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Biomedical subjects

T Wong

Publications and source records attributed to T Wong.

At least 163 records · Page 9Linked to original sources
PubMed1989

Resectable bronchogenic carcinoma presenting with hypercalcemia: tumor-associated granulomatous reaction and probable production of 1,25-dihydroxyvitamin D.

A patient with hypercalcemia, increased levels of 1,25-dihydroxyvitamin D, and a resectable squamous cell bronchogenic carcinoma surrounded by numerous non-caseating epithelioid granulomas, achieved normocalcemia, decreased levels of 1,25-dihydroxyvitamin D, and no evidence of tumor recurrence at 30 months following complete resection of his tumor. We suggest that an excess production of 1,25-dihydroxyvitamin D, through the granulomatous reaction around the tumor, was the mechanism of hypercalcemia. To our knowledge, no such mechanism of hypercalcemia has been previously reported with bronchogenic carcinoma. Furthermore, a review of the literature reveals that in cases of bronchogenic carcinoma, hypercalcemia is almost always associated with large and unresectable tumors, with a median survival after the discovery of hypercalcemia of only one month. This case, then, is unique because it describes an unusual mechanism of hypercalcemia with bronchogenic carcinoma and it emphasizes the rare occurrence of the potentially curable patient presenting with bronchogenic carcinoma complicated by hypercalcemia.

Aged↗
PubMed1988

Increased transglutaminase activity during skin wound healing in rats.

Outer, middle and inner layers from wounded or unwounded rat dorsal skin were separated and extracted first with buffer and then with Triton X-100 and dithiothreitol. The extracts and residues were assayed for transglutaminase activity and tissue transglutaminase antigen. Transglutaminase activities in all skin layers are increased in the period 1-5 days after wounding. Most of the increased activity is in the buffer-soluble fraction in the inner skin layer though there is no corresponding increase in antigen in this fraction. This suggests that there is production of activated soluble tissue transglutaminase in the wounded inner layer. In the 3-5 day wounded outer layer the largest fraction of both activity and antigen is associated with the insoluble residue remaining after extraction with Triton X-100. On DEAE-cellulose chromatography Triton X-100 extracts of the inner layer of wounded skin showed a single major peak of activity, corresponding approximately with rabbit liver transglutaminase; the outer layer showed the same peak plus a different one, eluting at lower salt concentration, which is thought to be epidermal transglutaminase.

Animals↗
PubMed1988

Differential inhibition of the platelet activation sequence: shape change, micro- and macro-aggregation, by a stable prostacyclin analogue (Iloprost).

The relative sensitivities of adenosine diphosphate (ADP)-induced activation, and of prostaglandin-mediated inhibition, were determined for rates of platelet shape change (SC [Vs]), early platelet recruitment measured by electronic platelet counting (PA [PA3]), and turbidometrically-measured aggregation (TA [Va]). Studies were performed on stirred citrated platelet-rich plasma from 9 healthy human donors. The [ADP]1/2, [( ADP] giving half maximal rate) was determined for the sequence of activation steps: unactivated platelets----SC----PA----TA. Distinct ADP sensitivities were obtained from log dose-response studies, with a relative dose dependency for rates of change in the order of [ADP]1/2 TA greater than [ADP]1/2 PA greater than [ADP]1/2 SC of approximately 4:3:1. Differential inhibition of the above activation scheme was evaluated from log dose-response curves for Iloprost (ZK 36374), a stable carbacyclin analogue of prostacyclin (PGI2), with greater potency than PGI2 for the same platelet receptors. IC50 values corresponding to Iloprost concentrations causing 50% inhibition of rates of TA (Va), PA (PA3) and SC (Vs) were found in the relative ratios of 1: approximately 3: approximately 5, when measured at a common ADP concentration for all three parameters, or 1: approximately 2: approximately 3 when determined at respective [ADP]1/2 values for each parameter. Thus, about 3-5 times more Iloprost is required to respectively inhibit the rates of shape change (Vs) and early platelet recruitment (PA3), than that needed to inhibit the rate of turbidometrically-measured aggregation (Va).

Adenosine Diphosphate↗
PubMed1988

Atrial natriuretic peptide production in association with nonimmune fetal hydrops.

The presence and elevation of atrial natriuretic peptide in fetuses has not previously been demonstrated. This study of right atrial pacing in fetal lambs demonstrated a threefold to fourfold increase in atrial natriuretic peptide during the production of fetal hydrops. Its rate of return to a normal level paralleled the clearance of fetal hydrops. Its possible role in fetal cardiovascular hemodynamics is discussed.

