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Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 1,315 records · Page 73Linked to original sources

O6-methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung, and ovary.

The resistance of human tumor strains in culture to cell killing by alkylating nitrosoureas is correlated with their levels of the DNA repair activity O6-methylguanine-DNA methyltransferase. Strains with the Mer- phenotype have no activity and are extremely sensitive. However, the relationship between the sensitivity of human tumors in vivo and transferase levels is not known, and even the existence of Mer- human tumors in vivo has been questioned. In this study 73 human tumor and normal tissue samples from brain, lung, and ovary were assayed for transferase levels and methylpurine glycosylase activity. For each organ, transferase levels varied over 100-fold, and Mer- tumors were detected in each group. There was no correlation between transferase and glycosylase levels, indicating that the absence of transferase in some tumor samples was not an artifact due to necrosis or inactivation of enzymes in the extract.

Bacterial Proteins↗

Penicillin-enhanced chemiluminescence of the luminol-H2O2-Co2+ system.

The luminol-H2O2-Co2+ system has been widely used in chemical and biological analysis. We report here an investigation of the observation that penicillins have the ability to prolong and enhance the intensity of chemiluminescence from luminol. The basis of this phenomenon appears, as revealed by difference spectroscopy, to be the formation of a complex between the beta-lactam and the superoxide ion. The latter is the oxidizing species responsible for the oxidation of luminol in alkaline solution and has a mean lifetime, in solution, of milliseconds. The stabilization of the superoxide ion by penicillin complexation extends the effective lifetime of the superoxide ion by a few orders of magnitude and thereby allows for more efficient oxidation of the beta-lactam. Several penicillins were determined by their enhancement of luminol chemiluminescence. A detection limit of 100 ng mL was obtained for penicillin G with a less-than-ideal detection system.

Catalysis↗

Quantitative analysis of the molecular species of monosialogangliosides by continuous-flow fast-atom bombardment mass spectrometry.

Negative-ion continuous-flow fast-atom bombardment mass spectrometry was evaluated as a means for the quantitative analysis of N-acetylneuraminyl-galactosyl-glucosyl-ceramide (NeuAc-GM3) and N-acetylgalactosaminyl-(N-acetylneuraminyl)galactosyl-glucosyl-ceramide (NeuAc-GM2). This study was carried out on a 7070-EQ mass spectrometer (VG Analytical, Manchester, UK) using a home-made continuous-flow fast-atom bombardment probe with a mixture of methanol + water + triethanolamine (70:27:3, v/v/v) as the mobile phase. Utilizing 100 ng of acetyl-lysogalactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)g alactosyl-glucosyl-ceramide (acetyl-lysoGM1) as an internal standard, standard curves for NeuAc-GM3 d18:1-16:0, NeuAc-GM3 d18:1-18:0 and Neuac-GM2 d18:1-18:0 were found to be linear over the range 5-250 ng, with associated correlation coefficients of 0.990-0.997. The lower limit of detection was found to be 2.5 ng. Satisfactory results could also be obtained when the calibration curves were derived from the deprotonated molecular ions of a mixture of the NeuAc-GM2 and NeuAc-GM3 classes. Using this approach, quantitative determination of NeuAc-GM3 d18:1-16:0 from rat adrenal gland was performed using N-acetylneuraminic acid assay as a test control. We found 278 +/- 36 ng of this species in 1 mg of tissue (three replicate experiments). The procedure represents a sensitive method for the quantitation of monosialogangliosides and its capability to give molecular species information.

Adrenal Glands↗

Simultaneous pancreaticoduodenal and renal transplantation in one diabetic patient with end-stage renal disease.

The diabetic patient with renal failure underwent simultaneous pancreaticoduodenal and renal transplantation. Duodeno-cystostomy was performed for the drainage of exocrine secretion. Immediately after grafting, the pancreatic and the renal graft regained normal function, and there was no operative complication whatever. The patient had functioning pancreatic graft and became insulin-independent for more than 3 months, although two transplanted kidneys were rejected. Immunosuppression consisted of cyclosporine A, azathioprine and prednisone. Our results suggest that hemorrheological parameters may serve as early indicators of acute rejection and be used to estimate the efficacy of anti-rejection and anti-coagulation therapy.

