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H Chin

Publications and source records attributed to H Chin.

At least 55 records · Page 3Linked to original sources

Genetic mapping of the mouse genes encoding the voltage-sensitive calcium channel subunits.

The genes encoding the alpha 1 and beta subunits of voltage-sensitive calcium channel were mapped in the mouse by analysis of the progeny of two multilocus crosses. The alpha 1, beta 2, and beta 4 subunit genes, termed Cchna1, Cchb2, and Cchb4, are located at different sites on proximal Chr 2, while the beta 3 subunit gene Cchb3 maps to Chr 15 near Wnt1. These results together with previous mapping data indicate that the calcium channel genes are dispersed in the mouse genome, unlike the sodium channel genes, which are clustered.

Animals↗

Transcriptional regulation of the neuronal L-type calcium channel alpha 1D subunit gene.

1. The transcriptional regulation of the rat brain L-type calcium channel alpha 1D subunit (RB alpha 1D) gene was investigated using NG108-15 neuroblastoma-glioma cells. 2. Differentiation of NG108-15 cells in the presence of prostaglandin E1 or retinoic acid resulted in the appearance of mRNA encoding the RB alpha 1D subunit detected using Northern blot analysis. 3. A rat genomic DNA library was screened, and a 15.2-kb clone was isolated and partially sequenced which included part of the 5' upstream sequence through the initial part of intron 2 of the RB alpha 1D gene. 4. Deletion analysis, using a CAT reporter gene and transfected NG108-15 cells, revealed that the 1.2-kb 5'-upstream sequence from the RB alpha 1D gene contains cis-acting positive and negative regulatory elements. A deletion of the 3' end of exon 1 also suggested the presence of regulatory elements in the first exon. 5. DNase footprinting of exon 1 of the RB alpha 1D gene revealed two regions protected from digestion by specific protein binding, and the second region included an (ATG)7 trinucleotide repeat sequence. Electrophoretic mobility shift assays confirmed nuclear protein(s) binding to the (ATG)7 sequence. 6. The (ATG)7 sequence functions as a enhancer when linked to a thymidine kinase promoter and a CAT reporter gene. 7. These results provide the initial description of the transcriptional regulation of the RB alpha 1D gene and identify a novel enhancer that consists of an (ATG)7 trinucleotide repeat sequence.

Alprostadil↗

Dynamics of Björk-Shiley Convexo-Concave mitral valves in sheep.

The outlet strut of Björk-Shiley (BSCC) Convexo-Concave heart valves has fractured in some implanted valves resulting in disc escape and emergency reoperation or death. The closing dynamics of BSCC heart valves was studied in situ to determine the forces acting on the outlet strut during valve closure. BSCC valves with strain gages attached to the outlet strut were implanted in the mitral position in sheep. Impact forces were measured under various circumstances including anesthetized, sedentary, and exercise conditions. Left ventricular (LV) pressures were recorded simultaneously via catheter-tip pressure transducers. Impact forces increased with the 1/3 power of left ventricular pressure rise and the square root of LV pressure at valve closure. Good agreement between the in vivo measurements and theoretical models was observed. Based on this study, it is concluded that sheep provides a good in situ model for the testing of mechanical mitral valves.

Anesthesia, General↗

Integrated clinical database in a health maintenance organization.

This paper describes the development and implementation of the first phase of a comprehensive clinical information system in the Kaiser Permanente Northwest Region. This system integrates information from disparate departmental systems into a single clinical database. By using periodic batch downloads of patient data from departmental systems into the clinical database, rather than requiring real-time updates, we have been able to implement this system with relative ease and speed. It contains patient demographics, lab, outpatient pharmacy, radiology, pathology, dictated consults, admission histories and physicals, discharge summaries, and other dictated reports for over 380,000 Health Plan Members. The system is fast, intuitive, reliable, and user-friendly. In March 1994, there were approximately 1,600 active users. These individuals accounted for approximately 410,000 transactions in the month, with an average daily transaction volume of 11,450. Quantifiable cost-savings, in terms of decreased chart pulls and decreased phone calls for information, have offset the cost of development and implementation to some extent. Less quantifiable improvements in the quality of care and the associated cost-savings may eclipse the quantifiable benefits. This system lays the foundation for our clinical information system efforts.