Animals↗
PubMed1988

Functional interaction between transcriptional elements in the long terminal repeat of reticuloendotheliosis virus: cooperative DNA binding of promoter- and enhancer-specific factors.

Transcription from reticuloenodotheliosis virus strain T (REV-T), an avian retrovirus unrelated to avian leukosis and sarcoma viruses, is modulated by sequences in at least five functional domains. A promoter containing a TATA and multiple CCAAT motifs in U3 of the long terminal repeat was absolutely required for transcription. Transcriptional efficiency was greatly augmented by an enhancer immediately upstream, which contained a 22-base-pair repeated sequence. Transcription was further influenced by a negative-acting domain in the 5' region of U3 and two downstream domains in the transcribed non-protein-coding region. One of these latter domains contained a consensus enhancer core sequence and positively affected transcription in both mammalian and avian cells; the other acted negatively in a dog cell line. Transcription from REV-T in vivo required cellular factors which could be competed for specifically by the promoter or enhancer domain. The downstream domains competed with reporter genes containing these domains, but not directly with the U3 sequences. The promoter, enhancer, and the positive-acting downstream domains formed multiple complexes with distinct classes of cellular factors in both avian and mammalian cell extracts. Binding of factors to the promoter and enhancer domains was cooperative when these domains were joined in cis.

Animals↗
PubMed1988

Characterization of CDPdiacylglycerol hydrolase in mitochondrial and microsomal fractions from rat lung.

CDPdiacylglycerol pyrophosphatase (E.C. 3.6.1.26) activity has been examined in rat lung mitochondrial and microsomal fractions. While the mitochondrial hydrolase exhibited a broad pH optimum from pH 6-8, the microsomal activity decreased rapidly above pH 6.5. Apparent Km values of 36.2 and 23.6 microM and Vmax values of 311 and 197 pmol.min-1.mg protein-1 were observed for the mitochondrial and microsomal preparations, respectively. Addition of parachloromercuriphenylsulphonic acid led to a marked inhibition of the microsomal fraction but slightly stimulated the mitochondrial activity at low concentrations. Mercuric ions were inhibitory with both fractions. Although biosynthetic reactions utilizing CDPdiacylglycerol require divalent cations, addition of Mg2+, Mn2+, Ca2+, Zn2+, Co2+, and Cu2+ all inhibited the catabolic CDPdiacylglycerol hydrolase activity in both fractions. EDTA and EGTA also produced an inhibitory effect, especially with the mitochondrial fraction. Although addition of either adenine or cytidine nucleotides led to a decrease in activity with both fractions, the marked susceptibility to AMP previously reported for this enzyme in Escherichia coli membranes, guinea pig brain lysosomes, and pig liver mitochondria was not observed. These results indicate that rat lung mitochondria and microsomes contain specific CDPdiacylglycerol hydrolase activities, which could influence the rate of formation of phosphatidylinositol and phosphatidylglycerol for pulmonary surfactant.

Animals↗
PubMed1986

Induced rapid phospholipid methylation and arachidonic acid release by dimethyl sulfoxide-treated human promyelocytic leukemic HL-60 cells.

The incubation of undifferentiated promyelocytic HL-60 cells with DMSO resulted in the rapid transmethylation of phosphatidyl ethanolamine (PE) into phosphatidylcholine (PC) which was maximal at 60 secs. This rapid generation of PC was followed by a decrease of the methylated phospholipid and the release of arachidonic acid. Thus, the rapid DMSO-induced phospholipid methylation coupled with release of arachidonic acid (precursor for eicosanoids) prior to morphological evidence of cellular differentiation may represent early biochemical events which result in the generation of intracellular chemical signals which may program the promyelocytic cells into a differentiation mode.

Arachidonic Acid↗
PubMed1986

Effect of sodium intake and sodium delivery to the macula densa on renal renin content and juxtaglomerular apparatus morphology.

Active and inactive renin were measured in individual juxtaglomerular apparatus (JGA) and in whole kidney homogenates. The morphology of the JGA was examined in microbiopsy glomerular specimens and in kidneys fixed by arterial perfusion. In rats on high and normal salt intake the total renin content of a single JGA was 14 (s.e.m. = 3) and 29 (s.e.m. = 4) ng AI/h, respectively. The amount of cystoplasm occupied by renin granules was 20% and 27%. Crystalline cores were seen in 1.5% and 7% of the granules, respectively. Increased delivery of NaCl to the macula densa did not alter total renin, but decreased inactive renin from 30% to 0, crystalline core-containing cells from 33% to 14% and decreased the percentage of granules with crystalline cores from 12% to 2.2%. Increased sodium in the diet and increased delivery of NaCl to the macula densa decreased the proportion of renin present in the inactive form and decreased the proportion of crystalline cores. These coincidental alterations suggest that crystalline cores contain inactive renin and suggest that the delivery of sodium to the macula densa activates renin.

