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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 325 records · Page 18Linked to original sources
PubMed1996

Inhibition by verapamil of cholecystokinin-enhancement of pancreatic carcinogenesis induced by azaserine in Wistar rats.

The effect of a calcium channel blocker, verapamil, on cholecystokinin (CCK)-enhancement of pancreatic carcinogenesis induced by azaserine was investigated in Wistar rats. During and after 25 weekly injections of azaserine, each rat received alternate-day injections of CCK-octapeptide (CCK-8) and/or verapamil. Carcinogen-induced pancreatic lesions staining for mu class glutathione S-transferase (GST-mu) were examined histochemically at week 62. Prolonged administration of CCK-8 significantly increased the number and area as a percentage of parenchyma of GST-mu-positive lesions. Concomitant administration of verapamil significantly attenuated the enhancing effect of CCK-8. These findings indicate that calcium may play an important role in CCK-enhancement of pancreatic carcinogenesis.

Animals↗
PubMed1996

Tissue norepinephrine depletion as a mechanism for calcium chloride inhibition of gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The effects of oral calcium chloride (CaCl2) on sodium chloride (NaCl)-enhanced induction of gastric carcinogenesis by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, and the norepinephrine (NE) concentration in the gastric wall, were investigated in Wistar rats. Animals were given the carcinogen for 25 weeks and then chow pellets containing 10% NaCl with or without 8% or 4% CaCl2. In week 52, the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of antral epithelial cells were significantly greater in rats fed NaCl alone than in untreated control rats. Concomitant oral treatment with CaCl2 at 8%, but not 4%, significantly reduced the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of the antral epithelial cells in week 52 compared with those in rats fed NaCl alone. Because NE concentration reflects sympathetic nervous system activity, our findings suggest that the sympathetic nervous system could play a role in NaCl-enhanced gastric carcinogenesis. Our findings also suggest that NE depletion by CaCl2 may be related to its inhibition of NaCl-enhanced carcinogenesis.

Animals↗
PubMed1996

Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax.

We examined the genetic expression of 2 CXC chemokines (IL-8, IP-10), 5 CC chemokines (MCP-1, MIP-lalpha, MIP-1beta, RANTES, 1309) and 1 C chemokine (SCM-1/lymphotactin/ATAC) in various human T-cell lines. By Northern blot analysis, HTLV-1-positive T-cell lines were found to express a number of chemokine genes at variable levels and in different combinations. However, none of the chemokine genes was expressed in HTLV-1-negative T-cell lines. We further confirmed secretion of 3 chemokines (IL-8, MIP-1alpha and RANTES) by some HTLV-1-positive T-cell lines. To examine the role of the HTLV-1-encoded transactivator Tax in the induction of these chemokine genes, we used JPX-9 and JPX-M, which were stably transformed with tax and non-functional tax, respectively, under the control of a metallothionein promoter. Induction of tax in JPX-9 with Cd2+ was accompanied by rapid induction of IL-8, IP-10, MIP-1alpha, MIP-1beta, 1309 and SCM-1 as determined by reverse transcription PCR. No such induction was seen in JPX-M. We thus suggest that Tax is, at least in part, responsible for constitutive expression of certain chemokine genes in HTLV-1-infected T cells. Aberrant production of various chemokines by HTLV-1- infected T cells may impact on the pathophysiology of HTLV-1-associated diseases.

Cells, Cultured↗
PubMed1996

Thymus-related liposarcoma: report of a case and review of the literature.

We report herein the case of a 77-year-old woman who was admitted to our hospital for further evaluation of an abnormal shadow in the right upper mediastinum that had been revealed by a routine chest X-ray. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed the presence of a thymic tumor, but did not show any evidence of invasion into the central vessels or adjacent structures. Thus, an extended thymectomy with resection of the tumor was performed. Microscopically, normal thymic tissue was found among the tumor cells, and a pathological diagnosis of well-differentiated liposarcoma was established. From the operative and microscopic findings, it is apparent that the tumor was related to the thymus. Postoperative irradiation of 60 Gy was delivered to the operative site and the patient has remained free of disease for 29 months since the operation.

Aged↗
PubMed1996

The induction of cytotoxicity by a bispecific antibody against CEA positive cell line, in vitro.

