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M Bai

Publications and source records attributed to M Bai.

At least 73 records · Page 4Linked to original sources
PubMed1996

Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells.

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that plays a key role in extracellular calcium ion homeostasis. We have engineered 11 CaR mutants that have been described in the disorders familial benign hypercalcemia (FBH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcaemia (ADH), and studied their function by characterizing intracellular calcium [Ca2+]i transients in response to varying concentrations of extracellular calcium [Ca2+]o or gadolinium [Gd3+]o. The wild type receptor had an EC50 for calcium (EC50[Ca2+]o) (the value of [Ca2+]o producing half of the maximal increase in [Ca2+]i) of 4.0 mM (+/- 0.1 SEM). However, five missense mutations associated with FBH or NSHPT, (P55L, N178D, P221S, R227L, and V817I) had significantly higher EC50[Ca2+]os of between 5.5 and 9.3 mM (all P < 0.01). Another FBH mutation, Y218S, had an EC50[Ca2+]o of > 50 mM but had only a mildly attenuated response to gadolinium, while the FBH mutations, R680C and P747fs, were unresponsive to either calcium or gadolinium. In contrast, three mutations associated with ADH, (F128L, T151M, and E191K), showed significantly reduced EC50[Ca2+]os of between 2.2 and 2.8 mM (all P < 0.01). These findings provide insights into the functional domains of the CaR and demonstrate that mutations which enhance or reduce the responsiveness of the CaR to [Ca2+]o cause the disorders ADH, FBH, and NSHPT, respectively.

Calcium↗
PubMed1996

A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.

BACKGROUND: The calcium-sensing receptor regulates the secretion of parathyroid hormone in response to changes in extracellular calcium concentrations, and mutations that result in a loss of function of the receptor are associated with familial hypocalciuric hypercalcemia. Mutations involving a gain of function have been associated with hypocalcemia in two kindreds. We examined the possibility that the latter type of mutation may result in a phenotype of familial hypocalcemia with hypercalciuria. METHODS: We studied six kindreds given a diagnosis of autosomal dominant hypoparathyroidism on the basis of their hypocalcemia and normal serum parathyroid hormone concentrations, a combination that suggested a defect of the calcium-sensing receptor. The hypocalcemia was associated with hypercalciuria, and treatment with vitamin D resulted in increased hypercalciuria, nephrocalcinosis, and renal impairment. Mutations in the calcium-sensing-receptor gene were identified by DNA-sequence analysis and expressed in human embryonic kidney cells (HEK-293). RESULTS: Five heterozygous missense mutations (Asn118Lys, Phe128Leu, Thr151Met, Glu191Lys, and Phe612Ser) were detected in the extracellular domain of the calcium-sensing-receptor gene and shown to cosegregate with the disease. Analysis of the functional expression of three of the mutant receptors in HEK-293 cells demonstrated shifts in the dose-response curves so that the extracellular calcium concentrations needed to produce half-maximal increases in total inositol phosphate in the cells were significantly (P=0.02 to P<0.001) lower than those required for the wild-type receptor. CONCLUSIONS: Gain-of-function mutations in the calcium-sensing receptor are associated with a familial syndrome of hypocalcemia with hypercalciuria that needs to be distinguished from hypoparathyroidism.

Adolescent↗
PubMed1996

Agonists of the Ca(2+)-sensing receptor (CaR) activate nonselective cation channels in HEK293 cells stably transfected with the human CaR.

Calcium (Ca2+) ions serve multiple roles both intra- and extracellularly. We recently cloned a cell surface, Cao(2+)-sensing receptor (CaR) that plays a central role in Cao2+ homeostasis by enabling direct regulation by Cao2+ of parathyroid hormone (PTH) secretion and the function of other tissues involved in mineral ion homeostasis. In parathyroid cells, the CaR activates phospholipase C, thereby raising the levels of inositol trisphosphate (IP3) and releasing Ca2+ from intracellular stores. High Cao2+ also activates Ca2+ influx into parathyroid cells through poorly defined mechanisms that may involve Ca(2+)-permeable, nonselective cation channels (NCC). We now show that human embryonic kidney (HEK293) cells also have NCC and, furthermore, that these channels are regulated by the CaR. We have utilized the cell-attached configuration of the patch clamp technique to characterize the properties of these channels as well as their regulation by various CaR agonists added to the external bath solution. The polycationic CaR agonist, neomycin (100 microM), as well as an elevated concentration of Cao2+ (3 mM), both of which activate the cloned CaR, significantly increased the probability of channel opening (Po) in HEK cells stably transfected with the CaR but not in nontransfected HEK cells which do not contain the receptor. Thus, the activation of the CaR enhances the activity of Ca(2+)-permeable NCC in these cells, which could contribute to the sustained increase in Cai2+ in parathyroid cells which is observed in response to elevated Cao2+. The CaR may also regulate the membrane functions of other CaR-expressing cells (e.g., those in the brain), at least in part, by modulating similar channels.

