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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 415 records · Page 23Linked to original sources

Protection by galanin against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of prolonged administration of the neuropeptide galanin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, the norepinephrine concentration in the gastric wall, and the labeling index of the gastric mucosa were investigated in Wistar rats. The rats received 2 or 4 micrograms/kg body weight of galanin s.c. every other day after 25 weeks oral treatment with the carcinogen. Prolonged administration of galanin at 4 micrograms/kg body weight, but not at 2 micrograms/kg body weight, significantly decreased the incidence of gastric cancers in experimental week 52. However, it did not influence the histological types of cancers. Galanin at 4 micrograms/kg body weight also significantly decreased the labeling index of the antral epithelial cells but not the norepinephrine concentration in the gastric wall. These findings indicate that galanin inhibits gastric carcinogenesis and suggest that its effect may be related to the suppression of proliferation of the antral epithelial cells.

Animals↗

Expression of c-myc mRNA as an aid in histologic differentiation of adenoma from well differentiated adenocarcinoma in the stomach.

BACKGROUND: Using prospective follow-up studies, the authors examined the value of the expression of c-myc mRNA in biopsy specimens obtained from elevated gastric lesions as an aid in the differentiating between adenomas and well differentiated elevated-type adenocarcinomas. METHODS: By in situ hybridization, the authors determined the expression of c-myc mRNA in biopsy specimens of elevated gastric lesions. The 31 patients who had borderline lesions with and without overexpression of c-myc were followed with repeated endoscopic examinations and gastric biopsies. RESULTS: Endoscopic follow-up examinations showed that gastric cancer was detected in 5 of 11 patients (46%) with elevated lesions that stained positively for c-myc mRNA during an observation period of 15 months (range, 2-32 months). The cancers were confirmed histologically in gastrectomy specimens. No cancers were found in patients with elevated lesions that stained negatively. The difference was statistically significant (P < 0.01). CONCLUSIONS: The overexpression of c-myc mRNA may present a new tool for distinguishing between adenomas and well differentiated adenocarcinomas of the elevated type.

Adenocarcinoma↗

Monoamine oxidase B inhibitor enhances experimental carcinogenesis in rat colon induced by azoxymethane.

The effects of prolonged administration of the monoamine oxidase (MAO)-A inhibitor N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)propylamine (clorgyline) and the MAO-B inhibitor N-methyl-N-2-propynyl-benzylamine (pargyline) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the norepinephrine (NE) concentration in the colon wall and the labeling index of colon mucosa were investigated in Wistar rats. Rats were treated s.c. with 7.4 mg/kg body weight of AOM once a week for 10 weeks, and also s.c. with 5 mg/kg body weight of clorgyline or 50 mg/kg body weight of pargyline in 0.9% NaCl until the end of the experiment. Treatment with pargyline significantly increased the incidence of colon tumors in week 35. However, it did not influence the histological appearance of the colon tumors or the histological types and depth of involvement of colon adenocarcinomas. Furthermore, it significantly increased the NE concentration in the colon wall and the labeling index of the colon mucosa during and after AOM-treatment. In contrast, clorgyline had no influence on the development or histological appearance of colon tumors. These findings indicate that the MAO-B inhibitor, but not the MAO-A inhibitor, enhanced colon carcinogenesis, and that its effect may be related to its effect in increasing the NE concentration in the colon wall and subsequently increasing the proliferation of colon epithelial cells.

Animals↗

Expression of desmoglein I in squamous cell carcinoma of the esophagus.

Desmoglein I (DGI) is major component of the desmosomal membrane core that plays an important role in epithelial cell adhesion. The aim of this study was to explore the correlation between the expression of DGI and the clinicopathological findings of esophageal cancer. DGI expression was immunohistochemically examined using an anti-DGI monoclonal antibody in 139 patients with squamous cell carcinoma of the esophagus. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. According to the intensity and pattern of DGI expression, the cancerous tissues were divided into three groups: DGI (++), DGI (+), and DGI (-). Of the 139 tumors, 35 (25%) were DGI (++), 65 (47%) were DGI (+), and 39 (28%) were DGI (-). A good inverse correlation between DGI expression and tumor invasion, lymph node metastasis, lymphatic invasion, and vessel invasion was observed. These results indicate that DGI expression may be a significant factor for invasion, metastasis, and prognosis of human esophageal cancer.

