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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 91 records · Page 5Linked to original sources
PubMed2001

Can sentinel node navigation surgery reduce the extent of lymph node dissection in gastric cancer?

Our group has conducted several studies of sentinel node navigation surgery (SNNS) for the management of early gastric cancer. To determine the distribution of nodal metastases and micrometastases, we used immunohistochemical staining with anticytokeratin antibody to examine 2605 lymph nodes obtained from 108 consecutive patients with submucosal gastric cancer. When nodes were negative by routine hematoxylin and eosin (H&E) examination, micrometastases were confined to one regional lymphatic pathway near the primary tumor; however, when nodes were H&E-positive, micrometastases were distributed more widely. The wide and complicated lymphatic stream from a gastric tumor contributed to the relatively high (23%) incidence of micrometastases and the frequent occurrence of skip metastasis. In another study, we used a combination of blue dye and radiopharmaceutical to perform SNNS in 18 patients with early gastric cancer. The rate of sentinel node detection was 94%, and the average number of sentinel nodes per patient was three. Technical issues included size of particles, method of injection, accuracy of frozen section examination, and standard criteria for defining a sentinel node. SNNS for gastric cancer is a promising technique; further study of various anatomic and pathologic factors will indicate whether it can be used to determine the extent of lymphadenectomy necessary in patients with early gastric cancer.

Coloring Agents↗
PubMed2001

[HIV seroprevalence in patients with tuberculosis].

The number of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) in our hospital is increasing year after year. Although most patients were HIV tested because of miliary tuberculosis or extra-pulmonary tuberculosis, some patients were found HIV seropositive by chance. In order to determine the incidence of HIV seropositivity among TB patients, HIV testing was carried out in TB patients for two years from January 1998 with the consent of patients. TB patients who received anti-HIV antibody examination were 164 in 1998, and 149 in 1999 and among them HIV seropositive TB patients were 4 in 1998 and 6 in 1999. The incidence of HIV seropositivity was 3.2% in all TB patients, 28.6% in miliary TB patients, and 1.0% in typical TB patients. The number of patients co-infected with HIV and TB in Tokyo was estimated by using these HIV seropositivity, it was 23 cases/year among miliary TB patients and 16 cases/year among typical TB patients. As there were many HIV-infected persons and many TB patients in Tokyo, it was thought that HIV testing in TB patients was important for the early detection of HIV infection and the early initiation of HIV treatment.

Adolescent↗
PubMed2001

[A case of multiple pulmonary fibroleiomyomatous hamartoma].

A 50-year-old woman had been followed up at another hospital since 1996 because of multiple nodular shadows in both lung fields on chest radiography and CT. She was admitted to our hospital on 27 July 1999 to undergo further examination for the chest shadows, which had become enlarged since 1998. One of them was surgically removed by using video-assisted thoracoscopy. Its pathological features showed a mass composed of spindle-shaped smooth muscle cells, located adjacent to the bronchiolar wall and connected with the bronchiolar smooth muscle. Moreover, the mass had cystic spaces covered only with monolayered bronchiolar epithelium. Therefore, the mass was considered to be a hamartomatous proliferation of bronchiolar smooth muscle rather than a metastatic tumor of uterine leiomyoma. This case was thought to be important, since there are few reports concerning the pathological features of multiple pulmonary fibroleiomyomatous hamartomas.

Diagnosis, Differential↗
PubMed2001

[New trends in neuropathy practice: clinical approach to CIDP].

