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Biomedical subjects

W Shen

Publications and source records attributed to W Shen.

At least 163 records · Page 9Linked to original sources
PubMed1997

Mitochondrial tRNA(Leu(UUR)) gene mutation diabetes mellitus in Chinese.

OBJECTIVE: To ascertain the prevalence and clinical features of mitochondrial tRNALeu(UUR) gene nucleotide (nt) 3243 A-->G mutation diabetes mellitus in Chinese and to establish the approaches for genetic diagnosis of this subtype of diabetes during routine daily clinical practice. METHODS: Mitochondrial nt 3243 A-->G mutation was screened among 207 unrelated non-insulin-dependent diabetes mellitus (NIDDM) patients by using polymerase chain reaction (PCR)/Apa I restriction endonuclease digestion. Samples with positive result were confirmed by DNA sequence analysis. Genetic and clinical analysis were carried out in family members of the proband with positive genetic diagnosis. RESULTS: Positive results were found in two subjects during screening of unrelated NIDDM patients, which account for 2.4%-11.1% of NIDDM subjects with uncommon clinical features (with early age-of-onset, with low body-mass-index and on insulin therapy) or with positive family history of diabetes consistent with or unable to exclude from maternal inheritance. Genetic diagnosis was positive in 10 out of 25 family members in the pedigrees of these two probands. CONCLUSIONS: Mitochondrial tRNALeu(UUR) gene nt 3242 A-->G mutation should be considered in diabetic patients with the above-mentioned clinical features. The genetic diagnosis in daily clinical practice can be performed with allele specific priming amplification, or PCR/Hae III or Apa I digestion which are technically simple to perform and diagnostically easy to define.

Adolescent↗
PubMed1996

Three distinct domains in the HOX-11 homeobox oncoprotein are required for optimal transactivation.

HOX-11 (tcl-3) is a homeobox oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation recurring in T-cell acute lymphoblastic leukemia. Here we demonstrate that the HOX-11 homeoprotein mediates transactivation of reporter genes through various promoters in both mammalian and yeast cells. By deletion analysis, the transactivation domains of HOX-11 have been mapped to three amino acid stretches in the homeoprotein, the glycine-proline-rich region at the amino terminus, the homeodomain and the glutamine-rich region at the carboxyl terminus. The three distinct functional domains of HOX-11 act in concert for optimal transactivation. In addition, the homeodomain of HOX-11 appears to be differentially utilized in a promoter-dependent manner. Our data support the notion that the HOX-11 homeoprotein functions as an oncogenic transcription activator in leukemogenesis.

3T3 Cells↗
PubMed1996

A truncated hMSH2 transcript occurs as a common variant in the population: implications for genetic diagnosis.

Germline mutations of the hMSH2 gene are responsible for many cases of hereditary nonpolyposis colorectal cancer. While screening for hMSH2 gene mutations in hereditary nonpolyposis colorectal cancer kindreds, we observed that a previously reported germline mutation is in fact a common, alternatively spliced variant in the population. Using RT-PCR and the protein truncation test, the hMSH2 exon 13 deletion variant was found in more than 90% of individuals. The exon 13 deletion transcript was only present in lymphocyte RNA, no abnormalities were detected in genomic DNA flanking exon 13, and the deletion transcript is apparently not translated. These findings highlight further that caution should be exercised in providing genetic risk assessment on the basis of currently used germline mutation detection strategies.

Colorectal Neoplasms↗
PubMed1996

Reoperation for persistent or recurrent primary hyperparathyroidism.