Health Maintenance Organizations↗

Strategies for cell biological studies in oxytocinergic neurons.

Hypothalamic magnocellular neurons expressing the neurohypophysial peptides, oxytocin (OT) and vasopressin (AVP), have historically served as valuable models for cell biological studies of peptidergic neurons. This is because of the relative ease with which the perikarya, axons, and nerve terminals of these cells can be isolated for anatomical, biochemical, and physiological analysis. A popular strategy is to harness the regulatory elements in the OT and AVP genes in order to target specific molecules to these cells in vivo, so as to elucidate various cell biological issues, e.g., pacemaker, prohormone processing, axonal transport, and secretion mechanisms. The peptide genes are good sources for regulatory controls since they are relatively abundantly and specifically expressed in these neurons in the CNS. The major problem has been to identify the critical regulatory elements in these genes which are responsible for the cell-specific expression. Recent transgenic studies have implicated various 3'-untranslated nucleotide sequence regions in the OT and AVP genes which appear to contain these regulatory elements. A structural analysis of these regions in the mouse genes will be discussed. A second problem has been the availability of appropriate model systems to test constructs for "cell-specific" expression. Transgenic mice have been effective models in this regard but are costly and labor-intensive. An alternative approach using biolistic techniques to transfect slice-explants containing the primary OT and AVP neurons in culture will be described.

Animals↗

The inducible form of nitric oxide synthase (NOS2) isolated from murine macrophages maps near the nude mutation on mouse chromosome 11.

Nitric oxide synthase has been shown to mediate streptozocin-induced diabetes and to act as an antimicrobial agent in murine macrophages. Using a cDNA probe for the inducible form of nitric oxide synthase (Nos2) isolated from murine macrophages we have determined that the gene maps within 1 cM of the nude mutation on mouse Chromosome 11. The position of Nos2 was also mapped relative to the markers 115, Evi2, Cchlbl (previously unmapped), and Gfap. This map location is discussed relative to map locations for disease susceptibility loci involved in mediating cutaneous leishmaniasis (ScII) and autoimmune type-I diabetes (Idd4).

Animals↗

[Experimental studies on the morphological changes in the endocrine pancreas after gastrectomy].

I report the detailed morphological changes of the endocrine pancreas after gastrectomy, by PAP stain method, using gastrectomized rats. Regarding the number-ratio and the occupied area-ratio of the B and A cells in each Langerhans islet, there was no difference in each group. But regarding the D cell in totally gastrectomized rats, especially in EJ group (total gastrectomy, esophagojejunostomy with Braun anastomosis), the most notable morphological changes were recognized, namely the occupied area-ratio and the number-ratio of the D cell in each Langerhans islet increased to 3.57 +/- 1.64% and 11.73 +/- 3.89%. In gastrectomized rats, the structure of the B and A cells in each Langerhans islet was comparatively well-preserved. In totally gastrectomized rats, especially in EJ group, the more remarkable increase of the D cell in each Langerhans islet was recognized. It is though that because of the loss of the stomach, the secretory changes of the gut hormones and the accelerated intestinal transit and etc., the D cell increased compensatorily.

Animals↗

[A case of resected gastric cancer in which cancer had apparently disappeared by preoperative administration of tegafur].

This paper reports a case of gastric carcinoma in which cancerous tissue was not found in the resected specimen, apparently due to preoperative tegafur administration. The patient was a 56-year-old woman who was diagnosed by initial endoscopic examination including endoscopic biopsy as having an advanced gastric cancer of Borrmann type 2. During the waiting period for operation, she was placed on oral administration of tegafur (Futrafur capsule) 600 mg 3 times a day for 31 days. The second endoscopic examination 14 days later showed reduction of both marginal elevation and central excavation of the lesion, and biopsy at this time was negative for carcinoma. Because of the initial definite diagnosis of cancer, a gastric resection was performed 31 days later, but no cancerous tissue was found in the resected specimen. This case was considered to be a carcinoma especially sensitive to tegafur.

