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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 55 records · Page 3Linked to original sources

Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms.

To demonstrate the association of Epstein-Barr virus (EBV) with primary epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45 thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization. EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313 gastric carcinomas were differentiated poorly to moderately carcinomas with prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and 11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in other epithelial neoplasms that originated from the lung, esophagus, breast, colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was associated with only some gastric carcinomas but not with other epithelial neoplasms originating from the lung, esophagus, breast, colon, pancreas, and thyroid in southern Japan.

Adenocarcinoma↗

Sensory potentials evoked by tactile stimulation of different indentation velocities at the finger and palm.

Previous studies suggest that the rate of indentation of a tactile probe determines which skin mechanoreceptors are activated. To further investigate this possibility, indentations of 300 microm at velocities of 100 (T100) and 400 microm/ms (T400) were applied to the tip (FT) and the proximal phalanx of digit III (PP) and the thenar eminence (Pm) of ten healthy volunteers, and compared with responses after electrical stimulation at the FT. Compound sensory action potentials (CSAPs) were recorded from the median nerve through needle electrodes at the wrist and elbow. The maximal sensory conduction velocities (SNCVs) between wrist and elbow were similar with electrical and T400 stimulation, but on average were 15% lower with T100 stimulation (P < 0.001). With both indentation velocities, SNCVs were similar regardless of stimulation sites. Amplitudes of tactile CSAPs with FT stimulation were 1--2 microV at T400 and 0.3--0.4 microV at T100. The CSAP areas evoked by T100 stimulation showed a reduction from fingertip to proximal finger to palm (P < 0.05-0.005), whereas those obtained with T400 stimulation showed a reduction only at the palm (P < 0.05). The results support previous studies indicating that fast indentation at 400 microm/ms activated deeply placed Pacinian corpuscles as well as superficially situated Meissner corpuscles, whereas slower indentation at 100 microm/ms activated primarily Meissner corpuscles.

Adult↗

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus.

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.

Aged↗

Induction by bombesin of peritoneal metastasis of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

BACKGROUND: We investigated the effect of the gastrointestinal regulatory peptide, bombesin, on the development of peritoneal metastasis from gastric cancers induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on Rho activity in the gastric cancers. METHODS: Rats were allocated to three groups. All groups received MNNG (100 micrograms/ml) solution for 25 weeks from the start of the experiment. Group 1 (controls) received olive oil injections from the start of MNNG treatment; group 2 animals received alternate-day s.c. injections of bombesin (40 micrograms/kg body weight) in olive oil from the start of the experiment until the end of the experiment at week 52; and group 3 received the s.c. bombesin injection on alternate days from week 26 until week 52. The effect of bombesin on Rho activity in gastric cancer was examined by Western blotting. RESULTS: Bombesin given from the start of the experiment (group 2) and after the MNNG treatment (group 3) both significantly increased the incidence of gastric cancer metastasis, compared with controls, at week 52: The incidence of metastasis was significantly higher in group 2 than in group 3. Bombesin from the start of the experiment (group 2) significantly increased the incidence of tumors with deeper invasion or more infiltrative growth pattern, or lymphatic vessel tumor invasion, while bombesin after MNNG treatment (group 3) significantly increased the incidence of lymphatic vessel invasion. Bombesin also increased the activity of Rho protein in the tumors. CONCLUSION: Bombesin significantly increased the incidence of peritoneal metastasis from gastric cancers through the activation of Rho protein.

Animals↗

Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer.

BACKGROUND: The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer. METHODS: MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody. RESULTS: Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor. CONCLUSIONS: We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.

Adult↗

Clinical significance and prognostic value of apoptosis related proteins in superficial esophageal squamous cell carcinoma.