Our recent study showed that the overall prevalence of CIDP was estimated as 2.2 per 100,000 population in Aomori Prefecture, in Northan Honshu of Japan. In our series of more than 80 cases with CIDP, a chronic acquired inflammatory demyelinating polyneuropathy, nearly 30% showed clear laterality of weakness, and electrophysiologic laterality or multifocality was apparent in almost all cases. Nearly 90% of patients were able to walk without walking aids or other assistance. Sixty% showed distal dominant muscular weakness. In 12 patients with age of onset under 15, pes cavus deformity was seen in 5. Two thirds complained numbness in the extremities during progressive phase. Four cases initially showed severe sensory ataxia associated with motor conduction block. It should be, thus, reminded that clinical spectrum of CIDP is enormously wide: chronic acquired demyelinating multiple mononeuropathy showing asymmetric involvement (Lewis-Summer syndrome) should be put on one side of the clinical presentation of CIDP. Multifocal motor neuropathy (MMN) is, on the other hand, an unique syndrome mimicking amyotrophic lateral sclerosis (ALS). There may be, however, true association syndrome of CIDP and ALS presenting both peripheral nerve demyelination and pyramidal sign with progressive bulbar involvement. Recently, several atypical varieties of CIDP showing only one-limb involvement, upper limb weakness rather than lower limb power loss, or proximal weakness, etc ... have been reported in the literature. To realize such clinical variations of chronic acquired demyelinating neuropathy is important for early diagnosis and commencement of treatment of CIDP. Clinical guideline for suspicion of CIDP could be useful for general physicians and neurologists unfamiliar to peripheral neuropathies.

Chronic Disease↗
PubMed2000

A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1.

RNA helicase A (RHA) has two double-stranded (ds) RNA-binding domains (dsRBD1 and dsRBD2). These domains are conserved with the cis-acting transactivation response element (TAR)-binding protein (TRBP) and dsRNA-activated protein kinase (PKR). TRBP and PKR are involved in the regulation of HIV-1 gene expression through their binding to TAR RNA. This study shows that RHA also plays an important role in TAR-mediated HIV-1 gene expression. Wild-type RHA preferably bound to TAR RNA in vitro and in vivo. Overexpression of wild type RHA strongly enhanced viral mRNA synthesis and virion production as well as HIV-1 long terminal repeat-directed reporter (luciferase) gene expression. Substitution of lysine for glutamate at residue 236 in dsRBD2 (RHA(K236E)) reduced its affinity for TAR RNA and impaired HIV-1 transcriptional activity. These results indicate that TAR RNA is a preferred target of RHA dsRBDs and that RHA enhances HIV-1 transcription in vivo in part through the TAR-binding of RHA.

Amino Acid Sequence↗
PubMed2000

Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma.

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Aged↗
PubMed2000

Geranylgeranylated SNAREs are dominant inhibitors of membrane fusion.

Exocytosis in yeast requires the assembly of the secretory vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (v-SNARE) Sncp and the plasma membrane t-SNAREs Ssop and Sec9p into a SNARE complex. High-level expression of mutant Snc1 or Sso2 proteins that have a COOH-terminal geranylgeranylation signal instead of a transmembrane domain inhibits exocytosis at a stage after vesicle docking. The mutant SNARE proteins are membrane associated, correctly targeted, assemble into SNARE complexes, and do not interfere with the incorporation of wild-type SNARE proteins into complexes. Mutant SNARE complexes recruit GFP-Sec1p to sites of exocytosis and can be disassembled by the Sec18p ATPase. Heterotrimeric SNARE complexes assembled from both wild-type and mutant SNAREs are present in heterogeneous higher-order complexes containing Sec1p that sediment at greater than 20S. Based on a structural analogy between geranylgeranylated SNAREs and the GPI-HA mutant influenza virus fusion protein, we propose that the mutant SNAREs are fusion proteins unable to catalyze fusion of the distal leaflets of the secretory vesicle and plasma membrane. In support of this model, the inverted cone-shaped lipid lysophosphatidylcholine rescues secretion from SNARE mutant cells.

Cell Membrane↗
PubMed2000

K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid.

The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation.

Administration, Oral↗
PubMed2000

Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05 and P<0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Adult↗
PubMed2000

The cooperative role of p27 with cyclin E in the prognosis of advanced gastric carcinoma.

