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Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 1,171 records · Page 65Linked to original sources
PubMed1994

Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat).

The progression from ischemic injury to pannecrosis that occurs in the rat brain several hours after occluding a large artery may be partly attributable to a worsening of the circulation through the microvessels. The objective of this study was to quantitate selected structural changes involving astrocytes and endothelial cells within an area of focal brain ischemia created by the occlusion of a middle cerebral artery. The magnitude of these structural changes was correlated with alterations in the patency to a circulating macromolecule through the microvessels (< or = 15 mu in diameter) located within the territory of the occluded artery. One hundred eighty-five adult male Wistar rats had the right middle cerebral artery occluded after threading a nylon monofilament through the external carotid artery. Experiments were terminated by either cardiovascular perfusion or decapitation and immersion fixation at intervals ranging between 30 minutes and 7 days after the arterial occlusion. Randomly selected animals from each experimental subgroup were injected intravenously with horseradish peroxidase (molecular weight 44 kd) approximately 20 minutes before death. The progressive decline in the area fraction comprised by the vessels filled with horseradish peroxidase was preceded at 30 to 60 minutes by an increase in the surface area occupied (on a cross-section of a microvessel) by endothelial cells (both nucleus and cytoplasm). This was followed by an increase of 23.7% in the mean diameter of astrocytes nuclei and a decrease of approximately 35% in lumenal surface of the microvessels. These observations suggest that the occlusion of a large cerebral artery causes prompt swelling of endothelial cells and astrocytes; both of these early biological responses may interfere with erythrocyte circulation and oxygen delivery, which (after the arterial occlusion) are entirely dependent on the circulation provided by the collateral arterial connections. Through its interference with microvascular patency and oxygen delivery, cell swelling may influence the rate at which neurons become necrotic. In this model of brain infarct the number of necrotic neurons peaks approximately 72 hours after middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment.

The aim of this study was to assess the prevalence of human papillomavirus (HPV) DNA in women who had received a renal transplant and to compare this with two control groups. Women who had a functioning renal transplant for greater than 6 months (n = 69) were compared with women on maintenance dialysis (n = 89) and women with impaired renal function (creatinine 0.15-0.39 mmol/l) (n = 22). Women were excluded if they had had a hysterectomy, were older than 65 years, or were not yet sexually active. A questionnaire and cervical scrape were obtained from each participant. The cervical scrape was analysed for HPV DNA using PCR and the L1 consensus primers. The participation rate of transplant patients, dialysis patients and those with impaired renal function ('normal' group) was 69, 68, and 78% respectively. The characteristics of the three groups of women at enrollment were similar. No cytological abnormalities were present in the 'normal' population but 11 of 89 patients on maintenance dialysis and nine of 69 transplant patients had cytological abnormalities of atypia or greater (P = 0.08 and P = 0.07, for 'normal' compared to dialysis and transplant groups respectively). One (4.5%) of the 'normal' women had evidence of HPV DNA, while 18 (20%) of patients on maintenance dialysis and 15 (22%) of transplant patients were positive (P = 0.07 and P = 0.05, for 'normal' compared to dialysis and transplant groups respectively). This study suggests that not only transplant recipients but also dialysis patients may have a higher prevalence of risk factors (cytological abnormalities and HPV DNA) for the development of cervical cancer.

Adult↗
PubMed1994

Dysfunction of the Myc-induced apoptosis mechanism accompanies c-myc activation in the tumorigenic L929 cell line.

Activation of the c-myc protooncogene, resulting in deregulated, over-expression of the c-Myc protein, can induce both cell proliferation and programmed cell death (apoptosis) in nontransformed cells. Yet, c-myc activation is commonly tolerated in many tumors. This apparent paradox can be resolved if activation of c-myc in transformed cells is associated with loss of Myc-induced apoptosis. To examine this hypothesis, we characterized both the mechanisms of c-myc activation and programmed cell death in the tumorigenic L929 cell line. We showed that activation of c-myc in the L929 cell line involves several distinct mechanisms, including dysfunction of the Myc autosuppression pathway and alteration of c-Myc protein expression. In addition, we demonstrated that L929 cells do not undergo Myc-induced apoptosis. Analysis of somatic cell hybrids revealed that this abrogation of programmed cell death can be partially restored and is likely due to one or more genetic lesions. Our results support the hypothesis that the dysfunction of the Myc-induced apoptosis mechanism can accompany c-myc activation and provide an in vivo example illustrating two cooperative events which can contribute to tumor progression.

Animals↗
PubMed1994

Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat).