Acute Kidney Injury↗

The classifier problem in Chinese aphasia.

In recent years, research on the relationship between brain organization and language processing has benefited tremendously from cross-linguistic comparisons of language disorders among different types of aphasic patients. Results from these cross-linguistic studies have shown that the same aphasic syndromes often look very different from one language to another, suggesting that language-specific knowledge is largely preserved in Broca's and Wernicke's aphasics. In this paper, Chinese aphasic patients were examined with respect to their (in)ability to use classifiers in a noun phrase. The Chinese language, in addition to its lack of verb conjugation and an absence of noun declension, is exceptional in yet another respect: articles, numerals, and other such modifiers cannot directly precede their associated nouns, there has to be an intervening morpheme called a classifier. The appropriate usage of nominal classifiers is considered to be one of the most difficult aspects of Chinese grammar. Our examination of Chinese aphasic patients revealed two essential points. First, Chinese aphasic patients experience difficulty in the production of nominal classifiers, committing a significant number of errors of omission and/or substitution. Second, two different kinds of substitution errors are observed in Broca's and Wernicke's patients, and the detailed analysis of the difference demands a rethinking of the distinction between agrammatism and paragrammatism. The result adds to a growing body of evidence suggesting that grammar is impaired in fluent as well as nonfluent aphasia.

Aphasia, Broca↗

The noun-verb problem in Chinese aphasia.

Previous studies have shown that Broca's aphasics experience a selective difficulty with action naming inside or outside of a sentence context. Conversely, it has been suggested that Wernicke's aphasics are particularly impaired in object naming. A number of explanations have been offered to account for this double dissociation, including grammatical accounts according to which the main verb problem in agrammatic Broca's aphasics is viewed as a by-product of their syntactic and/or morphological impairment, due perhaps to the greater morphological load carried by verbs (compared with nouns). In the Chinese language, there are no verb conjugations and no declensions. Hence there is no reason to expect a relationship between morphological impairment and deficits in action naming. We examined comprehension and production of object and action names, outside of a sentence context, in a sample of Chinese-speaking Broca's and Wernicke's aphasics. There was an interaction between patient group and object/action naming, but no corresponding interaction on the comprehension task. We conclude that action-naming deficits in Broca's aphasia (and/or the corresponding sparing of action names in Wernicke's aphasia) cannot be attributed to morphological differences between nouns and verbs. We also found a sublexical variant of the noun/verb dissociation applied to the internal structure of compound words made up of a verbal and a nominal element: Broca's aphasics tended to lexicalize the verbal portion of these words more often than the nominal compound, while Wernicke's showed the opposite pattern. These sublexical effects are difficult to explain in syntactic terms nor do they fit the standard lexical view. A modified lexical account is proposed, emphasizing semantic/conceptual effects in a distributed lexicon.

Adult↗

Polyamines in the anemia of end-stage renal disease.

The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera from patients with ESRD inhibited erythroid colony (CFU-E) (N = 10) formation to a significantly (P less than 0.01) greater degree than granulocyte-macrophage (CFU-GM) (N = 7) colony formation in mouse bone marrow (MBM) cultures. The polyamines spermine (SP) (18 to 560 nm/ml) and spermidine (SD) (4 to 648 nm/ml) exerted a more significant (P less than 0.05) inhibition of CFU-E (N greater than or equal to 5) than that of CFU-GM (N greater than or equal to 5) growth. Concentrations of 0.80, 1.0, and 1.5 nm/ml of putrescine (PU) were 92%, 85%, and 77% of erythroid colony (CFU-E) controls (N = 4) and 104%, 130%, and 127% of CFU-GM controls (N = 4). Putrescine (PU) at 1.5 nm/ml also produced a significant (P less than 0.05) inhibition of CFU-E, whereas CFU-GM were stimulated by PU. These data suggest that predialysis sera from uremic patients, as well as SP, SD, and PU, are selectively more inhibitory to CFU-E than CFU-GM growth. The immunoreactivity of EPO was not significantly changed when it was coincubated with SP, SD and PU and measured by radioimmunoassay. PU was found to inhibit noncompetitively the bioactivity of EPO in a CFU-E assay. These data support the hypothesis that polyamines may be important uremic toxins in the anemia of ESRD.