Calcium-Binding Proteins↗
PubMed1996

Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor.

Nearly 30 mutations have been identified to date in the coding region of the extracellular calcium-sensing receptor (CaR) that are associated with inherited human hypo- and hypercalcemic disorders. To understand the mechanisms by which the mutations alter the function of the receptor may help to discern the structure-function relationships in terms of ligand-binding and G protein coupling. In the present studies, we transiently expressed eight known CaR mutations in HEK293 cells. The effects of the mutations on extracellular calcium- and gadolinium-elicited increases in the cytosolic calcium concentration were then examined. Seven inactivating mutations, which cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, show a reduced functional activity of the receptor because they may 1) reduce its affinity for agonists; 2) prevent conversion of the receptor from a putatively immature, high mannose form into the fully glycosylated and biologically active form of the CaR, in addition to lowering its affinity for agonists; or 3) fail to couple the receptor to and/or activate its respective G protein(s). Conversely, one activating mutation, which causes a form of autosomal dominant hypocalcemia, appears to increase the affinity of the receptor for its agonists.

Blotting, Western↗
PubMed1996

Widespread Castleman disease: CT findings.

The widespread form of Castleman disease is a rare condition with aggressive, often fatal course. We describe the imaging findings of two patients with extensive Castleman lymphadenopathy. The duration of the disease was 8 years in one patient and 4.5 months in the other.

Castleman Disease↗
PubMed1996

Ontogeny of the extracellular calcium-sensing receptor in rat kidney.

We recently cloned extracellular Ca(2+)-sensing receptors (CaRs) from bovine parathyroid and rat kidney that play key roles in Ca2+ homeostasis. Inactivating mutations of the CaR in the inherited human disorder, familial hypocalciuric hypercalcemia, cause reduced responsiveness of the parathyroid to extracellular Ca2+ (Cao2+), as well as abnormally avid renal tubular reabsorption of both Ca2+ and Mg2+ in the distal tubule, suggesting an important role for the CaR in regulating parathyroid hormone (PTH) secretion and renal handling of divalent cations. High Cao2+ also inhibits vasopressinstimulated adenosine 3',5'-cyclic monophosphate accumulation in the medullary thick ascending limb (MTAL) and water reabsorption in the collecting duct (CD) and modulates various other aspects of renal function. The relevance of the CaR to these processes, however, is uncertain. Reduced responsiveness of vasopressin-and PTH-mediated actions on the kidney have been described in the newborn that could potentially reflect effects of the CaR on these aspects of renal function. To define further the role of the CaR in regulating renal function, including the above-mentioned changes during the perinatal period, therefore, we have studied its ontogeny in rat kidney. Northern and Western blot analyses, as well as immunohistochemistry with CaR-specific probes, demonstrate that there is little prenatal expression of the extracellular Ca(2+)-sensing receptor, except in large tubules and branching ureteric buds of developing nephrons. Postnatally, CaR mRNA and protein increase markedly during the 1st wk, related principally to expression of the receptor in the developing TAL and, to a lesser extent, in the CD. The level of expression of the receptor remains nearly constant after postnatal day 14. These results demonstrate that the perinatal increases in expression of CaR mRNA and protein parallel its tissue-specific renal expression. Furthermore, it is possible that some of the previously described changes in renal handling of divalent cations and water in the perinatal and immediate postnatal period are related, in part, to the increasing levels of expression of the CaR and resultant inhibitory effects on the actions of PTH and antidiuretic hormone on the developing nephron.

Aging↗
PubMed1996

Combination therapy with recombinant human erythropoietin, interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in idiopathic myelofibrosis.

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.

Aged↗
PubMed1996

[Glutamine dipeptide enriched nutritional solutions attenuate bacterial translocation in rats after 60% intestinal resections].

OBJECTIVE: To investigate the effects of alanyl-glutamine dipeptide (Ala-Gln) enriched parenteral nutrition solution on intestinal mucosa or gut barrier since traditional parenteral nutrition leads to bacterial translocation. METHODS: The moderate operation stress was induced by 60% resection of small intestine. Qualified rats distributed in three groups: Chow group (n = 10) received standard rat chow, PN group (n = 10) received traditional parenteral nutrition solution only, and Ala-Gln group (n = 10) received glutamine dipeptide enriched nutritional solutions (3% Ala-Gln). Rats were maintained on their respective diets for 7 days. RESULTS: Chow group and Ala-Gln group maintained serum glutamine concentration, villus height and mucosal thickness. The bacterial translocation rate in Chow group and Ala-Gln group was 20% and in PN group 70%. CONCLUSION: Results demonstrate that Ala-Gln enriched nutritional solutions maintain intestinal adaptation and gut barrier function after massive intestinal resection.

