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Biomedical subjects

D Chang

Publications and source records attributed to D Chang.

At least 127 records · Page 7Linked to original sources
PubMed1996

Peritoneal carcinomatosis from adenocarcinoma of the colon.

Peritoneal carcinomatosis is a major cause of surgical treatment failure in patients with colorectal cancer. In the past patients with this condition have had a lethal outcome. In this study, 64 consecutive patients were treated by the cytoreductive approach, which involved surgery to maximally resect all cancer in the abdomen and pelvis, early postoperative intraperitoneal chemotherapy with 5-fluorouracil (5-FU) and mitomycin C, and three cycles of adjuvant intraperitoneal 5-FU with systemic mitomycin C. The clinical features that may affect prognosis were assessed and critically analyzed statistically. Peritoneal implant size of < 5 cm present in the abdomen and pelvis at the time of exploration correlated with a good prognosis (p < 0.0001), as did complete cytoreduction with tumor removed to nodules < 2.5 mm (p < 0.0001). Involvement of only one or two of the five abdominopelvic regions, compared to three or more regions, was a significant determinant of prognosis (p < 0.0001). Finally, a mucinous histologic type correlated adversely with prognosis when compared to intestinal-type adenocarcinomas (p < 0.001). These data suggest that patients with small-volume peritoneal seeding from colon cancer should be treated with cytoreductive surgery and aggressive regional and systemic chemotherapy in an attempt to achieve long-term disease-free survival.

Adenocarcinoma↗
PubMed1996

Production of the antigen and the antibody of the JC virus major capsid protein VP1.

The DNA of the major capsid protein VP1 of the human polyomavirus JC virus (JCV), Taiwan-3 strain, was generated from the urine of an autoimmune disease patient by polymerase chain reaction (PRC). The VP1 DNA was cloned into a prokaryotic expression vector, pGEX-4T-1, for expression in E. coli. The nucleotide sequences and the deduced amino acid sequences were determined and compared with the JC virus prototype, Mad-1. Thirty nucleotides were different between these two strains. Six of the altered nucleotides affected amino acid coding and ten of them caused changes in endonuclease recognition sites. The recombinant VPI protein was purified and used to raise monospecific antiserum in rabbit. Recombinant JCV VP1 protein and its monospecific antiserum are important clinical reagents and could possibly be developed as a subunit vaccine and as a serological diagnostic antigen in the future. In addition, the region between amino acid residues 40 and 80 of JCV VP1 is predicted to be an antigenic epitope on the basis of its hydropathy plot and comparison with the VP1 sequences of SV40 and BK virus.

Amino Acid Sequence↗
PubMed1996

Developmental profile of corticotropin releasing hormone messenger RNA in the rat inferior olive.

Corticotropin releasing hormone is a neurotransmitter in the inferior olive complex of marsupials and mammals. The ontogeny of corticotropin releasing hormone gene expression in the rat inferior olive has not been described. Using in-situ hybridization histochemistry in 25 animals, we established the developmental profile of the peptide's messenger ribonucleic acid in the postnatal rat. CRH-messenger RNA was first detectable in two of four animals on the fifth postnatal day. Subsequently, gene expression increased linearly with age: by day 14, CRH was expressed in all olivary complex nuclei, and the distribution and relative abundance on day 18 were comparable to those in the adult. The developmental profile of CRH-mRNA in the rat inferior olive differs from those in the mouse and opossum, and from the pattern in the rat hypothalamus, suggesting species- and site-specificity of the peptide's function.

Animals↗
PubMed1996

Increasing hepatic arterial flow to hypovascular hepatic tumours using degradable starch microspheres.

The effect of degradable starch microspheres (DSM) on the intrahepatic distribution of a low molecular weight marker, 99Tcm-labelled methylene diphosphonate (MDP), was studied in rats with hypovascular HSN liver tumours. MDP was injected regionally, via the hepatic artery, alone or co-administered with DSM, with or without subsequent occlusion of either the hepatic artery or the portal vein. Tumour vascularity was measured with 57Co-labelled microspheres. Co-injection with DSM immediately significantly increased hepatic retention of marker in both tumour (T) (median 22.40 (range 16.82-39.58)% injected dose) and normal liver (N) (9.08 (4.85-12.59) %ID) the greater effect seen in T (P < 0.01). After DSM degradation, very little MDP remained in N (0.61 (0.28-1.40) %ID) but there was significant retention in T (10.01 (6.73-20.28) %ID, P < 0.01). Clamping the hepatic artery had minimal effect on the retention of MDP when administered alone. Regional injection of 16.5 microM 57Co microspheres resulted in a N:T ratio of 2.25:1. Concomitant injection of the 40 microM DSM was 57Co microspheres reversed this ratio to 1:2. The results indicate that DSM selectively enhances the retention of MDP to a hypovascular hepatic tumour, not by causing intra-tumour stasis, but by directing a greater arterial flow to hypovascular areas in the liver.

