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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 1,099 records · Page 61Linked to original sources
PubMed1992

Pharmacology of intrathecal VP-16-213 in dogs.

VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01-1.0 mg.kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3-4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration.

Animals↗
PubMed1992

Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages.

Biotinylated hyaluronan (HA) binding complex (HABC) from bovine articular cartilage proteoglycan was used as a histological probe to study the localization of HA in human skin. The distribution of HA was compared with its presumptive cell surface receptor, CD44, using monoclonal antibodies. In epidermis both HA and CD44 were found in the basal and spinous cell layers, but neither was present in the stratum granulosum and stratum corneum. In the keratinizing parts of hair follicles, i.e. in the outer and inner epidermal root sheath, pilosebaceous duct and the actual hair, HA and CD44 were found between the vital but not the terminally differentiated cells. In the sebaceous glands a small amount of HA was found around all cells, whereas CD44 was restricted to the basal cell layer. The secretory acini of the sweat glands stained intensively with anti-CD44 antibodies but only weakly with HABC. In the sweat gland, CD44 was localized on the basal and lateral surfaces of the clear cells, whereas the dark cells and the myoepithelial cells were negative. Both the lower and upper layers of the sweat gland ducts showed a faint but constant staining for CD44 and only minor amounts of HA. While in the keratinizing skin epithelia both HA and its CD44 receptor showed an intense staining with a close co-distribution, in the sweat and sebaceous glands their distribution patterns were not similar. It is suggested that in epithelia with divergent differentiation programs the functions of CD44 and HA may be different.

Biotin↗
PubMed1992

A sensitive and specific radioimmunoassay for platelet-activating factor.

A platelet-activating factor (PAF) analog with a reactive omega-aldehyde group at the sn-1 position was synthesized. The hapten-thyroglobulin conjugate was used to immunize rabbits to produce specific antibodies to PAF. The purified immunoglobulin G (IgG) fraction was found to bind stereo-specifically to tritiated PAF and to crossreact minimally with lysoPAF, plasmalogens, and other phospholipids. The radioimmunoassay detected as little as 20 pg of PAF per assay tube and was used to explore agonist-induced synthesis of PAF in rabbit neutrophils. Calcium ionophore A23187 at 1 microM induced PAF synthesis peaking at 2 min and reaching basal levels after 5 min. N-Formyl-Met-Leu-Phe (FMLP) at 0.1 microM also stimulated rapid synthesis and degradation of PAF with a peak at 5 min. Both A23187 and FMLP stimulated PAF synthesis in a dose-dependent manner. The radioimmunoassay should be applicable to the quantitation of PAF in biological samples.

Animals↗
PubMed1992

Detection of surface antigen expression of pre- and post-cultured normal adult's bone marrow cells by using ABC technique and its significance.

The expression of surface antigens on both normal adult's bone marrow and multipotential progenitor cells (CFU-Mix) was detected by use of ABC technique. The culture system of CFU-Mix was an ideal model for studying the differentiation direction of hematopoietic cells. The monoclonal antibodies (McAb) CD3, CD4, CD8 specific for T-lymphocytic lineage, CD22 for B-lymphocytic lineage and CD11, CD13, CD14 for granulocytomonocytic lineage were all demonstrated in certain proportion in cultured CFU-Mix, which might be associated with the control of hematopoiesis. A decrease in the positive rate of OKT9 and CD34 in cultured cells might be related to the differentiation of hematopoietic cells. SZ-2 and SZ-21 could contribute to the identification of the presence of megakaryocytes in CFU-Mix.

Adult↗
PubMed1992

Determination of carcinogenic potency of alkytoxynol-741 (AP-741) by rat peritoneal cell cultures.