BACKGROUND: The purpose of the present study was to examine the expression of cell cycle regulators [p53, p21WAF1/CIP1 (p21), and Rb] and apoptosis related proteins Bax and Bcl-X(L) and to evaluate the relationship between their expressions and clinicopathological findings in patients with superficial squamous cell carcinomas of the esophagus. METHODS: We immunohistochemically investigated the expression of p53, p21, Rb, Bax, and Bcl-X(L) in 79 patients with superficial esophageal carcinoma. RESULTS: p21 overexpression was found in mucosal carcinoma (P = 0.05) and a high Bcl-X(L) score was observed for submucosal carcinoma (P = 0.03). The patients with high Bcl-X(L) score had more frequent lymphatic invasion and lymph node metastasis than did those with low Bcl-X(L) score (P < 0.05). Univariate analysis revealed significantly shorter survival in patients with high Bcl-X(L) expression than in those with low Bcl-X(L) expression, but Bcl-X(L) expression was not identified as an independent prognostic factor by multivariate analysis. CONCLUSIONS: Because Bcl-X(L) expression correlated well with depth of tumor invasion, lymphatic invasion, and lymph node metastasis, examination of Bcl-X(L) expression will help to estimate the properties in superficial squamous cell carcinoma of the esophagus.

Adult↗

Expression of vascular endothelial growth factor in thoracic sarcomas.

BACKGROUND: A body of data indicates that vascular endothelial growth factor (VEGF) expression by carcinomas is closely related to the prognosis of carcinomas. However, the relationship between VEGF expression and the prognosis of sarcomas is contradictory. METHODS: Tissue from 27 cases of thoracic sarcoma was analyzed immunohistochemically for VEGF expression while tumor vascularity was quantified using an antibody directed against endothelial CD34. The relationship between VEGF expression and the prognosis of patients with sarcomas was then evaluated semiquantitatively. RESULTS: The microvessel count in sarcomas with strong VEGF expression was significantly higher than that in sarcomas with absent or faint VEGF expression. The disease-free survival rates of sarcomas with strong VEGF expression were significantly lower than those of sarcomas with absent or faint VEGF expression. We found that strong VEGF expression impacted on the disease-free survival in multivariate analyses. CONCLUSIONS: VEGF expression of thoracic sarcomas is directly related to angiogenesis and tumor vascularity, and our findings suggest that strong VEGF expression is an independent prognostic factor in patients with thoracic sarcomas.

Adolescent↗

Diterpenoids from Euphorbia paralias.

Two segatane diterpenoids containing a bicyclic [4,3,1] ring system were isolated, together with 11 known diterpenoids, four segetanes, five jatrophanes and two paralianes, from the aerial parts of Euphorbia paralias. The structures of the new compounds were established by spectroscopic means, including by 2D NMR and CD spectroscopic analyses. The antifeedant and antiviral activities of the isolated compounds are also described.

Animals↗

Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common human cancers, and many efforts have been paid to discover aberrant expression control in HCC, however the specific molecular mechanisms involved in hepatocarcinogenesis remain to be determined. METHODS: To investigate genomic changes that occur in human primary hepatocellular carcinomas (HCC), we carried out restriction landmark genomic scanning. This two-dimensional electrophoretic system displays 2000-3000 NotI-landmark sites in a single gel. RESULTS: We detected one landmark spot that showed diminished signal intensities in a majority of the HCCs we examined. Cloning revealed that this spot represented a NotI-cluster sequence that was enriched with CpG dinucleotides in the promoter region of a gene encoding Janus kinase (JAK)-binding protein, SSI-1 (also known as JAB1 or SOCS-1). Expression of the SSI-1 gene was markedly reduced in half of eight HCCs analyzed. CONCLUSIONS: This protein regulates the Janus kinase signal transducers and activators of transcription signal transduction pathway, which transmits signals from cytokines to the intracellular apparatus. These data suggest that dysregulation of the pathway relate with progression of HCC.

