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Biomedical subjects

D Chang

Publications and source records attributed to D Chang.

At least 199 records · Page 11Linked to original sources
PubMed1991

The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour.

Regional chemotherapy for colorectal liver metastases has not demonstrated a convincing survival benefit over systemic chemotherapy. This may be due to poor delivery of chemotherapeutic drugs to hypovascular liver tumour. Since vasoactive agents may influence hepatic blood flow this study investigated the effects of systemic and regional vasoconstrictors on the delivery of a regionally delivered marker in an experimental model of liver tumour. Systemic administration of angiotensin II caused a significant retention of marker in normal liver, but not in tumour compared to controls. Regional delivery of angiotensin II and phenylephrine caused significantly greater retention of marker in tumour than liver with an overall 4-fold increased retention of marker one minute after its injection. Ninety minutes after injection there was still significant retention of marker compared to control animals. Regional delivery of hepatic artery vasoconstrictors increase delivery of marker and may increase delivery of chemotherapeutic drug to liver tumour.

Angiotensin II↗
PubMed1991

The effects of vasopressin infusion on hepatic haemodynamics in an experimental model of liver metastases.

Vasoactive drugs have a variety of effects upon splanchnic and hepatic haemodynamics which may alter tumour blood flow and potentiate the delivery of a chemotherapeutic drug to hepatic tumour. We have investigated the effects of vasopressin infusion on hepatic tumour blood flow in an experimental model of liver tumour. Hepatic tumour was induced by the intraportal inoculation of HSN sarcoma cells. Hepatic and splanchnic blood flow was determined using a dual reference microsphere technique before and after an intravenous infusion of vasopressin at a dose of 0.1 mU kg-1 min-1 for 10 min. There was a significant increase in systemic arterial blood pressure associated with a rise in portal venous inflow (P less than 0.01, Wilcoxen Signed rank Test) and a significant fall in hepatic arterial flow (P less than 0.05). The tumour: liver blood flow ratio was significantly increased by vasopressin infusion (P less than 0.02). Vasopressin infusion decreases hepatic arterial flow and increases tumour blood flow which may potentiate the delivery of a regionally delivered chemotherapeutic drug to hepatic tumour.

Animals↗
PubMed1991

Intracellular pH regulates basolateral K+ and Cl- conductances in colonic epithelial cells by modulating Ca2+ activation.

The role of intracellular pH as a modulator of basolateral K+ and Cl- conductances in epithelial cells was studied using digitonin-permeabilized colonic cell layers so that cytosolic pH could be clamped at specific values, while basolateral K+ and Cl- conductances were activated by stepwise increases in intracellular free Ca2+. Increasing the intracellular pH from 6.6 to 8.0 enhanced the sensitivity of both ionic conductances to intracellular Ca2+, but changing extracellular pH had no effect. Maximal K+ and Cl- currents activated by Ca2+ were not affected by changes in intracellular pH, suggesting that protons do not alter the conduction properties of the channels. Hill analysis of the Ca2+ activation process revealed that raising the cytosolic pH from 6.6 to 8.0 reduced the K1/2 for Ca2+ activation. In the absence of Ca2+, changes in intracellular pH did not have a significant effect on the basolateral K+ and Cl- conductances. These results are consistent with the notion that changes in cytosolic pH can modulate basolateral conductances by modifying the action of calcium, perhaps by acting at or near the activation site to provide a mechanism of variable "gain control."

Animals↗
PubMed1991

Big endothelin in plasma and amniotic fluid.

UNLABELLED: We previously demonstrated that endothelin-1 (ET-1) exists both in the peripheral circulation and the amniotic fluid (AF). The objects of the present study were (a) to measure the concentrations of ET-1 and big endothelin (big ET) in plasma and AF by radioimmunoassay (RIA) and (b) to characterize the molecular forms of endothelin in human AF by high-performance liquid chromatography (HPLC) coupled with RIAs. Plasma samples from healthy male and female volunteers, and AF samples from full-term and mid-trimester pregnant women were extracted by C18 cartridges. Big ET, like ET-1, exists both in plasma and in AF. Significant increases (p less than 0.01) of big ET and ET-1 in AF from mid-trimester to full-term pregnancy were observed. The reverse-phase HPLC elution profile of immunoreactive (ir-) ET-1 presented a single major peak at a position corresponding to that of the standard ET-1 in the extracted AF. Two major components of ir-big ET were revealed: one corresponded to the elution position of standard big ET; the other one to that of the standard endothelin fragment [22-38] (EF). IN CONCLUSION: (a) Three molecular forms of ET exist in AF: ET-1 as a major form, big ET, and EF. (b) ET-1 and big ET are both present in higher concentrations in AF at full-term pregnancy than during mid-trimester.

