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Biomedical subjects

K Chowdhury

Publications and source records attributed to K Chowdhury.

At least 37 records · Page 2Linked to original sources
PubMed1998

Follicular cells of the thyroid gland require Pax8 gene function.

The thyroid gland develops from two distinct embryonic lineages: follicular cells (which produce thyroxine) and parafollicular C-cells (which produce calcitonin) are of endodermal and neural crest origin, respectively. Little is known about the molecular mechanisms governing the generation of these different cell types. Mice lacking the transcription factor Ttf1 lack both cell types and thus are unable to develop a thyroid gland. By analysis of Pax8-/- mice, we demonstrate that Pax8 is required for the formation of the follicular cells in the thyroid. We present evidence that Pax8 is necessary for providing cues for the differentiation of competent endoderm primordia into thyroxin-producing follicular cells.

Animals↗
PubMed1997

Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.

The functional unit of the endocrine pancreas is the islet of Langerhans. Islets are nested within the exocrine tissue of the pancreas and are composed of alpha-, beta-, delta- and gamma-cells. beta-Cells produce insulin and form the core of the islet, whereas alpha-, delta- and gamma-cells are arranged at the periphery of the islet and secrete glucagon, somatostatin and a pancreatic polypeptide, respectively. Little is known about the molecular and genetic factors regulating the lineage of the different endocrine cells. Pancreas development is known to be abolished in Pdx1-mutant mice and Pax4 mutants lack insulin-producing beta-cells. Here we show that the paired-box gene Pax6 is expressed during the early stages of pancreatic development and in mature endocrine cells. The pancreas of Pax6 homozygous mutant mice lack glucagon-producing cells, suggesting that Pax6 is essential for the differentiation of alpha-cells. As mice lacking Pax4 and Pax6 fail to develop any mature endocrine cells, we conclude that both Pax genes are required for endocrine fate in the pancreas.

Animals↗
PubMed1997

Evidence for the stochastic integration of gene trap vectors into the mouse germline.

A large scale insertional mutagenesis experiment was performed in embryonic stem (ES) cells by introducing two types of gene trap vectors into the genome. These cell lines carrying mutations were introduced into the mouse germline. In order to assess the feasibility of a large scale cloning of the targeted genes from these lines, we have isolated and characterized 55 trapped exons from the corresponding ES cells. Analysis of the data has revealed that vectors containing or lacking an internal ribosome entry site (IRES) can integrate into the ES cell genome stochastically. The targeted genes comprise 30% known genes, 20% expressed sequence tags (ESTs) and 50% novel or unknown genes. The known genes belong to several major classes and represent complete or partial knockouts. Using currently available methods or modifications of them, it should be feasible to do a large scale cloning of trapped genes from the mouse ES cell lines.

Animals↗
PubMed1997

The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas.

The mammalian pancreas contains two distinct cell populations: endocrine cells which secrete hormones into the bloodstream, and exocrine cells, which secrete enzymes into the digestive tract. The four endocrine cell types found in the adult pancreas-(alpha, beta, delta and PP-synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. All of these endocrine cells arise from common multipotent precursors, which coexpress several hormones when they start to differentiate. Expression of some homeobox genes in the early developing pancreas has been reported. The Pax4 gene is expressed in the early pancreas, but is later restricted to beta cells. Inactivation of Pax4 by homologous recombination results in the absence of mature insulin- and somatostatin-producing cells (beta and delta, respectively) in the pancreas of Pax4 homozygous mutant mice, but glucagon-producing alpha cells are present in considerably higher numbers. We propose that the early expression of Pax4 in a subset of endocrine progenitors is essential for the differentiation of the beta and delta cell lineages. A default pathway would explain the elevated number of alpha cells in the absence of Pax4.

Animals↗
PubMed1997

An alpha-E-catenin gene trap mutation defines its function in preimplantation development.

Catenins are proteins associated with the cytoplasmic domain of cadherins, a family of transmembrane cell adhesion molecules. The cadherin-catenin adhesion system is involved in morphogenesis during development and in the maintenance of the integrity of different tissue types. Using a gene trap strategy, we have isolated a mouse mutation for the gene encoding the alpha-E-catenin. This form of the alpha-catenin appears frequently coexpressed with E-cadherin in epithelial cell types. The mutation obtained eliminates the carboxyl-terminal third of the protein but nevertheless provokes a complete loss-of-function phenotype. Homozygous mutants show disruption of the trophoblast epithelium (the first differentiated embryonic tissue), and development is consequently blocked at the blastocyst stage. This phenotype parallels the defects observed in E-cadherin mutant embryos. Our results show the requirement of the alpha-E-catenin carboxy terminus for its function and represent evidence of the role of the alpha-E-catenin in vivo, identifying this molecule as the natural partner of the E-cadherin in trophoblast epithelium.

Animals↗
PubMed1996

Elucidation of the role of Arg 110 of murine leukemia virus reverse transcriptase in the catalytic mechanism: biochemical characterization of its mutant enzymes.

