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Biomedical subjects

W Shen

Publications and source records attributed to W Shen.

At least 217 records · Page 12Linked to original sources

Binding of Escherichia coli to Penrose rubber drains--an in vitro study.

Ten different isolates of Escherichia coli were used to compare bacterial attachment to Penrose rubber drains at different temperatures and to investigate a possible relation with cell surface hydrophobicity and charges, as well as the capacity of autoaggregation. Penrose rubber drain pieces of 1 cm2 were incubated with 4.8 x 10(6) E. coli cells for 1 h at 22, 37 and 42 degrees C, respectively. After rinsing with phosphate buffered saline (PBS), the number of adhering bacteria on the drain pieces was calculated by measuring cellular ATP (adenosine triphosphate) bioluminescence. Bacterial cell surface properties at different temperatures were determined by two-phase partitioning and autoaggregation was determined by arbitrary scoring under the dissecting microscope. For most strains of E. coli, the number of adherence to Penrose rubber drain was higher at 22 degrees C than at 37 degrees C and 42 degrees C. Bacterial cell-surface properties and autoaggregation capacity were influenced by the growth temperature, but without correlation to bacterial ability to attach to rubber drains. Thus, the present study demonstrates that attachment of E. coli to Penrose rubber drains was significantly influenced by temperature, but bacterial cell-surface hydrophobicity and charge as well as autoaggregation capacity had no influence on bacterial attachment ability.

Bacterial Adhesion↗

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

OBJECTIVE: There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. SUMMARY BACKGROUND DATA: Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. METHODS: From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. RESULTS: Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. CONCLUSIONS: Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.

Adenoma↗

Isolation of STD1, a high-copy-number suppressor of a dominant negative mutation in the yeast TATA-binding protein.

The TATA-binding protein (TBP) is an essential component of the transcriptional machinery of all three nuclear RNA polymerase enzymes. Comparison of the amino acid sequence of TBPs from a number of species reveals a highly conserved 180-residue C-terminal domain. In contrast, the N terminus is variable in both size and amino acid sequence. Overexpression of a TBP protein with a deletion of the nonconserved N terminus (TBP delta 57) in Saccharomyces cerevisiae results in a dominant negative phenotype of extremely slow growth. Associated with the slow-growth phenotype are defects in RNA polymerase II transcription in vivo. We have screened a high-copy-number yeast genomic library for suppression of the slow-growth phenotype and have isolated plasmids which encode suppressors of TBP delta 57 overexpression. Here we report the sequence and initial characterization of one suppressor, designated STD1 for suppressor of TBP deletion. The STD1 gene contains a single continuous open reading frame with the potential to encode a 50.2-kDa protein. Disruption of the STD1 gene indicates that it is not essential for vegetative growth, mating, or sporulation. High-copy-number suppression by the STD1 gene is not the result of a decrease in TBP delta 57 protein accumulation or DNA-binding activity; instead, STD1 suppression is coincident with the elimination of TBP delta 57-induced RNA polymerase II defects in both uninduced and induced transcription in vivo.

Amino Acid Sequence↗

Evaluation of 90:10 poly(D,L-lactide-co-glycolide) microspheres containing norethisterone: drug release and biodegradation.

Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20% norethisterone (NET) were prepared by solvent evaporation method. Microspheres in the size ranges of 65 to 100 microns were sterilized by irradiation and used for further study. In vitro release showed fairly constant release of NET from the above microspheres over more than 90 days. However, in vivo drug release determined by residual NET analysis after i.m. injection in rats indicated a faster release rate. About 95% of NET was released in a period of 45 days. At the dose of 80 mg of microspheres, vaginal estrus cycles were inhibited for 45 days compared to 27 days for the same dose of NET crystals in rats. Biodegradation of the microspheres was tested by direct measurement of molecular weight losses and SEM observation of morphological changes of the microspheres, which showed continuous erosion in the internal matrix of microspheres with the decrease of molecular weight of PLG until total collapse of microspheres, and biodegradation was faster in rats than in human serum at 37 degrees C in vitro. Total degradation of 90:10 PLG microspheres was less than 7 months in rats and more than 9 months in vitro.

Animals↗

Effects of an orally active NO-releasing agent, CAS 936, and its active metabolite, 3754, on cardiac and coronary dynamics in normal conscious dogs and after pacing-induced heart failure.

