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Biomedical subjects

M W Wang

Publications and source records attributed to M W Wang.

At least 55 records · Page 3Linked to original sources
PubMed1992

Induction of acute hyperglycemia, hyperlactemia and hypocalcemia in fed and fasted BALB/c mice by intravenous amylin injection.

Amylin has been reported to influence carbohydrate metabolism in rats, dogs and cats. We report here that intravenous injection of 50 micrograms amylin (640 nmol/kg) induced hyperglycemia, hyperlactemia, and hypocalcemia in both fed and 5-hour fasted mice. Peak glucose and lactate increments occurred within 15 minutes of treatment, followed by a slower decline of plasma calcium levels. To determine dose-response characteristics of these effects, fasted animals were given amylin doses ranging from 0.005 micrograms to 500 micrograms (64 pmol/kg to 6.4 mumol/kg). Median effective doses (ED50) for the hyperglycemic, hyperlactemic, and hypocalcemic effects were 155, 16.9 and 190 nmol/kg, respectively, with maximum increases of 6.27 mM for glucose, 1.85 mM for lactate and maximum decrease of 0.37 mM for calcium. The estimated half-life (t1/2) of exogenous amylin in the circulation was 5.0 minutes in fasted mice. These results indicate that amylin is bioactive in mice. The kinetic data predict that biologically effective doses of exogenous amylin result in plasma concentrations comparable to pathophysiological concentrations of endogenous hormone previously reported.

Amyloid↗
PubMed1992

DNA content and its relationship with pathology and prognosis of colorectal carcinoma.

The DNA content of 181 colorectal cancers was investigated by flow cytometry on paraffin-embedded specimen. The relationship of flow cytometric DNA patterns of colorectal cancer to Dukes's stage, histological type and grade, tumor size and patient's prognosis were analysed. The DNA aneuploid carcinomas were found in 53.04% of the patients (hypodiploid 22.10%, hyperdiploid 20.99%, polyploid 9.94%). Diploidy was found in 46.96% of the patients with colorectal cancer. The proportions of aneuploidy were significantly lower in the patients with Dukes' stage A (25.00%) and B (47.14%) than those with Dukes' stage C (64.71%) and D (68.42%). Aneuploid frequency was higher in the patients with poorly differentiated adenocarcinoma (84.62%), mucinous adenocarcinoma (62.50%) and tubular adenocarcinoma (52.75%) than those with villous adenocarcinoma (22.86%). The proportion of aneuploidy was significantly higher in the patients with poorly differentiated tumor (71.79%) than in those with moderately (50.00%) and well differentiated tumors (44.83%). Five-year survival rate of the patients with DNA aneuploid tumors was 33.80% compared with 66.67% of those with diploid tumors. Analysis of Cox regression revealed that DNA ploidy and Dukes' stage significantly influenced the patient's prognosis. It is suggested that DNA ploidy might be an important prognostic factor in colorectal cancer.

Adenocarcinoma↗
PubMed1991

Amylin is more potent and more effective than glucagon in raising plasma glucose concentration in fasted, anesthetized rats.

Amylin is a 37 amino-acid peptide secreted from the pancreatic beta-cells. It has actions on carbohydrate metabolism in vivo, including elevation of blood glucose. In this study, the hyperglycemic effect of intravenous bolus injections of amylin was compared with similar injections of glucagon in 20-hour fasted rats lightly anesthetized with halothane. Administered doses ranged from 0.01 micrograms to 1000 micrograms (about 7 pmol/kg--750 nmol/kg for amylin and 8 pmol/kg--800 pmol/kg for glucagon). Control animals received an equal volume of saline. A single intravenous injection of amylin or glucagon led to an increase of plasma glucose levels, which peaked approximately at 1 hour after treatment. The calculated ED50 for amylin was 1.48 nmol whereas that for glucagon was 7.46 nmol; the maximum glucose increment was 4.3 mM for amylin, and 2.9 mM for glucagon. These results show that amylin is a more potent and more effective hyperglycemic agent than glucagon under these experimental conditions.

Amyloid↗
PubMed1991

8-37h-CGRP antagonizes actions of amylin on carbohydrate metabolism in vitro and in vivo.

8-37hCGRP is a potent antagonist at calcitonin gene-related peptide (CGRP) liver membrane receptors; it also blocks vasodilator actions of CGRP and the related peptide, amylin, in intact rats. We now report that 8-37hCGRP antagonizes amylin inhibition of insulin-stimulated labelled glucose uptake into isolated rat soleus muscle, and inhibits amylin-evoked elevation of plasma lactate and glucose in fasted anaesthetized rats. The different relative potencies of the 3 ligands (amylin, CGRP, 8-37hCGRP) on the liver receptor and on the soleus muscle point to distinct CGRP receptors in liver membranes and amylin receptors on muscle cells.

