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Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 271 records · Page 15Linked to original sources

Regulation of the renal Na-HCO(3) cotransporter. XI. Signal transduction underlying CO(2) stimulation.

We have previously shown that CO(2) stimulation of the renal Na-HCO(3) cotransporter (NBC) activity is abrogated by general inhibitors of protein tyrosine kinases. The more selective inhibitor herbimycin also blocked this effect at concentrations known to preferentially inhibit Src family kinases (SFKs). We therefore examined a role for SFKs in CO(2)-stimulated NBC activity. To this end, we engineered OK cells to express the COOH-terminal Src kinase (Csk), a negative regulator of SFKs. CO(2) stimulated NBC activity normally in beta-galactosidase-expressing and untransfected control cells. In contrast, Csk-expressing cells had normal baseline NBC activity that was not stimulated by CO(2). CO(2) stimulation increased both total SFK activity and specific tyrosine phosphorylation of Src. The specific MEK1/2 inhibitor PD-98059 completely inhibited the CO(2) stimulation of NBC activity as well as the accompanying phosphorylation and activation of ERK1/2. Our data suggest the involvement of both SFKs, probably Src, and the "classic" MAPK pathway in mediating CO(2)-stimulated NBC activity in renal epithelial cells.

Animals↗

Regulation of mesangial cell hexokinase activity by PKC and the classic MAPK pathway.

Phorbol esters increase glucose (Glc) uptake and utilization in a variety of cell types, and, in some cells, these changes have been attributed to increased Glc phosphorylation and better functional coupling of hexokinases (HKs) to facilitative Glc transporters. Phorbol esters are potent mesangial cell mitogens, but their effects on HK-catalyzed Glc phosphorylation and metabolism are unknown. When examined in murine mesangial cells, active, but not inactive, phorbol esters increased HK activity in a time- and dose-dependent manner. Maximal induction of HK activity at 12-24 h was accompanied by parallel increases in both Glc utilization and lactate production and was blocked by the specific MEK1/2 inhibitor PD-98059 (IC(50) approximately 3 microM). This effect involved early activation of protein kinase C (PKC), MEK1/2, and ERK1/2, and the prolonged time course of subsequent HK induction was attributable, in part, to requirements for ongoing gene transcription and de novo protein synthesis. Mesangial cell HK activity thus exhibits novel regulatory behavior involving both PKC and classic MAPK pathway activation, suggesting specific mechanisms whereby PKC activation may influence Glc metabolism.

Animals↗

Changes of beta-1,4-galactosyltransferase with the development of endometrial cancer.

To elucidate the mechanism of the type 2 carbohydrate chain accompanying the development of endometrial cancer, we studied the expression of beta-1,4-galactosyltransferase (beta-1,4GT) in normal endometrial and endometrial cancer tissues. An immunohistochemical study revealed that beta-1,4GT was diffusely positive in the cytoplasm of endometrial cancer cells, and that the level of its expression was increased compared with that in normal endometrium. Also, beta-1,4GT mRNA corresponding to 4.7 kb was very low in normal endometrium, while an intense signal was detected in endometrial cancer. Our results suggest that the increase of beta-1,4GT contributes to the expression of the type 2 carbohydrate chain in endometrial cancer.

Endometrial Neoplasms↗

Basolateral Na(+)/HCO(3)(-) cotransport activity is regulated by the dissociable Na(+)/H(+) exchanger regulatory factor.

In the renal proximal tubule, the activities of the basolateral Na(+)/HCO(3)(-) cotransporter (NBC) and the apical Na(+)/H(+) exchanger (NHE3) uniformly vary in parallel, suggesting that they are coordinately regulated. PKA-mediated inhibition of NHE3 is mediated by a PDZ motif-containing protein, the Na(+)/H(+) exchanger regulatory factor (NHE-RF). Given the common inhibition of these transporters after protein kinase A (PKA) activation, we sought to determine whether NHE-RF also plays a role in PKA-regulated NBC activity. Renal cortex immunoblot analysis using anti-peptide antibodies directed against rabbit NHE-RF demonstrated the presence of this regulatory factor in both brush-border membranes (BBMs) and basolateral membranes (BLMs). Using a reconstitution assay, we found that limited trypsin digestion of detergent solubilized rabbit renal BLM preparations resulted in NBC activity that was unaffected by PKA activation. Co-reconstitution of these trypsinized preparations with a recombinant protein corresponding to wild-type rabbit NHE-RF restored the inhibitory effect of PKA on NBC activity in a concentration-dependent manner. NBC activity was inhibited 60% by 10(-8)M NHE-RF; this effect was not observed in the absence of PKA. Reconstitution with heat-denatured NHE-RF also failed to attenuate NBC activity. To establish further a physiologic role for NHE-RF in NBC regulation, the renal epithelial cell line B-SC-1, which lacks detectable endogenous NHE-RF expression, was engineered to express stably an NHE-RF transgene. NHE-RF-expressing B-SC-1 cells (B-SC-RF) exhibited markedly lower basal levels of NBC activity than did wild-type controls. Inhibition of NBC activity in B-SC-RF cells was enhanced after 10 microM of forskolin treatment, consistent with a postulated role for NHE-RF in mediating the inhibition of NBC activity by PKA. These findings not only suggest NHE-RF involvement in PKA-regulated NBC activity, but also provide a unique molecular mechanism whereby basolateral NBC and apical NHE3 activities may be coordinately regulated in renal proximal tubule cells.