The carcinogenic potency of AP-741 was tested in rats using the Nashed method of rat peritoneal cell short-term carcinogenic test. N-methyl-N-nitro-N'-nitrosoguanidian (MNNG) was used as positive control; saline and nonoxynol-9 (NP-9) were used as negative control. Two doses of AP-741 (4 mg/kg and 40 mg/kg equivalent to 4 and 40 times human doses) were tested. The result showed that no colonies of more than 9 cells were seen in the saline and NP-9 groups, and the two dose groups of AP-741. However, 12 +/- 8.3 colonies (9-29 cell/colony) and 4.5 +/- 4.2 colonies (30-300 cell/colony) were seen in the MNNG group. According to the Nashed criterion, we can say MNNG has potential carcinogenesis, while AP-741 does not have any potential carcinogenesis and its use as a vaginal contraceptive drug is safe.

Animals↗
PubMed1992

Relative effects of intrathecal administration of fentanyl and midazolam on A delta and C fibre reflexes.

The effects of fentanyl and midazolam, administered intrathecally, on somatosympathetic reflexes evoked by tibial nerve stimulation were investigated in 12 anaesthetized and paralysed dogs. Fentanyl depressed both the C and A delta fibre evoked reflexes in a dose ratio of approx 1:2. In contrast, midazolam had a greater effect on A delta compared with C fibre reflexes; while A delta reflexes were abolished by a total dose of 3 mg midazolam, C fibre reflexes were depressed by only 50%. The effect of fentanyl was reversed by naloxone (2 mg, i.v.) and that of midazolam by flumazenil (1 mg, i.v.). The results suggest that fentanyl and midazolam have different relative effects on A delta and C fibre pathways.

Anesthesia, Spinal↗
PubMed1992

Effects of insulin and insulin-like growth factors on neurofilament mRNA and tubulin mRNA content in human neuroblastoma SH-SY5Y cells.

Insulin-like growth factors (IGFs) are implicated in the development of the vertebrate neural circuitry, and increase neurite growth in vitro and in vivo. The construction of the cytoskeleton is necessary for growth of axons and dendrites, and the neurofilament (NF) 68 kDa and 170 kDa proteins assemble to help form major fibrillar elements of the neurite cytoskeleton. We report that physiological concentrations of insulin, IGF-I or IGF-II increased the contents of 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs, relative to total RNA, in cultured human neuroblastoma SH-SY5Y cells. In contrast, the relative contents of histone 3.3 mRNA, and poly(A)+ RNA were not increased. Ligand concentrations which increased NF mRNAs were very similar to those which increased neurite outgrowth. Although each gene was evidently independently regulated, the 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs were nevertheless all transiently elevated over approximately the same time interval in response to insulin. These data, when considered together with studies by others with nerve growth factor, show that the 68 kDa and 170 kDa NF mRNAs are elevated in a biochemical pathway activated in common during neurite outgrowth directed by insulin, IGF-I, IGF-II, and nerve growth factor.

Gene Expression Regulation, Neoplastic↗
PubMed1992

Culture, meaning and disability: injury prevention campaigns and the production of stigma.

The potential production of stigma through health promotion campaigns is a problem that has not received attention in the current literature on the sociology of health promotion. Cultural production studies can shed light onto the ways in which injury prevention campaigns, and public health campaigns more generally, may call for life-saving interventions at the social expense of people with disabilities or other stigmatized conditions. Questioned here are not only the presumed benefits of health promotion campaigns, but also our conventional understandings of 'health' and 'disability'. This paper examines the way in which cultural production studies can contribute to a theory of the production of stigma by public health professionals. One view of cultural production views culture as a reflection of economic relationships between the dominant and the dominated. A second approach emphasizes the 'reception' of cultural works, or how audiences experience culture. Third, cultural production is sometimes analyzed in terms of texts, or the content of cultural artifacts. Insight into the dilemmas of health promotion can be provided by analyzing health promotion strategies in terms of their production, reception, and content as cultural works. Focusing on the case study of injury control and disability rights, health promotion campaigns are seen as potentially contributing to the production of stigma for people who already possess the attributes targeted for prevention. This analysis moves toward a broader theoretical foundation with which to grasp the unintended, even harmful consequences of prevention strategies, and the shared and oppositional interests of people with stigmatized conditions, targeted audiences of prevention, and public health advocates.