A mouse anti-human carcinoembryonic antigen (CEA) x anti-human CD3 bispecific antibody, AB5C10*UCHT1, was developed. This antibody-heteroconjugate was chemically prepared by cross-linking the AB5C10 monoclonal antibody reactive with human CEA with the monoclonal antibody, UCHT1, which binds to CD3 on human T-lymphocytes. The AB5C10*UCHT1 recognized both CEA expressed on the KATOIII cell line and CD3 expressed on T-lymphocytes, as determined using flowcytometry. Next, AB5C10*UCHT1-mediated cytolysis was analyzed by 51Cr-release assay. When 51Cr-labeled target KATOIII cells were incubated for 6 h with effector cells that had been pretreated with AB5C10*UCHT1 for 60 min at 4 degrees C, the percentage specific lysis was significantly increased compared to that of untreated effector cells. Using peripheral blood mononuclear cells (PBMC) and lymphokine-activated killer (LAK) cells pretreated with AB5C10*UCHT1 for effector cells, the percentage specific lysis was determined to be 16.3% and 57.4% at effector: target (E:T) ratios of 100:1 and 12.5:1, respectively. On the other hand, the percentage specific lysis of untreated PBMC and LAK cells determined to be 3.0% and 35.8% at E:T ratios of 100:1 and 12.5:1, respectively. The minimum effective dose of AB5C10*UCHT1 required for antibody-mediated cytotoxicity was 0.1 mu g/ml. The results of this study suggest that AB5C10*UCHT1 could be useful for augmenting the cytotoxicity of CD3-positive T-cells against CEA-positive target cells in vitro.

Animals↗
PubMed1996

The unusual presentation of mucinous carcinoma in the colon making preoperative diagnosis difficult: report of a case.

A 51-year-old man was admitted to our hospital for investigation of fever, lower abdominal pain, and pain on micturition. Barium enema and endoscopic findings revealed an extracanal large cavity of the rectosigmoid colon, which suggested an abscess caused by penetration. Histological examination of the endoscopic biopsy specimen demonstrated no malignancy. A preoperative diagnosis of malignant lymphoma was strongly suspected from the imaging findings; however, intraoperative inspection revealed a large tumor invading the urinary bladder. An intraoperative incisional biopsy was performed and histological examination demonstrated mucinous carcinoma. The patient subsequently underwent pelvic exenteration about 1 week later followed by adjuvant chemotherapy and radiotherapy.

Adenocarcinoma, Mucinous↗
PubMed1996

Heat shock induces HIV-1 replication in chronically infected promyelocyte cell line OM10.1.

A long period of clinical latency before development of symptoms is characteristic of human immunodeficiency virus type 1 (HIV-1) infection. OM10.1, a promyelocyte cell line latently infected with HIV-1, has been developed as a model for studying the mechanism of viral latency and the activation of virus expression. We found that this latently infected cell line with heat shock at 42 degrees C for 2 h resulted in a high level of HIV-1 production without addition of any cytokines. The mechanism of activation was analyzed by using anti-TNF-alpha antibody and various inhibitors. Although the TNF-alpha level in culture supernatants was below the sensitivity of an ELISA assay system, addition of anti-TNF-alpha antibody in culture medium could partially suppress the heat shock induced HIV-1 production. Staurosporine (PKC inhibitor), pentoxifylline (NF-kappa B inhibitor), and Ro5-3335 (HIV-1 Tat inhibitor) also inhibited significantly the heat shock induced virus activation. In particular, staurosporine achieved approximately 90% inhibition of the HIV-1 antigen expression in heat shock-treated OM10.1 at a non-toxic concentration. Although the mechanism of HIV-1 activation with heat shock has not been fully elucidated yet, it is presumed PKC plays an important role in HIV-1 activation. Thus, the present observations will provide a further insight into the pathogenesis of HIV-1 infections.

Alkaloids↗
PubMed1996

2-Glycineamide-5-chlorophenyl 2-pyrryl ketone, a non-benzodiazepin Tat antagonist, is effective against acute and chronic HIV-1 infections in vitro.

In the search for effective Tat-dependent transcription inhibitors using a screening assay system that has recently been developed, 2-glycineamide-5-chlorophenyl 2-pyrryl ketone (GCPK) has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. This compound was inhibitory to HIV-1 replication in both acutely and chronically infected cells. The 50% effective concentration (EC50) of GCPK in acutely infected MOLT-4 and CEM cells was 0.62 and 0.13 microgram/ml, respectively. These values were similar to those of the known Tat-dependent transcription inhibitors Ro5-3335 and Ro24-7429. Like these inhibitors, GCPK could inhibit HIV-1 replication in MOLT-4/IIIB (MOLT-4 cells chronically infected with HIV-1) and tumor necrosis factor-alpha-(TNF-alpha)-induced viral activation in OM10.1 cells (a HL-60 clone latently infected with HIV-1). GCPK is distinct from Ro5-3335 and Ro24-7429 in that this novel Tat-dependent transcription inhibitor has no benzodiazepin ring.

