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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 163 records · Page 9Linked to original sources

The role of human T-lymphotropic virus type 1 (HTLV-1)-infected dendritic cells in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis.

The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4(+) T cells and CD8(+) T cells in a viral dose-dependent manner. However, the proliferation level of CD4(+) T cells was five- to sixfold higher than that of CD8(+) T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4(+) T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4(+) and CD8(+) T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.

Antigen-Presenting Cells↗

So-called carcinosarcoma of the esophagus: A clinicopathologic, immunohistochemical and DNA flow-cytometric analysis of 6 cases.

Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.

Aged↗

Cooccurrence of reduced expression of alpha-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer.

BACKGROUND AND OBJECTIVES: Even though the pathological background contributes to lymph node metastasis, the biological characteristics of tumors have also gained wide attention. In this study, the expression of the cadherin-catenin complex and p53 was studied in early gastric cancer. Their correlation with lymph node metastasis and the predictability of lymph node metastases, by combining these factors, were also discussed. METHODS: One hundred and one specimens obtained from surgery were studied by immunohistochemistry using monoclonal anti-E-cadherin, anti-alpha-catenin and anti-p53 antibodies. RESULTS: Expression of E-cadherin and alpha-catenin was reduced in 50.5 and 64.4%, respectively. p53 protein staining was positive in 29.7%. There was a significant correlation between E-cadherin and alpha-catenin expression, but no correlation was found between p53 expression and E-cadherin or alpha-catenin expression. A reduction in alpha-catenin expression and p53 overexpression correlated to lymph node metastases, respectively. Multivariate analysis showed that cooccurrence of reduced expression of alpha-catenin and overexpression of p53 was an independent factor indicating lymph node metastases. CONCLUSION: A study of both alpha-catenin and p53 expression may be helpful to predict lymph node metastases in early gastric cancer.

Adult↗

Inhibition of human immunodeficiency virus replication by RD6-Y664, a novel benzylhydroxylamine derivative.

We have examined novel benzylhydroxylamine derivatives for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in cell cultures. Among the series, O-(2-chloro-6-fluorobenzyl)hydroxylamine (RD6-Y664) was found to be the most potent inhibitor of HIV-1. The EC50 for HIV-1 strain IIIB was 1.6 micrograms/ml with a selectivity index greater than 38 in MT-4 cells. It also inhibited the replication of other HIV strains including a non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutant, a nucleoside RT inhibitor-resistant mutant and HIV-2, in acutely infected cells. However, the compound did not affect HIV-1 production in chronically infected cells. A time-of-addition experiment and detection of proviral DNA synthesis suggested that RD6-Y664 targeted an early step of the viral replication cycle, presumably a process prior to reverse transcription. In fact, an assay for HIV-1 RT revealed that the compound did not suppress enzyme activity. Furthermore, RD6-Y664 did not show any inhibition of gp120-CD4 interaction, or binding of anti-CXCR4 antibody to CXCR4.

Anti-HIV Agents↗

Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217.

The non-nucleoside reverse transcriptase (RT) inhibitor RD4-2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4-2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 microM) of the compound. The strains obtained, III(B/2217RE/0.05) and III(B/2217RE/0.25,) were two- and 15-fold resistant to RD4-2217, respectively, whereas III(B/2217RE/1) and III(B/2217RE/10) displayed 161- and >238-fold resistance, respectively. Both III(B/2217RE/1) and III(B/2217RE/10) had two amino acid substitutions, V1891 and T2401, in the RT. Furthermore, RD4-2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 microM, indicating that the V1891 plus T2401 mutation confers high-level resistance to RD4-2217. Interestingly, the replicability of III(B2217RE/1) and III(B/2217RE/10) appeared to be lower than that of wildtype III(B) in MT-4 cells, suggesting that the V1891 plus T2401 mutation may impair the enzymatic activity of HIV-1 RT.

Anti-HIV Agents↗

[Crohn's disease with the onset resembling systemic lupus erythematosus].

We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

Administration, Oral↗

EM2487, a novel anti-HIV-1 antibiotic, produced by Streptomyces sp. Mer-2487: taxonomy, fermentation, biological properties, isolation and structure elucidation.

For the purpose of discovering novel agents that inhibit HIV-1 replication at the transcriptional level, we have established cell lines reflecting the HIV-1 long terminal repeat-driven gene expression. Using these cell lines, we have screened approximately 10,000 microorganism products and found that the culture supernatant of Streptomyces sp. Mer-2487 suppresses the HIV-1 Tat-induced gene expression without affecting the basal or tumor necrosis factor-alpha-induced transcription. The purified active component has a unique structure, as shown in Fig. 1. This compound has an inhibitory effect on HIV-1 replication in chronically infected cells as well as acutely infected cells, suggesting that the inhibition occurs at a postintegration step of HIV-1 proviral DNA in the HIV-1 replication cycle.

Anti-Bacterial Agents↗

[Coronary artery bypass grafting in two patients with single coronary artery].

