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Biomedical subjects

J Pang

Publications and source records attributed to J Pang.

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

The impact of crystallinity on Brequinar sodium hygroscopicity.

The hygroscopicity of Brequinar sodium, an organ transplant immunosuppressant, at 75% relative humidity highly depends on the crystal form or crystallinity of the drug substance. Hygroscopicity and ease of water uptake of three lots of Brequinar sodium were investigated. Those lots contained different impurities at levels ranging from 0.26% to 0.5%. DSC thermograms of the hydrated samples suggest that unbound/loosely bound water was released around 90 degrees C and water of hydration was released at 175 degrees C. At equilibrium, 2% of the water was tightly bound. Stoichiometry suggests that this is a hemihydrate. Unbound/loosely bound water has no impact on the hemihydrate crystal structure as indicated by x-ray powder diffraction patterns. The results suggest that the less perfect crystals exhibited a faster water uptake and converted to a stable hemihydrate when stored at 75% relative humidity. Both the anhydrous and the hemihydrate forms of Brequinar sodium exhibited rapid dissolution rate and comparable water solubility.

Biphenyl Compounds↗
PubMed1995

Polymerization of recombinant Hb S-Kempsey (deoxy-R state) and Hb S-Kansas (oxy-T state).

In order to investigate the role of the R (relaxed) to T (tense) structural transition in facilitating polymerization of deoxy-Hb S, we have engineered and expressed two Hb S variants which destabilize either T state (Hb S-Kempsey, alpha 2 beta 2 Val-6,Asn-99) or R state structures (Hb S-Kansas, alpha 2 beta 2 Val-6, Thr-102). Polymerization of deoxy-Hb S-Kempsey, which shows high oxygen affinity and increased dimer dissociation, required about 2- and 6-fold higher hemoglobin concentrations than deoxy-Hb S for polymerization in low and high phosphate concentrations, and its kinetic pattern of polymerization was biphasic. In contrast, oxy- or CO Hb S-Kansas, which shows low oxygen affinity and increased dimer dissociation, polymerized at a slightly higher critical concentration than that required for polymerization of deoxy-Hb S in both low and high phosphate buffers. Polymerization of oxy- and CO Hb S-Kansas was linear and showed no delay time, which is similar to oversaturated oxy- or CO Hb S. These results suggest that nuclei formation, which occurs during the delay time prior to deoxy-Hb S polymerization, does not occur in T state oxy-Hb S-Kansas, even though the critical concentration for polymerization of T state oxy-Hb S-Kansas is similar to that of T state deoxy-Hb S.

Carboxyhemoglobin↗
PubMed1995

Characterization of carrier females and affected males with X-linked recessive nephrolithiasis.

X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.

Adolescent↗
PubMed1994

A subtype of the metabotropic glutamate receptor family in the olfactory system of Atlantic salmon.

A plasma membrane rich fraction was prepared from olfactory rosettes of Atlantic salmon and used to study binding of L-glutamic acid and activation of phospholipase C (PLC). Glutamate binding was saturable, high affinity, and inhibited by aspartic acid and taurocholate but not by alanine and lysine. Binding of glutamate was potently inhibited by various ligands for rat brain metabotropic glutamate receptors (mGluR) and also by kainate and N-methyl-D-aspartate. Glutamate stimulated phosphatidylinositol 4,5-bisphosphate breakdown consistent with G protein-dependent activation of PLC. Northern blot analyses demonstrated the presence of olfactory rosette RNA that hybridizes with cDNA probes for mGluR1 and mGluR4 under low stringency conditions. The results indicate the salmon olfactory system includes a subtype of the metabotropic glutamate receptor family.

Animals↗
PubMed1994

Erosion of a new family of biodegradable polyanhydrides.