Adult↗

A case of allergic liver injury induced by tegafur.

A 51-year-old woman constitutionally susceptible to allergy presented with acute allergic liver injury. She was taking tegafur for treatment of carcinoma of the uterus. The acute liver injury appeared 3 weeks after the first drug administration. She had marked elevation of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT), moderate jaundice, and eosinophilia. The virus markers revealed hepatitis B surface antigen (HBsAg) (-) antibody to hepatitis B surface antigen (HBsAb) (+), and immunoglobulin M HA antibody (IgM HA Ab) (-). The laparoscopic and histologic findings were compatible with drug-induced liver injury. Further, the results of the lymphocyte stimulation test (LST) and challenge test by tegafur were positive. From the above findings, the liver injury was diagnosed to be an allergic reaction induced by tegafur. The hepatic function returned to normal about 20 days after tegafur administration was suspended. Allergic liver injury induced by tegafur is very rare. We report the case with a short review of the literature.

Drug Hypersensitivity↗

Cytotoxic effect of extracellular ATP on L1210 leukemic cells and normal hemopoietic stem cells.

The cytotoxic effect of extracellular adenosine triphosphate (ATP) was examined on normal murine hemopoietic stem cells and a representative leukemic cell line (L1210). After L1210 cells were incubated with 4 mM ATP for 3 h, 3H-thymidine incorporation was almost completely inhibited. The number of viable L1210 cells was also significantly decreased and L1210 colony formation was suppressed to approximately 30% of the control level after treatment. The CFU-GM survival rate was reduced to 70%, however, CFU-S and marrow nucleated cell numbers were not changed after the same treatment with ATP. All mice that were injected with the untreated mixture of normal marrow cells (3.3 x 10(4)) and L1210 cells (3.3 x 10(3)) died of leukemia within 18 days. On the contrary, 85% of the recipients given ATP-treated grafts survived more than 70 days. These findings indicate that ATP extra vivo treatment is useful for purging the residual leukemic cells in autologous bone marrow transplantation.

Adenosine Diphosphate↗

Inhibition by shi-quan-da-bu-tang (TJ-48) of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of Shi-Quan-Da-Bu-Tang (TJ-48) on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and also from the start of the experiment, regular chow pellets containing 2.0 or 4.0% TJ-48 until the end of the experiment. Preneoplastic and neoplastic lesions staining for the placental type of glutathione-S-transferase (GST-P) or gamma-glutamyl transpeptidase (GGT) were examined histochemically. In week 15, quantitative histological analysis showed that prolonged administration of either 2.0 or 4.0% TJ-48 in the diet significantly reduced the size, volume and/or number of GST-P-positive and GGT-positive hepatic lesions. This treatment also caused a significant increase in the proportion of interleukin-2 receptor-positive lymphocytes among the lymphocytes infiltrating the tumours as well as a significant decrease in the labelling index of preneoplastic lesions. These findings indicate that TJ-48 inhibits the growth of hepatic enzyme-altered lesions, and suggests that its effect may be in part due to activation of the immune system.

Animals↗

Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization.