Animals↗
PubMed1996

Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration.

Increased hydrostatic pressure in solid tumor nodules decreases the penetration of chemotherapy into cancerous tissue. This is true for both i.v. and i.p. chemotherapy. The purpose of this study was to determine the influence of increasing intra-abdominal pressures on the pharmacokinetics and tissue distribution of doxorubicin administered i.p. Four groups of 10 Sprague Dawley rats were given i.p. doxorubicin (4 mg/kg) during 60 min combined with no pressure (control), 10, 20 and 30 mm Hg pressures. During the course of i.p. chemotherapy, peritoneal fluid and blood were sampled. Two other groups of 10 rats received the same dose of i.p. doxorubicin during 10 min combined with no pressure and 30 mm Hg pressure. At the end of experiments animals were sacrificed and tissue samples were collected. Doxorubicin concentrations in peritoneal fluid, plasma and tissues were determined by HPLC. Pharmacokinetic studies showed that increased intra-abdominal pressures of 10, 20 and 30 mm Hg did not alter peritoneal fluid AUCs, the plasma AUCs and the peak ratios of i.p. doxorubicin when compared to the control group (no pressure). A subset analysis of high intra-abdominal pressure groups (20 and 30 mm Hg) versus control group showed statistically significant differences in peritoneal fluid AUCs, plasma AUCs and AUC (peritoneal fluid/plasma) ratios. For all groups, the highest tissue concentrations of doxorubicin were found in tissues associated with the parietal peritoneum: the bladder, the abdominal wall and the diaphragm. After 10 min of i.p. chemotherapy, the group treated with 30 mm Hg pressure showed a significant increase of doxorubicin concentrations in these tissues as compared to the control group. This significant increase of tissue doxorubicin concentrations was not found after 60 min of pressure with i.p. chemotherapy; prolonged intra-abdominal pressure was associated with a high incidence of intestinal ischemia. In conclusion, intra-abdominal pressure of 20 and 30 mm Hg significantly decreased the AUC ratios of i.p. doxorubicin but concomitantly increased tissue uptake of doxorubicin in bladder, diaphragm and abdominal wall during the first 10 min of i.p. administration. These findings may have significance in the design of improved strategies to increase tissue concentrations of chemotherapy delivered by an i.p. route.

Abdomen↗
PubMed1996

Interactions of recombinant human pulmonary surfactant protein D and SP-D multimers with influenza A.

To further study the structure and function of surfactant protein D (SP-D), recombinant human SP-D (rhSP-D) was isolated from the culture medium of Chinese hamster ovary (CHO)-K1 cells stably transfected with a full-length hSP-D cDNA. Although a significant fraction of the secreted rhSP-D was recovered as dodecamers similar to recombinant rat SP-D (rrSP-D), a major fraction accumulated as multimers of dodecamers indistinguishable from human proteinosis SP-D. As previously shown for the rat protein, rhSP-D agglutinated specific strains of influenza A virus (IAV), inhibited viral hemagglutinin activity, and protected neutrophils (PMN) from deactivation by IAV. However, the potency of rhSP-D multimers was severalfold greater than for purified dodecamers, comparable to natural, proteinosis hSP-D. Although rhSP-D multimers were also more potent than the serum collectins in mediating viral aggregation and protection of PMN, they were less potent than conglutinin in inhibiting infectivity in vitro. These studies establish that the propensity of hSP-D to form multimers of dodecamers is determined by its primary structure and demonstrate carbohydrate recognition domain valency-dependent interactions of SP-D with IAV.

Animals↗
PubMed1995

Detection of neu differentiation factor with a biospecific affinity sensor during chromatography.

A technique using a biospecific affinity sensor, BIAcore, was applied to monitor and determine mammalian cell-derived neu differentiation factor (NDF) in column fractions during chromatography. Specific purified polyclonal antibody against Escherichia coli-derived NDF was chemically bound to the surface of BIAcore sensor chips and the derivatized sensor chips were used to detect the specific binding of NDF. The measurement of NDF at very low levels can be assessed by injecting small volumes of the crude media or column fractions into the BIAcore sensor containing antibody-bound sensor chips. This automated procedure performed under computer programming control allows direct measurement of multiple NDF samples in a short period of time and provides excellent quantitative data, which is not possible using other related methods such as Western blotting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stimulatory activity assay on receptor autophosphorylation.