Based on the projected three-dimensional equivalence of conserved amino acids in the catalytic domains of DNA polymerases, we propose Arg 110 of MuLV RT to be an important participant in the catalytic mechanism of MuLV RT. In order to obtain evidence to support this proposition and to assess the functional importance of Arg 110, we carried out site directed mutagenesis of Arg 110 and replaced it with Lys, Ala, and Glu. The mutant enzymes were characterized with respect to their kinetic parameters, ability to bind template-primers, and the mode of DNA synthesis. All the three substitutions at 110 position resulted in severe loss of polymerase activity without any significant effect on the RNase H function. In spite of an approximately 1000-fold reduction in kcat of polymerase activity with three mutant enzymes, no significant reduction in the affinities for either template-primer or dNTP substrates was apparent. Mutant enzymes also did not exhibit significant sulfur elemental effect, implying that the chemical step, i.e., phosphodiester bond formation, was not defective. Examination of the mode of DNA synthesis by the mutant enzymes indicated a shift from processive to the distributive mode of synthesis. The mutants of R110 also displayed significant loss of pyrophosphorolysis activity. Furthermore, the time course of primer extension with mutant enzymes indicated severe reduction in the rates of addition of the first nucleotide and even further reduction in the addition of the second nucleotide. These results suggest that the rate limiting step for the mutant enzymes may be before and after the phosphodiester bond formation. Based on these results, we propose that Arg 110 of MuLV RT participates in the conformational change steps prior to and after the chemical step of polymerase reaction.

Animals↗
PubMed1995

Segment-specific expression of the neuronatin gene during early hindbrain development.

The developing hindbrain is segmented in a series of repetitive bulges called neuromeres or rhombomeres. In the mouse, first molecular evidence for segmentation of the hindbrain came from rhombomeres 3- and 5-specific expression of the Krox-20 gene. The hindbrain segments are linked with the expression of different Hox genes which have a role in patterning the hindbrain and branchial region of the vertebrate head. Here we identified by subtractive hybridization a gene, mouse neuronatin, that is downregulated in P19 embryo carcinoma cells that have undergone a partial differentiation process. Neuronatin encodes putative transmembrane proteins of 54, 55, and 81 amino acids that might serve as protein ligands, cofactors, or small cell adhesion molecules. The neuronatin gene is transiently expressed in rhombomeres 3 and 5 during early hindbrain development and in the floor of the foregut pocket. In addition, expression is observed in the early Rathke's pouch, in the derived adenohypophysis, and in the developing inner ear. During later embryogenesis the neuronatin gene is strongly expressed in the major part of the central and peripheral nervous system. These results suggest that neuronatin participates in the maintenance of segment identity in the hindbrain and pituitary development and maturation or maintenance of the overall structure of the nervous system.

Alternative Splicing↗
PubMed1995

Diagnosis and treatment of intracranial complications of paranasal sinus infections.

Complications and local extension of paranasal sinus infections most often involve the orbit and periorbita. Because of the widespread use of antibiotics since World War II, intracranial extension of maxillofacial sinusitis is rarely seen today. Nevertheless, the clinician must be aware of the potential for these complications, because late recognition of this condition and delays in treatment can increase morbidity and mortality rates. A comprehensive, current review of sinogenic intracranial complications is presented, with illustrative cases of brain abscess, subdural empyema, meningitis, cavernous sinus thrombosis, epidural abscess, and osteomyelitis. The mechanisms and potential for intracranial spread of infection from the frontal, sphenoid, and ethmoid sinuses are discussed in detail. The management of each type of complication is outlined, including the use of computed tomography and magnetic resonance imaging, and the role of surgical drainage.

Adolescent↗
PubMed1994

Regulated expression of Brachyury(T), Nkx1.1 and Pax genes in embryoid bodies.

Embryonic stem cells (ES) can be exploited to analyze in vitro mechanisms of cellular differentiation. We have utilized ES-derived embryoid body formation in an attempt to study cell types resulting from in vitro differentiation. To this end, a variety of molecular markers, preferably those which have been associated with regulatory events during mouse embryogenesis, was employed. Specifically, Brachyury (T), Pax-3 and Pax-6 genes as well as Nkx-1.1 were used. We could demonstrate that the expression of these genes in vitro was regulated by growth factors such as activin A or bFGF. Implications of these findings and the possible applications for identifying new genes are discussed.

Animals↗
PubMed1994

Development and evaluation of rapid monoclonal antibody-based coagglutination test for direct detection of Vibrio cholerae O139 synonym Bengal in stool samples.

A monoclonal antibody-based coagglutination test directly detected Vibrio cholerae O139 synonym Bengal in 83 of 120 watery diarrheal stool specimens; on culture, 90 samples were positive. Thus, with 92% sensitivity, 100% specificity, and 100% positive and 95% negative predictive values, the coagglutination test is a useful rapid test for V. cholerae O139.

Agglutination Tests↗
PubMed1993

Glutamate induces the growth factors NGF, bFGF, the receptor FGF-R1 and c-fos mRNA expression in rat astrocyte culture.