Anti-HIV Agents↗
PubMed1996

Antiviral activities of nucleotide heterodimers against human immunodeficiency virus type 1 in vitro.

Nucleotide heterodimers were synthesized and examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1), including HIV-1 reverse transcriptase (RT) inhibitor-resistant mutants. 3'-Azido-3'-deoxythymidilyl-(5')-phospho-(5')-6-[(3', 5'-dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]uracil (AZT-P-E-HEPU-dM) and 3'-azido-3'-deoxythymidilyl-(5')-phospho-(5')-2', 3'-dideoxyinosine (AZT-P-ddI) proved to be highly potent and selective inhibitors of HIV-1 (IIIB strain) in MT-4 cells. The mechanism of inhibition by these heterodimers may be attributed to their degradation and the formation of each constituent. AZT-P-E-HEPU-dM was also markedly inhibitory to an AZT-resistant mutant (HIV-1-IIIB/AZT) and an E-HEPU-dM-resistant mutant (HIV-1-IIIB-R). However, AZT-P-ddI was found to have a less inhibitory effect on HIV-1-IIIB/AZT than on HIV-1-IIIB. The heterodimers of (5',5') AZT and ribavirin (AZT-P-Ribavirin) and (5',5') ddI and ribavirin (ddI-P-Ribavirin) were also synthesized: AZT-P-Ribavirin inhibited HIV-1 replication, but ddI-P-Ribarvirin did not.

Anti-HIV Agents↗
PubMed1996

Complete inhibition of viral breakthrough by combination of MKC-442 with AZT during a long-term culture of HIV-1 infected cells.

We have investigated viral breakthrough during a long-term culture of HIV-1-infected cells with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) 6-benzyl-1-ethoxymethyl-5-isopropyluracil (MKC-442), nevirapine and loviride (alpha-APA). When the compounds were examined for their inhibitory effects on HIV-1 (HE strain) replication in MT-4 cells on day 4 after virus infection, the 50% effective concentrations (EC50) of MKC-442, nevirapine and loviride were 9.4, 98 and 21 nM, respectively. After a 48-day culture period, MKC-442, nevirapine and loviride completely inhibited viral breakthrough at concentrations of 1, 5 and 1 microM, respectively. These concentrations were 50-100-fold higher than their EC50 values. When the cells were treated with either MKC-442 (0.04 and 0.2 microM), nevirapine (0.2 and 1 microM) or loviride (0.04 and 0.2 microM) in combination with AZT (0.005 microM), only the combination of 0.2 microM MKC-442 with 0.005 microM AZT could completely inhibit the breakthrough of HIV-1 after a 68-day culture period. Polymerase chain reaction (PCR) analysis revealed that no proviral DNA was detected in the cells treated with this combination. Except for two combinations (0.04 microM MKC-442 + 0.005 microM AZT and 0.04 microM loviride + 0.005 microM AZT), all of the viruses isolated during combination treatments had various amino acid mutations in their reverse transcriptase (RT). These results indicate that the combination treatment with a relatively high dose of MKC-442 and a low dose of AZT may have potential to suppress the emergence of drug resistance during a long-term treatment in vivo and should be further pursued in HIV-1-infected patients.

Acetamides↗
PubMed1996

Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity.

The structure-activity relationship of the non-nucleoside HIV-1-specific reverse transcriptase (RT) inhibitors 4-phenyl-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives was investigated with respect to their anti-HIV-1 activity, RT inhibition, and lipophilicity. 4-Phenyl-1,2,5-thiadiazol-3-yl N,N-dimethylcarbamate inhibited HIV-1-induced cytopathic effect (CPE) by 50% at a concentration of 28.8 microM in MT-4 cells. The activity increased more than 100-fold when the hydrogens at the 2-position and the 6-position in phenyl moiety were substituted by chlorines. However, the derivative with a chlorine at the 4-position of phenyl moiety did not show any inhibition of HIV-1 replication at its non-toxic concentrations. All of the 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-yl N-methyl-N-alkylcarbamates proved inhibitory to HIV-1 replication in the nanomolar concentration range. The TDA derivatives that showed anti-HIV-1 activity also inhibited RT activity in an enzymatic assay. However, the TDA derivatives did not show any specific inhibition of a non-nucleoside RT inhibitor (NNRTI)-resistant mutant and its RT activity. When the TDA derivatives were examined for their inhibitory effect on HIV-1 replication in the presence of 50% human serum, the activity significantly decreased depending on-their lipophilicity.