Under nutrient-deficient conditions, the yeast S. cerevisiae sequesters its own cytoplasmic components into vacuoles in the form of "autophagic bodies" (Takeshige, K., M. Baba, S. Tsuboi, T. Noda, and Y. Ohsumi. 1992. J. Cell Biol. 119:301-311). Immunoelectron microscopy showed that two cytosolic marker enzymes, alcohol dehydrogenase and phosphoglycerate kinase, are present in the autophagic bodies at the same densities as in the cytosol, but are not present in vacuolar sap, suggesting that cytosolic enzymes are also taken up into the autophagic bodies. To understand this process, we performed morphological analyses by transmission and immunological electron microscopies using a freeze-substitution fixation method. Spherical structures completely enclosed in a double membrane were found near the vacuoles of protease-deficient mutant cells when the cells were shifted to nutrient-starvation media. Their size, membrane thickness, and contents of double membrane-structures corresponded well with those of autophagic bodies. Sometimes these double membrane structures were found to be in contact with the vacuolar membrane. Furthermore their outer membrane was occasionally seen to be continuous with the vacuolar membrane. Histochemical staining of carbohydrate strongly suggested that the structures with double membranes fused with the vacuoles. These results indicated that these structures are precursors of autophagic bodies, "autophagosomes" in yeast. All the data obtained suggested that the autophagic process in yeast is essentially similar to that of the lysosomal system in mammalian cells.

Alcohol Dehydrogenase↗

Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus.

OBJECTIVE: This study evaluated the impact of aggressive surgery on survival in patients with carcinoma of the thoracic esophagus. SUMMARY BACKGROUND DATA: Prognostic value of lymph-node status for patients with esophageal carcinoma was emphasized, although it is currently under debate whether extensive lymph node dissection improves survival. METHODS: Two hundred ninety-five patients with thoracic esophageal carcinoma were admitted to Kagoshima University Hospital from December 1982 to December 1990. Esophagectomy was performed on 244 (82.7%) of these patients; 106 of whom underwent three-field lymphadenectomy (bilateral cervical, mediastinal, and abdominal regions) were analyzed regarding lymph-node status, tumor recurrence, and the effect of prognostic factors on survival using Cox's proportional hazards model. RESULTS: Hospital mortality and morbidity were 10.4% (11/106) and 65.1%, respectively. Seventy-eight patients (73.6%) had nodal involvement, including 49 patients with abdominal lymph-node metastases and 46 patients with recurrent nerve-node metastases. Five-year survival rates were 54.5% for 16 patients with a solitary nodal metastasis, 30.3% for stage III, 17.4% for stage IV, and 7.2% for 28 patients with six or more metastatic nodes. The most frequent sites of recurrence were the upper mediastinal region and the lung--its incidence increased significantly as the number of positive nodes increased. The most unfavorable prognostic factors included regional or recurrent nerve-node metastasis and patient age of more than 71 years. CONCLUSIONS: Three-field lymphadenectomy, including especially the removal of bilateral recurrent nerve nodes in the cervical region, is essential for improving the survival of patients with carcinoma of the upper two thirds of the thoracic esophagus.

Adult↗

Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of HIV-1 replication in vitro.

OBJECTIVE: To determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1 in vitro. DESIGN: A sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides. METHODS: Activity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was measured by a p24 antigen capture enzyme-linked immunosorbent assay. RESULTS: DS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152. CONCLUSION: DS-4152 has the potential, from these in vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.

Antiviral Agents↗

Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived from a non-hepatitic, non-cirrhotic hepatitis B virus carrier.

We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1 (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These cell lines differed considerably from each other in morphology, proliferation pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion, modal chromosome number and transplantability to nude mice. Histologic examinations also revealed differences between them. Amplification of N-myc, L-myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV-DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1, but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying the question of whether hepatocarcinogenesis is directly caused by HBV infection.

Adult↗

Fecal IgE levels in infants at 1 month of age as indicator of atopic disease.

Fecal IgE levels were investigated in 165 asymptomatic infants at 1 month of age under two nutritional regimens, breast-feeding and formula feeding, and the possibility of predicting by fecal IgE levels the onset of atopic disease was studied in these infants. IgE levels were measured by time-resolved fluoroimmunometric assay. IgE antibodies are detectable in fecal extracts, and we have already reported that IgE levels are increased in food-allergy patients after administration of food allergens, and this increase in fecal IgE levels may be a specific consequence of the local immune response to food-allergen stimulation in the gut mucosa. The presence of atopic disease and the feeding method during the nursing period were surveyed by questionnaire in 89 of these 165 infants when they were 18 months old. In an analysis of the present results, IgE values above 0.015 U/ml, the lower limit of measurement, were considered to be high. Forty-eight (29%) of the 165 subjects showed a high fecal IgE level. Thirty-seven (35%) of 105 formula-fed infants had high fecal IgE levels, whereas only 11 (18%) of 60 breast-fed infants had high levels (P < 0.05). With respect to atopic family history, 30 (39%) of the 77 infants with atopic family history had high fecal IgE levels, as compared with 18 (20%) of the 88 infants without atopic family history (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Effect of interferon-gamma on HLA class 2 expression by antigen-presenting cells inducing Dermatophagoides farinae-specific interleukin-2 responsiveness of lymphocytes in asthmatic children.