Adult↗
PubMed1991

The Bedouin Infant Feeding Study: study design and factors influencing the duration of breast feeding.

A longitudinal study of infant feeding practices, growth and morbidity among Bedouin Arab infants residing in the Negev, Israel, was conducted during a 3-year period (1981-1983). Follow-up samples were restricted to healthy newborns. The majority of newborns are breast fed at birth but, by 2 months, 50% are also introduced to a milk supplement. Based on the bivariate analysis using the logrank test to examine the factors associated with exclusive versus partial breast feeding during the first 6 months, those born during the wet cool months are exclusively breast fed longer than those born during the dry season. More traditional women, living in tents rather than houses or huts, exclusively breast feed for at least 6 months. In a multiple logistic regression model, parity, house type and birth season are independently associated with the odds of exclusively breast feeding for the first 6 months of life. Factors influencing the duration of any breast feeding for the first 18 months include: house type, place of residence, birthweight, and whether the infant was stunted at 6 months.

Animals↗
PubMed1991

Developmental expression of pulmonary surfactant protein D (SP-D).

Surfactant protein D (SP-D) is a collagenous, surfactant-associated, carbohydrate-binding protein that is synthesized by pulmonary epithelial cells. In the present studies, we examined the expression of SP-D and SP-D mRNA during late fetal (day 17, 19, 21) and early postnatal (day 5) rat lung development using immunochemical, cell-free translation, and Northern hybridization assays. SP-D mRNA and immunoreactive SP-D protein were first detected in guanidine extracts of whole rat lung at 21 days of gestation and reached even higher concentrations during the postnatal period. Likewise, immunoperoxidase studies of rat lung using affinity-purified antibodies to SP-D showed no staining at day 17 or 19, but demonstrated strong cytoplasmic staining of cuboidal epithelial cells lining immature airspaces at day 21 and strong cytoplasmic staining of type II and nonciliated bronchiolar cells in adult lung. SP-D also appeared in amniotic fluid by day 21 and was partially purified by affinity chromatography on maltosyl-agarose under conditions used for the isolation of rat lung SP-D. These studies indicate that the production of SP-D is increased shortly prior to birth, and that the increases in total lung SP-D and SP-D mRNA are temporally correlated with SP-D secretion and the appearance of SP-D in amniotic fluid.

Amino Acid Sequence↗
PubMed1991

Surfactant protein D. Increased accumulation in silica-induced pulmonary lipoproteinosis.

Surfactant protein D (SP-D) (CP4) is a collagenous surfactant-associated carbohydrate binding protein that is synthesized and secreted by alveolar epithelial cells. Previous studies have shown that intratracheal administration of crystalline silica to rats elicits a marked increase in the alveolar accumulation of surfactant lipids and surfactant protein A (SP-A). The authors examined the accumulation of SP-D using this animal model of alveolar proteinosis. Immunoperoxidase localization of SP-D studies at 2 weeks after silica instillation showed intense staining of intra-alveolar exudates, and cytoplasmic staining of hypertrophic type II cells. Immunoelectron microscopy showed that airspace SP-D was specifically associated with granular material, but not tubular myelin or other membranous structures. SP-D was quantified in bronchoalveolar lavage by immunoassay using antibodies specific for SP-D, and by reversephase HPLC after affinity purification of SP-D on maltosyl-agarose. Within 2 weeks after silica instillation, there was a greater than 45-fold increase in lavage SP-D per lung compared with saline controls, including an almost ten-fold increase in the insoluble or surfactant-associated protein. These studies indicate that the extracellular accumulation of SP-D is markedly increased in silica-induced lipoproteinosis, and that SP-D is associated with amorphous components identified by electron microscopy.

Animals↗
PubMed1990

Surfactant protein D is a divalent cation-dependent carbohydrate-binding protein.