OBJECTIVE: To analyze the causes and outcomes of reoperation for persistent or recurrent primary hyperparathyroidism. DATA SOURCES: Medical records of 102 patients with persistent or recurrent primary hyperparathyroidism who underwent reoperation by 1 surgeon between 1985 and 1995. STUDY SELECTION: Only patients with persistent or recurrent primary hyperparathyroidism were selected; patients with secondary hyperparathyroidism, parathyroid cancer, familial hyperparathyroidism, and previous thyroid operations were omitted. DATA EXTRACTION: Performed by a single unblinded researcher. DATA SYNTHESIS: Reasons for failed parathyroid operations included tumor in ectopic position (53%), incomplete resection of multiple abnormal glands (37%), adenoma in normal position missed during previous surgery (7%), and regrowth of previously resected tumor (3%). Of the ectopic glands, 28% were paraesophageal, 26% in the mediastinum (nonthymic), 24% intrathymic, 11% intrathyroidal, 9% in the carotid sheath, and 2% in a high cervical position. Eighty-three percent of ectopic glands were accessible via cervical incision. The success rate of reoperations was 95%. One patient (1%) became permanently hypocalcemic after reoperation; 1 patient (1%) suffered permanent unilateral vocal cord paralysis. The sensitivities of preoperative localization studies were as follows: technetium Tc 99m sestamibi scan, 77%; magnetic resonance imaging, 77%; selective venous catheterization for intact parathyroid hormone, 77%; thallium-technetium scan, 68%; ultrasonography, 57%; and computed tomography, 42%. CONCLUSIONS: Repeated parathyroidectomy can be avoided in more than 95% of patients if an experienced surgeon performs bilateral cervical exploration during the initial parathyroid operation. For patients with persistent or recurrent primary hyperparathyroidism, preoperative localization studies and a focused surgical approach can result in a 95% success rate with minimum complications.

Adult↗
PubMed1996

Glottic carcinoma with a fixed true vocal cord: outcomes after neoadjuvant chemotherapy and supracricoid partial laryngectomy with cricohyoidoepiglottopexy.

Twenty patients with glottic squamous cell carcinoma and a fixed true vocal cord underwent neoadjuvant chemotherapy followed by supracricoid partial laryngectomy with cricohyoidoepiglottopexy. Phonation, respiration, and deglutition were preserved. Local control was better than has been previously reported for either extended vertical partial laryngectomy or radiation therapy. All patients were monitored for at least 3 years or until death. The Kaplan-Meier 3-year survival, local recurrence, nodal recurrence, distant metastasis, and second primary rates were 75%, 10.8%, 5%, 10.8%, and 10.8%, respectively. Overall local control was achieved in all cases, and laryngeal preservation in 90%. Our experience suggested that neoadjuvant chemotherapy with supracricoid partial laryngectomy with cricohyoidoepiglottopexy deserves further consideration in the treatment of glottic tumors with a fixed true vocal cord.

Adult↗
PubMed1996

Loss of nitric oxide production in the coronary circulation after the development of dilated cardiomyopathy: a specific defect in the neural regulation of coronary blood flow.

1. The aims of our study were to determine the role of nitric oxide (NO) in cholinergic reflex dilation of the coronary circulation in normal healthy conscious dogs and after the development of pacing-induced dilated cardiac myopathy and overt congestive heart failure. 2. Dogs were instrumented using sterile surgical techniques under general anaesthesia and allowed to fully recover. The Bezold-Jarisch reflex was stimulated by the intra-atrial injection of veratrine or the intravenous injection of PGI2, while the carotid chemoreflex was stimulated by the intracarotid injection of nicotine. Experiments were performed before and after the development of overt congestive heart failure (HF) caused by rapid left ventricular pacing for 4 weeks. 3. The release of NO, or NO-mediated vascular relaxation following administration of acetylcholine (ACh) may have little physiological significance since as ACh is released from nerve endings in vivo. Stimulation of the Bezold-Jarisch or carotid chemoreflex resulted in typical vagal cholinergic reflex coronary vasodilation, an increase in coronary blood flow and a decrease in coronary vascular resistance, which was substantially reduced following NO synthesis inhibition with nitro-L-arginine. 4. After the development of severe congestive HF, the production of NO by sieved coronary microvessels from the heart was markedly reduced accompanied by a 60-80% reduction in both the mRNA (northern blot) and protein (western blot) for endothelial NO synthase in the aorta. 5. After the development of severe pacing-induced HF, activation of the Bezold-Jarisch or carotid chemoreflex no longer resulted in coronary vasodilation due to the disappearance of NO production from the coronary circulation. 6. Therefore, cholinergic reflex coronary vasodilation is mediated by NO. Because coronary blood vessels lose the ability to produce NO after the development of HF, reflex cholinergic coronary vasodilation is markedly altered, uncovering a previously undiscovered specific defect in the integrated control of the coronary circulation in the failing heart.

