Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 361 records · Page 20Linked to original sources

PubMed1993

Termination of early pregnancy in the rat, rabbit, and hamster with RU 486 and anordrin.

The effectiveness of oral RU 486 and anordrin given alone and in combination for terminating early pregnancy was tested in the rat, rabbit, and hamster. In the rat and rabbit, the combination of RU 486 and anordrin is more effective in terminating pregnancy than either of the two compounds used alone. A non-effective dose of RU 486 combined with a non-effective or a sub-effective dose of anordrin, or a low effective dose of RU 486 in combination with a non-effective dose of anordrin, exerted additive or synergistic effects resulting in resorption of embryos and termination of pregnancy in rats and rabbits. The serum progesterone as well as estradiol concentrations were significantly suppressed by these combinations when pregnancy was terminated. In the hamster, however, RU 486 was not effective in interrupting early pregnancy, even at a 4-fold higher dose than was effective in the rat, due to the fact that RU 486 does not bind to the progestin receptor in this species. Unexpectedly, there were also no effects of anordrin on pregnancy termination in the hamster even at high doses. It is concluded that in rat and rabbit, the synergistic action between RU 486 and anordrin not only greatly enhances efficacy in terminating pregnancy but also reduces substantially the doses required to produce this effect.

Abortifacient Agents, Steroidal↗

PubMed1993

Anordiol is more potent than anordrin for terminating pregnancy when administered with RU 486.

In view of the unexpected ability of anordrin to synergize with RU 486 in terminating pregnancy, it was pertinent to examine the actions of the dihydroxylated metabolite of anordrin, anordiol, alone and in combination with RU 486. Does of RU 486 (1 mg/kg/day) and anordiol (0.6 mg/kg/day) that were ineffective when given alone terminated pregnancy with complete resorption of embryos when administered together. A smaller dose of anordiol than anordrin is required to achieve this synergistic effect with RU 486. This anordrin metabolite increased uterine weight in the ovariectomized rat similar to estradiol. The estrogenicity of anordiol in the uterine weight assay was about 1/120 of that of estradiol. Anordiol does not exert antiestrogenic activity in the uterine weight assay when administered at doses that terminate pregnancy. Administration of anordiol at doses that do not terminate pregnancy resulted in a significant suppression of serum progesterone concentrations during the period of medication; these observations suggest that anordiol has an inhibitory effect on progesterone biosynthesis. When the same dose of anordiol was given concomitantly with sufficient RU 486 (e.g., 1 mg/kg/day) to terminate pregnancy, the progesterone levels were reduced to low levels throughout the experiment. These observations support the postulate that the actions of anordrin are mediated by its metabolite, anordiol. The administration of anordiol plus RU 486 results in a more dramatic change in the functional progesterone:estradiol ratio than when either agent is administered alone.

Abortifacient Agents, Steroidal↗

PubMed1993

Postcoital use of anordrin and RU 486 for prevention of implantation in the rat.

Because RU 486 synergizes with anordrin and its dihydroxylated metabolite to terminate established pregnancy in the rat and rabbit, the interactions of these agents were studied at two days postcoitally in the rat. RU 486 at a dose of 4 mg/kg did not prevent pregnancy when the animals were killed 12 days post insemination. A 2.5 mg/kg dose of anordrin prevented pregnancy in 14% of animals. By contrast, none of the animals became pregnant when treated with 2.5 mg/kg of anordiol. A non-effective dose of RU 486 (2 or 4 mg/kg) combined with a non-effective dose of anordrin (1.25 or 2.5 mg/kg) prevented pregnancy in all animals treated; there was no evidence of implantation sites or embryos when the animals were killed on day 12 post insemination. The same synergistic effect was observed when a small dose of RU 486 (e.g., 1 mg/kg) was combined with 0.6 mg/kg anordiol. To investigate the mechanism of pregnancy prevention, animals were treated two days postcoitally with 4 mg/kg of RU 486 plus 2.5 mg/kg of anordrin or 2 mg/kg of RU 486 plus 0.6 mg/kg of anordiol and were killed short intervals after treatment. These drugs had no effect by 6 h, but the numbers of embryos in oviducts were significantly reduced 12 h after treatment. By 24 h following treatment, no embryos were recovered from either the oviduct or the uterus. Progesterone and estradiol levels in serum collected 24 h after treatment were not significantly different from those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Endogenous and exogenous modulation of gap junctional intercellular communication: toxicological and pharmacological implications.