Attitude to Health↗
PubMed1992

Effect of androgens on the brain and other organs during development and aging.

Androgens have important biological effects on accessory sexual organs and have a broad range of effects on metabolic processes. Male hormones have been shown to have important organizational and activational effects on morphological, behavioral, and cognitive activity in experimental animals. Sexual dimorphic effects on cognitive and behavioral activities in animals have been linked to androgens during the fetal period. The effects of testosterone on sexual drive are well established in humans, although the threshold for such activity appears to be lower than that required for many of the other and organic effects of testosterone. There are suggestive data to link fetal androgen levels to cognitive and behavioral activities in children and adults, but the behavioral activities may be modified by social and other learning processes. Androgen levels fall in older men at a time when impaired sexual function, osteopenia, and decreased muscle mass can be identified. The relative importance of androgen deficiency in these disorders requires further study, since they are likely to be multifactorial in pathogenesis. Replacement therapy of elderly men who have lowered testosterone levels has been proposed to decrease bone and muscle loss as well as to improve sexual function and general well-being. Careful studies will be required to assess the risk-to-reward ratio of such treatment, since theoretical adverse effects on prostate and cardiovascular diseases may occur. While conservation in management has its virtues, we should be reminded that several decades ago estrogen replacement of postmenopausal women was highly criticized until data supporting its favorable therapeutic ratio were demonstrated.

Aged↗
PubMed1992

Evaluation of testicular function.

The evaluation of testicular function is based primarily on a detailed medical history, a careful physical examination, basal measurements of FSH, LH and testosterone and a routine semen analysis. In a patient with androgen deficiency, the diagnosis can often be made with these basic tests. The clinician will then decide on other investigations to localize the organic lesion and to plan further treatment for the patient. Sperm function tests are often performed in patients presenting with infertility. These newer tests may help to delineate the abnormality of the spermatozoa at each stage during the achievement of fertilizing capacity such as adequate forward motility, penetration of cervical mucus, acrosome reaction, development of hyperactivated motility, binding to the zona pellucida, and fusion with the oocyte. Currently, many of these sperm function tests depend on cumbersome bioassays with many limiting factors contributing to their availability, accuracy and precision. The development of biochemical tests as markers of sperm function may allow more precise definition of sperm functional abnormalities. With the continued improvement of computer-aided sperm analysis, objective motion parameter measurements are possible and morphological assessment are being developed. These newer objective methods of semen analysis have to be shown to be valuable in the clinical assessment of patients with testicular dysfunction.

Endocrine System Diseases↗
PubMed1992

Developments in the control of testicular function.

Clinicians and clinical investigators have developed improved means for controlling testicular function in men. New and refined approaches for stimulation and inhibition of the hypothalamic-pituitary-testicular axis are now available. This chapter reviewed the most successful ways to inhibit the reproductive axis in men and its current application to the treatment of precocious puberty, metastatic prostate cancer, benign prostate hyperplasia and as prospective male contraceptives. Safe, effective and reversible medical approaches to male contraception are now approaching reality. Azoospermia and severe oligozoo/azoospermia can now be accomplished in the majority of men with combined GnRH antagonists and replacement doses of testosterone. Androgens and androgen-progestogen concentrations will induce azoospermia in over 90% of Asian men and azoospermia or severe oligospermia in Caucasian ethnic groups. Field trials are ongoing to determine whether testosterone administration will be more effective than condoms as contraceptives. True precocious puberty can now be managed more effectively than in the past by suppression of gonadotropin secretion with GnRH analogues. Precocious puberty due to other causes can be treated more effectively with inhibitors of steroidogenesis and blockers of androgen action. Metastatic prostate cancer, previously treatable with either castration or oestrogens, is now amenable to suppression of androgen secretion. GnRH analogues are given either alone or combined with blockers of androgen action. While significant palliative effects are observed with endocrine ablative therapy in most men with Stage C or D prostate cancer, modest increases in duration of survival may be seen. Benign prostate hyperplasia was previously approachable only with surgical intervention. Recent data have suggested that medical treatment with 5 alpha-reductase inhibitors and/or selective alpha-adrenergic blockers may offer non-surgical alternatives in some patients. More data are needed to determine the role of medical management of this common disorder.