Animals↗

Chemiluminescent detection of AFLP markers.

Nonradioactive amplified fragment-length polymorphism (AFLP) marker detection, a PCR-based, DNA-fingerprinting technique, was achieved by blotting AFLP products after electrophoresis onto a nylon membrane and subsequently hybridizing the blot with an alkaline phosphatase-labeled AFLP probe. Similar AFLP profiles were obtained by both a nonradioactive, chemiluminescent detection technique and by conventional AFLP marker detection using 32P-labeled AFLP primers. The suitability of the method using different gel systems combined with subsequent chemiluminescent detection of AFLP markers is validated by similar dendrograms that were generated using the unweighted pair group method with arithmetic averages (UPGMA). Moreover, chemiluminescent detection of AFLP markers using a universal AFLP nonradioactive probe has been successfully applied on prokaryotes such as Agrobacterium and eukaryotic genomes such as soybean and fungi.

Chromosome Mapping↗

A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk.

We previously reported (J. Chen et al., Cancer Res., 56: 4862-4864, 1996; J. Ma et al., Cancer Res., 57: 1098-1102, 1997) that a 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism (677C-->T, ala-->val) was associated with lower risk of colorectal cancer. In this study, we examined the relationship of a polymorphism (2756A-->G, asp-->gly) in the gene (MTR) for methionine synthase, another important enzyme in the same folate/methionine/homocyst(e)ine metabolic pathway, with risk of colorectal cancer among 356 cases and 476 cancer-free controls. The frequency of the homozygous variant genotype (gly/gly) was slightly lower among cases (3%) than controls (5%). The odds ratio for the gly/gly genotype was 0.59 [95% confidence interval (CI), 0.27-1.27] compared with those with the homozygous wild type (asp/asp). There were no significant differences in plasma levels of folate, vitamin B12, and homocyst(e)ine (tHcy) among the MTR genotypes, in contrast to the MTHFR polymorphism. However, similar to the interaction observed for the MTHFR polymorphism among men who consumed less than 1 alcoholic drink/day, those with the gly/gly genotype had a lower risk of colorectal cancer with an odds ratio of 0.27 (95% CI, 0.09-0.81) compared with those with the asp/asp genotype. The possible association of the MTR polymorphism with lower risk of colorectal cancer especially among those with low alcohol consumption, in the same direction as for the MTHFR polymorphism, is intriguing. However, our study had limited statistical power because of the low frequency of the MTR variant genotype, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States.

A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finland recently reported an unexpected, strong protective effect of vitamin E against prostate cancer incidence and mortality. Our objective was to prospectively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population. In 1986, we identified 47,780 U.S. male health professionals, free from diagnosed cancer, who completed a dietary and lifestyle questionnaire; supplemental vitamin E and prostate cancer incidence were updated biennially through 1996. We estimated relative risks (RRs) from multivariate pooled logistic regression models. There were 1896 total (non-stage A1), 522 extraprostatic, and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986-1996. Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 (95% confidence interval [CI], 0.95-1.20) for total and 1.14 (95% CI, 0.82-1.59) for metastatic or fatal prostate cancer compared with those consuming none. Current use, dosage, and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk. However, among current smokers and recent quitters, those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 (95% CI, 0.18-1.07) for metastatic or fatal prostate cancer compared with nonusers. Thus, supplemental vitamin E was not associated with prostate cancer risk generally, but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation.

Adult↗

[Ultrastructural changes of arterial wall from different body parts of rats during simulated weightlessness].