We experienced two patients with single coronary artery who underwent CABG using arterial grafts successfully. In two patients coronary angiography demonstrated a single coronary artery which was originated in left coronary sinus and was bifurcated to LAD and LCx, and then RCA branched off proximal LAD, passing in front of the right ventricular out flow tract (Sharbaugh Type L-IIa). To the first patient, a 52-year-old man who had angina on exertion due to long stenosis of RCA, CABG to RCA using RITA was carried out. To the second patient, a 57-year-old man who had inferior myocardial infarction due to 90% stenosis of proximal LAD, CABG to RCA using RITA and LAD using LITA was carried out. Single coronary artery without additional congenital cardiac anomalies may lead to myocardial ischemia, necessitating CABG as coronary reconstructions.

Coronary Angiography↗

[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].

To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.

Adolescent↗

[Hepatitis A].

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Biomarkers↗

Expression of p21WAF1/Cip1 in the p53-dependent pathway is related to prognosis in patients with advanced esophageal carcinoma.

The proteins p53 and p21 are important components that regulate G1-S transition through the cell cycle. We immunohistochemically investigated p53 and p21 expression in 111 patients with esophageal squamous cell carcinoma. We also evaluated whether the expression of either of these proteins is a prognostic factor according to the p53-dependent and -independent pathways. The positive rates of p53 and p21 expression were 42.8 and 43.2%, respectively. Clinicopathological findings according to p53 and p21 expression did not differ significantly. The 5-year-survival rates between p21 positive and negative expression did not differ significantly in the p53-positive group. In the p53-negative group, the 5-year-survival rate of patients with p21-positive expression was 22.9%, which was significantly better than that of patients with p21-negative expression (12.7%; P<0.05). Multivariate analysis revealed that p21 expression in the p53-dependent pathway was an independent prognostic factor. Accordingly, the prognostic values of p21 expression between the p53-dependent and -independent pathways differed. Examination of p21-positive expression in the p53-dependent pathway will help to estimate the favorable prognosis of patients with advanced esophageal carcinoma.

Adult↗

[A case of clinically diagnosed corticobasal degeneration with unilateral cortical reflex myoclonus showing so-called giant SEP].

We report a 66-year-old woman clinically diagnosed as having a corticobasal degeneration (CBD), who showed electrophysiologically cortical reflex myoclonus. She developed a clumsiness and action myoclonus on the right extremities, and aphasia. The extrapyramidal signs such as dystonia and rigidity were also noted on the right side. Sequential MR images showed a progressive brain atrophy in the left frontoparietal area, where a blood perfusion was reduced on single photon emission computed tomography (SPECT). The median nerve stimulation on the affected right side, but not left side, elicited an enhanced long-loop reflex. The onset latency of the long-loop reflex (43.8msec) was similar to that of the reported cases of CBD (Thompson et al, 1994); but, significantly shorter than that reported in the patients with typical cortical reflex myoclonus. The right median nerve stimulation also elicited so-called giant somatosensory evoked potentials (SEPs). On the basis of the scalp topography of the giant SEPs, we found the high amplitude central P22-N30 components to reflect a radial dipole. We also recorded the myoclonus-related cortical spike by jerk-locked back averaging. Both the giant SEP and myoclonus-related cortical spike were recorded only on the left scalp. We therefore suggest that these two cortical activities are similar in terms of wave form, scalp topography and time relationship to either the long-loop reflex or myoclonus and may be located in the precentral area. This is the first report of a patient with CBD presenting both the giant SEP and myoclonus-related cortical spike.

Aged↗

[A case of traumatic aneurysm of innominate artery with occlusion of right subclavian artery].

A 42-year-old woman with history of chest blunt trauma from an automobile accident 250 days earlier had suffered easy fatigability of the right upper extremity. She had difference of blood pressure between upper extremities, 94/60 mmHg in the right and 126/70 mmHg in the left. Chest CT showed dilation of the innominate artery which compressed the trachea. Aortography showed an aneurysm of the innominate artery and occlusion of the right subclavian artery at its origin. The aneurysm of the innominate artery was resected and replaced with a 6 mm Dacron graft with aid of the external shunt. The right subclavian artery was also reconstructed with same graft. The aneurysm of the innominate artery should be suspected as a rare complication in blunt trauma of the chest.

Adult↗

[Detection of early hilar lung cancers with fluorescence bronchoscopy].

The development of fluorescence bronchoscopy has made it possible to diagnose locally superficial hilar lung cancers such as carcinoma in situ, and in some cases atypical squamous metaplasia thought to be precancerous lesions. The selection of a treatment modality can be difficult for early hilar lung cancers due to problems associated with multiple lung carcinomas and the large number of heavy smokers afflicted. Many patients also have decreased pulmonary function. If carcinoma in situ and microinvasive carcinomas can be detected early, it may be possible to treat them radically with a less invasive method than surgery, such as endoscopic laser therapy. Centrally arising squamous cell carcinoma of the tracheobronchial tree, especially in heavy smokers, is thought to develop in multiple stages from squamous metaplasia, to atypical squamous metaplasia, followed by carcinoma in situ, and finally invasive cancer. However, it is hoped that preventive medicine for lung cancer will be established whereby patients with localized atypical squamous metaplasia detected by fluorescence bronchoscopy can be carefully monitored and motivated to stop smoking, and also administered chemopreventive agents.

Adult↗