Amino Acid Sequence↗
PubMed1991

Amylin injection causes elevated plasma lactate and glucose in the rat.

Intravenous injections of 25.5 nmol rat amylin into fasted anesthetized rats caused a rapid increase in plasma lactate followed by an increase in plasma glucose; there was a transient fall in blood pressure. Subcutaneous injection of 25.5 nmol amylin also caused increases in lactate and glucose but did not change blood pressure. Similar responses were observed during somatostatin infusion and in the absence of changes in catecholamines. These results fit with a scheme in which amylin elicits muscle glycogenolysis, release of lactate, and increased hepatic gluconeogenesis due to increased supply of substrate.

Amyloid↗
PubMed1991

Induction of long-term survival of hamster heart xenografts in rats.

The aim of this study was to determine the mechanisms responsible for concordant xenograft rejection using the hamster-to-rat heart graft model. Even though it was known that rat CD4 positive T cells proliferated to hamster stimulators in mixed lymphocyte reactions, the depletion of CD4 positive T cells in rat recipients did not lead to an extension of xenograft survival. Suppression of T cell immunity using other monoclonal antibodies or cyclosporine also failed to improve survival. Only by depleting complement with cobra-venom factor could hamster xenograft survival be prolonged, and long-term survival was achieved by combining CsA with COF. High-antibody titers to hamster cells were found after transplantation of hamster hearts, and evidence is presented that rejection of these "concordant" xenografts is mediated primarily by antibody-complement mechanisms. The antihamster antibodies were produced in the absence of T cell help, which suggests that antibody-mediated graft destruction cannot be inhibited by suppression or depletion of T cells. Pharmacologic depletion of complement for the clinical application of concordant xenografts is a promising avenue of future research.

Animals↗
PubMed1991

Presence of human chromosome 1 with expression of human decay-accelerating factor (DAF) prevents lysis of mouse/human hybrid cells by human complement.

Xenogeneic organs transplanted to phylogenetically distant species are subject to rapid destruction mediated by complement. In humans, the complement activation is regulated by several proteins encoded by a series of closely linked genes (RCA locus) located on chromosome 1. The mouse/human hybrid cell line B10 was found to have retained human chromosome 1. FACS analysis confirmed that RCA products such as decay-accelerating factor (DAF) were expressed on the membrane surface of B10 cells. When exposed to human or rabbit complement in the presence of 'naturally occurring' human anti-mouse antibodies these cells were not lysed by human complement but were killed by rabbit complement. This effect could be abrogated by addition of anti-DAF monoclonal antibody (IC6). The results offer potential for genetic manipulation of the human complement regulatory products in animals to overcome xenograft hyperacute rejection.

Animals↗
PubMed1991

A monoclonal antibody to progesterone interrupts pregnancy in the hamster by curtailing secretion of the luteotropic complex of prolactin and follicle-stimulating hormone.

A single ip injection of 6.5 nmol of a monoclonal (immunoglobulin G) antibody to progesterone (MAB-P4), administered on the morning of implantation (day 4), interrupted pregnancy by day 8 in 75% of treated hamsters. Pregnancy was unaffected until day 6 although histologically, the embryos contained very few mitotic figures. However, by day 7, the swellings began to regress and were completely eliminated by day 8. The onset of embryonic reabsorption coincides with a drastic fall in free (nonantibody-bound) serum progesterone (P4), in vitro production of P4, and in vitro and in vivo increases in estradiol. The effects of MAB-P4 are completely reversible by a concurrent injection of 1 mg P4 on day 4, whereas deferred injection of P4 to day 6 is ineffective. The onset of functional and structural luteolysis is paralleled by a significant decline in the minimal luteotropic complex of PRL and FSH but with no change in LH. The effects of MAB-P4 are partially reversible by daily injection of FSH or PRL but not LH. We interpret these results as follows: normally during early pregnancy in the hamster endogenous P4 positively reinforces secretion of the luteotropic complex. MAB-P4 with its long half-life of 69 h binds serum P4 and therefore reduces circulating levels of free P4. Consequently, the secretion of PRL and FSH is curtailed without affecting LH. Thus, in the hamster when 6.5 nmol MAB-P4 is injected on day 4, the deprivation of P4 at the uterine level appears to be a secondary event to functional and structural luteolysis.

Animals↗
PubMed1991

Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies.

Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti-DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence and structural comparisons suggest that residues associated with VH CDR3 and VL CDR3 may have a key role in determining the efficiency of anti-idiotypic immunization against progesterone. The variability in outcome of using anti-idiotypic reagents against a defined panel of related antibodies is relevant to the use of anti-idiotypes as surrogate antigens.

Amino Acid Sequence↗
PubMed1990

Effect of passive immunization against progesterone on its distribution in circulation and tissues of mice.