Adenocarcinoma↗

Regional expression and chromosomal localization of the delta opiate receptor gene.

The delta opiate receptor gene has been cloned from the mouse neuroblastoma-rat glioma hybrid cell NG108-15. The clone that we isolated is apparently identical to that reported by Evans et al. [Evans, C. J., Keith, D. E., Jr., Morrison, H., Magendzo, K. & Edwards, R. H. (1992) Science 258, 1952-1955] and essentially identical with that of Kieffer et al. [Kieffer, B. L., Befort, K., Gaveriaux-Ruff, C. & Hirth, C. G. (1992) Proc. Natl. Acad. Sci. USA 89, 12048-12052]. We have found full-length transcripts of the gene in mouse brain but in no other tissues examined. Within the brain the gene is expressed at low levels in many regions but transcripts are found in particularly large amounts in the anterior pituitary and pineal glands. Since these tissues are located outside the blood-brain barrier, opioid peptides easily can reach receptors in these areas from the blood. The gene, which is present as a single copy, has been mapped to the distal region of mouse Chromosome 4.

Amino Acid Sequence↗

Rat brain expresses an alternatively spliced form of the dihydropyridine-sensitive L-type calcium channel alpha 2 subunit.

We have cloned and sequenced a cDNA (rB-alpha 2) encoding an alpha 2 subunit of the voltage-sensitive L-type calcium channel (dihydropyridine receptor) of rat brain. The cDNA (3823 base pairs) encodes a protein of 1091 amino acids with a Mr of 123,822. The deduced amino acid sequence of rB-alpha 2 cDNA is highly similar (95% amino acid identity) to that of rabbit skeletal muscle alpha 2 subunit. The rB-alpha 2 protein is distinct from the previously cloned skeletal muscle alpha 2-subunit protein [Ellis, S. B., Williams, M. E., Ways, N. R., Brenner, R., Sharp, A. H., Leung, A. T., Campbell, K. P., McKenna, E., Koch, W., Hui, A., Schwartz, A. & Harpold, M. M. (1988) Science 241, 1661-1664] because it contains an insertion of 7 amino acid residues and a deletion of a 19-amino acid segment between putative transmembrane domains 1 and 2. We show that the rB-alpha 2 and skeletal muscle alpha 2-subunit transcripts are the variants produced by alternative splicing of the primary transcript and that they are differentially expressed in brain and skeletal muscle, respectively.

Amino Acid Sequence↗

Expression of dihydropyridine-sensitive brain calcium channels in the rat central nervous system.

We have localized dihydropyridine (DHP-sensitive calcium channels in rat brain by in situ hybridization and immunohistochemistry. The mRNA for the dihydropyridine-sensitive calcium channel alpha 1 subunit (DHPR-B) is prominently localized in neuronal cells in the olfactory bulb, dentate gyrus, hippocampus, arcuate nucleus, paraventricular nucleus, ventromedial nucleus, cerebral cortex, superior colliculus and the cerebellar Purkinje cell layer. Strong expression of DHPR-B mRNA was also found in the pituitary and pineal glands. DHP-sensitive calcium channel alpha 1 subunit distribution has also been examined immunohistochemically with polyclonal antibodies raised against synthetic peptides specific for the DHPR-B alpha 1 subunit protein. The results from immunohistochemistry were in good agreement with those from in situ hybridization. Thus, regional distribution and localization of DHPR-B mRNA and alpha 1 subunit protein in rat brain suggest that this type of DHP-sensitive brain calcium channel may play an important role in excitation-secretion coupling functions in the neuroendocrine system.

Amino Acid Sequence↗

Angiographic embolization in the management of hemorrhagic complications of pregnancy.