Surfactant protein D (SP-D, CP4) is a collagenous surfactant-associated glycoprotein synthesized by lung type II epithelial cells. SP-D can be selectively and efficiently eluted from isolated rat surfactant with glucose, maltose, and certain other saccharides. We therefore examined the ability of the purified protein to interact with carbohydrates in vitro. Saccharide-substituted bovine serum albumins (BSA neoglycoproteins) were adsorbed to plastic wells, and binding of purified SP-D was quantified with monospecific antibodies to SP-D using an indirect immunoassay. SP-D showed specific calcium-dependent binding to alpha-D-glucosidophenyl isothiocyanate-BSA and maltosyl-BSA, but negligible binding to beta-D-glucosidophenyl isothiocyanate-BSA or unconjugated BSA. The most efficient inhibitors of SP-D binding were alpha-glucosyl-containing saccharides (e.g. isomaltose, maltose, malotriose). SP-D showed quantitative binding to maltosyl-agarose and was specifically eluted with maltose or EDTA. High affinity binding to maltosyl-BSA was also demonstrated using a solution-phase polyethylene glycol precipitation assay. These studies demonstrate that SP-D is a calcium dependent lectin-like protein and that the association of SP-D with surfactant is mediated by carbohydrate-dependent interactions with specificity for alpha-glucosyl residues.

Animals↗
PubMed1990

Seasonality of births among Bedouin Arabs residing in the Negev Desert of Israel.

From 1 January 1981 to 31 December 1982 information on all births to Bedouin Arab women residing in the Negev Desert of Israel showed a previously unreported seasonal pattern. The peak season, November-February, coincided with the period of cool temperatures and the Bedouin Arab cultural seasons of winter and spring. This pattern is different from those of Jewish and Christian groups in the same region, a difference not attributable to religion alone. Sociodemographic factors associated with the peak season of birth include traditional occupations of fathers, multiparae 2+, and traditional place of residence. This pattern has persisted over the past 15 years although it is less apparent among the more recently sedentarized Bedouin Arabs.

Birth Rate↗
PubMed1990

Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor.

Tumor necrosis factor (TNF) receptor (TNFR) was isolated as a 68-kDa glycoprotein from UC/HeLa 2-5 cells developed from a parental B-cell line (UC cells) to overexpress the receptor. Tryptic digests of two separate TNFR preparations provided amino acid sequences of four different peptides. Amino-terminal analysis indicated the presence of the amino-acid sequence Val-Ala-Phe-Thr-Pro, reported to be the amino-terminal sequence of a 30-kDa urinary TNF-binding protein II. Examination of the cultured medium of UC/HeLa 2-5 cells showed an abundance of a 40-kDa TNF-binding protein, indicating that the previously cited 30-kDa TNF-binding protein II is likely to be a shed form of the TNFR. Based on the peptide sequences, oligonucleotides were synthesized, and two of these were used as primers in the polymerase chain reaction to amplify cDNA sequences from poly(A)+ RNA of UC/HeLa 2-5 cells. These PCR fragments were radiolabeled and used to screen a cDNA library made from UC/HeLa 2-5 mRNA. Further analysis identified cDNA sequences that encoded the amino acid sequences of all four TNFR peptides. RNA blot-hybridization analysis of UC/HeLa 2-5 mRNA revealed a 3.8-kilobase transcript of the same size as the mRNA in the parental UC cells. Genomic Southern blots indicated the presence of a single gene in parental cells and a second, amplified gene in TNFR-overexpressing cells, suggesting amplification of the transfected gene as a possible mechanism for the increase in TNFR numbers in UC/HeLa 2-5 cells.

Amino Acid Sequence↗
PubMed1990

Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans.

Recent interest has focused on the potential role of amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). This 37-amino acid peptide is found in extracellular amyloid deposits in approximately 50% of pancreatic islets of patients with NIDDM and has been shown to inhibit skeletal muscle glycogen synthesis in vitro. Immunocytochemical studies have colocalized amylin and insulin within beta-cell secretory granules in nondiabetic humans, provoking the following questions. Is amylin cosecreted with insulin? Are circulating amylin concentrations higher in patients with NIDDM either before or after food ingestion? To answer these questions, we developed a sensitive and specific immunoassay to measure plasma concentrations of amylin in humans. Use of this assay indicated that, in lean nondiabetic subjects, glucose ingestion resulted in an increase (P less than 0.001) in the plasma concentration of amylin (from 2.03 +/- 0.22 to 3.78 +/- 0.39 pM) and insulin (from 48.3 +/- 3.1 to 265 +/- 44 pM). There was a significant correlation between the concentrations of insulin and amylin (r = 0.74, P less than 0.001) and the increase in insulin and amylin concentration (r = 0.65, P less than 0.005). Fasting concentrations of amylin did not differ in diabetic and weight-matched nondiabetic subjects and showed a similar pattern of change after ingestion of a mixed meal. We conclude that amylin is secreted in response to ingestion of either glucose or a mixed meal and circulates at concentrations that do not differ in patients with NIDDM and nondiabetic subjects. It remains to be determined whether amylin at physiological concentrations influences carbohydrate metabolism and if so whether its effects differ in diabetic and nondiabetic humans.

Adult↗