OBJECTIVE: To test the nature of remodeling of arteries in different body parts in adapting to local hemodynamic changes induced by tail-suspension. METHOD: Ultrastructural changes of hindlimb and cerebral arteries from 4-wk tail-suspended (SUS-4), 1-wk recovered (REC-1), and control (CON) rats were studied by transmission electron microscopy. RESULT: For the hindquarter arteries, like the femoral artery and anterior tibial artery, there were fewer smooth muscle layers, less myofilaments in the smooth muscle cell (SMC), and more intercellular substance in SUS-4 group than in CON group. After 1-wk recovery, the internal elastic lamina of the arteries thickened, the amount of myofilaments in SMC increased, the content of intercellular substance restored, and neoformative SMCs emerged under the endothelium. With respect to arteries in the neck region and the brain, like the common carotid artery and basilar artery, SMCs of contractile phenotype were converted to that of synthetic phenotype, and migration and hyperplasia of SMCs also happened. After 1-wk recovery all these alterations were somewhat restored. CONCLUSION: It provided further evidence that peripheral effector mechanism might play an important role in the genesis of postflight orthostatic intolerance.

Actin Cytoskeleton↗

[Effects of simulated weightlessness on vasoreactivity of hindlimb arterial bed in rats].

OBJECTIVE: To investigate the alterations in vasoreactivity of hindlimb arterial bed after simulated weightlessness. METHOD: The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoreactivity of arterial bed were examined in vitro using isolated, constant flow perfused hindlimb of 2-wk suspended rats and control rats. RESULT: Perfusion flow-pressure relationship of hindlimb arterial bed showed no significant differences between suspended rats and control rats; but vascular responses to KCl (20-100 mM) and PE(10(-8)-10(-4) M) were decreased in hindlimb arterial bed of suspended rats as compared with that of control rats. CONCLUSION: Contractile ability of resistance vessels was diminished in simulated weightlessness rats, and a compromised ability of resistance vessels to increase peripheral resistance may play an important role in occurrence of orthostatic intolerance.

Adaptation, Physiological↗

Unearthed ancient Chinese medical literatures currently preserved in Russia.

An outline probing a Russian exploration team exploiting the ancient literature remains existed in the vast northwestern region in China was made in this paper for the medical literatures already publicized which are collected at the Heicheng Department of Ayrmita Museum attached to the Petersburg Branch of Oriental Institute of Russian Academy of Sciences. The process of excavation and its collection preserved in the Museum is first dealt with, followed in order by the Museum filed numbers of medical literatures unearthed by the Russians in Dunhuang, Heicheng and Khotan and their book titles, authors, contents and care.

China↗

Messenger RNA expressions of vasopressin system and aquaporin-2 in adriamycin-induced nephrotic rats and effects of astragalus membranaceus.

OBJECTIVE: To investigate the expressions of hypothalamic arginine vasopressin (AVP) mRNA, renal AVP V2 receptor mRNA, and AVP-dependent aquaporin-2 (AQP2) mRNA in rats with adriamycin-induced nephrotic syndrome. Effects of Chinese herb Astragalus membranaceus (AM) were also tested. METHODS: Sprague-Dawley rats with four weeks of adriamycin-induced nephrotic syndrome (NS) were used in this study. Another group NS + AM was set to testify the effects of AM given 0.5 g/kg daily on NS. Hypothalamic AVP mRNA expression was examined by dot blot method. Reverse transcription polymerase chain reaction was applied for detection of renal cortical and medullary V2 receptor and AQP2 mRNA. The results were normalized by mRNA of glyceraldehyde-3-phosphate dehydrogenase from the same sample. RESULTS: All rats receiving adriamycin presented typical nephrosis. No obvious difference in plasma osmolality was detected among NS, NS + AM, and normal control (NC) rats. Hypothalamic AVP mRNA expression was higher in NS rats than NC (53.59 +/- 5.49 vs 25.72 +/- 1.96, P < 0.01). AM completely reversed this up-regulated expression (21.88 +/- 1.25). In both cortex and medulla of the kidney, nephrotic rat had increased AVP V2 expressions by 169% and 55%, respectively, compared with normal control rat. The increment of expression of AQP2 mRNA was consistent with that of V2 receptor in NS rat. AM could partially however significantly correct these up-regulations of V2 and AQP2 mRNA expressions (P < 0.01). CONCLUSION: The up-regulated mRNA expressions of hypothalamic AVP, renal V2 receptor and AQP2 might play a role in edema formation in adriamycin-induced nephrotic rats. AM exerts its therapeutical effects on nephrosis partially through this mechanism.