The mechanism of action of nitrates, compounds that have been used classically in the treatment of heart failure, appears to be the stimulation of guanylate cyclase in vascular smooth muscle, perhaps the same physiologic action as endothelium-derived relaxing factor, now thought to be synonymous with nitric oxide (NO). Drugs that release NO either inside cells or in plasma have been developed recently. One such compound, CAS 936, when taken orally, is converted to an active metabolite, 3754. The goal of our studies was to determine the effects of CAS 936 and 3754 on cardiovascular function in conscious dogs before and after the development of pacing-induced heart failure. CAS 936 (10 mg/kg, p.o.) increased large coronary artery diameter 9.1 +/- 1.2% and reduced left ventricular end diastolic pressure (LVEDP) 2.5 +/- 0.5 mm Hg, but had no significant effects on coronary blood flow or vascular resistance. The metabolite 3754 caused dose-related increases in coronary artery diameter, and large reductions in LVEDP. The effect of these compounds on large coronary artery diameter was significantly greater (p < 0.05) than that of nitroglycerin (25 micrograms/kg). After heart failure, both CAS 936 and 3754 caused significant increases in large coronary artery diameter (10%) and a reduction in preload, up to 10 mm Hg, which was even larger than in normal dogs. Thus, these NO-releasing agents are potent selective large-vessel dilators that also reduce preload and maintain this unique vasodilator profile even in the failing heart.

Administration, Oral↗

Polymorphous ventricular tachycardia after intracoronary papaverine: a report of 3 cases.

Three cases with polymorphous ventricular tachycardia following a standard dose of intracoronary papaverine during 102 measurements of coronary flow reserve are reported. This study suggests that all patients should be closely monitored while receiving intracoronary papaverine and that extreme caution should be employed when the drug is administered to patients with QT interval prolongation and poor coronary flow reserve.

Adult↗

Atrial fibrillation and coronary artery disease.

A retrospective study of the incidence of atrial fibrillation in 703 consecutive patients who had undergone selective coronary arteriography and left ventricular catheterization between November 1986 and May 1992 was undertaken. The study group included 136 patients with significant coronary stenosis (> 50% diameter reduction) without previous myocardial infarction (group I), 157 with a history of myocardial infarction (group II), 326 with chest pain and normal coronary angiography (group III), 72 with valvular disease (group IV), and 12 with cardiomyopathy (group V). Clinical and electrocardiographic evidence of atrial fibrillation was documented in 75 patients (10.7%), including 2 (1.5%) in group I, 6 (3.8%) in group II, 36 (11%) in group III, 27 (37.5%) in group IV, and 4 (33.3%) in group V. The rate of occurrence of atrial fibrillation was lower in groups I and II than in groups III, IV and V. Atrial fibrillation was rarely found in coronary artery disease.

Aged↗

Clinical and experimental studies on shallow needling technique for treating childhood diarrhea.

Treatment of diarrhea in children by shallow needling and by drugs was studied in 3 separate groups for comparison. For Group I, the lateral line II of the forehead was taken, i.e. the upper, middle and lower points of the line staring from Toulinqi (UB 15) vertically downwards to the place 1 cm below the hairline were selected. For Group II, shallow needling was done on body acupoints, the main points selected being Qihai (Ren 6), Shuifen (Ren 9), bilateral Tianshu (St 25), and bilateral Zusanli (St 36); the adjuvant acupoints were Taibai (Sp 3) and Gongsun (Sp 4). The depth of shallow needling was merely puncturing the skin. For Group III the drugs used were Liteling, Berberine, Gentamycin, Ampicillin, and SMZ Co. The results of treatment in Group I and II differed insignificantly, while both were significantly superior to drugs in Group III. Experimental studies also showed that shallow needling enhanced the humoral and cellular immunity and promoted the intestinal peristaltic function.

Acupuncture Therapy↗

Normocalcemic hyperparathyroidism. Biochemical and symptom profiles before and after surgery.

Patients with normocalcemic hyperparathyroidism represent a diagnostic and therapeutic challenge. It is unclear to what extent these patients benefit from surgery in terms of correction of their serum chemistry abnormalities and their symptoms. We studied 142 patients: 23 with normocalcemic hyperparathyroidism (serum calcium levels below 2.62 mmol/L), 35 with intermittent hypercalcemia, and 84 with hypercalcemic hyperparathyroidism. Serum chemistry analyses and a standardized questionnaire of symptoms were completed before and after surgery. Overall, patients in the normocalcemic group reported a similar frequency of preoperative symptoms; had a similar reduction in postoperative symptoms; and had a similar normalization of serum calcium, parathormone, and phosphate levels as those in the two control groups. This study indicates that factors other than elevated serum calcium levels are in large part responsible for the symptoms of hyperparathyroidism and that these patients benefit from operation.

Adenoma↗

Characterization of a Gy4 glycinin gene from soybean Glycine max cv. forrest.