During the evolution of single-celled organisms to multicellular metazoans, a family of highly conserved genes coding for proteins (connexins), which as hexameric units (connexins), has evolved to form intercellular channels (gap junctions). These gap junctions allow ions and small molecular weight molecules to flow between coupled cells, thereby facilitating synchronization of electrotonic or metabolic cooperation. Control of cell proliferation, cell differentiation and adaptive responses of differentiated cells have been speculated to be biological roles of gap junctions. The regulation of these gap junctions can occur at the transcriptional, translational and posttranslational levels. Transient downregulation by endogenous or exogenous chemicals can bring about adaptive or maladaptive consequences depending on circumstances. Stable abnormal regulation of gap junction function has been associated with the activation of several oncogenes. Several tumor suppressor genes have also been associated with the up-regulation of gap junction function. Since gap junctions exist in all organs of the multi-cellular organisms, the dysfunction of these gap junctions by various toxic chemicals which have cell type/tissue/organ specificity could bring about very distinct clinical consequences, such as embryo lethality or teratogenesis, reproductive dysfunction in the gonads, neurotoxicity of the CNS system, hyperplasia of the skin, and tumor promotion of initiated tissue. Understanding how many non-mutagenic chemicals might alter normal gap junction function should form the basis of "epigenetic" toxicology. On the other hand, restoring normal gap junction function to cells which have dysfunctional intercellular communication could be the basis for a new approach for therapeutic pharmaceuticals.

Animals↗

PubMed1993

Purification, sequencing and characterization of single amino acid-substituted phospholipase A2 isozymes from Trimeresurus gramineus (green habu snake) venom.

Two phospholipases A2 named PLA2-III and IV were newly isolated from Trimeresurus gramineus (green habu snake) venom in addition to PLA2-I and II reported previously [ODA et al. (1991) Toxicon 29, 157; Fukagawa et al. (1992) Toxicon 30, 133]. Their isoelectric points were determined to be about 4.5. PLA2-III and IV exhibited almost unchanged lipolytic activity toward egg-yolk when compared with PLA2-I. The amino acid sequences were determined by sequencing the native proteins and the peptides produced by enzymatic (Achromobacter protease I and clostripain) and chemical (hydroxylamine) cleavages of the S-carboxamidomethylated derivative of the proteins. Both proteins consisted of 122 amino acid residues. When compared with PLA2-I, PLA2-III showed only a single amino acid substitution at the N-terminal position; namely from His to Asn. PLA2-IV also showed a single substitution from Ala to Asp at position 72. It was inferred that these amino acid substitutions between PLA2-I and PLA2-III or IV are due to the single base substitution at the corresponding codons of genes, which might be preserved independently. The unique presence of Phe at position 28, where Tyr is commonly located and assumed to be a part of the Ca(2+)-binding loop, was conserved in both PLA2-III and IV as in PLA2-I. There was no significant difference in the dissociation constants (4.3-5.2 x 10(-4) M) for Ca2+ between these PLA2S and Tyr-28-containing PLA2S. These results suggested that the p-hydroxy group of Try-28 does not play a crucial role in binding of PLA2S to Ca2+.

Amino Acid Sequence↗

PubMed1993

Osteonecrosis: current perspectives on pathogenesis and treatment.