Obstetric hemorrhage continues to be a major cause of maternal mortality and morbidity. Recent developments in percutaneous angiographic embolization techniques have afforded the ability to control persistent bleeding from pelvic vessels while avoiding the morbidity of surgical exploration. We report the use of angiographic embolization in 10 cases of pregnancy-related hemorrhage, including persistent postcesarean bleeding (three cases), vaginal wall hematomas (four cases), cervical ectopic pregnancies (two cases), and postpartum bleeding as a secondary complication of uterine myomas (one case). The embolization procedures were successful in all cases. Nine of 10 patients experienced postprocedural fever with eight cases resolving with antibiotic therapy alone and one patient requiring vaginal drainage of the hematoma-abscess. The mean length of time for the procedure was 167 minutes (range 70 to 270). The average length of hospitalization was 8 days (range 2 to 13). These data indicate that angiographic embolization is effective in treating hemorrhagic complications of pregnancy in hemodynamically stable patients and is preferable to surgery in selected cases.

Angiography↗

The gene for the dihydropyridine-sensitive calcium channel alpha 2 subunit (CCHL2A) maps to the proximal region of mouse chromosome 5.

A rat brain cDNA probe for the gene encoding the alpha 2 subunit of the dihydropyridine-sensitive L-type calcium channel was used as a hybridization probe for the Southern blot analysis of Chinese hamster x mouse somatic cell hybrids and the progeny of an intersubspecies backcross. This gene, termed Cchl2a, was mapped near the centromeric end of the Chromosome 5 linkage group with gene order: centromere-Pgy-1-Cchl2a-Il-6-Pgm-1.

Animals↗

The gene for the alpha 1 subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (Cchl1a3) maps to mouse chromosome 1.

Cchl1a3 encodes the dihydropyridine-sensitive calcium channel alpha 1 subunit isoform predominantly expressed in skeletal muscle. mdg (muscular dysgenesis) has previously been implicated as a mutant allele of this gene. Hybridization of a rat brain cDNA probe for Cchl1a3 to Southern blots of DNAs from a panel of Chinese hamster x mouse somatic cell hybrids suggested that this gene maps to mouse Chromosome 1. Analysis of the progeny of an inbred strain cross-positioned Cchl1a3 1.3 cM proximal to the Pep-3 locus on Chr 1.

Animals↗

The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family.

Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP. We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides. A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe. The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain. Cyclic GMP concentrations in cells transfected with GC-A were half-maximally elevated at 3 nM ANP, 25 nM brain natriuretic peptide (BNP), and 65 nM atriopeptin 1, while 25 microM ANP, 6 microM BNP, and greater than 100 microM atriopeptin 1 were required for half-maximal stimulation of GC-B. The potencies of natriuretic peptides on GC-A and GC-B activity are therefore markedly different; furthermore, despite the specificity of GC-B for BNP, the relatively high BNP concentration required to elicit a response suggests the possible presence of a more potent, unidentified natural ligand.

Amino Acid Sequence↗

Antibodies to an alpha subunit of skeletal muscle calcium channels regulate parathyroid cell secretion.

We have shown previously that Ca2+-channel agonists, which open Ca2+ channels, inhibit parathyroid hormone (PTH) secretion from dispersed bovine parathyroid cells, whereas Ca2+-channel antagonists, which close Ca2+ channels, stimulate PTH release. We now have tested the effects of mouse antibodies specific for purified alpha subunits of rat skeletal muscle Ca2+-channel proteins on PTH secretion by bovine parathyroid cells in vitro. Mouse antisera (MC-2, MC-3, MC-4) blocked the secretion of PTH from parathyroid cells incubated with 0.5 mM Ca2+ ions. Affinity-purified MC-4 antibodies inhibited PTH release in a concentration-dependent manner. Incubation of parathyroid cells with pertussis toxin markedly reduced MC-4-dependent inhibition of PTH secretion. Parathyroid cell membrane proteins were fractionated by NaDodSO4/polyacrylamide gel electrophoresis under either reducing or nonreducing conditions and immunoblotted with MC-4 antiserum. Antibodies bound to one major band of protein with Mr approximately equal to 150,000. These results suggest that the antibodies bind to Ca2+-channel alpha subunits and act as agonists that open the channels and inhibit PTH release.

Animals↗