BACKGROUND: Cyclin E and p27 play opposing roles in the cell cycle. This study investigated the protein expression of p27 with cyclin E in the progression and prognosis of gastric carcinoma. METHODS: Of 241 patients with advanced gastric carcinoma, 38 had muscular layer invasion, 113 had subserosal layer invasion, and 90 had serosal invasion. Anti-p27 and cyclin E antibodies were used for immunohistochemical staining. RESULTS: Positive expression of p27 and cyclin E was 32.4% and 38.2%, respectively. Both p27 and cyclin E expression were related to histology of tumors but not to depth of invasion, lymph node metastasis, or stage grouping. A positive correlation was observed between p27 and cyclin E expression (P < 0. 05). Tumors were divided into two groups according to the expression of cyclin E. Within the cyclin E positive tumors, the five-year survival rate was higher in patients with a p27 positive tumor than in those with a p27 negative tumor (P < 0.05). Patients with cyclin E positive tumors showing low expression of p27 had a poor prognosis. In cyclin E negative group tumors, no significant differences were observed irrespective of p27 expression. CONCLUSIONS: Reduced p27 expression is a negative prognostic factor for patients with cyclin E positive tumors.

Adult↗
PubMed2000

Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia.

Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextran and were down-regulated in the expression of CD1a and CD86 antigens (Ags). Monocytes from the patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest intrinsic abnormalities of monocytes and a defect of DC maturation in ATL patients. Therefore, we examined the influence of HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down-regulated in the expression of CD14 Ags, and immature DCs obtained from them expressed CD1a poorly and were impaired in the ability to take up FITC-dextran. Mature DCs differentiated from these cells could not stimulate autologous CD4(+) T cell or CD8(+) T cell proliferation, even after being secondarily pulsed with HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected monocytes cannot properly differentiate to DCs and that this might be one of the important mechanisms producing dysfunctional DCs in ATL patients.

Adult↗
PubMed2000

MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase.

Mitogen-activated protein kinase upstream kinase/dual leucine zipper-bearing kinase/leucine-zipper protein kinase (MUK/DLK/ZPK) is a MAPKKK class protein kinase that induces JNK/SAPK activation. We report here a protein named MBIP that binds to MUK/DLK/ZPK. MUK-binding inhibitory protein (MBIP) contains two tandemly orientated leucine-zipper-like motifs with a cluster of basic amino acids located between the two motifs. MBIP interacts with one of the two leucine-zipper-like motifs of MUK/DLK/ZPK and inhibits the activity of MUK/DLK/ZPK to induce JNK/SAPK activation. Notably, no similar effect was observed with another JNK/SAPK-inducing MAPKKK, COT/Tpl-2, showing the specificity of MBIP action. Furthermore, the overexpression of MBIP partially inhibits the activation of JNK by 0.3 m sorbitol in 293T cells. Taken together, these observations indicate that MBIP can function as a regulator of MUK/DLK/ZPK, a finding that may provide a clue to understanding the molecular mechanism of JNK/SAPK activation by hyperosmotic stress.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2000

Inhibition of the RNA-dependent transactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37.

Human immunodeficiency virus type 1 (HIV-1) is unique in that it encodes its own transcriptional activator Tat, which specifically binds to the viral mRNA sequence TAR (transactivation response) element and activates viral transcription at the step of elongation as well as initiation. We recently reported that fluoroquinoline derivatives inhibited HIV-1 replication most likely by blocking viral transcription. In this report, we investigated the mechanism of action of one such compound 7-(3, 4-dehydro-4-phenyl-1-piperidinyl)-1, 4-dihydro-6-fluoro-1-methyl-8-trifluoromethyl-4-oxoquinoline-3-carbox ylic acid (K-37). We demonstrated that K-37 inhibited not only Tat but also other RNA-dependent transactivators. No effect was observed with DNA-dependent transactivators such as p65 (NF-kappaB) and Gal4VP16. Moreover, K-37 did not inhibit carboxyl-terminal domain (CTD)-kinase activities of CDK-activating kinase (CAK) and positive transcription elongation factor b (P-TEFb), which are known to be involved in Tat-mediated transactivation at the step of transcriptional elongation. It is suggested that RNA-mediated transactivation may involve a common unknown factor to which K-37 directly interacts. Since K-37 did not appear to block DNA-mediated transactivation and thus did not show strong nonspecific cytotoxicity as reported previously, K-37 and its derivative compounds are considered to be feasible candidates for a novel AIDS therapy.