Nontraumatic osteonecrosis results from impairment of circulation to the affected bone. The femoral head is affected most frequently. The underlying cause for the circulatory defect in osteonecrosis varies and may involve both local and systemic changes. Steroid use, alcohol consumption, pancreatitis, and lipid disorders appear to lead to bone death either by development of fat emboli in the microcirculature surrounding the affected bone or by fatty infiltration of the marrow. Decompression syndrome results from the presence of gaseous emboli in the microcirculature. In Legg-Calvé-Perthes disease other associated features are present such as short stature, suboptimal growth velocity, and/or hormonal imbalances, and it is likely that osteonecrosis may be secondary to systemic abnormalities, although specific factors have not been identified. Other frequently suggested pathogenic factors that play a role in the development of osteonecrosis include increased intraosseous pressures, the presence of cytotoxic cellular factors, intravascular coagulation, venous stasis, and the hyperviscosity syndrome. Some investigators have attempted, without success, to find a common etiology for all cases of osteonecrosis. In addition, patients have developed osteonecrosis without any known risk factors; this syndrome has been coined idiopathic avascular necrosis. In advanced stages of femoral head osteonecrosis, total hip arthroplasty appears to be the best therapeutic modality, particularly in older individuals.

Adrenal Cortex Hormones↗

PubMed1993

Suppression of growth by dietary fish oil of human breast carcinomas maintained in three different strains of immune-deficient mice.

It has been reported that high levels of dietary fish (menhaden) oil, compared with corn oil, suppress the growth of MDA-MB231 and MCF-7 human breast carcinomas maintained in female athymic nude (T lymphocyte-deficient) mice. The purpose of this study was to determine whether dietary fish (menhaden) oil, compared with corn oil, can also suppress the growth of these carcinomas when maintained in female beige-XID-athymic nude (T lymphocyte- and NK/LAK cell-deficient) mice and in female severe combined immune-deficient (SCID) mice (total lack of functional T and B lymphocytes). Results clearly show that dietary fish (menhaden) oil can significantly (p < 0.05) suppress the growth of these carcinomas in the beige-XID-athymic nude mouse and the SCID mouse. Such results provide evidence that the growth suppression of MDA-MB231 and MCF-7 human breast carcinomas, induced by dietary fish oil, is not mediated by immune system mechanisms involving T lymphocytes, B lymphocytes, and/or NK/LAK cells.

Animals↗

PubMed1993

A comparison between vecuronium and atracurium in myasthenia gravis.

We evaluated the effect of vecuronium bromide and atracurium besylate on the train-of-four response in the management of muscle relaxation in 20 patients with myasthenia gravis (MG) who were undergoing thymectomy. We confirmed the safe use of these two non-depolarizing muscle relaxants in MG patients. Vecuronium (0.04 mg.kg-1) demonstrated a lesser clinical duration than did atracurium (0.2 mg.kg-1) (38 +/- 19 vs 50 +/- 21 min, mean +/- s.e.mean). The recovery time for vecuronium patients was shorter than that for atracurium patients (22 +/- 18 vs 38 +/- 18 min), but the time until onset of neuromuscular blockade was longer with vecuronium (246 +/- 105 vs 107 +/- 103 s). During spontaneous recovery from neuromuscular relaxation, at T1/C of 25% and 100%, the train-of-four fade with vecuronium was significantly greater than that with atracurium (0.04 +/- 0.02, 0.16 +/- 0.03 vs 0.17 +/- 0.01, 0.83 +/- 0.03), suggesting that vecuronium had a greater prejunctional effect than did atracurium.

Adult↗

PubMed1993

Transmitter-mediated local contracture of the endplate region of the focally innervated mouse diaphragm treated with anticholinesterase.

1. Local contraction of the endplate region in response to nerve stimulation was studied in isolated mouse diaphragms. In normal preparations, muscle contractions involved the whole length of the muscle fibre with rise and decay times in the order of tens of ms whether evoked with a single or train of pulses. 2. When acetylcholinesterase was inhibited with neostigmine, tetanic stimulation produced a twitch-like phasic contraction and a delayed tonic contracture. A brief train of pulse (10 ms, 300 Hz) was enough to trigger a full size tonic contracture which reached an amplitude about one tenth that of control tetanus and had a duration of about 4 s. 3. Tetanic stimulation evoked a non-propagating prolonged depolarization at the endplate region lasting for about 1 s following a few muscle action potentials. 4. mu-Conotoxin, a specific inhibitor of muscle Na+ channel, selectively abolished the phasic contraction and the muscle action potentials leaving the tonic contracture and the prolonged depolarization unaffected. 5. Both the tonic contracture and the prolonged depolarization were highly sensitive to blockade by tubocurarine (IC50 0.05-0.1 microM) and vesamicol (1 microM, an inhibitor of packaging acetylcholine into synaptic vesicles), were attenuated by increasing Ca2+ concentration and were prolonged by decreasing Ca2+. 6. The results suggest that prolonged activation of endplate nicotinic receptors by endogenously released transmitter can produce substantial contractions of the endplate region when acetylcholinesterase are inhibited. The source of Ca2+ for the contraction seems to come mainly from intracellular stores.