Animals↗
PubMed1996

[Glutamine dipeptide attenuate mucosal atrophic changes and preservation of gut barrier function following 5-FU intervention].

Traditional parenteral nutrition (PN) and chemotherapy may lead to changes mucosal morphology and gut barrier function. To investigate the effects of alanyl-glutamine on intestinal mucosal morphology and gut barrier function in PN-fed rats challenged with 5-FU male Wistar rats were central catheterized and randomily divided into two groups: PN group (n = 10) that received traditional parenteral nutrition solution only, and Ala-Gln group (n = 10) that received glutamine dipeptide enriched nutritional solution (3% Ala-Gln). The rats were maintained on their respective diets for 7 days. 5-FU (75 mg/kg) was injected intraperitoneally at 8 am on day 4. All rats were gavaged with lactulose (100 mg) and mannitol (50 mg) in 2ml before and three days after administration of 5-FU. Ala-Gln group maintained serum glutamine concentration, intestinal mucosal morphology. While bacterial translocation rates in ala-Gln group was 30%, in PN group was 90% (P < 0.05). Similar intestinal permeability was observed on day 3 in both groups. The control group had a significantly increased intestinal permeability on day 7 (P < 0.05), while Ala-Gln group maintained the intestinal permeability. It was suggested that alanyl-glutamine maintained intestinal morphology and gut barrier function in PN-fed rats challenged with 5-FU.

Animals↗
PubMed1995

Cutaneous lymphocytic vasculopathy in lymphoproliferative disorders--a paraneoplastic lymphocytic vasculitis of the skin.

In this report the histopathology and the natural history of cutaneous lymphocytic vasculopathy (lymphocytic vasculitis) in patients with lymphoproliferative diseases, is described. Between January 1986 and June 1992, 116 patients with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (CLL) were followed. Among them 3 patients with NHL, one with angioimmunoblastic lymphadenopathy/lymphoma and 7 with CLL developed cutaneous vasculitic changes during the course of their disease (incidence of 9.5%). All patients had advanced stage disease. Lymphomas were of B-cell origin and either low or intermediate grade. The median time between the diagnosis of NHL or CLL and the appearance of skin manifestations was 18 months. Recurrent vasculitic changes involving exclusively the skin, was characterized by a (maculo)papular rash, most commonly found in the upper and lower extremities. Pruritus of varying intensity was present in 82% of the patients. In the biopsy, all had perivascular and/or vessel wall lymphocytic infiltration of the dermis with occasional red cell extravasation. Immunohistochemical staining revealed that these infiltrates were mainly composed of T-lymphocytes. We conclude, that cutaneous lymphocytic vasculopathy is a relatively common paraneoplastic skin manifestation in patients with lymphoproliferative diseases and histologically is characterized as lymphocytic vasculitis with (peri)vascular infiltration by non-malignant T lymphocytes.

Aged↗
PubMed1995

[The change of gut barrier function and gene expression after surgical stress and parenteral nutrition].

Surgical stress and parenteral nutrition (PN) may cause gut mucosal atrophy and alter barrier function. Gene expression of growth factors and enzymes in small intestine may change. The effects of alanyl-glutamine dipeptide (Ala-Gln) on gut barrier and the gene expression of insulin-like factor I (IGF-I) and glutaminase in parenteral infusion rats with massive small intestine resection were investigated. Twenty Wistar rats were catheterized with 60% small bowel resectin. They were divided into two groups. Control group (n = 10) received traditional parenteral nutritional solution, and study group (n = 10) received Ala-Gln enriched nutritional solution (3% Ala-Gln). The rats were maintained with their respective diets for 7 days. The rats in the study group maintained serum glutamine concentration (844.0 +/- 13.2uMol: 640.4 +/- 17.2uMol, P < 0.05), mucosal architecture (mucosal thickness 591 +/- 12uM: 486 +/- 8uM, P < 0.05) and villus height (404 +/- 7uM: 303 +/- 5uM, P < 0.05). Bacterial translocation rate decreased in the study group (70%: 20%, P < 0.05). Ileal mucosal IGF-I mRNA and jejunal mucosal glutaminase mRNA in the study group increased twofold and threefold respectively. The results suggest that Ala-Gln may enhance gut growth and improve gut mucosa integrity and barrier function in part by means of stimulating IGF-I and glutaminase expression in surgical stress.