Anti-progesterone monoclonal antibody, injected into mice 32 h after mating at a dose that blocks the establishment of pregnancy, produced a significant reduction in the concentration of progesterone in the ovary and uterus within 6 h after treatment. Uterine concentrations remained lower in treated compared with control animals for at least 24 h after injection. There was an associated transient increase in plasma LH and FSH concentrations, but there was no change in plasma prolactin values. The percentage of total progesterone in the circulation that was unbound was reduced after treatment, but the concentration of unbound progesterone was increased. Studies of antibody binding of steroid in the presence of uterine progesterone receptor protein showed that there was a stoichiometric relationship in the distribution of ligand between the two binders. The present findings suggest that the effects of passive immunization against progesterone are associated with perturbation of tissue concentrations of steroid in the target organ as a result of high antibody concentrations in the circulation.

Animals↗
PubMed1990

Pregnancy-blocking progesterone antibody targets specifically the uterus through its progesterone-binding sites.

Passive immunization with a mouse monoclonal antibody against progesterone, designated DB3, blocks pregnancy in several species. We have previously reported that DB3 localizes in the mouse uterine epithelium shortly before normal implantation. This phenomenon is pregnancy dependent and specific for the progesterone antibody. In this study we demonstrate that DB3 is present in the lumen of the uterus 36 h after an i.p. injection; this correlates with the time of maximum antibody reaction on the uterine epithelium. Incubation of DB3 with free progesterone, progesterone-hemisuccinate or progesterone-bovine serum albumin before administration prevented its localization on the epithelium, indicating that the localization requires free progesterone-binding sites and thus probably depends upon progesterone binding. In addition, studies in vitro show that DB3 can effectively bind to progesterone carried by high-affinity progesterone-binding protein purified from coypu plasma. We suggest that specific targeting of DB3 may be through progesterone associated with a progesterone-binding molecule on the membrane of the uterine epithelia. This may be an important part of the mechanism of antibody action against implantation.

Animals↗
PubMed1990

The antifertility effect of passive immunization of mice against progesterone is influenced by genetic factors other than H-2 haplotype.

The anti-fertility effect of passive immunization against progesterone is influenced by genotype in mice. In order to quantify this finding we determined the effective dose that blocks pregnancy in 50% of treated mice (ED50) for two different anti-progesterone monoclonal antibodies (DB3 and 11/32) in four different strains of mice (BALB/cJ, CBA/Ca, Tuck's no. 1 and F1C). Efficacy was greatest in the two inbred strains (BALB/cJ and CBA/Ca) with ED50 values of 0.46-1.4 nmol. The F1C hybrid mice were more resistant to antibody treatment (ED50 2.2-3.0 nmol), while the outbred Tuck's no. 1 strain required much higher doses (ED50 7.0-8.2 nmol). There were no intrastrain differences between the two monoclonal antibodies. We have examined the possible role of the H-2 haplotype on antibody efficacy in different strains and crosses. The antibody was highly effective in blocking implantation in three congenic BALB strains of different H-2 haplotype, in another inbred strain CBA/Ca, and in reciprocal BALB/cJ x CBA/Ca crosses. The F1 hybrid crosses were somewhat resistant, but the C57BL/10Sn and B10.BR congenic strains were most resistant to treatment. The results show that the pregnancy-blocking effect of the anti-progesterone antibody was not influenced by the H-2 haplotype, but rather by background genes.

Animals↗
PubMed1989

Blocking of pregnancy in mice by immunization with anti-idiotype directed against monoclonal anti-progesterone antibody.

Passive transfer of monoclonal anti-progesterone antibodies shortly after mating blocks the onset of pregnancy in different species (mouse, rat, and ferret). Here we report that BALB/c mice can be actively immunized against progesterone, and hence against pregnancy, by means of rabbit anti-idiotypic antibodies specific for a mouse monoclonal anti-progesterone antibody, DB3. Some of the anti-idiotypic antibodies reacted with the steroid-combining site on the DB3 molecule. In response to repeated anti-idiotypic immunization, mice produced serum anti-progesterone antibodies (up to 100 micrograms/ml) that resembled DB3 in idiotypy, affinity, and specificity for progesterone and other steroid ligands. Thus an anti-idiotype can mimic the antigenicity of a steroid hormone with a high degree of accuracy. Compared with immunization with a progesterone-bovine serum albumin conjugate, the anti-progesterone response to anti-idiotype was considerably lower and clonally restricted. When mated after completion of the immunization course, the fertility rate of anti-idiotype-immunized mice was reduced to 30% from a control level of 91%. The anti-fertility effect was correlated with the circulating anti-progesterone concentration in individual animals and persisted for 4 or 5 estrous cycles. Active immunization with progesterone-bovine serum albumin was a highly effective means of rendering mice infertile; it reduced the fertility rate to zero over 16 or 17 estrous cycles. Our results suggest that anti-idiotypes may form the basis of contraceptive vaccines.

Animals↗