The glycinin gene family encoding the glycinin subunits in soybean plants is composed of at least five gene members. A genomic clone lambda S312 containing the Gy4 gene from a genomic library of cv. Forrest was isolated and partially characterized. The organization of this gene was found to be similar to that of a null allele from cv. Raiden, but different from the Gy4 gene from cv. Dare. The complete nucleotide sequence of this gene has been determined. It is 2599 bp long consisting of four exons and three introns. Comparing the DNA sequences between this gene and the gene from Dare and a null allele from Raiden, the difference found in the coding region was 5'-GCAGTGCAAG-3' (nt 824 to 833) in the former case versus 5'-TGGAGTTGCAATT-3' (nt 1314 to 1326) in the latter case in the exon 2 domain, resulting in three amino acid differences and one amino acid absence. Some other differences were also found in the non-coding region. The coding sequence and 5'-flanking region of the Gy4 gene, when compared with that of other legumin genes as well as group 1 glycinin subunit genes, revealed some interesting features: (1) a transposable element-like sequence was found in the hypervariable region (HVR) of the exon 3 domain, which was lacking in the legumin and the glycinin group 1 genes; (2) in the 5'-flanking region from nt -145 to -1, two high-homology sequences were found: one from nt -141 to nt -132, the other from nt -118 to nt -92 which includes the 'legumin box' and the RY repeat element.

Amino Acid Sequence↗

A new 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for testing macrophage cytotoxicity to L1210 and its drug-resistant cell lines in vitro.

Activated by interferon gamma (IFN gamma)(50 U/ml) and lipopolysaccharide (50 ng/ml), mouse peritoneal macrophages were cocultured with the L1210 parental cell line (L1210/PRT) and its Adriamycin-, cisplatin-resistant cell lines (L1210/ADM, L1210/CDDP) for 24 h at effector: target (E:T) ratios of 10:1, 5:1 and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT)-cleavage assay, a new improved indirect MTT assay, and the colony-formation assay were used to quantify macrophage-mediated suppression of these non-adherent tumour targets. The results showed that the macrophages can produce formazan at a high level, which can interfere with the final results of a direct MTT assay. The new indirect MTT assay can avoid such interference because the effectors are separated from the targets before the assay is performed, so the real viability of the targets is reflected. An indirect MTT assay, as developed in this study, could be better than the direct assay for examining the suppressive effect of activated macrophages on non-adherent tumour cells in vitro. This study also revealed that all the L1210 cell lines can be suppressed significantly by the macrophages at E:T ratios of 10:1 and 5:1 while the two drug-resistant cell lines have lower survival rates at an E:T ratio of 10:1, indicating that they are more susceptible than their parental cell line.

Animals↗

Acetaminophen-induced cytotoxicity in cultured mouse hepatocytes: effects of Ca(2+)-endonuclease, DNA repair, and glutathione depletion inhibitors on DNA fragmentation and cell death.

Hepatotoxic alkylation of mouse liver cells by acetaminophen is characterized by an early loss of ion regulation, accumulation of Ca2+ in the nucleus, and fragmentation of DNA in vitro and in vivo. Acetaminophen-induced DNA cleavage is accompanied by the formation of a "ladder" of DNA fragments characteristic of Ca(2+)-mediated endonuclease activation. These events unfold well in advance of cytotoxicity and the development of necrosis. The present study utilized cultured mouse hepatocytes and mechanistic probes to test whether DNA fragmentation and cell death might be related in a "cause-and-effect" manner. Cells were isolated by collagenase perfusion, cultured in Williams' E medium for 22-26 hr, and exposed to acetaminophen. Aurintricarboxylic acid, a general Ca(2+)-endonuclease inhibitor, and EGTA, a chelator of Ca2+ required for endonuclease activation, significantly decreased DNA fragmentation at 6 and 12 hr and virtually abolished cytotoxicity. N-Acetylcysteine also eliminated DNA fragmentation and cytotoxicity. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase-stimulated DNA repair, failed to alter the amount of DNA fragmentation at 6 hr but substantially increased acetaminophen cytotoxicity in hepatocytes at 12 hr. With the exception of when DNA repair was inhibited by 3-aminobenzamide, Ca2+ accumulation in the nucleus, DNA fragmentation, and hepatocyte death varied consistently and predictably with one another. Collectively, these findings suggest that unrepaired damage to DNA contributes to acetaminophen-induced cell death in vivo and may play a role in necrosis in vivo.

Acetaminophen↗

The inhibitory effects of 21 mimics of superoxide dismutase on luminol-mediated chemiluminescence emitted from PMA-stimulated polymorphonuclear leukocyte.

Four groups comprising 21 superoxide dismutase (SOD) mimics synthesized by us were comparatively studied for their inhibitory effects on luminol-mediated chemiluminescence emitted from phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocyte (PMNL). Among these groups, 20-membered macrocyclic bicopper(II) complexes and 13-membered macrocyclic dioxotetramine copper(II) complexes exhibited relatively higher activities of scavenging reactive oxygen species (ROS) produced by PMA-stimulated PMNL as compared with polyamine Cu(II)-Zn(II) complexes and copper(II) complexes of bis-shiff-base. Moreover, distinctly different effects of SOD mimics in the biological system have been found even in the same group. It is suggested that the biological effects of some SOD mimics are related to their structures.