Animals↗

[Vasoconstrictor responsiveness of rat basilar artery enhanced by simulated weightlessness].

OBJECTIVE: To investigate the effects of simulated weightlessness on contractile responsiveness of the basilar artery. METHODS: Rats were subjected to tail-suspension for 4-wk to simulate the effect of weightlessness, responses of perfused isolated basilar arterial rings to various vasoactive compounds were examined. RESULTS: Maximal isometric contractile responses to KCl [ (10~100) mmol/L], arginine vasopressin [AVP, (10(-15)~10(-7) mol/L], or 5-hydroxytryptamine [5-HT, (10(-12) ~ 10(-4) mol/ L] were significantly enhanced in arterial rings isolated from 4-wk tail-suspended as compared with that from simultaneous control rats. CONCLUSION: These results indicate that medium-term simulated weightlessness may result in an enhanced contractile responsiveness in rat basilar artery, and strongly support the hypothesis of cerebrovascular syncope-initiating mechanism.

Aerospace Medicine↗

[Alterations of arterial vasoconstrictor responsiveness in rats during and after tail-suspension].

Objective. To characterize the time course of alterations in vasoconstrictor properties of arteries during simulated weightlessness, and to examine whether these alterations are reversible. Method. The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoconstrictor response were examined in vitro using isolated arterial rings. Result. Compared with that of controls, contractile tension evoked by KCl and phenylephrine (PE) were lower in abdominal aortic, mesenteric and femoral arterial rings from 2 wk tail-suspended rats (P<0.05); after 4 wk tail-suspension, the responses of mesenteric and femoral arterial rings to KCl or PE were further decreased (P<0.05); but contraction responses of arterial rings from 8 wk tail-suspended rats were similar to that of 4 wk simulated microgravity rats. The reversibility of altered arterial vasoreactivity after 4 wk tail-suspension was observed for 5 wk. Vasoreactivity of abdominal aortic rings was recovered after first week of recovery, but it took five weeks that altered vasoreactivity of mesenteric and femoral artery got back to normal. Conclusion. The alterations in constrictor properties of arteries are dependent on both the duration of tail-suspension and the position of artery, the diminished vasoconstrictor properties appear to reach a new steady state after 4 wk tail-suspension, and the changes are reversible.

Animals↗

[Changes in lumen diameters of vessels in arteriolar network in rat soleus muscle after simulated weightlessness].

Objective. To elucidate whether simulated weightlessness can induce changes in lumen diameters of vessels in arteriolar networks in hindlimb muscles and whether these changes are reversible. Method. Changes in lumen diameters of the vessels in the arteriolar network in soleus muscle of 4 wk tail-suspended (SUS-4), 1 wk (REC-1) and 5 wk (REC-5) recovered rats were examined and compared with that of control (CON) rats by use of the method of intra-arterial infusion of a carbon suspension. Result. The lumen diameters of the feeding arteries and arcade arterioles, and the transverse arterioles of the order of both V and II in the SUS-4 group were reduced by 31%, 29%, 28%, and 41%, respectively, as compared with that of the CON group (P<0.01). The diameters of these arterioles in REC-1 group were partially restored but remained significantly less than that of the CON group (P<0.05, or P<0.01). In REC-5 group, except for the transverse arterioles of order II, the diameters of all the other arterioles were fully recovered. Conclusion. These findings indicate that a 4 wk simulated weightlessness might induce atrophic changes in the arterioles of the hindlimb muscles. It also suggests that structural changes in arteriolar network might be an important mechanism accounting for postflight orthostatic intolerance.

Animals↗

[Adenocarcinoma of the urinary bladder: a report of 27 cases].

OBJECTIVE: To analyze the therapeutic results of urinary bladder adenocarcinoma. METHODS: Twenty-seven urinary bladder adenocarcinoma patients were treated from 1970 through 1997. There were 12 cases of urachal adenocarcinoma and 15 cases of bladder adenocarcinoma. Hematuria with or without urinary tract irritation symptoms was the most common clinical manifestation. RESULTS: The overall 5-year survival rate was 25.9%. Among patients with urachal adenocarcinoma, 7 received extended partial bladder resection. None of them had local recurrence. Patients with bladder adenocarcinoma mainly received partial bladder resection, with which 4 developed local recurrence at the primary site. The 5-year survival rate of urachal adenocarcinoma and bladder adenocarcinoma was 33.3% and 20.0%, respectively. One patient of bladder adenocarcinoma with skin and inguinal lymph node metastases and 2 patients of urachal adenocarcinoma with lung metastasis treated with chemotherapy and radiotherapy survived 24, 28 and 60 months, respectively. CONCLUSION: Extended partial bladder resection is the treatment of choice for urachal adenocarcinoma while radical cystectomy for bladder adenocarcinoma. Comprehensive therapy should be given to patients with metastatic or recurrent disease to improve survival.