Carcinoma, Hepatocellular↗

Fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

BACKGROUND: A new strategy in the treatment of squamous cell carcinoma of the tracheobronchial tree is the detection and eradication of preinvasive bronchial lesions before they become invasive cancers. It is, however, difficult to detect preinvasive lesions by conventional white-light bronchoscopy alone. PURPOSE: we conducted a detailed investigation on the use of fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. METHODS: 64 participants with sputum cytology suspicious or positive for malignancy were examined with both white light and fluorescence bronchoscopy (LIFE group). Earlier to this study, before fluorescence bronchoscopy became available in our institute, 48 participants having sputum cytology suspicious or positive for malignancy were examined with white light bronchoscopy alone (control group). Biopsy specimens for pathological examinations were taken of all abnormal areas discovered by white light or fluorescence bronchoscopy examination. RESULTS: In sputum cytology suspicious or positive for malignancy, the diagnosis of preinvasive bronchial lesions was greatly enhanced in the LIFE group as compared with the control group (45 vs. 7 lesions). The percentage of participants with preinvasive bronchial lesions was also significantly higher in the LIFE group than in the control group (40.6 vs. 12.5%, P = 0.00087, respectively). CONCLUSIONS: Our study suggests that the use of fluorescence bronchoscopy in addition to conventional white-light examination could greatly enhance the detection and localization of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

Aged↗

Transfer of bcl-xs plasmid is effective in preventing and inhibiting rat hepatocellular carcinoma induced by N-nitrosomorpholine.

To examine the effect of the bcl-xs gene on the sequence from hepatic precancerous lesions, foci and neoplastic nodules, to hepatocellular carcinomas, Sprague-Dawley rats were given water containing 175 mg/l N-nitrosomorpholine (NNM) for 8 weeks. At weeks 1, 4 and 7, the left lobe of the rat liver was exposed and injected with the bcl-xs plasmid (pCR3.1-rat bcl-xs cDNA) or pCR3.1 encapsulated in cationic empty liposomes each at a dose of 80 microg plasmid/kg body weight. One minute later, low-field-strength, long-duration electric pulses were applied to the left lobe using a pincette electrode with circular poles 1 cm in diameter. The in vivo electroporation procedure significantly increased the transfer of the reporter gene chloramphenicol acetyl transferase (CAT) plasmid via empty liposomes. Thus, CAT mRNA was expressed not only at the sites of electrode contact but at sites 0.5-1.0 cm away from the electrode, and expression also increased with increasing doses of plasmid, meaning that in vivo electroporation enabled the expression of plasmid DNA throughout an extensive area of the rat liver. By week 11, the neoplastic nodules were significantly fewer and smaller in the bcl-xs group than in the pCR3.1 group at the two sites, one with and the other without electrode contact. No hepatocellular carcinomas were found in the rats that had received the bcl-xs plasmid, whereas these tumors were observed in 30% of the rats given pCR3.1. Moreover, overexpression of the bcl-xs protein was detected, and apoptotic activity was significantly increased in the neoplastic nodules, foci and hepatocytes adjacent to the hepatic lesions. These results indicate that the bcl-xs plasmid inhibits the occurrence and growth of rat hepatocellular carcinoma and may thus be effective for the prevention and treatment of human liver tumors.

Animals↗

Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells.

Human T lymphotropic virus type I (HTLV-I) induces HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). The development of HAM/TSP is associated with rapid maturation of dendritic cells (DCs), while ATL is accomplished with their maturation defect. The DC maturation is induced by cell-to-cell contact with CD4+ T cells expressing CD40 ligand (L). We determined the influence of CD40L expressed on various HTLV-I-infected T cells on the DC maturation. Around 60% of CD4+ T cells infected with HTLV-I for 1 week, expressed CD40L molecules involved in DC maturation. DCs matured by the CD40L+ T cells activated autologous CD4+ and CD8+ T cells. HTLV-I-immortalized T-cell lines established from healthy donors consistently expressed CD40L molecules for 3 months, however, some lines lost the expression soon thereafter. Interleukin (IL)-2-independent and transformed lines lacked that expression. Furthermore, T cells obtained from HAM/TSP patients expressed CD40L molecules for at least 3 weeks, whereas T cells from ATL patients did not express that. The CD40L T cells did not induce DC maturation, and required exogenous CD40L molecules for maturation. The CD40L+ T-cell-induced maturation was blocked by anti-CD40L antibody. Therefore, the lack of CD40L expression on HTLV-I-infected T cells may be associated with the development of ATL.