Action Potentials↗

PubMed1993

Secular trend of mortality from cerebral infarction and cerebral hemorrhage in Taiwan, 1974-1988.

BACKGROUND AND PURPOSE: Pathological patterns of stroke are different in various races, with the predominant stroke type in the Chinese being intracerebral hemorrhage. A total of 31,078 deaths from cerebral infarction and 77,773 deaths from cerebral hemorrhage in Taiwan were reported for groups of subjects aged 40-79 years during the period 1974-1988 to elucidate their secular trends. METHODS: Vital statistics and demographic data were collected for analyzing the truncated age-adjusted mortality rates. Poisson regression analysis was used to estimate the relative risk and 95% confidence interval. RESULTS: The mortality rates for cerebral hemorrhage were greater than those for cerebral infarction. The mortality rates increased exponentially with age for both subtypes. The decline in age-specific mortality for the period 1974-1983 was much more striking for cerebral hemorrhage than for cerebral infarction. Mortality from cerebral infarction and hemorrhage increased with age for all birth cohorts except the cerebral hemorrhage mortality of the oldest cohort. Male/female ratios for both cerebral infarction and hemorrhage were greater in the younger age groups. The cerebral hemorrhage/infarction ratio during the period 1984-1988 was highest for the younger age groups and lowest for the oldest age groups. CONCLUSIONS: The different secular trends of mortality from cerebral infarction and hemorrhage imply that these two patterns of stroke may be associated with some different risk factors.

Adult↗

PubMed1993

Pentoxifylline inhibits the proliferation and glycosaminoglycan synthesis of cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial myxoedema.

Excessive amounts of glycosaminoglycans accumulate in the extraocular muscles of patients with Graves' ophthalmopathy and in the affected skin of patients with pretibial myxoedema. It is widely accepted that fibroblasts are the sources of glycosaminoglycan synthesis. Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin and from skin of patients with some fibrotic disorders. Our objective was to determine whether pentoxifylline has similar effects on fibroblasts derived from patients with Graves' ophthalmopathy and pretibial myxoedema and could serve as a candidate for the treatment of these manifestations. Fibroblasts from the extraocular muscles of two patients with Graves' ophthalmopathy and normal extraocular muscles of two subjects with strabismus, as well as the affected skin of two patients with pretibial myxoedema were cultured in vitro in the presence and absence of pentoxifylline to assay its effect on the proliferation of fibroblasts and their production of glycosaminoglycans. In subconfluent fibroblast cultures, pentoxifylline treatment caused a dose-dependent inhibition of serum-driven fibroblast proliferation. In confluent fibroblast cultures both in the presence and absence of serum, exposure to pentoxifylline similarly resulted in a dose-dependent inhibition of glycosaminoglycan synthesis for all these different kinds of fibroblasts. These findings may form the rationale for a clinical trial using pentoxifylline for the treatment of Graves' ophthalmopathy and pretibial myxoedema.

Adult↗

PubMed1993

Asthma mortality: another opinion--is it a matter of life and ... bread?