Studies investigating the erosion mechanism of the newly developed poly (fatty acid dimer: sebacic acid) polyanhydride (p:[FAD:SA]) are described. The overall erosion of different monomer compositions of p(FAD:SA) copolymers was examined to determine whether and to what extent copolymer properties affected polymer erosion. Increasing the hydrophobic monomer (FAD) content up to 50 wt% in the copolymer resulted in longer erosion, whereas further increases up to 70 wt% decreased the erosion period. Polymer crystallinity depended on copolymer FAD content. Copolymer degradation was studied by examining anhydride bond hydrolysis using infrared spectroscopy. Much faster hydrolysis was found in p(FAD:SA) 70:30 compared with more crystalline copolymers of higher SA content. Light microscopy indicates the presence of an erosion zone, a distinct area where mass loss occurs. This erosion zone moves from the outside toward the interior of the polymer matrix. It plays an important role in erosion because any water or monomer must diffuse through this eroded layer.

Biodegradation, Environmental↗
PubMed1994

Trisomy 12 in chronic lymphocytic leukemia. An interphase cytogenetic study by fluorescence in situ hybridization.

B-cell chronic lymphocytic leukemia (CLL) is a rare disorder in the Chinese population. We evaluated the use of fluorescence in situ hybridization (FISH) with a chromosome 12-specific probe in the detection of trisomy 12 in interphase cell of 19 Chinese CLL patients. FISH successfully detected trisomy 12 in two cases, one of which had normal conventional cytogenetic findings, giving an incidence of 10%. The low incidence of trisomy 12 in our CLL patients may also reflect a biologic difference of this rare disorder in our population, compared to that of the West.

Adult↗
PubMed1994

Signal transduction for taurocholic acid in the olfactory system of Atlantic salmon.

Conjugated bile acids such as taurocholic acid (TChA) are potent olfactory stimuli for Atlantic salmon (Salmo salar). A plasma membrane rich fraction was derived from salmon olfactory rosettes and used to investigate TChA signal transduction and receptor binding. In the presence of GTP gamma S, TChA caused dose-dependent stimulation of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown, half maximal at less than 10(-7) M TChA. Stimulation of PIP2 breakdown by TChA required GTP gamma S, was blocked by GDP beta S, and was mimicked by A1F4-, consistent with a G protein requirement. A1F4- and Ca2+ stimulated breakdown of PIP2, but not phosphatidylcholine, arguing against a non-specific lipase activation. Stimulation of PIP2 breakdown by TChA was maximal at low Ca2+ concentration, < or = 10 nM. Conventional binding analysis with 3H-TChA was inconclusive due to a high degree of non-specific binding and to lack of tissue specificity expected for an olfactory receptor. Analysis of odorant amino acid binding indicated possible interaction of TChA with a putative acidic amino acid receptor but no interaction of TChA with a putative neutral amino acid receptor. We conclude that olfactory discrimination between amino acids and bile acids occurs in part at the receptor level while both classes of odors appear to use the same signal transduction mechanism, G protein mediated activation of phosphoinositide specific phospholipase C (PLC).

Amino Acids↗
PubMed1994

[An investigation on the distribution of leptospirae interrogans in water and soil in southwest of Yunnan Province].

The conservation of pathogenic leptospirae in water and soil is one of the important problems of geography-epidemiological survey of leptospirosis. We have conducted this investigation by using of filtration-culture isolation method in five counties in the west and southwest of Yunnan during 1988-1992. The results showed that the isolates from samples of water and soil collected between July and September in Menglian and Huaping county were leptospirae biflexa while in the samples of water and soil collected between November and December in three counties, 8 strains of L. interrogans were isolated from the samples of Gengma and Baoshan county. The total positive rate was 3.31% (8/242). The positive rate of water and soil was 2.14% (3/140) and 4.9% (5/102) respectively. Strains obtained in this investigation belong to six serogroups: Icterohaemorrhagiae and Pyrogenes in 2 respectively. Canicola, Grippotyphosa, Sejroe and Australis in 1 respectively. These serogroups of leptospirae obtained from water and soil were corresponded with the serogroups obtained from the patients and animals with leptospirosis in local area. This survey provided new data for expounding the structure of the focus of leptospirosis.

China↗
PubMed1994

A study of calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis.