Animals↗
PubMed1996

Modulation by atrial natriuretic factor of receptor-mediated cyclic AMP-dependent responses in canine pulmonary artery during heart failure.

1. Pacing-induced congestive heart failure (CHF) in dogs is associated with increased plasma levels of atrial natriuretic factor (ANF) and inhibition of receptor-mediated cyclic AMP-dependent relaxation in isolated pulmonary arteries (PA). Since ANF is known to be negatively coupled to adenylate cyclase, we studied cyclic AMP-mediated relaxation to isoprenaline (Iso) and arachidonic acid (AA) in PA from control dogs (C), dogs with pacing-induced CHF (CHF) and dogs with bilateral atrial appendectomy and CHF (ATR APP+CHF). 2. In CHF, plasma ANF levels increased from a baseline of 80 +/- 8 pg ml-1 to 283 +/- 64 pg ml-1 (P < 0.05), but the ATR APP+CHF group failed to show this increase (67 +/- 7 pg ml-1 vs 94 +/- 15 pg ml-1, P = NS). Plasma ANF levels, however, did not influence myocardial dysfunction in CHF. 3. The relaxation of 49 +/- 5% to 1 microM Iso in C was reduced to 23 +/- 4% in CHF (P < 0.05), but relaxation of 49 +/- 12% was observed in the ATR APP+CHF group (P = NS vs C). Relaxation responses to 10 microM AA were as follows: 77 +/- 5% (C, n = 8), 27 +/- 8% (CHF, n = 10, P < 0.05 vs C), and 93 +/- 5% (ATR APP+CHF, n = 5). The presence of CHF, or the plasma ANF levels, did not affect responses to cyclic GMP-mediated relaxing agents in PA. 4. These data indicate that the myocardial performance in CHF is not influenced by plasma ANF levels. However, altered cyclic AMP-mediated relaxation in PA during CHF is, in part, modulated by circulating ANF levels.

Acetylcholine↗
PubMed1996

Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro. Implications for the development of heart failure.

The mechanism responsible for the regulation of cardiac function by endogenous nitric oxide (NO) remains unclear. In this investigation, O2 consumption by freshly isolated myocardial muscle segments from the left ventricular free wall of canine hearts was quantified by a Clark-type O2 electrode at 37 degrees C. S-nitroso-N-acetylpenicillamine (SNAP, 9 +/- 3% to 50 +/- 8%), bradykinin (BK, 14 +/- 3% to 30 +/- 5%), or carbachol (CCh, 15 +/- 4% to 29 +/- 4%) significantly attenuated tissue O2 consumption at doses of 10(-7) to 10(-4) mol/L (mean +/- SE, P < .05). The effects of BK and CCh, but not SNAP, were blocked by 10(-4) mol/L NG-nitro-L-arginine, consistent with both BK and CCh stimulating NO biosynthesis and with SNAP decomposing to release NO, respectively. Similar doses of 8-Br-cGMP caused a respiratory inhibition, but to a lesser extent (9 +/- 2% to 14 +/- 6%). A mitochondrial uncoupler, 2,4-dinitrophenol (at 1 mmol/L), blocked the effects of 8-Br-cGMP, but not those of SNAP, BK, or CCh, suggesting that the major site of action of NO is on mitochondrial electron transport. Myocardial muscle from dogs with pacing-induced heart failure had a basal O2 consumption rate of 251 +/- 21 nmol.min-1.g-1, which was 54% higher than the rate seen in muscle from normal healthy canine hearts. The inhibitory effects of BK and CCh on O2 consumption were not observed in failing cardiac tissue, but SNAP showed an unaltered inhibitory effect. Therefore, our results indicate that NO released from microvascular endothelium by BK, stimulation of muscarinic receptors, and perhaps flow velocity may play an important physiological role in the control of cardiac mitochondrial respiration, and the loss of this regulatory function may contribute to the development of heart failure.

