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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 451 records · Page 25Linked to original sources
PubMed1993

Sulfonic acid polymers are potent inhibitors of HIV-1 induced cytopathogenicity and the reverse transcriptases of both HIV-1 and HIV-2.

Four novel sulfonic acid polymers were evaluated for their in vitro HIV-1 and HIV-2 reverse transcriptase (RT) inhibitory activity and found to be equipotent against both RTs. The aromatic polymers demonstrated IC50 values that were approximately 10(3)-fold lower than those observed with the aliphatic polymers. Among the aromatic polymers, poly(4-styrenesulfonic acid) (PSS) (MW 8000; IC50 = 0.02 microgram/ml) was 3-fold more potent than poly(anetholesulfonic acid) (PAS) of approximately the same molecular weight range. The activity of PSS polymers increased in proportion to the size of the polymers and, relative to suramin, activity could be enhanced over 200-fold. These polymers also inhibited the cytopathic effect of HIV-1 at concentrations that were non-toxic to MT-4 cells. The potent RT inhibitory properties of these stable sulfonic acid polymers suggest that structure-activity studies are warranted to yield agents capable of inhibiting multiple stages of the viral process.

Animals↗
PubMed1993

Enhancement by isoproterenol of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of isoproterenol 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 s.c. injections of isoproterenol or vehicle every other day for 13 weeks. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 13. Prolonged administration of isoproterenol resulted in a significant increase in the number of GGT-positive, but not GST-P-positive, lesions. The incidence, number and size of hepatocellular carcinomas were also significantly greater in rats treated with isoproterenol than in controls. Administration of isoproterenol significantly increased the intracellular cAMP and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that isoproterenol enhances hepatocarcinogenesis and that this may be related to its enhancing effect, mediated by cAMP, on cell proliferation in neoplastic lesions and surrounding hepatocytes.

Animals↗
PubMed1993

Detection of hepatitis C virus genome in human serum by multi-targeted polymerase chain reaction.

A multi-targeted "hemi-nested" PCR (M-PCR) assay in which the primer pairs derived from the 5' non-coding (5'NC) and the nonstructural protein 3 (NS3) regions of HCV genome were concurrently used for amplification in order to compare the sensitivity and specificity of polymerase chain reaction (PCR) with different primer pairs in detecting hepatitis C virus (HCV) genome. Sera from patients with virus-associated liver diseases were examined for the presence of HCV RNA by the M-PCR method following reverse transcription to cDNA. The amplified products derived from both the 5'NC and the NS3 regions were detected in 28 (70%) of the 40 HCV RNA-positive samples. However, 12 samples (30%) were devoid of the signal of NS3-derived product. Sensitivity tests using serial dilutions of HCV RNA revealed that the 5'NC-derived band was still detectable in the 10(5)-fold diluted sample by the M-PCR method, yet the NS3-derived band could hardly be detected in the 10(4)-fold diluted sample. Thus, as previously demonstrated by a single-targeted "nested" PCR assay, the present study using the M-PCR assay has clearly shown that the 5'NC-derived primers are more sensitive and specific than the NS3-derived primers in detecting HCV RNA.

BK Virus↗
PubMed1993

Dose study of the immunosuppression of FK 506 in canine lung allo-transplantation.

The immunosuppressive effect of FK506 (FK) in comparison to cyclosporine A (CsA) on lung graft rejection was demonstrated using 24 mongrel dogs with left lung allotransplantation. The cytotoxic activity of peripheral blood mononuclear cells was evaluated using donor skin fibroblasts. In eight dogs not given immunosuppression, the grafted lungs lost aeration 5-10 days postoperatively, and histologic findings revealed grade II rejection and cytotoxic activity elevated to between 10.7 and 60.5%, being an average of 31.2% at an effector/target (E/T) ratio of 50. Of 12 dogs treated with FK, none demonstrated a cytotoxic activity of 10% or more at an E/T ratio of 50. Moreover, histologic examinations of the specimens obtained by open chest biopsy revealed no signs of rejection during the first 10 postoperative days of FK administration, except in one dog showing grade I rejection from the FK 0.05 mg/kg group. A dose study of the duration until the onset of graft rejection and the elevation of cytotoxic activity after the termination of FK administration revealed approximately 1-2 weeks in the FK 0.05 mg/kg group, 3-4 weeks in the 0.1 mg/kg group, and later in the 0.4 mg/kg and 2.0 mg/kg groups. However, severe body weight loss was seen in the 0.4 mg/kg and 2.0 mg/kg groups postoperatively, without recovery even after the termination of FK. In fact, two dogs died of pneumonia possibly derived from general emaciation. These results suggest the optimal concentration of FK in canine lung allo-transplantation to be 0.1 mg/kg intramuscularly.

Animals↗
PubMed1993

Selective inhibition of human cytomegalovirus replication by naphthalenedisulfonic acid derivatives.