There is a general consensus that the mortality rates for asthma in much of the developed world have been increasing for the past 10-15 years. This has occurred despite an improved information base regarding diagnosis and management as well as the development of novel and more effective therapeutic modalities. Several explanations have been proposed for this increase, including a statistical artifact based on a change in the coding criteria for asthma from the International Classification of Diseases Version 8 (ICD-8) to ICD-9, worsened pollution, delays in seeking medical help, behavioral changes, deficits in asthma education of both patients and primary care providers, toxicity of beta agonists, and noncompliance with medications. We suggest that although all of these are potential etiological factors, there may exist still another major etiological risk. There have been dramatic changes in our eating habits and food preparation. In general, we eat less total calories, more meals outside the home, and more refined or prepared foods. With the emphasis on reducing the intake of saturated fats and cholesterol, we eat more polyunsaturated fats both by choice and secondary to manufacturers' attempts to improve the appeal of foods to health-conscious government and the public. The drive to remove animal fats and cholesterol from our diet has resulted in the replacement of animal fats with vegetable oil in food manufacture, fast-food frying, and even home preparation. One result of these dietary habits has been a doubling from 8 to 15% of the percentage of the polyunsaturated linoleic acid in body fat. We postulate that this, and other nutritional changes, will render asthma a more difficult syndrome to manage and will contribute adversely to the inflammatory abnormalities in airways.

Adrenergic beta-Agonists↗

PubMed1993

The sick building syndrome. I. Definition and epidemiological considerations.

It has been difficult to confirm that a given building is responsible for allergic symptomatology, exacerbation of asthma, or immunological dysfunction. In fact, in most studies, few objective immunological parameters have been studied and only rarely has there been any quantitation of IgE or secondary mediators. Furthermore, although many studies deal with rhinitis or respiratory tract irritation, there is a misconception that all such symptoms are allergic in nature, and studies attempting to prove that allergies are caused by buildings frequently neglect to prove that these are indeed true allergic responses. In addition, many of the symptoms that people attribute to sick building syndrome (SBS) or building-related illness, such as headaches, dizziness, fatigue, nausea, cough, and eye irritation, are subjective, and studies often fail to take into account other possible causes that may be inherent in the subjects, such as sinusitis, hyperventilation syndrome, or psychosomatic illness. Unfortunately, most clinical studies on SBS pay little attention to the preexisting conditions that a subject may have and discount the possibility that the inciting agent does not cause symptoms, but merely exacerbates a preexisting condition. Moreover, they offer no information about the nature of the mechanisms of action or pathophysiological relationships. Clearly, further studies are necessary to further explain the complexity of complaints that currently exist. Indeed, SBS might properly be paraphrased as "what is it?--if it is!"

Air Pollutants, Occupational↗

PubMed1993

The sick building syndrome. II. Assessment and regulation of indoor air quality.

Indoor air pollution is closely associated with health problems and exacerbation of asthmatic symptoms. However, it is difficult to find objective data regarding the nature of these illnesses and the degree of exposure necessary to elicit symptoms in building occupants. Clinicians must be encouraged to take seriously, and without bias, workers' complaints about their work environment. However, this is often a problem because of subjective complaints, potential malingerers, mass hysteria, and lack of impartial clinical and laboratory findings. Clearly, in any building, a major priority must be to provide and maintain an environment conducive to occupant health and well-being. Allowable levels of air pollutants must be scientifically determined by health investigators based on government regulations. Unfortunately, regulations are often ill defined, unenforceable, and burdened by a void as to who is responsible for achieving a healthful indoor environment. The elucidation of the multiple causes of illnesses secondary to indoor air pollution can be addressed by greater attention to design, construction, and operation of buildings where people live and work. Finally and most important, the federal government should bear the responsibility for funding the necessary research to solve the nation's indoor air quality problems.

Air Pollutants, Occupational↗

PubMed1993

Characterization of gap junctional communication-deficient mutants of a rat liver epithelial cell line.

To understand the mechanism(s) regulating gap junctional communication, we isolated gap junctional intercellular communication-deficient (GJIC-) mutant clones of a rat liver epithelial cell line, WB F-344, which is hypoxanthine-guanine phosphoribosyl transferase deficient (HGPRT-). The cells were exposed to a mutagenesis regimen and cocultured with the wild type HGPRT+ cells. Four GJIC- and one positive clones were characterized in the present study. Northern analysis of RNA isolated from both mutant and parental cells showed a single RNA species of about 3.0 kb which hybridized to connexin43 (Cx43) cDNA. Western blot analysis confirmed the expression of this junctional protein in all these clones. However, in the GJIC- clones the slowest migrating band corresponding to a hyperphosphorylated form, P2, of Cx43 protein (approximately 46 kDa) was absent suggesting that loss of this phosphorylated form of Cx43 may be involved in the failure of the mutants to establish cell-cell communication. Immunofluorescence analysis of the mutants did not reveal any differences in the distribution and localization of Cx43 between GJIC+ and GJIC- clones suggesting that the loss of phosphorylation did not affect the membrane association of this protein. Taken together, these data suggest that one mechanism for the loss of communication in these GJIC- mutants may be the consequence of a change in the intrinsic phosphorylation state of Cx43 protein.