Anemia↗

Human placental acetylcholine.

The human placenta contains both acetylcholine (ACh) and choline acetyltransferase, and in vitro bilaterally perfused placental lobules release ACh. The function of this placental cholinergic system has not yet been clearly defined, although changes occur in it during parturition and it may be linked to placental prostaglandin generation at this time. It has also been suggested that ACh may regulate placental amino-acid transport and/or blood flow. It has been found that ACh release from fetal vessels of bilaterally perfused placental lobules is reduced during preeclampsia but is not necessarily correlated with any change in perfusion pressure or materno-fetal transfer of the nonmetabolizable amino acid alpha-aminoisobutyric acid. However, a correlation has been found between releases from human placental explants of ACh (when inhibited by (2-benzoylethyl)trimethylammonium or vesamicol) and of prostaglandins E2 and F2 alpha. Thus, although the evidence for a role of ACh in the control of placental amino-acid transfer or vascular tone is not conclusive, inhibition of the human placental cholinergic system has been shown to be associated with reduced output of prostaglandins from this tissue.

Acetylcholine↗

Specific reduction of I-compound levels in DNA from spontaneous hepatomas of 22-24 month old male C3H mice.

As previously shown by 32P-postlabeling, I-compound levels are reduced in target tissue DNA of animals exposed to one of several non-genotoxic hepatocarcinogens, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin, carbon tetrachloride, peroxisome proliferators and choline-devoid diet. I-compound levels are further reduced, sometimes to undetectable levels, in chemically induced, transplantable rat (Morris) hepatomas and hepatocellular carcinomas induced by peroxisome proliferators or choline-devoid diet. The current study investigated I-compounds in spontaneous hepatic adenomas of genetically susceptible male C3H mice. DNA samples from individual tumors, background livers (non-tumor bearing lobe from tumor bearing mouse) and non-tumor bearing normal livers taken from 22-24 month old animals were analyzed by 32P-postlabeling. I-compound profiles were qualitatively comparable among the three types of tissues. However, levels of most I-compounds were 2.6-5.0 times lower in tumors than in background liver and non-tumor bearing normal liver. There were virtually no differences between background liver and normal liver. Taken together with the previously reported I-compound deficiency in carcinogen-induced hepatomas, the present observations on genetically initiated neoplasms suggest that this phenomenon may play a role in hepatocarcinogenesis and maintenance of neoplasia.

Aging↗

Eyebrow revascularization.

A 41-year-old man suffered from an incompletely avulsed right eyebrow and forehead after a windshield injury in a traffic accident. Microsurgical techniques were used to revascularize the avulsed tissue of the right eyebrow and forehead with anastomosis of one branch of the frontal branch of the right superficial temporal artery. The revascularized eyebrow and forehead remained viable and provided a good cosmetic result. An aggressive microsurgical approach, either by direct arterial anastomosis or bypass with vein graft, should be encouraged in all incompletely avulsed tissue with inadequate blood supply in the face, hand, and foot.

Adult↗

Second toe wrap-around flap.

The microsurgical second toe wrap-around technique is an ideal treatment option for reconstruction of the distal half of the finger with circumferential loss of skin and nail associated with an uninjured proximal interphalangeal joint and an intact insertion of the flexor digitorum superficialis tendon. Follow-up of 13 flaps in 10 patients from 1986 to 1989 demonstrates rapid and adequate functional recovery as well as satisfactory aesthetic appearance in all patients.

Adolescent↗

Evidence for direct and indirect pathways in the generation of the alloimmune response against pancreatic islets.