Several naphthalenedisulfonic acid derivatives were found to be selective inhibitors of human cytomegalovirus (CMV) replication in MRC-5 cells. Among the test compounds, the bis-naphthalenedisulfonic acid derivative having an hexamethylene spacer emerged as the most potent inhibitor of CMV replication. Its 50% antivirally effective concentration (EC50) for AD-169 strain was 12 microM, whereas the compound did not affect the growth of mock-infected MRC-5 cells at concentrations up to 500 microM. The naphthalenedisulfonic acid derivatives were also inhibitory to CMV clinical isolates. Virus yield reduction assay revealed that the compounds significantly reduced virus growth in CMV-infected MRC-5 cells. The bis-naphthalenedisulfonic acid derivatives with an hexamethylene spacer suppressed the expression of CMV-induced immediate early, and early antigens at a concentration of 20 microM, whereas the anti-CMV nucleoside ganciclovir did not do so even at the concentration that was 10-fold higher than its EC50 for CMV-induced plaque formation. Furthermore, naphthalenedisulfonic acid derivatives had to be present at the time of virus infection to exert their anti-CMV activity. These results suggest that the compounds are targeted at an early event in the virus replicative cycle, presumably, virus adsorption.

Antigens, Viral↗
PubMed1993

Inhibition by amiloride of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of amiloride on the incidence and histological types of gastric cancers in Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index and proliferative fraction of gastric mucosa were investigated. After oral treatment with MNNG for 25 weeks, rats received s.c. injections of amiloride (0.25 mg kg-1 or 5.0 mg kg-1 body weight) in depot form every other day until the end of the experiment. Prolonged administration of 5.0 mg kg-1, but not 2.5 mg kg-1 of amiloride significantly decreased the incidence of gastric cancers in Week 52. However, it did not influence the histological features of the gastric cancers. It also significantly decreased the labelling index and proliferative fraction of the antral mucosa. These findings indicate that amiloride inhibits the development of gastric cancers, and that its effect may be related to its effect in decreasing cell proliferation of the antral mucosa.

Adenocarcinoma↗
PubMed1993

Inhibition by verapamil of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of verapamil 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 received i.p. injections of verapamil or vehicle every other day for 16 weeks from the start of the experiment. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 16. Prolonged administration of verapamil resulted in a significant decrease in the number of GGT-positive and GST-P-positive lesions. The incidence and volume as a percentage of parenchyma of hepatocellular carcinomas were also significantly less in rats treated with verapamil than in controls. Administration of verapamil significantly decreased the labelling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that verapamil inhibits hepatocarcinogenesis and that this may be related to its inhibitory effect on cell proliferation in neoplastic lesions and surrounding hepatocytes.

Animals↗
PubMed1993

Enhancement by thyroxine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The affects of L-thyroxine (T4) on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index of gastric mucosal epithelial cells were investigated in Wistar rats. After oral treatment with MNNG for 25 weeks, the rats received s.c. injections of T4 (0.2 microgram kg-1) in depot form every other day until the end of the experiment in Week 52. This long-term treatment with T4 significantly increased the incidence of gastric cancers in Week 52. However, it did not influence the histological type of the gastric cancers. It also caused significant increases in the labelling indices of the fundic and antral epithelial cells. These findings indicate that T4 enhances the development of gastric cancers, and that its effect may be related to its effect in increasing proliferation of gastric epithelial cells.

Administration, Oral↗
PubMed1993

Inhibition by somatostatin of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of somatostatin 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 s.c. injections of 200 micrograms/kg body wt of somatostatin every other day from the beginning of the experiment until the end of week 16. Pre-neoplastic and neoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of somatostatin for 16 weeks resulted in significant reduction in the percentage volume of GGT-positive and GST-P-positive lesions. The incidence, number and size of hepatocellular carcinomas were significantly less in rats treated with somatostatin than in untreated rats. Administration of somatostatin significantly decreased the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that somatostatin inhibits hepatocarcinogenesis and that this effect may be related to its effect in decreasing cell proliferation in pre-neoplastic lesions.

Animals↗
PubMed1993

Enhancement by the tricyclic antidepressant, desipramine, of experimental carcinogenesis in rat colon induced by azoxymethane.

The effects of the tricyclic antidepressant drug desipramine on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the serum norepinephrine (NE) concentration and the labeling index of colon mucosa were investigated in Wistar rats. Rats were treated s.c. with 7.4 mg AOM/kg body wt once a week for 10 weeks, and also s.c. with 10 mg desipramine hydrochloride (desipramine)/kg body weight until the end of the experiment. Treatment with desipramine significantly increased the incidence, but not the number, of colon tumors in week 35. However, it did not influence the location and the histological appearance of the colon tumors or the histological types of colon adenocarcinomas. Furthermore, it significantly increased the serum NE level and the labeling index of colon mucosa during and after AOM treatment. These findings indicate that desipramine enhanced the development of colon tumors and that its effect may be related to its effect in increasing proliferation of colon epithelial cells.