Animals↗

PubMed1993

Plasma PTH and PTH-rP levels and clodronate therapy in cancer patients with hypercalcemia.

To investigate the roles of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTH-rP) in hypercalcemic patients with various malignancies, we measured the plasma levels of intact PTH and intact PTH-rP in five hypercalcemic patients with hematologic malignancies and 29 hypercalcemic patients with solid cancers. Ten eucalcemic cancer patients with either hepatocellular carcinoma or squamous cancer of the lung served as controls. The results showed a suppressed PTH level in all of the 34 hypercalcemic cancer patients. The PTH-rP levels were within normal limits (< 2.5 pg/mL) for all of the eucalcemic cancer controls, all of the five hematologic cancer patients with hypercalcemia, and only two out of the 29 hypercalcemic patients with solid cancers. The PTH-rP level was elevated in nearly all (27/29) hypercalcemic patients with or without bony metastasis. There was a good correlation between the corrected total serum calcium level and the natural log of PTH-rP level in 39 patients (10 eucalcemic and 29 hypercalcemic) with solid cancers (r = 0.75, p < 0.001). These results suggest that PTH-rP plays an important role in the hypercalcemia of patients with solid cancers, but this was not the case in our patients with hematologic malignancies. True ectopic secretion of PTH is unlikely in most of these patients. The mean serum total calcium levels of 17 hypercalcemic patients (13 solid cancers, four hematologic malignancies) dropped significantly after the third day of treatment with a new-generation bisphosphonate-clodronate product. This treatment consisted of 300 mg daily intravenous infusion for seven days, followed by oral administration (800 mg, bid) for the following three weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Clodronic Acid↗

PubMed1993

Chemical modification of amino groups in cardiotoxin III from Taiwan cobra Naja naja atra) venom.

Cardiotoxin III (CTX III), a major cardiotoxin analogue isolated from the Taiwan cobra (Naja naja atra) venom was modified, either with trinitrobenzene sulfonate (TNBS) or 4-chloro-3,5-dinitrobenzoate (CDNB). Under the conditions of limited reagent availability, three mono-TNP derivatives modified at Lys-5, 12, or 44, and three mono-CDNP derivatives at Lys-12, 23, or 44 were isolated, respectively. The biological activities of CTX III were more or less affected after each of these reactive amino groups were modified. In particular, the hemolytic activity to human erythrocytes and cytotoxicity on NS-1 cells of CTX III decreased to 31% and 50%, respectively, when Lys-12 was trinitrophenylated. More pronounced alteration in these activities was observed as this amino group was carboxydinitrophenylated. A good correlation between the hemolytic activity and cytotoxicity was found. These results indicate that epsilon-amino group at Lys-12 is most closely related to the hemolytic and cytotoxic activities of CTX III. The antigenicity of modified derivatives still remained intact as measured by ELISA.

Animals↗

PubMed1993

Probing the functional sites in Naja naja atra (Taiwan cobra) cardiotoxin III with monoclonal antibody.

One monoclonal antibody (mAb) against Naja naja atra cardiotoxin III was prepared by using the hybridoma technique. The cytotoxic activity of cardiotoxin III which inhibited human lymphocyte proliferation was effectively neutralized by the mAb at a molar ratio of antibody to toxin of 1:2. On the contrary, the mAb did not exert a significant inhibition on the hemolytic activity of cardiotoxin III. These results suggest that the functional site responsible for the cytotoxicity might be different from that for the hemolytic activity of cardiotoxin III.

Animals↗