Hypercalcaemia can occur in patients with tuberculosis. To further characterize the calcium and vitamin D metabolism in this disorder, serum calcium, 25(OH)D, 1,25(OH)2D and parathyroid hormone and the interrelationships between serum calcium, 25(OH)D and 1,25(OH)2D were compared in 24 untreated Chinese patients with culture-positive pulmonary tuberculosis and 24 age and sex-matched controls in Hong Kong. Albumin adjusted serum calcium was significantly higher in patients (2.33 +/- 0.07 compared with 2.20 +/- 0.09 mmol l-1, P < 0.001), despite a lower calcium intake (426 +/- 208 compared with 564 +/- 335 mg day-1). No significant group difference was found in serum 25(OH)D or 1,25(OH)2D concentrations. There was a positive correlation between serum 25(OH)D and 1,25(OH)2D concentrations in the patient group (r = 0.50, P < 0.02), but a negative one in the control group (r = -0.48, P < 0.05). Serum parathyroid hormone was significantly lower in patients (20.9 +/- 8.5 compared with 38.2 +/- 14.5 pmol l-1, P < 0.001). In the patient group, no correlation between the radiographic extent of disease and serum calcium or 1,25(OH)2D concentrations was seen. Our findings confirmed that serum calcium is raised in tuberculosis but the effect may be reduced by a low calcium intake and a low parathyroid hormone level. Although the calcium and vitamin D metabolism appeared to be altered in tuberculosis, no direct relationship between serum calcium and 1,25(OH)2D, was found.

Adult↗
PubMed1993

Third component of trout complement. cDNA cloning and conservation of functional sites.

Of the 30 distinct complement proteins recognized to date, C3 is probably the most versatile and multifunctional molecule known, interacting with at least 20 different proteins. It plays a critical role in both pathways of complement activation and participates in phagocytic and immunoregulatory processes. Structural and functional analysis of C3 from different species, in addition to phylogenetic information, provides insights into the structural elements mediating the various functions. This study describes the cDNA cloning of one of two isoforms of the third complement component, C3-1, of rainbow trout (Salmo gairdneri) and the analysis of its functional sites. By screening a trout liver lambda gt11 library with anti-trout C3 chain-specific antibodies and polymerase chain reaction we have determined the cDNA sequence of trout C3-1. The obtained sequence is in complete agreement with the protein sequence of several tryptic peptides, corresponding to different regions of trout C3-1. C3-1 consists of 1640 amino acids with a calculated molecular mass of 181,497 Da. The sequence contains two potential N-glycosylation sites, one on each chain of C3. The deduced protein sequence showed 44.1, 43.3, 44.2, 44.9, 43.1, 43.8, 45.9, 29.9, and 33.1% amino acid identities to human, mouse rat, guinea pig, rabbit, cobra, frog, hagfish, and lamprey C3, whereas the identities to human C4, C5, and alpha 2M are 30.4, 28, and 22.9%, respectively. The trout C3 amino acid sequence shows clusters of high and low similarity to C3 from other species. In the regions of high similarity belong the C3 domains that contain the thiolester site and the properdin binding sites, whereas the regions that correspond to regions of human C3 where CR1 and CR2 bind show low amino acid sequence similarity. The deduced amino acid sequence shows that the C3 convertase cleavage site (Arg-Ser) is conserved in trout C3, whereas the factor I cleavage sites are Arg-Ala and Arg-Thr instead of Arg-Ser, which is found in the C3 of other species. Protein sequencing of the trout C3 fragments fixed on zymosan during complement activation confirmed the cleavage of trout C3 by trout C3 convertase and factor I at Arg-Ser and Arg-Thr, respectively.

Amino Acid Sequence↗
PubMed1993

Characterization of the gene for the human high affinity IgE receptor (Fc epsilon RI) alpha-chain.