2,4-Dinitrophenol↗
PubMed1996

Function and production of nitric oxide in the coronary circulation of the conscious dog during exercise.

This study determined the changes in NO production from the coronary circulation of the conscious dog during exercise. The role of endogenous NO as it relates to coronary flow, myocardial work, and metabolism was also studied. Mongrel dogs were chronically instrumented for measurements of coronary blood flow (CBF), ventricular and aortic pressure, and ventricular diameter, with catheters in the aorta and coronary sinus. Acute exercise (5 minutes at 3.6, 5.9, and 9.1 mph) was performed, and hemodynamic measurements and blood samples were taken at each exercise level. Nitro-L-arginine (NLA, 35 mg/kg IV) was given to block NO synthesis, and the exercise was repeated. Blood samples were analyzed for oxygen, plasma nitrate/nitrite (an index of NO), lactate, glucose, and free fatty acid (FFA) levels. Acute exercise caused significant elevations in NO production by the coronary circulation (46 +/- 23, 129 +/- 44, and 63 +/- 32 nmol/min at each speed respectively, P < .05). After NLA, there was no measurable NO production at rest or during exercise. Blockade of NO synthesis resulted in elevations in myocardial oxygen consumption and reductions in myocardial FFA consumption for comparable levels of CBF and cardiac work. The metabolic changes after NLA occurred in the absence of alterations in myocardial lactate or glucose consumptions. NO production by the coronary circulation is increased with exercise and blocked by NLA. The absence of NO in the coronary circulation during exercise does not affect levels of CBF, because it shifts the relationship between cardiac work and myocardial oxygen consumption, suggesting that endogenous NO modulates myocardial metabolism.

Animals↗
PubMed1996

Mitigation of nitrofurantoin-induced toxicity in the perfused rat liver.

1. Nitrofurantoin is an antimicrobial agent which produces hepatotoxicity caused by the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress. 2. Our goal was to determine treatment strategies which could mitigate nitrofurantoin-induced toxicity in the isolated perfused rat liver. We co-infused various agents which blocked early or late events in the progression to toxicity. Tissue levels of glutathione and protein thiols were measured as indicators of the progression to toxicity and lactate dehydrogenase leakage into the perfusate was used as a marker of irreversible cell death. 3. Five treatments significantly (P < 0.05) decreased LDH leakage (reported as thousands of units accumulated in perfusate at 300 min, mean+/-standard error, n = 3-4) when compared to nitrofurantoin alone (274 +/- 37). These treatments were adenosine-2'-monophosphate (120 +/- 53), penicillamine (90 +/- 29), N-(2-mercaptopropionyl)-glycine (120 +/- 49) and bromosulfophthalein with (80 +/- 29) or without 5,5'-difluro-1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraace tic acid (101 +/- 46). Two other treatments, N-acetylcysteine (183 +/- 7) and dithiothreitol (166 +/- 59) delayed the onset of toxicity. Finally, calpeptin (319 +/- 34) which blocks activation of nonlysosomal proteases was ineffective. 4. We concluded that early intervention on the pathway to toxicity was most effective. The strategies detailed here may prove beneficial in treating hepatotoxicity seen following nitrofurantoin therapy.

Acetylcysteine↗
PubMed1996

Interaction between prostacyclin and nitric oxide in the reflex control of the coronary circulation in conscious dogs.

