 3 min whereas later on the radioactivity was concentrated in low-density structures present in Golgi-endosome fractions. To characterize the ligand-associated structures better, endosome-enriched fractions were prepared from a microsomal fraction by isopycnic centrifugation in a sucrose gradient and a Nycodenz gradient. The radioactivity was in one peak with a median density of 1.096 g/cm3 in the Nycodenz gradient fractions. The peak of radioactivity was distinct from that of galactosyltransferase activity which appeared at a median density of 1.114 g/cm3. The labelled material eluted from the various subcellular fractions appeared as intact hGH. Upon in-vivo interaction with male rat hepatocytes, 125I-Labelled hGH was internalized with a sequential association with plasma membranes and endocytic structures distinct from Golgi elements.

Animals↗

PubMed1987

Ligand-induced changes in the subcellular distribution of insulin receptors in rat liver: effects of colchicine.

The in vivo effects of colchicine on the subcellular distribution of insulin receptors have been studied in insulin-injected rats and in control animals. Colchicine (0.1 mg/100 g or 10 mg/100 g body weight, i.v.) did not affect the ability of plasma membranes and Golgi fractions of control rats to bind insulin. As previously reported (Desbuquois et al., 1982), the injection of native insulin (8 nmol, i.v.) caused a 50% decrease in the insulin binding activity of plasma membranes and a concomitant 50% increase in insulin binding to Golgi fractions. These changes occurred at 4 and 40 min after insulin injection but were no longer detectable at 3 h. Colchicine treatment did not affect the initial changes in the distribution of insulin receptors induced by insulin; however, in rats treated with the low dose of colchicine, insulin binding to plasma membranes at 3 h was not fully restored. Colchicine treatment did not alter the amount of acid-extractable insulin associated with Golgi fractions of insulin-injected rats. The time course of uptake of 125I-insulin was similar in plasma membranes, microsomal fraction and Golgi fractions of colchicine-treated (0.1 mg/100 g) and of untreated rats. These results suggest that colchicine does not interfere with the endocytosis of insulin receptors induced by their ligand and has little effect, if any, on the reinsertion of internalized receptors in the plasma membrane.

Animals↗

PubMed1987

[Regulation of receptors and mechanism of action of growth hormone].

The initial step in the action of growth hormone (GH) is interaction with specific sites localized in target cell membranes. Growth hormone receptors have been demonstrated in different tissues and have been extensively studied in the liver. 125I-human growth hormone injected IV in the intact male rat is internalized in the hepatocytes by a receptor-mediated process; the radioactive material is sequentially associated with plasma membranes, endocytic structures and lysosomes. A dramatic decrease in the number of hepatic growth hormone receptors has been demonstrated in several situations of growth defect in the rat. GH, insulin and estrogens play a role in the regulation of hepatic growth hormone receptors, but their mechanism of action is not clear. GH receptors have been partially purified; the binding subunit has an approximate MW of 110,000 in rat hepatocytes and adipocytes and in IM-9 lymphocytes, a MV of 50 to 70,000 in rabbit liver. Monoclonal antibodies raised against the GH receptor will facilitate studies of receptor structure and function. The postreceptor events in growth hormone action are unknown. No second messenger or mediator has been demonstrated. Elucidation of the early events that follow activation of the growth hormone receptor is a priority.

Animals↗

PubMed1982

Fate of injected human growth hormone in the female rat liver in vivo.

[125I]Iodohuman GH ([125I]iodo-hGH) was injected iv to female rats, and its subcellular distribution was studied with time using fractionation techniques. Uptake in the total particulate fraction was maximal by 15 min after injections; at that time, 7% of the radioactivity injected was recovered per g liver. Liver uptake of [125I]iodo-hGH was markedly inhibited by coinjection of native hGH. [125I]Iodo-hGH taken up by the liver underwent a time-dependent translocation process. In the first 5 min, the radioactivity was associated with membranes of high density sedimenting in the nuclear and microsomal fractions. Later on, it was progressively associated with microsomal subfractions of lower density, the Golgi fractions; labeling of these was maximum at 15 min. Fifteen and 30 min after injection, labeled material was recovered in the mitochondrial-lysosomal fraction. Further fractionation of the latter by centrifugation on a metrizamide gradient showed that all of the radioactivity was associated with lysosomal subfractions, with virtually no radioactivity associated with mitochondria. On linear sucrose density gradients, the radioactivity exhibited a broad, somewhat bimodal distribution; the component of highest density coincided with the lysosomal enzyme acid phosphatase. Triton WR 1339 treatment of rats resulted in a shift of the radioactivity and acid phosphatase toward lower densities, indicating that a high proportion of the former was associated with lysosomes. The labeled material eluted from the subcellular fractions prepared at different times appeared as intact hGH, ad judged by trichloroacetic acid precipitability and binding to membranes. Upon in vivo interaction with liver cells, [125I]iodo-hGH is internalized, with a sequential association with plasma membranes, Golgi elements, and lysosomes.

Animals↗

PubMed1980

[Growth hormone receptors in liver membranes of rats with renal insufficiency].

Binding sites for human growth hormone (hGH) were studied in liver membranes of rats with chronic renal insufficiency (CRI) associated with a marked growth defect. A subtotal nephrectomy was performed in young female rats. One month after surgery, the rats with a plasma creatinine greater than or equal to 3 times that of controls were killed. The specific binding of 125I-hGH to microsomal membranes of rats with CRI was low. The number of binding sites rather than the binding affinity was affected; the number of both lactogenic and somatotropic sites was decreased. The sites of the plasma membranes as well as intracellular sites of Golgi fractions were reduced. No modification of the plasma GH and PRL was found. The hormone level did not appear to be the main regulating factor of the GH binding sites in this system.

Animals↗

PubMed1978

[Analysis of the circadian rhythm of motor activity in white rats by using several pharmacologic agents which act on cerebral monoamines].

Three pharmacological agents, (disulfiram, imipramine and reserpine) influencing the brain monoamine transmitters have been studied to explain the mechanism involved in the motor circadian rhythm. The new results corroborate our previous ones : the norepinephrine transmitter responsible for the paradoxical sleep is unable to explain the depressed metabolic phase of the circadian rhythm; the negative results obtained with disulfiram and imipramine corroborate the previous results with nialamide. On the contrary, the agents which reduce the serotonine transmitter mechanisms (p-chlorophenylalanine) decrease the difference between active and sleep phases by their action involved in the non-activated sleep. Reserpine, supposed to reduce both transmitter mechanisms (serotonine and norepinephrine) shows a p-chlorophenylalanine-like effect, perhaps more strong. It thus appears that the non-activated sleep is responsible for the two essential sleep functions : the restitution function and the depressed phase of the circadian rhythm.

Animals↗