The results of several experimental studies of focal ischemia and anecdotal observations suggest that leukocytes may contribute to the injury initiated by an arterial occlusion. The timing and the nature of leukocyte responses in evolving brain infarcts (either human or experimental) are incompletely characterized. This is a study of experimental brain lesions in 96 Wistar rats that underwent occlusion of a large intracranial artery for variable intervals ranging between 30 minutes and 7 days. The experimental model, based on the occlusion of a middle cerebral artery ostium via the insertion of a nylon monofilament through the external carotid artery, does not require opening the skull; therefore, the inflammatory response is not influenced by the effects of craniotomy and changes in intracranial pressure are only those induced by the ischemic lesion. All 96 animals having the same type of arterial occlusion developed an ischemic brain lesion (limited to the territory of the corresponding artery) that evolved into an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by pan-necrosis (infarct) approximately 60 hours later. In this study, leukocytes (in particular polymorphonuclear cells) were detected in the microvessels (capillaries and venules) of the ischemic hemisphere as early as 30 minutes after the arterial occlusion. Numbers of intravascular neutrophils peaked at 12 hours, whereas intraparenchymal granulocytes were most numerous at 24 hours; a few granulocytes were visible in the brain infarct as late as day 7. Circulating monocytes were first detected within the capillaries/venules of the ischemic area after 4 to 6 hours. Platelet aggregates were more abundant in the arterial than the venous side of the circulation, and luminal obstruction of arteries by platelet aggregates became noticeable only 48 hours after the arterial occlusion. Fibrin thrombi were conspicuous for their absence. These observations provide the background for studies that will attempt to unravel the relationship between the biological responses of leukocytes and neuronal necrosis secondary to focal ischemia.

Animals↗
PubMed1994

FS2. a mamba venom toxin, is a specific blocker of the L-type calcium channels.

The peptide FS2 is a mamba venom toxin, consisting of 60 amino acids, three residues of which are different from those of calciseptine (CaS), a natural L-type Ca2+ channel blocker. The biological activities of synthetic FS2 for L-type Ca2+ channels were determined under comparisons to those of CaS and nitrendipine, a 1,4-dihydropyridine derivative. Similar to CaS, FS2 competitively inhibited the binding of [3H]nitrendipine to rat brain synaptosomal membranes on Lineweaver-Bulk plot, with Kd value of 210 nM, which was similar to that of CaS being 290 nM, but did not affect binding of an N-type Ca2+ channel ligand omega-[125I]-conotoxin GVIA to the membranes. Pretreatment of A7r5 cells with either FS2 or CaS at concentrations of 10(-8) M and greater for 5 min significantly and dose-dependently reduced 10(-6) M Bay K8644-induced increase in the cytosolic free Ca2+ concentration ([Ca2+]i) of the cells determined by the fluorescent Ca2+ indicator fura-2, with the half inhibitory concentrations (IC50) of 2.3 x 10(-8) and 2.7 x 10(-8) M, being similar to that of the IC50 value of nitrendipine (4.4 x 10(-8) M). These observations indicate that FS2, similar to CaS, is an active natural L-type Ca2+ blocker sharing the binding site on the channels with the 1,4-dihydropyridines.

Amino Acid Sequence↗
PubMed1993

Fos induction by nerve growth factor in the adult rat brain.

The distribution of Fos, the protein product of the immediate early gene c-fos, was studied with immunocytochemistry in the adult male rat brain after nerve growth factor (NGF) administration. NGF was injected in the lateral cerebral ventricle through a previously implanted cannula. The total number of Fos-immunoreactive (ir) neurons in the brain was 2-3 times higher after NGF administration than in control animals (untreated or injected with cytochrome c). With respect to control rats, in the NGF-treated cases Fos-ir cells were more numerous in the anterior olfactory nucleus, in the medial prefrontal and anterior cingulate cortices, in the basal forebrain, in the preoptic and ventromedial nuclei of the hypothalamus, as well as anterior hypothalamic area, in the thalamic midline nuclei, and in some brainstem structures, such as the parabrachial nucleus. The relative quantitative increase of Fos-ir neurons varied in the different structures. In addition, Fos-ir neurons were evident after NGF administration in areas devoid of immunopositive cells in control animals. These included: frontoparietal and occipital cortical fields, the hypothalamic arcuate nucleus, and many brainstem structures, such as the dorsal nucleus of the lateral lemniscus, posterodorsal tegmental, medial and lateral vestibular, ventral cochlear, and prepositus hypoglossal nuclei. These findings demonstrate that the intracerebroventricular administration of NGF can induce c-fos expression in neurons in vivo. The distribution of Fos-ir neurons indicates that NGF can induce activation of functionally and chemically heterogeneous neuronal subsets in the brain.

Animals↗
PubMed1993

Specificity and properties of MAb RS7-3G11 and the antigen defined by this pancarcinoma monoclonal antibody.