Animals↗
PubMed1995

Studies on the structure and function of glycosylated and nonglycosylated neu differentiation factors. Similarities and differences of the alpha and beta isoforms.

Comparative analyses of both glycosylated and nonglycosylated neu differentiation factor (NDF) isoforms revealed significant similarities and differences of their overall structures and functions. Biophysical analyses confirmed that all NDF isoforms are monomeric, but have an extended ellipsoidal shape in solution. All full-length NDFs are similar in secondary and tertiary structures and they contain no alpha-helix but are abundant in beta-strand structures. A small NDF fragment containing only the epidermal growth factor domain is also rich in beta-strand structures, but exhibits tertiary structure different from the long NDF forms. Monoclonal antibodies that selectively recognize epidermal growth factor domains of human NDF-alpha and -beta can specifically bind the respective NDF-alpha and -beta isoforms independent of NDF origins. Western blot analysis and quantitative binding assays further identify that an NDF preparation produced naturally from Rat1-EJ cells contains both alpha and beta isoforms in a 3 to 2 ratio. In receptor-binding competition experiments, human and rat NDF-beta isoforms have higher affinity than NDF-alpha isoforms. NDF-beta isoforms can dramatically enhance the stimulation of DNA synthesis for transfected NIH3T3 cells that overexpress HER-3 and HER-4 receptors, while NDF-alpha isoforms can only stimulate proliferation of HER-4-transfected cells with lower activity. Taken together, NDF-alpha and -beta isoforms share similar gross protein conformations but are biologically distinct.

3T3 Cells↗
PubMed1995

Induction of midbrain dopaminergic neurons by Sonic hedgehog.

Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can function in a dose-dependent manner to induce different cell types within the neural tube. Our results also provide the basis for a potential cell transplantation therapy for Parkinson's disease.

Animals↗
PubMed1995

Undernutrition among Bedouin Arab children: a follow-up of the Bedouin Infant Feeding Study.

After 10 y of urban settlement, 680 Bedouin Arab children, who had had anthropometric assessment from birth (1981-1982) through early childhood, were reassessed in 1991-1992 to compare the rates of stunting in early and later childhood as well as to describe the factors influencing current height-for-age. Stunting had dropped from 32.7% at 18 mo to 7.2% at 10 y in the 1981 birth cohort and dropped from 17.5% at 9 mo to 8.2% at 9 y in the 1982 birth cohort. Based on a multiple-linear-regression analysis, height in early childhood and maternal height were statistically significantly and positively associated with current mean height-for-age in both cohorts. In the 1982 cohort socioeconomic status in early childhood was positively and current family size was negatively and significantly associated with current mean height-for-age. Thus, conditions that were present in early childhood had the largest influence on current height. In 1992, 10% and 6% of the infant siblings of the 1981 and 1982 cohorts, respectively, were stunted compared with 17% and 1% of the siblings aged 1-2 y of the respective cohorts. Therefore, the high rates of early childhood stunting in 1981-1982 appeared to be a birth cohort-specific phenomenon.

Child↗
PubMed1995

Influence of malignancy on the pharmacokinetics of vancomycin in infants and children.

This prospective, controlled study evaluates the influence of malignancy on the pharmacokinetics and dosage requirements of vancomycin in 33 infants and children with cancer (age 5.72 +/- 4.11 years, mean +/- SD) compared with 31 patients without cancer (age 4.18 +/- 5.10 years) using a two-compartment Bayesian pharmacokinetic program. Patients in the malignancy group required a vancomycin dosage regimen of 71.5 +/- 13.9 mg/kg/day to attain a mean peak serum vancomycin concentration (SVC) of 22.38 +/- 4.54 mg/liter and a mean trough SVC of 6.84 +/- 2.78 mg/liter. Patients without cancer in the control group required a mean vancomycin dosage regimen of 50.2 +/- 13.0 mg/kg/day to attain a mean peak SVC of 21.70 +/- 6.70 mg/liter and a mean trough SVC of 8.05 +/- 3.01 mg/liter. Comparative analysis of pharmacokinetic data revealed an increase in vancomycin clearance (0.149 +/- 0.028 liter/hour/kg) in the malignancy group as compared with that (0.114 +/- 0.031 liter/hour/kg) in the control group. There were no significant differences with respect to the mean values of volume of distribution between two groups (0.638 +/- 0.079 liter/kg vs. 0.618 +/- 0.102 liter/kg). Analysis of the predictive performance of the Bayesian program indicated that final sets of peak and trough SVCs were predicted with minimal bias and accurate precision in both study groups. This study showed that the presence of malignancy in infants and children increased vancomycin clearance resulting in larger dosage requirements.

Anti-Bacterial Agents↗