The effect of glutamate on primary cultures of rat cortical astrocytes was studied using Northern blot hybridization. Incubation with glutamate (100 microM, 15 min) induced nerve growth factor (NGF), basic fibroblast growth factor (bFGF), FGF receptor (FGF-R1) and proto-oncogene c-fos gene expression in a time dependent manner. Maximal induction of NGF, bFGF and FGF-R1 mRNA was reached after 4 h of incubation (7.2-fold induction of NGF, 3-fold increase in bFGF and 3.6-fold induction of FGF-R1 mRNA). The induction kinetics of NGF, bFGF and FGF-R1 mRNA are similar. The rapid (1 h) 77-fold induction of the c-fos transcript precedes the induction of the other genes tested.

Animals↗
PubMed1992

Classification and treatment of zygomatic fractures: a review of 1,025 cases.

The treatment of zygomatic fractures varies among surgeons, and the cosmetic and functional results are frequently less than optimal. A treatment guideline based on a simple classification of zygomatic fractures is presented. The emphasis is placed on the indications for closed and open reduction, consistent methods of three-dimensional alignment and fixation, and the management of concomitant infraorbital rim and orbital floor fractures. Postoperative results with regard to infraorbital nerve and maxillary sinus dysfunction, malar asymmetry, and orbital complications in the treatment of 1,025 consecutive zygomatic fractures are presented.

Adolescent↗
PubMed1992

The ubiquitous transactivator Zfp-38 is upregulated during spermatogenesis with differential transcription.

We describe the complete nucleotide sequence of a full length cDNA clone encoding a new mouse zinc finger protein gene, Zfp-38 and localize it on chromosome 5 by the interspecific backcross analysis. The N-terminal domain of the Zfp-38 protein (64 kDa) contains 358 amino acids and the C-terminal domain of 197 residues encodes 7 zinc fingers. We also present evidence that Zfp-38 is a strong transcriptional activator. The transactivation domain was localized in the non finger region and a fusion protein containing 112 amino acid residues from this region of the Zfp-38 and the DNA binding domain of the yeast Gal 4 protein, very efficiently transactivated the expression of a reporter CAT plasmid, harboring the Gal4 target site. By in situ hybridization and northern blotting technique, the Zfp-38 transcript can be detected at a highly elevated level during spermatogenesis. Its expression accompanies the progression from pachytene spermatocytes to round spermatids. The undifferentiated spermatogonia or the haploid elongated spermatid and the spermatozoa do not show any detectable level of the transcript. Interestingly, other tissues express low levels of a slightly shorter transcript with a different 5' end as determined by RNase protection. The presence of both a transcriptional activating domain and 7 DNA binding zinc fingers, coupled with the cell type(s) specific expression pattern, suggests that Zfp-38 has the potential to regulate transcription during spermatogenesis.

Amino Acid Sequence↗
PubMed1992

Free radicals induce gene expression of NGF and bFGF in rat astrocyte culture.

Hydrogen peroxide (H2O2) is a type of active oxygen species produced mainly in blood by inflammation, ischemia or anoxia. Treatment of rat neonatal cortical astrocytes in culture with 0.2-1.0 mM H2O2 which is lethal for hippocampal neurons, increases nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) mRNA content in a time dependent manner. H2O2 also increases c-fos mRNA expression, which is probably involved in the gene regulation of both NGF and bFGF. Maximal induction was reached after 6 h of incubation (5.7-fold increase in NGF and 2.4-fold induction of bFGF mRNA). Hydrogen peroxide induced bFGF and NGF gene expression suggests that neurotrophic factors in astrocytes could be induced by lesion, consistent with their protective function in the CNS.

Animals↗
PubMed1991

Treatment of 813 zygoma-lateral orbital complex fractures. New aspects.

A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema. Implants of lyophilized dura or cartilage and autogenous bone were used to reconstruct orbital floor defects. Malar asymmetry is a frequent complication of zygoma fractures resulting from inadequate three-dimensional reduction. Methods for accurate reduction and stabilization, indications for closed and open reduction, and management of the fractured infraorbital rim are emphasized. The indications for miniplates vs wire ligatures for the infraorbital rim are discussed. Long-term follow up and evaluation of the results with regard to the fracture pattern, complications, maxillary sinus dysfunction, and facial and orbital symmetry are presented.

Bone Plates↗
PubMed1990

New type of POU domain in germ line-specific protein Oct-4.

Members of a family of murine octamer-binding proteins interact specifically with the octamer motif, a transcription regulatory element found in the promoter and enhancer regions of many genes. Oct-4 is a maternally expressed protein that is also present in the pre-implantation mouse embryo. Although many regulatory proteins are expressed in post-implantation embryos, transcription factors regulating pre-implantation processes have remained elusive. The Oct-4 gene is therefore a prime candidate for an early developmental control gene. Here we report the complementary DNA cloning of the mouse Oct-4 gene, and the characterization of the encoded protein(s) by sequential in vitro transcription, translation, DNA-binding and protease-clipping analysis. Deletion analysis shows that the DNA-binding activity is mediated by a POU domain encoded in an open reading frame corresponding to a 324-amino-acid protein. Sequence comparison with known POU domains reveals that Oct-4 is a novel member of the POU-family.

Animals↗