CD4-Positive T-Lymphocytes↗

Micrometastases in the cervical lymph nodes in esophageal squamous cell carcinoma.

Few studies have investigated the presence of lymph node micrometastases (MM) in the cervical region of patients with esophageal squamous cell cancer. The present study examines the presence of cervical MM and attempts to determine a way to predict the occurrence and site of such micrometastases. A total of 2203 cervical lymph nodes and 118 mediastinal recurrent nerve nodes obtained from 86 patients with esophageal carcinoma were examined immunohistochemically using cytokeratins. Cervical lymph nodes and mediastinal recurrent nerve nodes metastases were detected histologically in 33 and 41 of the 86 patients respectively. Cervical lymph node and mediastinal recurrent nerve node MM were immunohistochemically detected in 16 (18.6%) and 6 (7.0%) patients respectively. Of these 16 patients with cervical MM, seven were found to have lymph node metastases in different cervical regions, whereas cervical MM only were detected in nine patients. Among the former group of patients, five were diagnosed by ultrasound examination as having cervical lymph node metastases. Mediastinal recurrent nerve node metastases and MM correlated with the presence of cervical MM in all but one patient. Cervical lymph node metastasis, including micrometastasis, can be predicted by preoperative ultrasonography and the routine histologic examination of mediastinal recurrent nerve nodes.

Adult↗

Coexistence of five Cercopithifilaria species in the Japanese rupicaprine bovid, Capricornis crispus.

The Japanese serow, Capricornis crispus (Bovidae, Caprinae, Rupicaprini), is parasitized by five Cercopithifilaria species: C. shohoi, recently described, and reexamined in this paper, C. multicauda n. sp., C. minuta n. sp., C. tumidicervicata n. sp., and C. bulboidea n. sp. Coinfections are frequent. The location (skin or subcutaneous regions) in the host of adult worms differed between the species, as did many morphological characters of both adults and microfilariae. The location (limbs, trunk, etc.) in the host of adult worms and dermal microfilariae seemed to differ depending on the species. Male and female worms of the same species had similar head shapes, buccal capsules, and, in four species, swellings in the anterior region of the body (because of the presence of a giant ventral pseudocoelomocyte). The Cercopithifilaria spp. from C. crispus were related to the primitive forms of the genus, parasites of Bovidae and Cervidae, presently recorded in Africa and Europe. C. bulboidea was particularly close to the most primitive species, C. ruandae and C. dermicola, in Africa, with the pairs of caudal papillae numbered 8 and 9 being distant from each other, but the species also had several specialized characters. Like C. rugosicauda in a European cervid, the four other species had pairs 8 and 9 close to each other; they reflect an evolutionary trend (hypertrophy of pair 6, and reduction and posterior migration of pair 7) that suggests diversification in the host.

Animals↗

SPARC expression in primary human renal cell carcinoma: upregulation of SPARC in sarcomatoid renal carcinoma.