Chelating Agents↗

Antitumor activity of siwenmycin: a novel anthracycline antibiotic.

A novel anthracycline antibiotic, siwenmycin, isolated from the culture of Streptomyces galilaeus var. siwenesis, was examined for its antitumor activities against P388, K562, B16-F10, HeLa, HEp-2 and Lewis lung carcinoma cell lines. The results showed that siwenmycin was effective against P388, K562, HeLa and HEp-2 tumor cell lines in vitro, and significantly inhibited the growth of the Lewis lung carcinoma cell line in vivo. Siwenmycin could also suppress spontaneous and artificial pulmonary metastases of B16-F10 and Lewis lung carcinoma cell lines in C57BL/6 mice. The inhibitory effect of siwenmycin on spontaneous pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice was even stronger than that of adriamycin (ADM), which is, at present, commonly used in clinical practice. Furthermore, the double-labeling test used in this study has verified that siwenmycin can inhibit cellular RNA synthesis at about one tenth the concentration required to inhibit DNA synthesis to the same degree, indicating that the antitumor mechanism of siwenmycin also differs from that of ADM. The acute toxicity of siwenmycin was very low, and it was as effective in vivo as in vitro, suggesting that this newly found antibiotic should be studied for possible clinical antitumor applications.

Aclarubicin↗

Single photon imaging computed tomography (SPECT) for localization of epileptogenic focus in patients with intractable complex partial seizures.

Interictal and ictal HIPDM-SPECT brain scans were obtained in 38 patients who eventually underwent temporal lobectomy for treatment of medically intractable complex partial seizures (CPS). Interictal studies revealed decreased regional cerebral perfusion (rCP) in the temporal lobe corresponding to the eventual site of surgery in 76% of the patients. Similarly, ictal studies demonstrated increased rCP in 91% of the patients. Of the 33 patients who had both interictal and ictal SPECT studies, 23 (70%) showed increased rCP in the ictal state and decreased rCP in the interictal state in the same temporal lobe which was subsequently removed. The SPECT scans were particularly helpful in providing confirmatory evidence for localization and in deciding to undertake temporal lobectomy in 16 patients whose EEG studies had provided less secure localization. Our experience suggests that interictal and ictal SPECT brain imaging can be easily obtained and provides reliable localizing information in the epileptic patients being considered for temporal lobectomy.

Adolescent↗

Acetaminophen-induced cytotoxicity in cultured mouse hepatocytes: correlation of nuclear Ca2+ accumulation and early DNA fragmentation with cell death.

Hepatotoxic doses of acetaminophen cause widespread alkylation of liver and early loss of cytosolic Ca2+ regulation. Although the precise location and target of lethal alkylation are not known, Ca2+ accumulation is viewed as a possible link between cell alkylation and cell death. We have recently shown that Ca2+ accumulates in the nucleus and that DNA fragments in vivo before the development of acetaminophen-induced necrosis in mice. The present study examined cultured hepatocytes for nuclear damage and its association with cell death in vitro. Positive results would argue for two key points. (1) Nonparenchymal cell damage does not explain DNA fragmentation induced by acetaminophen in vivo. (2) A chemical that causes necrosis can produce DNA damage considered characteristic of apoptosis. Hepatocytes from NIH Swiss mice were isolated by collagenase perfusion, cultured in Williams' E medium for 24 hr, and exposed to acetaminophen. Cytotoxicity was assessed by lactate dehydrogenase leakage and release of [3H]adenine from a prelabeled nucleotide pool. Genomic DNA fragmentation was assessed quantitatively by colorimetric analysis and qualitatively by agarose gel electrophoresis. Acetaminophen caused DNA damage from 1-4 hr onward and produced significant release of lactate dehydrogenase and [3H]adenine nucleotides at later times. Agarose gel electrophoresis revealed a "ladder" of DNA fragments characteristic of Ca(2+)-mediated endonuclease activation. Cytotoxicity correlated with nuclear Ca2+ accumulation (r greater than 0.895, p less than 0.05) and with percentage DNA fragmentation (r greater than 0.835, p less than 0.05). Nuclear changes in vitro generally reproduced those observed in vivo. Collectively, these findings demonstrate that nuclear Ca2+ accumulation and DNA fragmentation appear as early events that correlate directly with later cytotoxicity. These changes may contribute to acetaminophen-induced injury leading to cell death in vitro and necrosis in vivo.

Acetaminophen↗