Adult↗

[Expression and clinical study of multidrug resistance gene and multidrug resistance associated protein gene in acute leukemia].

OBJECTIVE: To evaluate the relationship between the expression of multidrug resistance gene (mdr1) or multidrug resistance-associated protein gene (MRP) and the prognosis in patients with acute leukemia (AL). METHODS: The expression of mdr1 and MRP were measured in 55 patients with AL by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mdr1 and MRP gene expression levels in the relapsed AL and the blastic phase of CML group (0.735 +/- 0.249, 1.157 +/- 0.447) were significantly higher than those in the untreated group (0.408 +/- 0.186, 0.465 +/- 0.253) (P < 0.01). The complete remission (CR) rate in high mdr1 and MRP expression group was significantly lower than that in low mdr1 and MRP expression group (P < 0.01) in a follow up of 40 AL patients. CONCLUSION: Increased expression of mdr1 and MRP gene might be an important factor for predicting drug resistance, relapse and unfavorable prognosis in AL patients.

Acute Disease↗

[Gastric colonization and its effect on pathogenesis of nosocomial pneumonia].

OBJECTIVE: To study the gastric colonization and its effect on development of nosocomial pneumonia (NP). METHODS: We investigated the microorganism (mainly pathogens) constitution, isolating sequences and risk factors in gastric, oropharyngeal and lower respiratory tract flora. Microbiologic cultures of serially taken samples of gastric aspirates, oropharyngeal swabs and bronchoalveolar lavages (BALs) or sputums were performed at the time of ICU admission and subsequently every morning in 52 surgical patients with nasogastric tube. Etiologic diagnosis of NP was based on quantitative cultured of BAL or sputum. Sequences of colonization were examined by comparing isolates of the same species with concordance of minimum inhibitory concentration values to 12 antibiotics. RESULTS: A total of 237 pairs of gastric and oropharyngeal specimens were taken. 77 strains of gram- negative bacilli (GNB) isolated from stomach, more than the number of GNB isolated from oropharynx (51 strains), P = 0.007. Comparing the species, Enterobacteriaceae isolated from stomach was much more than that from oropharynx (46 vs 24 strains, P = 0.004), and in most instances stomach colonization was before oropharynx colonization one to two days. Isolating rates of Pseudomonas were the same in both kinds of specimens. On contrast, Acinetobacter colonization in oropharynx was much more than that in stomach (10 vs 3 strains, P = 0.049). Risk factors for GNB colonization in stomach included increased gastric pH, medications inhibiting gastric acid secretion (such as cimitidine, omeprazole), and systemic use of cephalosporins. 10 patients developed NP and 5GNB (Enterobacter cloacae 2, Pseudomonas aeruginosa 2, Acinetobacter anitratum 1) isolated from BAL or sputum in 4 of 10 patients. A sequence of colonization from the stomach to the respiratory tract leading to pneumonia was observed in 3 patients. CONCLUSIONS: It was suggested that the stomach is likely to be an important source of pathogens leading to NP, especially Enterobacteriaceae pneumonia.

Adult↗

[Dynamic monitoring of serum soluble HLA class I antigens in renal transplant recipients].

OBJECTIVE: To investigate the relations between serum soluble HLA class I antigens (sHLA-I) and the period of acute rejection and infection in renal transplant recipients. METHODS: We measured the serum levels of sHLA-I in 36 renal transplant recipients with ELISA dynamically. RESULTS: The serum sHAL-I levels were higher in uremia patients than in normal controls [(2.94 +/- 0.34) microg/L vs. (0.76 +/- 0.33) microg/L, P < 0.05]. After renal transplantation, the serum sHLA-I levels decreased significantly in stable patients [(0.63 +/- 0.33) microg/L], but increased significantly 3 days before acute rejection and 5 or 7 days after infection. CONCLUSIONS: The serum sHLA-I levels can be used as a parameter for monitoring acute rejection and infection in renal transplantation.

Adolescent↗