The murine monoclonal antibody (MAb) RS7-3G11 is an IgG1 with pancarcinoma reactivity, which has been raised against human squamous-cell carcinoma of the lung. Immunoperoxidase staining of frozen tissue sections demonstrated that the antigen defined by RS7-3G11 is present in tumors of the lung, stomach, bladder, breast, ovary, uterus and prostate. The rate and extent of internalization of RS7-3G11 into Calu-3, an adenocarcinoma of the lung cell line, was investigated using unconjugated MAb, followed by fluorescence labelling, and by binding 125I-RS7-3G11 followed by acid removal of surface-bound antibody. Rapid internalization of MAb RS7-3G11 into target cells was observed. Antibody internalization was noted at 30 min, and by 2 hr virtually all MAb RS7-3G11 was internal. Although MAb RS7-3G11 was raised against non-small-cell carcinoma of the lung, ME-180, a cervical-carcinoma cell line, expresses higher quantities of the antigen than the lung-carcinoma cell lines. Due to the higher antigen density in ME-180 cells, this line was used for immunoprecipitation studies and antigen purification. Immunoprecipitation studies using the ME-180 cervical-carcinoma cell line metabolically labeled with [3H]leucine or [3H]glucosamine demonstrated that the antigen defined by RS7-3G11 is a glycoprotein of M(r) 46 kDa. Deglycosylation by treatment with endoglycosidase-F resulted in a protein with a M(r) of 35 kDa. RS7-3G11-antigen was purified from ME-180 tissue-culture cells using affinity-column chromatography. By SDS-PAGE it was seen that the antigen was highly purified. The major band appeared at M(r) of 45 to 48 kDa. This result is in agreement with the immunoprecipitation studies. The broad band observed in the SDS-PAGE is typical of many glycoproteins, and suggests heterogeneity of glycosylation. Chemical and enzymatic treatments of the antigen, followed by Western blot analyses, suggest that the RS7-3G11 antigenic determinant is composed of a conformation-dependent peptide.

Animals↗
PubMed1993

Use of aromatase (CYP19) metabolite ratios to characterize electron transfer from NADPH-cytochrome P450 reductase.

Aromatase catalyzes the conversion of 4-androstene-3,17-dione to estrogen with the concomitant formation of the minor metabolites 4-androstene-19-hydroxy-3,17-dione(19-hydroxyandrostenedione) and 4-androstene-3,17,19-trione(19-oxoandrostenedione). Microsomes of chinese hamster ovary (CHO) cells expressing human aromatase were isolated to investigate androstenedione metabolism. Relatively greater amounts of the minor metabolites result after limitation of electron flux from NADPH-cytochrome P450 reductase to aromatase. Substitution of NADH for NADPH or limitation of NADPH availability increased minor metabolite formation relative to estrogen formation. Similar changes in metabolite ratios were observed when metabolism was conducted either at high pH (8.3) or in the presence of n-alcohols in the range of 5-200 mM alcohol concentrations. However, conditions of low pH (5.5) or high ionic strength (1 M KCl) resulted in minor changes in metabolite ratios, suggesting little or no effect on electron flux between NADPH-cytochrome P450 reductase and aromatase. Theoretical molar ratios of the resulting metabolites were predicted using a reaction scheme assuming sequential substrate oxidations without reversible intermediate release from the aromatase active site. This model was supported by a close agreement between theoretical and experimental metabolite ratios for a broad range of NADPH concentrations. The results indicate that metabolite ratios provide a sensitive indicator of aromatase-oxidoreductase interactions in the microsomal environment.

Androstenedione↗
PubMed1993

An analysis of a melanoma epidemic.

Between 1986 and 1988 the annual incidence of invasive melanoma in the Hunter area of New South Wales, Australia, almost doubled to 52.5 per 100,000 in men and 42.9 per 100,000 in women. These rates have been maintained and are similar to those reported for 1987 in Queensland, Australia, which are the highest in the world. Most of the increase in incidence was in melanomas less than 1.50 mm in thickness, and adults of both sexes and all ages were affected. Thicker melanomas also increased in incidence but only in adults 45 years and older, and mainly in men. An analysis of health insurance data on treatment of skin lesions and data from a histopathology laboratory suggested that diagnosis and treatment of skin lesions generally in the Hunter area had increased almost 2-fold over this period. Advancement of the time of diagnosis and a real increase in incidence were likely explanations for some of the observed trends. Increasing diagnosis of a non-metastasising form of thin melanoma, consequent upon increasing removal of pigmented skin lesions by medical practitioners, may also explain some of the observed increase in the incidence of the disease. This possibility has important implications for proposed population screening programs, and methods are needed to distinguish such lesions, if they exist, from potentially fatal melanoma.