SPARC (secreted protein acidic and rich in cysteine, also called osteonectin, BM-40, and 43K protein) is a matricellular protein and is associated with cell-matrix interactions during cell proliferation and extracellular remodeling. It is also implicated in the neovascularization, invasion, and metastasis of human malignancies. To investigate a potential role of the SPARC in renal tumorigenesis, we examined primary renal cell carcinomas (RCCs) for SPARC expression by Northern blot analysis and for protein distribution by immunohistochemistry. We found that 6 (100%) of 6 sarcomatoid and 25 (70%) of 36 clear-cell carcinomas had enhanced SPARC transcription compared with that of the corresponding normal kidney tissue. In contrast, papillary and chromophobe RCCs characterized by a hypovascular or avascular tumor phenotype had undetectable SPARC expression. Immunohistochemical analysis showed that SPARC was strongly stained in the cytoplasm of the sarcomatoid neoplastic cells in sarcomatoid RCCs, whereas it was expressed only in the vascular endothelial cells and fibroblasts in clear-cell RCCs. SPARC staining intensity in the stromal cells was increased in the invading portion in some clear-cell RCCs. These findings suggest that tumor development, including neovascularization and invasion in clear-cell RCCs, might be regulated by SPARC from stromal endothelial cells and fibroblasts and that sarcomatoid transformation from common-type RCCs is associated with upregulation of SPARC expression; SPARC may contribute to its aggressive tumor phenotype.

Blotting, Northern↗

Electrophysiological changes in diabetic neuropathy: from subclinical alterations to disabling abnormalities.

Clinical spectrum of diabetic neuropathy is variable; it may be asymptomatic, but once established as polyneuropathy, it is irreversible and may finally be disabling. To estimate the prevalence of subclinical diabetic polyneuropathy in the UAE, we undertook a pilot study by means of nerve conduction study (NCS) of peroneal motor and sural sensory studies in 60 diabetics with no symptoms of neuropathy. Neurological examination revealed clinical abnormalities suggesting polyneuropathy in 26 patients, 43% of the patients. NCS revealed abnormal values in 63% of the whole patients. Abnormal NCS was confirmed in 88% of the positive sign group. As to the negative sign group 44% had abnormalities in NCS. Prolonged F-wave latency was seen in 29% in no sign group and in 66% of the patients with positive signs. We found close association between neurological deficit score and abnormalities in NCS. Among various parameter of systemic nerve conduction study in subclinical patients, prolonged F-wave latency seems the commonest abnormality suggesting morphological changes in subclinical diabetic nerve. Decrease in amplitude of compound sensory action potential of sural nerve is another earlier abnormality, which is, then, accompanied by a fall in motor amplitude of peroneal nerve in advanced patients. Recently, our own group of Hirosaki has demonstrated that somatosensory central conduction time (CCT) between the spinal cord entry time and the arrival time to the sensory cortex is prolonged in diabetics. This abnormality might be partly responsible for the irreversible sensory deficits of diabetic neuropathy.

Action Potentials↗

Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor.

The present study was designed to examine the effect of aldose reductase (AR) overexpression on the development of diabetic neuropathy by using mice transgenic for human AR. At 8 weeks of age, transgenic mice (Tg) and non-transgenic littermates (Lm) were made diabetic with streptozotocin. After 8 weeks of untreated diabetes, plasma glucose levels and the reduction in body weight were similar between the groups of diabetic animals. Despite the comparable levels of hyperglycaemia, levels of sorbitol and fructose were significantly greater in the peripheral nerve of diabetic Tg than in diabetic Lm (both P < 0.01). Ouabain sensitive Na(+),K(+)-ATPase activity was similarly decreased in both diabetic Tg and Lm. Protein kinase C activity in the sciatic nerve membrane fraction was unaffected by diabetes in Lm, but was reduced by nearly 40% in the diabetic Tg. Although both groups of diabetic animals exhibited a significant decrease in tibial nerve motor nerve conduction velocity (MNCV), this decrease was significantly more severe (P < 0.01) in diabetic Tg than in diabetic Lm. Consistent with these findings, nerve fibre atrophy was significantly more severe in diabetic Tg than in diabetic Lm (P < 0.01). These findings implicate increased polyol pathway activity in the pathogenesis of diabetic neuropathy. In support of this hypothesis, treating diabetic Tg with an aldose reductase inhibitor (WAY121-509, 4 mg/kg/day) for 8 weeks significantly prevented the accumulation of sorbitol, the decrease in MNCV and the increased myelinated fibre atrophy in diabetic Tg.

Aldehyde Reductase↗