The Fc epsilon RI couples the mast cell-surface binding of IgE and Ag to a complex series of intracellular events culminating in cell activation and degranulation. The alpha-chain of Fc epsilon RI constitutes the Ig-binding subunit of this heterotetrameric receptor, and is itself a member of the Ig gene superfamily. We have isolated a human genomic DNA clone containing the entire Fc epsilon RI alpha gene, and completely sequenced a region from 1257 bp 5' of the transcription start site, to 513 bp 3' of the last exon of the gene. As with the previously characterized rat and mouse genes, human Fc epsilon RI alpha consists of five exons and four introns, and spans 5889 bp of genomic DNA. The splice donor and acceptor sites deduced by comparison with the cDNA sequence corresponded exactly to the locations found in analogous rodent genes. By mapping the 5' end of Fc epsilon RI alpha transcripts we found three major transcription initiation sites 24, 27, and 29 bp upstream of the ATG translation initiation codon. As well, several longer minor transcripts were seen, with a maximum of 60 nt of 5'-untranslated sequence. About 650 bp of DNA upstream of the ATG translation initiation codon were compared among human, rat, and mouse Fc epsilon RI alpha sequences in search of common motifs that might mediate conserved regulatory interactions with DNA binding proteins. A 172-bp region of the human Fc epsilon RI alpha 5'-flanking sequence was highly conserved in both rodent species. Further studies will be required to determine whether these or other sequences are involved in Fc epsilon RI alpha gene regulation.

Base Sequence↗
PubMed1993

The effects of inhaled corticosteroids on chronic airflow limitation.

A placebo-controlled, double blind, cross-over study of inhaled budesonide was carried out to examine its effectiveness in the treatment of chronic airflow limitation (CAL). Fourteen patients (11 males, mean age 66 years) with stable CAL received placebo treatment for four weeks followed by inhaled budesonide 400 micrograms BD for eight weeks. Response was assessed by measuring forced expiratory volume in one second (FEV1). There was no significant improvement in the overall spirometric measurements and symptom scores except a reduction in daily peak expiratory flow rate fluctuation (p < 0.05). However, individual patients showed significant increase in FEV1. Two patients (14%) had greater than 30% increase in FEV1 in response to inhaled corticosteroids. This response could not be predicted from history of allergy, skin test, bronchial challenge test, peripheral blood or sputum eosinophilia. We conclude that only a minority of patients with stable CAL may respond to inhaled budesonide. Nonetheless, patients who are symptomatic despite treatment with maximum doses of bronchodilators may have a trial of inhaled corticosteroids in order to demonstrate any additional benefit.

Administration, Inhalation↗
PubMed1992

Quantitation of human cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblast cells and human skin biopsies treated with retinoic acid.

A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid (RA) induction of cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblasts and human skin biopsies. The method utilizes reverse transcription and PCR (RT-PCR) to compare cellular CRABP-II RNA with a known amount of added internal standard RNA generated from a modified CRABP-II cDNA containing a 42 bp deletion. Thus, after RT-PCR of cellular and standard CRABP-II RNA in the same tube, the resulting DNA bands could be distinguished by size on ethidium bromide-stained, nondenaturing polyacrylamide gel. Serial dilutions of cellular RNA were co-amplified with a fixed amount of internal standard CRABP-II RNA, and the ratio of intensities of the two DNA bands was determined by computerized image analysis of the gel photograph. A linear relationship was found between the logs of this ratio and the input RNA. Absolute quantitation of cellular CRABP-II RNA was determined from the 'equivalence point', the dilution at which band intensities from cellular and standard RNAs were identical. Using this quantitative assay, the amount of CRABP-II RNA in cultured fibroblasts was 24 attomoles per microgram total RNA. A 4.2-fold increase in CRABP-II RNA was seen following 24 hours treatment with 10(-6) M RA. CRABP-II RNA content in skin biopsies taken from 3 human subjects ranged from 16 to 25 attomole/micrograms RNA. Topical treatment with 0.1% RA cream resulted in induction ranging from 3.9- to 12-fold over vehicle treatment. The method described here offers a rapid, sensitive and quantitative assay of specific RNAs, and should be especially useful for the measurement of RNA levels from small solid-tissue biopsies.

Base Sequence↗