Animals↗
PubMed1994

Primary lymphoma of the pericardium: report on a "cured" case and review of the literature.

This report describes a 62-year-old man with a primary diffuse, immunohistochemically proven B-cell lymphoma of large non-cleaved cell (centroblastic) type of the pericardium. The patient responded completely to systemic chemotherapy and remains free of disease 30 months after diagnosis. The use of non-cardiotoxic drugs in divided doses as initial treatment is emphasized. In addition, the authors reviewed the literature of the last decade regarding the management and outcome of patients with primary cardiac lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Vitronectin receptor antibodies inhibit infection of HeLa and A549 cells by adenovirus type 12 but not by adenovirus type 2.

The penton base gene from adenovirus type 12 (Ad12) was sequenced and encodes a 497-residue polypeptide, 74 residues shorter than the penton base from Ad2. The Ad2 and Ad12 proteins are highly conserved at the amino- and carboxy-terminal ends but diverge radically in the central region, where 63 residues are missing from the Ad12 sequence. Conserved within this variable region is the sequence Arg-Gly-Asp (RGD), which, in the Ad2 penton base, binds to integrins in the target cell membrane, enhancing the rate or the efficiency of infection. The Ad12 penton base was expressed in Escherichia coli, and the purified refolded protein assembled in vitro with Ad2 fibers. In contrast to the Ad2 penton base, the Ad12 protein failed to cause the rounding of adherent cells or to promote attachment of HeLa S3 suspension cells; however, A549 cells did attach to surfaces coated with either protein and pretreatment of the cells with an integrin alpha v beta 5 monoclonal antibody reduced attachment to background levels. Treatment of HeLa and A549 cells with integrin alpha v beta 3 or alpha v beta 5 monoclonal antibodies or with an RGD-containing fragment of the Ad2 penton base protein inhibited infection by Ad12 but had no effect on and in some cases enhanced infection by Ad2. Purified Ad2 fiber protein reduced the binding of radiolabeled Ad2 and Ad12 virions to HeLa and A549 cells nearly to background levels, but the concentrations of fiber that strongly inhibited infection by Ad2 only weakly inhibited Ad12 infection. These data suggest that alpha v-containing integrins alone may be sufficient to support infection by Ad12 and that this pathway is not efficiently used by Ad2.

Adenoviruses, Human↗
PubMed1994

[Bilateral testicular metastasis of an adenocarcinoma of the prostate].

Secondary testicular tumors are very rare. Since 1935, approximately 200 cases have been documented in the international literature. Testicular metastases of prostatic carcinoma are reported more frequently and other common primary tumor sites are the lung, kidney, colon, stomach and other sites. A review of the literature revealed 43 cases originating from prostatic carcinoma with 4 bilateral cases. The authors add a rare case of bilateral metastasis to the testis originating from prostatic carcinoma. This patient had been treated by transurethral resection of the prostate and bilateral orchidectomy 24 months previously.

Adenocarcinoma↗
PubMed1993

Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells.

The adenovirus penton base protein has a cell rounding activity and may lyse endosomes during virus entry into the cytoplasm. We found that penton base that was expressed in Escherichia coli also caused cell rounding and that cells adhered to polystyrene wells that were coated with the protein. Mutant analysis showed that both properties required an Arg-Gly-Asp (RGD) sequence at residues 340 to 342 of penton base. In flat adherent cells, virus mutants with amino acid substitutions in the RGD sequence were delayed in virus reproduction and in the onset of viral DNA synthesis. In nonadherent or poorly spread cells, the kinetics of mutant virus reproduction were similar to those of wild-type adenovirus type 2. Expression of the mutant phenotype exclusively in the flat cells that we tested supports a model in which penton base interacts with an RGD-directed cell adhesion molecule during adenovirus uptake or uncoating.

Adenoviruses, Human↗
PubMed1993

Clinical study of 100 cases of Kyasanur Forest disease with clinicopathological correlation.

100 cases of Kyasanur Forest Disease were studied clinically and autopsy or postmortem biopsies of various organs were done in 8 cases. 1. Our study showed that KFD passes through 4 stages each lasting for about a week. i.e. a prodromal stage with fever, hypotension hepatomegaly, a stage of complication characterized by haemorrhage, neurological manifestation or bronchopneumonia, a stage of recovery followed by a li stage of fever in some cases. 2. The exact of cause of haemorrhage could not be identified though Disseminated Intravascular Coagulation was suspected. 3. Hypotension in KFD could be of Myocardial origin. 4. Encephalopathy in KFD could be due to a metabolic cause probably of hepatic origin. 5. Lung signs could be due to intraalveolar haemorrhage and secondary infection.

Adolescent↗