OBJECTIVE: Our goal was to determine the role of nitric oxide (NO) on the coronary vasodilation induced by prostacyclin (PGI2) in conscious dogs. METHODS: Dogs were chronically instrumented for the measurements of coronary blood flow (CBF), left ventricular pressure (LVP), mean arterial pressure (MAP) and heart rate (HR). RESULTS: Intravenous injections of PGI2 caused dose-dependent increases in CBF, and decreases in MAP and late diastolic coronary resistance (LDCR). For instance, CBF increased by 128 +/- 19% (P < 0.05) from 30 +/- 3.5 ml/min and LDCR decreased by 73 +/- 3% (P < 0.05) from 2.57 +/- 0.20 mmHg/ml/min following injection of PGI2 (1.0 microgram/kg). After infusion of nitro-L-arginine (NLA, 35 mg/kg) intravenously, the coronary vasodilation induced by PGI2 was partially attenuated. PGI2 (1.0 microgram/kg) increased CBF by 55 +/- 15% from 33 +/- 5.3 ml/min and decreased LDCR by 42 +/- 9% (both P < 0.05, compared with before NLA) from 3.29 +/- 0.39 mmHg/ml/min. Infusion of L-arginine (100 mg/kg) reversed the action of NLA. For example, PGI2 (1.0 microgram/kg) increased CBF by 115 +/- 15% from 36 +/- 6 ml/min and decreased LDCR by 68 +/- 3% from 3.02 +/- 0.36 mmHg/ml/min (both P > 0.05, compared with before NLA). Atropine (0.1 mg/kg) partially attenuated the coronary vasodilation induced by PGI2 the magnitude of which was almost identical to that by NLA. NLA or atropine also blunted the coronary vasodilation induced by acetylcholine, while the coronary vasodilation induced by nitroglycerin was not affected by NLA. CONCLUSION: Our results indicate that the coronary vasodilation induced by PGI2 was partially attenuated by NLA or atropine, suggesting that the coronary vasodilation induced by PGI2 is due to two components: a reflex parasympathetic cholinergic vasodilation mediated by NO and a direct action of PGI2.

Acetylcholine↗
PubMed1996

[Surgery of primary malignant melanomas of the mucosa of the nasal fossa and facial sinuses].

A retrospective analysis of 22 patients with primary malignant melanoma of the nasal fossa and/or paranasal sinuses consecutively managed with surgery at our department from 1975 to 1993 was conducted. Fifteen patients had negative margins of resection. Neoadjuvant chemotherapy and post-operative radiation therapy was associated in 4 and 5 of these 15 patients, respectively. Four patients had positive margins. Adjunctive treatment was chemotherapy and postoperative radiation therapy in 2 and 3 of these 4 patients, respectively. The remaining 3 patients were managed with palliative treatment (debulking surgery and chemotherapy). No patients were lost to follow up. A 3-year follow-up was always achieved. In patients in whom surgical resection achieved negative margins, the 5-year actuarial survival, and local control estimate was 17.9%, and 26.9%, respectively. None of the variables under analysis were statistically related to local recurrence or survival. Death always occurred within 24 months from initial diagnosis in all 7 patients but one in whom surgical resection with negative margins was not achieved or debulking surgery was performed.

Aged↗
PubMed1996

Beneficial effects of captopril on prognosis in patients with acute myocardial infarction. Shanghai Secondary Prevention of Acute Myocardial Infarction Study Group.

OBJECTIVES: To assess the effects of early and long-term angiotensin-converting enzyme inhibitor treatment with captopril on clinical outcome in patients with acute myocardial infarction (AMI). METHODS: Eight hundred and twenty-two patients with AMI who were hospitalised within 72 hours of symptoms and had no cardiogenic shock were randomly allocated to captopril (n = 478, Group I) and conventional treatment (n = 344, Group II). Cardiac events including congestive heart failure, reinfarction, severe arrhythmias and cardiac death during hospitalization and follow-up period (average 20 months) were determined. RESULTS: The overall mortality rate during hospitalization was lower in group I than in group II (P = 0.0001), this was true for patients with anterior (P = 0.0003), inferior (P = 0.0411) and anterior inferior AMI (P = 0.0232). During follow-up, despite similar occurrence rate of reinfarction and severe arrhythmias in the two groups, the mortality rate (P = 0.0324) and total cardiac event rate (P = 0.055) were lower in group I than in group II. CONCLUSIONS: After AMI, early and long-term treatment with captopril exerts a beneficial effect on the prognosis of patients.

Aged↗
PubMed1996

Abnormal coronary flow reserve in patients with angina pectoris and hypertensive left ventricular hypertrophy.