5-alpha Reductase Inhibitors↗
PubMed1992

Effect of low and high concentrations of alfentanil administered intrathecally on A delta and C fibre mediated somatosympathetic reflexes.

We have studied the effects of alfentanil administered intrathecally on somatosympathetic reflexes evoked by stimulation of radial and tibial nerves in 10 anaesthetized and paralysed dogs. In five animals, alfentanil was administered in doses of 100, 100, 200 and 400 micrograms in 0.8 ml and 800 micrograms in 1.6 ml prepared from the formulation of 500 micrograms ml-1. Five others received alfentanil (high concentration formulation, 5 mg ml-1) in doses of 500 and 2000 micrograms in 0.5 ml and 5000 micrograms in 1 ml. C fibre tibial nerve reflexes were depressed by 100 micrograms and abolished with doses of 200-400 micrograms, but the A delta response remained unaffected. A delta responses were depressed also and abolished, respectively, by doses of alfentanil 2000 micrograms and 5000 micrograms. At the larger, but not the smaller, concentration there was evidence of baroreflex sensitization probably caused by systemic absorption of the drug.

Alfentanil↗
PubMed1992

O6-methylguanine-DNA methyltransferase activity in human tumors.

The distribution of O6-methylguanine-DNA methyltransferase (MGMT) activity in extracts of tumors from 74 patients was measured. The results demonstrated that there was considerable variation of MGMT activity in different human tumor tissues as well as in different individuals. The mean values (X +/- SD, pmol/mg of protein) in breast cancer, stomach cancer, small cell lung cancer, non-small cell lung cancer, renal cell carcinoma, esophageal carcinoma, brain tumors, colon carcinoma and malignant melanoma were 1.071 +/- 0.374 (9), 0.515 +/- 0.107 (5), 0.509 +/- 0.251 (5), 0.461 +/- 0.227 (24), 0.329 +/- 0.246 (5), 0.273 +/- 0.376 (5), 0.244 +/- 0.175 (14), 0.242 +/- 0.308 (5) and 0.201 +/- 0.161 (2) respectively. It was notable that six samples (1/24 non-small cell lung cancer, 3/5 esophageal carcinoma, 1/14 brain tumors and 1/5 colon carcinoma) did not have any detectable level of MGMT activity. Activity of glutamine pyruvic transaminase (GPT) was also measured in the same extracts used for the assay of MGMT activity. The activity of GPT in these samples with undetectable level of MGMT activity was similar to those with significant MGMT activity. These results further strengthen the assumption that a certain fraction of human tumors are Mer-.

Adult↗
PubMed1992

Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos.

The Drosophila gene pumilio is expressed maternally, and its function is essential during early embryogenesis for the formation of abdominal segments. Our molecular analysis reveals that pumilio is a large gene that encodes a protein of 160 kD whose RNA is enriched at the posterior pole of the egg. As with pumilio, the maternal effect gene nanos is specifically required for abdomen formation. The Nanos protein is expressed in a posterior-to-anterior concentration gradient in the developing embryo. Previous experiments demonstrated a genetic interaction between pumilio and nanos, and led to the suggestion that pumilio is required for the proper spatial distribution of the Nanos protein. Here, we show that the expression and distribution of nanos RNA and protein in embryos derived from pumilio mutant females are indistinguishable from wild type. We conclude that abdomen formation depends both on Nanos activity, spreading from the localized posterior source, and on Pumilio activity, present throughout the embryo.

Abdomen↗
PubMed1992

Cap-independent translation by the 5' untranslated region of Theiler's murine encephalomyelitis virus.