Animals↗
PubMed1986

Modulation of colony stimulating factor-induced murine myeloid colony formation by S-peptido-lipoxygenase products.

Prompted by the observation that the selective blockade of lipoxygenase pathway by known inhibitors of this pathway inhibited the colony stimulating factor (CSF)-induced colony formation in both mouse and human marrow cells and the fact that this inhibitory effect could be reversed by a crude total lipoxygenase extract from an incubation of rat peritoneal neutrophils and arachidonic acid, we investigated which of the two major classes of lipoxygenase products, mono- and dihydroxy fatty acids (5S-hydroxyeicosatetraenoic acid and 5S-, 12R-dihydroxyeicosatetraenoic acid) and the S-peptidohydroxy fatty acids (leukotrienes C4 and D4), is involved in the modulation of CSF-induced colony formation by mouse marrow cells. Data from incubations with synthetic lipoxygenase products revealed that (a) the culture of mouse marrow cells in the presence of varying amounts of purified CSF-I (Mia PaCa 2) with a low concentration (5 micrograms/ml) of nordihydroguaretic acid consistently suppressed CSF-induced colony formation by approximately 40-50%. This concentration of nordihydroguaretic acid selectively inhibits only the lipoxygenase pathway; (b) additions of two S-peptido-hydroxy fatty acids [5S-hydroxy-6R-S-glutathionyl-7,9,11,14-(E,E,Z,Z)-eicosatetraenoic acid and 5S-hydroxy-6R-S-cysteinglycyl-7,9,11,14-(E,E,Z,Z)-eicosatetraenoic acid] to these partially suppressed colonies restored the CSF-induced colony formation to control levels in a dose-dependent manner; and (c) additions of two mono- and dihydroxy acids, 5S-hydroxyeicosatetraenoic acid and 5S-12R-dihydroxyeicosatetraenoic acid [5S, 12R-dihydroxy-6,8,10,14-(Z,E,E,Z)-eicosatetraenoic acid], failed to restore the nordihydroguaretic acid inhibited colony formation. These novel observations underscore the importance of these peptido-5-hydroxy fatty acids and the lipoxygenase pathway in the mechanism of CSF-induced colony formation in mouse marrow cells.

Animals↗
PubMed1986

Lipoxygenation of arachidonic acid by differentiated and undifferentiated human promyelocytic HL-60 cells.

The human promyelocytic leukemia cell line HL-60 can be induced to differentiate into mature granulocytes by exposure to dimethyl sulfoxide (DMSO), as well as into cells of monocyte-macrophage lineage by exposure to 12-0-tetra-decanoylphorbol-13-acetate (TPA). Incubation of the promyelocytic leukemic HL-60 cells and the two chemically induced differentiated cells with carbon 14-labeled arachidonic acid overnight resulted in the incorporation of label mainly into cellular phospholipids. Stimulation of the labeled cells with Ca2+ ionophore (A23187) resulted in the generation of lipoxygenase products in all the cells. Notably, the DMSO-induced differentiated granulocytic cells biosynthesized predominantly the peptidoeicosatetraenoic acids LTC4 and LTD4 compared with the dihydroxyeicosatetraenoic acid LTB4. On the other hand, the TPA-induced differentiated monocytic-macrophage cells biosynthesized predominantly LTB4 compared with LTC4 and LTD4. The undifferentiated promyelocytic cells lacked the capacity to biosynthesize LTB4, as evidenced in the chemically induced differentiated cells. The monohydroxyeicosatetraenoic acid (HETE) 5-HETE, a metabolite of the 5-lipoxygenase pathway, was a minor component in these cells, and 12-HETE and 15-HETE were barely detectable. These results suggest that the two models of DMSO-induced and TPA-induced differentiated cells may be useful systems for further investigations of arachidonic acid metabolites in granulocytic and monocytic-macrophage functions.

Arachidonic Acid↗
PubMed1983

Effects of lysophosphoglycerides on cardiac arrhythmias.