OBJECTIVE: To assess coronary flow reserve using a computer-assisted method with intracoronary papaverine in patients with angina pectoris. PATIENTS AND METHODS: Coronary arterial diameter, cross-sectional area and blood flow velocity were measured during coronary arteriography before and after intracoronary papaverine in 26 control subjects, 45 patients with significant coronary artery disease (> 50% luminal narrowing), 16 patients with syndrome X and 14 patients with hypertension and left ventricular hypertrophy (LVH). RESULTS: After intracoronary administration of papaverine, proximal diameter, cross-sectional area, blood velocity, flow volume and reserve capacity of both left anterior descending and right coronary arteries were lower in patients with significant coronary stenosis than in the controls. Despite similar changes in diameter and cross-sectional area, the blood velocity, flow volume and reserve capacity of the two vessels were also lower in patients with syndrome X than in the controls. In 14 patients with hypertension and LVH, although the blood velocity and flow volume were augmented for the two arteries and did not differ from those in the controls, the flow reserve was reduced because of higher baseline blood velocity and flow volume. CONCLUSIONS: Coronary flow reserve is reduced in patients with coronary artery disease, syndrome X or hypertensive LVH, which may be related to abnormal changes at different levels of the coronary vasculature or resting flow states.

Angina Pectoris↗
PubMed1996

[The influence of HX- I on rabbit thyroid allografts].

We studied the anti-rejection effect of HX- I, a preparation of traditional Chinese herbs, on rabbit thyroid allografts. The transplantations were performed on 28 rabbits after total thyroidectomies. The grafting sites were in their pretrachial muscles. These animals were divided into four groups, namely, Group I: homografts: Group I: allografts without medication; Group II: allografts with dexamethason (0.25 mg/(kg.d) intramuscularly), and Group IV: allografts with HX-I water solution, (5g/(kg.d), peros). The medication lasted 28 days. Blood samples were drawn every week postoperatively. Serum T3 and T4 were tested by RIA. The grafts were removed for histopathological evaluation on the 28th day postoperatively. The histopathology of rejection and survival were scored and classified. On the 7th and 14th days, serum T3 and T4 levels were almost the same between groups. On the 21st and 28th days, the T3 and T4 levels were higher in Groups I and IV than those in Group II (P < 0.05). The histopathological findings were; in Group I, damaged follicles with much lymphocytes infiltration and fibrosis, and 6 cases being rejected; in Group II, two deaths and three cases with damaged thyroid tissue and much lymphocytes infiltration; in Group IV, three cases with damaged thyroid tissue and four intact grafts. Our results indicate that HX-I and dexamethason both can inhibit rejection in thyroid allografts in rabbits, but dexamethason has more side effects HX-I has many components and the machanism of its early anti-rejection effect is worthy of further study.

Animals↗
PubMed1996

[An experimental study on compound anisodine III for softening scar of mouse skin after burn].

OBJECTIVE: The aim of this study was to investigate the mechanism of compound anisodine (CA) III which can rapidly soften the cicatrized tissue in clinical practice. METHODS: 2 mol/L NaOH was applied onto the back of 36 mice for one minute to induce deep grade skin burn injury. After 1 week local cicatrization occurred. The mice were randomly divided into 3 groups: 1 ml saline was used in group I as control, hyaluronidase 150 U dissolved in 1 ml 2% procaine was used in group II and 0.005% CA 0.1 ml in 2% procaine 1 ml with hyaluronidase 150 U was used in group III. Subcutaneous injection once every other day for two weeks was the method of drug administration in all the 3 groups and then all the rats were euthanized. The burned skin was sectioned for HE and modified Masson's stains. RESULTS: Histopathology revealed there were epidermis proliferation, keratinization and fibrosis with disorderly arranged collagenous fibers invading into muscles and a large amount of inflammatory cells infiltrating the lesion in groups I and II. However, the skin was nearly normal in group III. CONCLUSIONS: CA III can inhibit the epidermic and collagenous proliferation, improve the tissue blood supply and have antiinflammatory effect to prevent scar formation and promote epidermic repair in the skin.

Animals↗