Animals↗
PubMed2000

Establishment of a CCR5-expressing T-lymphoblastoid cell line highly susceptible to R5 HIV type 1.

The beta-chemokine receptor CCR5 is considered to be an attractive target for inhibition of CCR5-using (R5 or macrophage-tropic) HIV-1. However, R5 HIV-1 cannot replicate in CD4+ T cell or monocyte lines because of the lack of CCR5 expression on their surface, which apparently hampers discovery and development of effective CCR5 antagonists against HIV-1 replication. In this study, we have established the CCR5-expressing T cell line MOLT-4/CCR5, highly permissive to the replication of R5 HIV-1. The cells express a considerable amount of CCR5 on their surface. When the cells were infected with the R5 HIV-1 strains Ba-L and JR-FL, the virus-induced cytopathic effect (syncytium formation) was observed, and the cells produced large amounts of HIV-1 p24 antigen in the culture supernatants. The analyses of progeny viruses for their coreceptor use and gp120 V3 nucleotide sequence revealed that they were R5 HIV-1. The parental cell line MOLT-4 was much less susceptible to Ba-L and totally insusceptible to JR-FL. Furthermore, MOLT-4/CCR5 cells could support the replication of an R5 clinical isolate, but MOLT-4 cells could not. When TAK-779, a novel small-molecule nonpeptide CCR5 antagonist, was examined for its inhibitory effect on R5 HIV-1 replication in MOLT-4/CCR5 cells, the compound displayed potent antiviral activity, as demonstrated in peripheral blood mononuclear cells. These results indicate that the established cell line will be an extremely useful tool for experiments with R5 HIV-1.

Amides↗
PubMed2000

Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma.

The lymph nodes of 59 patients with pN0 esophageal squamous cell carcinomas were examined immunohistochemically using cytokeratin (CK) antibody. Primary tumors were immunostained with cyclin D1 (CD1) and E-cadherin (E-cad) antibody. Lymph node micrometastasis (MM) was found in 39 (55.5%) patients. Tumor recurrence was found in 17 patients and all but one of them had MM. The 5-year survival rate was significantly poorer in patients with MM than in those without MM. Almost all patients with positive CD1 and negative E-cad expression had MM. The examination of CD1 and E-cad expression in primary tumors may be useful for predicting MM.

Adult↗
PubMed2000

Peripheral and central conduction abnormalities in diabetes mellitus.

OBJECTIVES: To investigate peripheral and central somatosensory conduction in patients with diabetes. METHODS: The authors recorded sensory nerve action potentials and 5-channel somatosensory evoked potentials (SEPs) with noncephalic reference after median nerve stimulation in 55 patients with diabetes and 41 age- and height-matched normal subjects. The authors determined onset or peak latencies of the Erb's potential (N9) and the spinal N13-P13 and the cortical N20-P20 components, and obtained the central conduction time (CCT) by onset-to-onset and peak-to-peak measurements. RESULTS: Both onset and peak latencies of all SEP components were prolonged in patients with diabetes. The mean onset CCT in the diabetic group was 6.3 +/- 0.5 msec (mean +/- SD)-significantly longer than that in the control group (6.1 +/- 0.2 msec)-whereas no significant difference was found in the peak CCT. The amplitudes of N9 and N13-P13 components (but not N20-P20) were significantly smaller in the diabetic group. The peripheral sensory conduction velocity was also decreased in the diabetic group, but there was no significant correlation between peripheral conduction slowing and the onset of CCT prolongation. CONCLUSIONS: Diabetes affects conductive function in the central as well as peripheral somatosensory pathways. The CCT abnormality does not coincide with lowering of the peripheral sensory conduction. The current results do not favor a hypothesis that a central-peripheral distal axonopathy plays an important role in development of diabetic polyneuropathy.

Adult↗