Animals↗
PubMed1993

Enhancing effects of calcium-deficient diet on gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of ad libitum feeding of calcium-deficient diet on the incidence, number and histological types of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in male Wistar rats. Rats were fed standard pellet diet containing 0.5% (normal-calcium diet) or 0.01% calcium (calcium-deficient diet) after oral treatment with MNNG for 25 weeks. Oral administration of the calcium-deficient diet resulted in a significant increase in the incidence, but not the number, of gastric cancers in experimental Week 52. However, it did not affect the histological types of cancer. The calcium-deficient diet also caused a significant increase in tissue norepinephrine concentration of the antral portion of the gastric wall and in the labeling index of the antral epithelial cells. These findings indicate that the calcium-deficient diet enhanced gastric carcinogenesis and suggest that its effect may be related to increase in norepinephrine in the gastric wall and consequent stimulation of proliferation of antral epithelial cells.

Adenocarcinoma↗
PubMed1993

A cancer-reactive human monoclonal antibody derived from a colonic cancer patient treated with local immunotherapy.

A human monoclonal antibody, YJ-37 (IgM) was generated through the fusion of human B lymphoblastoid cell line HO-323 with the regional lymph node lymphocytes from a colonic cancer patient who was treated with a local immunotherapy. This antibody was purified and conjugated with biotin, after which direct immunohistochemical staining was performed. The results revealed that YJ-37 selectively reacted with colonic cancer (7/19), gastric cancer (3/6), endometrial cancer (1/2) and colonic adenoma (7/13), but not with normal epithelia. Membrane immunofluorescence and FACS analysis also showed that YJ-37 bound to tumor cell surfaces. Furthermore, the chemical structure of the antigen defined by YJ-37 was analyzed by means of thin-layer chromatography immunostaining and ELISA. The results indicated that YJ-37 reacted with sialylated lacto-series carbohydrate chains, which have been reported to accumulate in cancer cells.

Adenoma↗
PubMed1993

Selective killing of murine leukemic cells by adenosine triphosphate (ATP): a study of the value of autologous bone marrow transplantation.

To assess the value of adenosine triphosphate (ATP) for ex vivo purging of leukemic cells in autologous bone marrow transplantation, its biological effects on the murine leukemic cell lines (WEHI3B and L1210) and normal murine bone marrow hemopoietic stem cells (CFU-C and CFU-S) were studied. After treatment with 4 mM of ATP for 6 h, the number of viable WEHI3B cells decreased to less than 0.1% of that of the control. Furthermore, 3H-thymidine incorporations were also completely inhibited in both WEHI3B cells and L1210 cells. These phenomena were related to the concentration and exposure period of ATP. Treatment of bone marrow mononuclear cells with ATP under the same condition reduced the number of CFU-C, day 9 CFU-S and day 12 CFU-S to only 58.5 +/- 8.7%, 92.6 +/- 8.2% and 83.5 +/- 28.5%, respectively, with no change in the number of marrow nucleated cells. Although the effect of ATP is not entirely specific to leukemic cells, these findings provide evidence that ATP is useful for purging residual tumor cells in autologous bone marrow transplantation.

Adenosine Triphosphate↗
PubMed1993

Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442.

In the search for 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives, we have found 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil (MKC-442) to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The IC50 value of MKC-442 for HIV-1 RT was 8 nM. MKC-442 did not inhibit HIV-1 RNase H, other RTs, or DNA polymerase alpha. Because its inhibitory pattern showed noncompetitive inhibition with regard to nucleotide substrates, its mode of action was considered to be allosteric inhibition. From the results of combination studies, MKC-442 was found to produce synergistic inhibition of HIV-1 RT with 3'-azido-2',3'-dideoxythymidine (AZT) 5'-triphosphate (AZT.TP). The dose of AZT.TP required for 50% inhibition was reduced to one tenth of control in the presence of a half dose of MKC-442. Although other allosteric inhibitors (Nevirapine, L-696,229, and R82,913) had the same specificity for enzyme inhibition, they did not show synergism with AZT.TP in the combination index and synergy plot analyses. Synergistic inhibition of HIV-1 replication by MKC-442 and AZT has also been observed in HIV-1-infected MT-4 cells. These results suggest that MKC-442 is a unique inhibitor of HIV-1 RT, and combination therapy with MKC-442 and AZT could be advantageous in the treatment of acquired immune deficiency syndrome.

Antiviral Agents↗
PubMed1993

[Analysis of 30 patients with hypercalcemia].

We have treated 30 patients with hypercalcemia from 1984 to 1991. Twenty four out of 30 patients were associated with primary hyperparathyroidism and the other six were associated with malignancy. Of 24 cases primary hyperparathyroidism, 15 were due to single parathyroid adenoma, five to MEN 1 and one to familial hyperparathyroidism. In the other three cases, it was difficult to identify the cause of the hyperparathyroidism. Following conclusions were obtained: 1. Hypercalcemia shows no specific and characteristic symptoms, so it is essential to keep hypercalcemia in mind in diagnosis of patients with vague or general complaints. Malignancy associated hypercalcemia shows high serum calcium level and PTH level. When considering malignancy, it is easy to diagnose that it might be the cause of hypercalcemia. 2. When serum PTH is over 2000pg/ml (high sensitivity PTH assay) in primary hyperparathyroidism, the probability of swelling of multiple parathyroid glands should be considered in evaluation of localization study and surgery. When serum PTH is high or swelling of multiple glands is found. It is essential to evaluate the possibility of MEN 1.

Adolescent↗