The RNA genome of Theiler's murine encephalomyelitis viruses, a picornavirus belonging to the genus Cardiovirus, is translated in infected cells to a polyprotein. Unlike cellular messages, the 5' end of the RNA is not capped, and the untranslated region (UTR) is quite long (1,064 nucleotides in size). In poliovirus and encephalomyocarditis virus, the 5'UTR is thought to mediate cap-independent translation. We report here experiments to determine the role of the Theiler's murine encephalomyelitis virus 5'UTR in translation. Recombinant DNAs were constructed that were transcribed into bicistronic mRNAs encoding 5' chloramphenicol acetyltransferase intercistronic sequences linked to luciferase and a poly(A) 3' tail. The sequences of the 5'UTR, either complete or with sequential 5' deletions, were inserted into the intercistronic region. Bicistronic RNA transcripts were translated in a rabbit reticulocyte lysate or used to transfect BHK-21 cells, and chloramphenicol acetyltransferase and luciferase synthesis was quantitated. The results strongly suggest that the Theiler's virus 5'UTR promotes cap-independent translation and that the 5' boundary of the relevant signals resides 3' to nucleotide 500. Monocistronic mRNAs were synthesized by using an expression vector in which the 5'UTR containing deletions at the 3' terminus was inserted 5' to the coding sequences for luciferase. Analysis of luciferase translation in a rabbit reticulocyte lysate suggests that the 3' end of the translation initiation signal lies between nucleotides 1043 and 1053.

Animals↗
PubMed1992

Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins.

A large proportion of the Newcastle disease virus (NDV) matrix (M) protein is found in the nuclei of infected chicken embryo cells. Kinetic analysis indicated that much of the M protein enters the nucleus early in infection, concentrating in discrete regions of the nucleus and remaining there throughout infection. The M protein was found in localized regions of the nuclei of a variety of cell lines infected with NDV. Immunostaining for both M protein and nucleolar antigens indicated that most of these regions represent nucleoli. Moreover, this nucleolar localization of the M protein was observed in chicken embryo cells infected with 11 different strains of NDV. Only the M protein of strain HP displayed a modified pattern, concentrating in the nucleolus early in infection but in the cytoplasm late in infection. M protein transiently expressed in COS-1 cells also localized to the nucleus and nucleolus, indicating that the M protein does not require other NDV proteins for this localization.

Animals↗
PubMed1992

Intracellular processing of the paramyxovirus F protein: critical role of the predicted amphipathic alpha helix adjacent to the fusion domain.

At a nonpermissive temperature, the group D temperature-sensitive mutants of Newcastle disease virus strain Australia-Victoria (AV) are defective in plaque formation, in inducing infected cells to fuse, and in incorporating the cleaved fusion glycoprotein, F1 + F2, into virus particles. In this study, the F protein of AV, expressed in chicken embryo cells, was able to complement these mutants in a plaque assay, identifying the F gene as the gene containing the group D temperature-sensitive lesions. The F genes of mutants D1, D2, and D3 were found to contain single mutations relative to the AV sequence, clustered within a predicted amphipathic alpha helix (AAH) adjacent to the hydrophobic amino terminus of F1. These mutant F proteins were inefficiently processed at the permissive temperature, a problem that was exacerbated at the nonpermissive temperature. Surprisingly, the AV F protein was also found to be partially temperature sensitive in processing. Its AAH is predicted to contain a break in the helix close to the D mutation sites, which are themselves predicted to further weaken the helix at this point. Interestingly, six revertants of the group D mutants were found to have an additional lesion in the AAH, repairing both the AV and mutant helices, resulting in a predicted perfect helix. The F protein of these revertants had overcome both the processing defects of the mutants and the temperature sensitivity of AV, indicating that the AAH region is critical for F protein processing. The lesions of a second group of revertants were localized within F2, suggesting an interaction with the F1 AAH region containing the original lesion.

Amino Acid Sequence↗