Anti-HIV Agents↗
PubMed1996

Early detection of specific IgE antibody against house dust mite in children at risk of allergic disease.

OBJECTIVES: House dust mite (HDM) is a representative inhalant allergen that triggers allergic disease in childhood. The aim of this study is early detection of HDM-specific IgE antibody and prediction of the risk of a positive reaction to this antibody by in vitro parameters in infants with allergic manifestations. STUDY DESIGN: Levels of HDM IgE in a range below the standard cutoff point of 0.35 U/ml, serum concentrations of IgE, and specific IgE antibodies against egg white, cow milk, and soybeans were determined in 108 infants with allergic manifestations at 6 months of age, and these infants were monitored for conversion of HDM IgE to positive levels greater than 0.35 U/ml up to 5 years of age. The presence of active allergic disease at 5 years of age in relation to HDM-specific IgE was also examined. RESULTS: We were able to determine reliably the HDM IgE values between 0.23 and 0.35 U/ml, using a fluorescent enzyme immunoassay that measured the intensity of fluorescence. The HDM IgE levels increased, resulting in positive values, in 54 of 108 subjects during the first 5 years of life. In multiple regression analysis, an HDM IgE value between 0.23 and 0.35 U/ml, a high serum IgE level, and a positive reaction to specific IgE antibody against egg white in infants at 6 months of age proved to be significant predictors of the future positive reaction to HDM IgE (p = 0.0006, 0.0043, and 0.0001). In particular, the sensitivity and specificity of specific IgE antibody against egg white for the conversion of HDM IgE to positive values were the best among these indicators. Moreover, active allergic diseases were observed significantly more often in children with positive HDM IgE values than in children with negative HDM IgE values at 5 years of age (p < 0.001 for each). CONCLUSIONS: A determination of these predictors in infants at 6 months of age can be used for early detection of HDM IgE and would be valuable in a screening test for later allergic disease among infants with allergic manifestations.

Allergens↗
PubMed1996

Ultrasonographic detection of lymph-node metastases in superficial carcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: The presence or absence of lymph-node metastasis is the single most important factor in determining the strategy for treating superficial carcinoma of the esophagus. In this study, ultrasound (US) and endoscopic ultrasonography (EUS) were used in the diagnosis of lymph-node metastases, and the accuracy and limitations of these methods were assessed. PATIENTS AND METHODS: Prospectively, 37 patients with superficial esophageal cancer were studied by US and EUS before surgery, and the results were compared with the histological findings. Twelve of the patients had histologically confirmed lymph-node metastases. Ultrasonographic images of the lymph nodes were classified into three types, based on their boundaries and internal echoes. RESULTS: The sensitivity, specificity, and accuracy of predicting mediastinal lymph-node metastasis by EUS diagnosis were 80.0%, 87.5%, and 86.5%, respectively. The sensitivity, specificity, and accuracy of US in the assessment of cervical and abdominal lymph-node metastasis were 71.4%, 86.7%, and 83.3%, respectively. In cases in which there was a solitary metastatic lymph node, the detection rate was higher than in cases with two or more positive nodes. Most metastatic lymph nodes correctly diagnosed by US and EUS were larger than 6 mm and had tumor involving more than one-third of their cross-sectional area. CONCLUSIONS: In patients with superficial esophageal carcinomas, US is accurate in staging cervical and abdominal lymph nodes. EUS is accurate in staging mediastinal lymph nodes.