As previously reported, antigen-specific IL-2 responsiveness of lymphocytes from patients with bronchial asthma was induced by stimulation with Dermatophagoides farinae, antigen-specifically, in the context of HLA-DQ antigen. We analysed the antigen-presenting processes in the induction of IL-2 responsiveness. Non-adherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, which decreased after prolonged culture of adherent cells for 72 h before recombination with fresh autologous non-adherent cells. HLA-DQ expression on cultured adherent cells also decreased in parallel with the reduction of their ability to induce IL-2 responsiveness. However, the treatment of adherent cells with IFN-gamma restored the expression of these HLA-Class 2 antigens mainly on CD14+ antigen-presenting cells (monocytes), but not on CD20+ cells (B cells), which overcame the decrease of Df-induced IL-2 responsiveness during prolonged culture. These data suggest that IFN-gamma potentiates the up-regulation of Df-specific IL-2 responsiveness, which is likely to depend on the restoration of HLA-DQ expression on monocytes.

Animals↗

Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro.

MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU) has recently been identified as a highly potent and specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Since the compound has favorable pharmacokinetic and toxicity profiles in vivo, we have evaluated MKC-442 for its inhibitory effect on the replication of HIV-1 in various cell cultures, including human peripheral blood lymphocytes and monocyte-macrophages. The 50 and 90% effective concentrations for HIV-1 (HTLV-IIIB strain) replication in MT-4 cells were 15 and 98 nM, respectively. MKC-442 was also inhibitory to HIV-1 replication in peripheral blood lymphocytes and monocyte-macrophages as determined by the production of p24 antigens in the culture supernatant. Fluorescence-activated cell sorter analysis revealed that MKC-442 was equally active against zidovudine-resistant mutants and zidovudine-susceptible strains. Furthermore, combinations of MKC-442 with either 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, or 2',3'-dideoxyinosine synergistically inhibited the replication of HIV-1. Thus, MKC-442 has been considered as a candidate for clinical efficacy studies.

Antiviral Agents↗

Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay.

We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.

Antibodies, Viral↗

Gm haplotypes in chronic inflammatory demyelinating polyradiculoneuropathy in Japanese patients.

We studied the serum Gm allotype of 58 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 236 nonrelated normal controls in Japan. The incidences of the Gm phenotype and haplotype in the patients were not significantly different from those in the normal controls. When CIDP was classified into two subgroups in terms of clinical course, the chronic relapsing (CR) and chronic nonrelapsing type (CNR), the distribution of all Gm haplotypes was significantly different between CR and CNR (total chi 2 = 8.319; corrected p < 0.05). Our findings suggest that the clinical course of CIDP may be associated with the Gm haplotype.

Chronic Disease↗

Correlation of somatosensory central conduction time with height.

To study the correlation between somatosensory central conduction time (CCT) and the subject's height, we recorded somatosensory evoked potentials (SEPs) from the neck and scalp elicited by median nerve stimulation in 72 normal young adults. We determined the CCT in each subject from peak-to-peak and onset-to-onset measurements. The mean value for the onset CCT was 6.2 +/- 0.4 msec and for the peak CCT, 5.7 +/- 0.5 msec. The peak CCT was significantly shorter but showed a wide range. There was a significant correlation between the onset CCT, but not the peak CCT, and height. Our findings confirm that the length of the central somatosensory pathway is proportional to the subject's height and indicate that the "conventional" peak CCT measurement of median nerve SEPs is inadequate.

Adolescent↗