Adult↗
PubMed1993

Long-term consequences of impaired regeneration on facial motoneurons in the C57BL/Ola mouse.

Peripheral nerves of the C57BL/Ola mouse mutant undergo markedly slowed Wallerian degeneration following injury. This is associated with impaired regeneration of both sensory and motor axons. Following a crush lesion of the facial nerve, there was no cell loss in facial nuclei of normal (C57BL/6J) adult mice, but 40% cell loss occurred in Ola mice and the survivors increased in size during the period when functional reinnervation was established. These results are interpreted as a result, first, of prolonged deprivation of target-derived trophic factor in the slowly regenerating Ola motoneurons and second, increased peripheral field size of the survivors. Within the regenerated facial nerve, there was marked heterogeneity of myelinated fibre size in Ola mice. Some Ola axons, both proximal and distal to the lesion site, had areas over twice as great as the largest 6J axons when measured 1 year following injury. A population of small diameter fibres, not observed in 6J nerves, persisted distal to the crush site in Ola nerves, and this was associated with an increase in the total number of myelinated axons in the distal nerve: on average, each parent Ola axon retained three persistent daughter axons. The delayed Wallerian degeneration in Ola mice not only impairs immediate axon regrowth, but also results in a breakdown of the normal mechanisms which regulate axon number and size in regenerating nerve.

Animals↗
PubMed1993

On the structure of calonyctin A, a plant growth regulator.

The plant growth regulator calonyctin A, isolated from the dried leaves of Calonyction aculeatum L. House (Yue-Guang-Hua), was separated into two pure components by high performance liquid chromatography. By use of mass spectrometry based on various ionization techniques, one- and two-dimensional NMR spectroscopy, IR spectrometry, and chemical methods the molecular structures of the two homologous glycosides were determined. Each molecule contains two hydroxy fatty acid residues and four 6-deoxyhexose units. The fatty acids are 3-hydroxy-2-methylbutanoic acid and 11-hydroxytetradecanoic acid or 11-hydroxyhexadecanoic acid. The 6-deoxyhexose residues (three of quinovose and one of rhamnose) comprise a tetrasaccharide having the following structure: [formula: see text] The long-chain hydroxy acid is linked glycosidically through its O-11 to Qui D and esterified to O-2 of Qui C, forming a macrocyclic lactone. The 3-hydroxy-2-methylbutanoic acid is ester-linked to O-3 of Qui C.

Carbohydrate Conformation↗
PubMed1993

Impaired motor axon regeneration in the C57BL/Ola mouse.

The delayed Wallerian degeneration which occurs in the C57BL/Ola mouse is associated with impaired motor axon regeneration. Following sciatic nerve crush, recovery of the sciatic functional index was delayed and incomplete when compared with recovery in C57BL/6J mice. After facial nerve crush, recovery of whisker movement in Ola mice was also delayed, and there was a prolonged period of partial recovery, not seen in 6J mice. Regeneration rate of the motor axons was measured by the axonal transport technique in sciatic nerve and was approximately 0.7 mm/d for Ola mice, and 4.0 mm/d for 6J mice. Combining these results from our previous work, we conclude that regeneration of both sensory and motor axons is impaired when Wallerian degeneration does not follow its usual time course after injury.

Animals↗
PubMed1993

Enantiomeric separation of fluorescent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, tagged amino acids.

A new derivatizing reagent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC), has been used successfully for chromatographic enantioseparation of 31 amino acids on cyclodextrin bonded stationary phases. AQC reacts with both primary and secondary amino acids to produce stable and highly fluorescent derivatives suitable for efficient and sensitive chromatographic determinations. The derivatization reaction proceeds without detectable racemization. The detection limit is in the femtomole range and approximately 0.0075% of the D-enantiomer in an excess of the L-enantiomer is detectable. High resolution values are needed when determining trace enantiomeric impurities.

Amino Acids↗
PubMed1993

The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo.

Melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in a dose-dependent manner. Total DNA-adduct formation after in vivo administration of 300 mg/kg safrole measured by 32P-postlabeling analysis of carcinogen-modified DNA in rat liver was 36,751 +/- 2290 counts/min/10 micrograms DNA. Coadministration of 300 mg/kg safrole with either 0.2 mg/kg (low dose) or 0.4 mg/kg (high dose) melatonin reduced DNA-adduct formation induced by safrole to 22,182 +/- 987 counts/min/10 micrograms DNA and 462 +/- 283 counts/min/10 micrograms DNA, respectively. Circulating melatonin concentrations at the termination of the study in safrole, low melatonin and high melatonin groups were 50 +/- 8, 3140 +/- 430 and 10,040 +/- 2610 pg/ml serum, respectively. The results suggest that melatonin protects against safrole associated DNA damage.

Animals↗