Carcinoma, Squamous Cell↗
PubMed1996

Assessment of tumor invasion of the distal esophagus in carcinoma of the cardia using endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Esophageal invasion by carcinoma of the cardia may affect the surgical approach. Accurate assessment of esophageal invasion is difficult using endoscopy, computed tomography, or barium contrast radiography. The aim of the present study was to evaluate the use of endoscopic ultrasonography (EUS) in the prediction of esophageal invasion by carcinoma of the cardia. PATIENTS AND METHODS: EUS (using a linear-array scanner) was carried out prospectively in 47 patients with carcinoma of the cardia who underwent subsequent surgical resection. The findings were correlated with the histopathological assessment of tumor infiltration in the esophagus in the resected specimen. RESULTS: An absence of esophageal invasion was correctly predicted by EUS in 12 of 13 patients. Histopathologically confirmed invasion of the esophagus was correctly predicted in 32 of 34 patients. With a margin of error of 10 mm, the accuracy of EUS in predicting or excluding histologically confirmed invasion of the esophagus was 85.1% (40 of 47 patients). False-positive results with EUS occurred in patients with prominent edematous or fibrous changes in the distal esophagus; false-negative results with EUS were seen in patients with scattered infiltration of a small number of tumor cells into the mucosal or submucosal layer. CONCLUSIONS: EUS can provide the surgeon with additional information on the extent of esophageal infiltration in patients with carcinoma of the gastric cardia, and can therefore assist in the selection of the surgical approach.

Adult↗
PubMed1996

Inhibitory effect of 4-(2, 6-dichlorophenyl)-1, 2, 5-thiadiazol-3-yl-N-methyl, N-ethylcarbamate on replication of human immunodeficiency virus type 1 and the mechanism of action.

In the search for effective antiviral agents, we have found 4-(2, 6-dichlorophenyl)-1, 2, 5-thiadiazol-3-yl-N-methyl, N-ethylcarbamate (RD4-2025) to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. The 50% effective concentration of RD4-2025 for HIV-1-induced cytopathic effect in MT-4 cells was 37 nM, yet no antiviral activity was observed against HIV-2. In HIV-1 reverse transcriptase (RT) assays, RD4-2025 inhibited both RNA-dependent and DNA-dependent DNA polymerase activities of a recombinant HIV-1 RT with 50% inhibitory concentrations of 0.11 and 3.5 microM, respectively. However, the compound did not affect the activity of human DNA polymerase alpha. Kinetic studies revealed that the inhibition was noncompetitive with respect to dGTP as the substrate and poly(C)/(dG) 12-18 as the template/primer. These results were in accordance with those of nonnucleoside RT inhibitors (NNRTIs), such as R89439 (an alpha-anilinophenylacetamide derivative) and nevirapine, indicating that RD4-2025 also belongs to the family of NNRTIs.

Carbamates↗
PubMed1996

Effect of selective and non-selective muscarinic blockade on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of baclofen, a gamma-amino-n-butyric acid receptor B agonist, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and how its effects are influenced by selective (M1) and non-selective (M1 and M2) pharmacological blockade of muscarinic receptors were investigated in inbred Wistar rats. Rats were given s.c. injections of 8 mg/kg body wt baclofen with and without 0.5 mg/kg body wt atropine (non-selective M1 and M2 muscarinic receptor antagonist) or 1.0 mg/kg body wt pirenzepine (selective M1 muscarinic receptor antagonist) every other day after a 25 week carcinogen treatment. At week 52 baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with atropine significantly attenuated the inhibition by baclofen of gastric carcinogenesis, but combined use with pirenzepine had no significant effect on the inhibition by baclofen of gastric carcinogenesis. Baclofen also significantly decreased the labeling index of the antral mucosa. Baclofen plus atropine attenuated the decrease in the labeling index of the antral mucosa due to baclofen, but baclofen plus pirenzepine had no significant effect on the labeling index. These results suggest that the inhibition of gastric carcinogenesis by baclofen is mediated through muscarinic receptors and M2 receptors, but not M1 receptors, are involved in this response.

Adenocarcinoma↗
PubMed1996

Prophylactic action of allopurinol against chemotherapy-induced stomatitis--inhibition of superoxide dismutase and proteases.

The activities of superoxide dismutase (SOD) and several proteases were measured in kidney of mice treated with allopurinol in order to elucidate the mechanism of prophylactic action of allopurinol against chemotherapy-induced stomatitis. The following results were obtained. Following 3 day administration of allopurinol 20 mg/day per os (Group C), the concentrations of allopurinol and oxipurinol in the renal tissue were 203.9 +/- 52.1 and 1141.7 +/- 194.8 micrograms/g, respectively. The SOD activity was significantly lower in Group C than in the untreated control group (p < 0.01). The enzyme activities of papain and trypsin were suppressed in Group C. However, the other proteases tested were not affected by the administration of allopurinol, indicating only weak anti-protease action of allopurinol. These results suggest that allopurinol may be effective to prevent chemotherapy-associated stomatitis via both direct and indirect actions to oral mucosa, that include inhibitory actions on xanthine oxidase as well as protease.

Allopurinol↗