The role of the direct and indirect pathways of alloantigen presentation in the generation of the alloimmune response was dissected using the murine mixed lymphocyte-islet coculture system (MLIC). Stimulator DBA/2J (H-2d) pancreatic islet populations consisted of whole islets (MHC class I+, II+) or FACS-purified beta cells (MHC class I+, II-). Responding C57Bl/6 (H-2b) splenocyte populations were either: (1) untreated; (2) depleted of helper T cells with anti-L3T4 monoclonal antibody plus complement; (3) depleted of cytotoxic T lymphocytes with anti-Lyt2 mAb plus complement; or (4) depleted of antigen-presenting cells by passage through a Sephadex G-10 column. Whole islets were capable of stimulating a significant C57Bl/6 anti-DBA cytotoxic T cell response if the responding population was untreated or treated with complement alone. Depletion of responding splenocytes with either anti-Lyt2 or anti-L3T4 mAb plus complement abrogated the generation of allospecific CTL. If the responding splenocyte population was depleted of APCs, the allo-CTL response against whole islets was decreased, but still significant. If, however, the stimulator population consisted of FACS-purified DBA 2J beta cells, APC-depleted C57Bl 6 splenocytes were incapable of generating any CTL response. Adding responder type (C57Bl/6) APCs back to the microwells restored the capacity for both whole islets and purified beta cells to stimulate a strong allo-CTL response. These data demonstrate that both indirect and direct pathways of alloantigen presentation function in the MLIC.

Animals↗

Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

The CT3 cytoplasmic localization mutant of SV40 T antigen is neither properly transported to the nucleus nor is it functional in rodent cells. Human precrisis cells are able to complement this mutation, as they are fully transformed by CT3 with wild-type efficiency. The human-specific factors responsible for this species-specific difference in response to CT3 were localized to human chromosome 6 by synteny in a panel of six somatic cell hybrids. A major human HSP70 heat shock protein located on chromosome 6 is expressed constitutively in human cells. Hsp70 proteins have been reported to play a role in intracellular movement of newly synthesized proteins. To test whether human HSP70 played a role in the complementation by human cells of the defect of CT3, we constructed a series of mouse cell lines expressing human HSP70 and tested them for their ability to localize CT3 T antigen in the nucleus and for their ability to be transformed by CT3 DNA. Mouse cell lines expressing human HSP70 protein were able to translocate mutant CT3 T antigen into the nucleus and were transformed by CT3 at rates comparable with wild-type SV40. Mouse-inducible HSP70 protein was not able to translocate cytoplasmic T antigen in Swiss 3T3 mouse fibroblast cells, even after heat shock. Apparently human HSP70 is capable of complementing directly or indirectly the structural and functional alterations in SV40 T antigen introduced by the CT3 mutation.

3T3 Cells↗

The effect of high and low ultraviolet-B dose exposure on the degree of hairless mouse skin wrinkling.

Chronic exposure of hairless mice to ultraviolet light (UVB 290-320 nm) causes degradative changes in the dermal matrix and wrinkle production. We compared the effects of two different UVB dosing regimens on wrinkle production and dermal damage in female Skh:HR-1 hairless mice using a bank of unfiltered FS-40 lamps. One group of mice, the low dose group, was exposed to a sub-erythemal UVB dose of 12 mJ/cm2 (1 MED = 14 mJ/cm2), 3 times per week for 20 weeks (total dose = 0.72 J/cm2). A second group, the high dose group, was exposed also 3 times per week for 15 weeks to a UVB dose which started with the sub-erythemal dose of 12 mJ/cm2 at Week 1, and 1 MED at week 2. The dose was then increased weekly by 1 MED until reaching 4 MED at week 5. The animals were then dosed at 4 MED for 10 additional weeks (total dose = 2.1 J/cm2). Visual results indicate that, as expected, within the same group, the degree of wrinkling was generally dependent on the total UVB dose administered. However, comparison between the low dose and high dose groups shows that equal cumulative UVB doses did not always result in identical wrinkle grades. For example, at a cumulative dose of 0.5 J/cm2, the mean wrinkle grade for the low dose group was 1.75 compared to that of 1.2 for the high dose group (age-matched = 0). This observation may suggest that there are other factors in addition to total cumulative dose which are important for the appearance of wrinkling in this model.

Animals↗