The accumulation of lysophosphoglycerides has been implicated as an important biochemical factor for cardiac arrhythmias. Recently, we demonstrated that lysophosphatidylcholine caused cardiac arrhythmias in the isolated hamster heart. In this study, the arrhythmogenic nature of various lysophosphoglycerides with respect to acyl chain lengths and base groups were assessed. We demonstrated that all naturally occurring lysolipids tested were arrhythmogenic at 0.05-0.10 mM. Arrhythmias were also observed with Triton X-100 or sodium laurylsulfate at 0.05-0.10 mM. Our data suggests that no correlation exists between the arrhythmogenic nature of the lysolipids and their critical micelle concentrations. We postulate that arrhythmias are produced by the detergent effect of lysophosphoglycerides.

Animals↗
PubMed1983

Evidence for the existence of a C25-sesterterpene pathway of steroidogenesis not involving cholesterol as an obligatory intermediate.

Previous in vitro studies had indicated the possibility of steroidogenesis through a C25-sesterterpene pathway in which squalene and cholesterol are not required as obligatory intermediates. To investigate whether such a pathway exists in vivo, the precursor role of [7-3H]23,24-dinor-5-cholene-3 beta,20-diol in the in vivo formation of cortisol by the guinea pigs was studied. The [3H]23,24-dinor-5-cholene-3 beta,20-diol was synthesized by reacting [3H]pregnenolone acetate with a Grignard reagent. The product was purified by chromatography and its radiochemical purity was established by the isotope dilution technique. In the first experiment a total of 134 X 10(6) dpm of [3H]23,24-dinor-5-cholene-3 beta,20-diol was injected subcutaneously into three guinea pigs. Urine was collected for 8 days and was pooled. Only 12% of the administered dose was excreted in the urine. The urine was extracted and a neutral extract (3 X 10(6) dpm) was obtained. From this extract 2.3 mg of cortisol containing 2.9 X 10(4) dpm was isolated. Radiochemical purity of the isolated cortisol was established by the isotope dilution technique. Radiochemical purity was further confirmed by conversion to cortisol 21-acetate and subsequently to 11 beta-hydroxyandrost-4-ene-3,17-dione and recrystallization to constant specific activity. The results of this experiment were confirmed by repeating the experiment with a higher specific activity [3H]23,24-dinor-5-cholene-3 beta,20-diol. These results indicate that the C25-sesterterpene pathway is a possible in vivo alternate pathway of steroidogenesis, not involving either squalene or cholesterol as obligatory intermediates.

Animals↗
PubMed1983

Pharmacokinetics of equilin and equilin sulfate in normal postmenopausal women and men.

The MCRs of equilin sulfate and equilin were determined in normal postmenopausal women and a normal man by single iv injections of either [3H]equilin sulfate or [3H] equilin. After the administration of [3H]equilin sulfate, blood was drawn at various time intervals, and the plasma obtained was fractionated into the unconjugated, sulfate, and glucuronide fractions. The bulk of radioactivity was present in the sulfate fraction, and from this, [3H]equilin sulfate, [3H]17 beta-dihydro-equilin sulfate, [3H]equilenin sulfate, and [3H]17 beta-dihydroequilenin sulfate were isolated and purified, and their concentrations were measured. The disappearance of radioactivity from plasma as equilin sulfate can be described as a function that is the sum of two exponentials. The initial fast component (half-life, 5.2 +/- 1.2 min) represents distribution and transfer from a space, with a mean volume of 12.4 +/- 1.6 liters. The mean value for the rate constant of total removal from the initial volume is 163 +/- 19 U/day, of which 15.8 +/- 2% is irreversible. The mean half-life of the slower component of equilin sulfate is 190 +/- 23 min, and the mean MCR is 176 +/- 44 liters/day . m2. Similarly, after the administration of [3H]equilin to a normal postmenopausal woman and a man, the disappearance of radio-activity from plasma as equilin could be fitted by a single straight line, consistent with a one-compartment system. The half-life of equilin was approximately 19-27 min, and the MCR of equilin was calculated to be 1982 liters/day/m2 in the normal man and 3300 liters/day/m2 in the normal postmenopausal woman. The bulk of [3H]equilin was very rapidly metabolized to mainly equilin sulfate. Small amounts of 17 beta-dihydroequilin sulfate and 17 beta-dihydroequilin were also isolated from the plasma. The in vivo formation of 17 beta-dihydroequilin and its sulfate may be of importance, as this estrogen is approximately 8 times more potent as a uterotropic agent than equilin sulfate.

17-Ketosteroids↗