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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 73 records · Page 4Linked to original sources
PubMed2001

Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery.

OBJECTIVE: To evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. SUMMARY BACKGROUND DATA: Several studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. METHODS: Blood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. RESULTS: CEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. CONCLUSIONS: A high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Aged↗
PubMed2001

Number of lymph node metastases determined by presurgical ultrasound and endoscopic ultrasound is related to prognosis in patients with esophageal carcinoma.

OBJECTIVE: To analyze the impact on prognosis of the number of lymph node metastases detected by ultrasound and endoscopic ultrasound in patients with esophageal carcinoma. SUMMARY BACKGROUND DATA: Ultrasound and endoscopic ultrasound are useful for diagnosing tumor depth and lymph node metastasis in patients with esophageal carcinoma. However, the clinical significance of the number of lymph node metastases before surgery has not been elucidated. METHODS: The authors evaluated lymph node metastases using preoperative ultrasound and endoscopic ultrasound in 329 consecutive patients who underwent esophagectomy with lymphadenectomy. TNM classification and one-to-one comparison of lymph node metastasis was performed between the preoperative and histologic diagnosis. The number of lymph node metastases was subdivided into four groups: zero, one to three, four to seven, and eight or more. RESULTS: The accuracy of preoperative ultrasound and endoscopic ultrasound diagnosis exceeded 70% in each category of TNM classification. The incidence of lymph node metastasis determined by preoperative and histologic diagnosis was 69.0% (234/339) and 59.3% (201/339), respectively. The correlation between preoperative and histologic diagnosis was significant (P <.0001). According to the subdivision of number of lymph node metastases, the accuracy rates associated with nodal involvement of zero, one to three, four to seven, and eight or more were 83.8%, 59.7%, 43.3%, and 96.0%, respectively. The clinical outcome between ultrasound and endoscopic ultrasound diagnosis and histologic diagnosis in stage grouping was almost similar. The 5-year survival rates of patients with zero, one to three, four to seven, and eight or more lymph node metastases determined by ultrasound and endoscopic ultrasound were 53.3%, 33.8% 17.0%, and 0%, respectively. The differences among groups were statistically significant. The survival curves associated with preoperative and histologic diagnosis were similar. CONCLUSIONS: Not only the stage grouping of TNM classification but also the number of lymph node metastases determined by ultrasound and endoscopic ultrasound before surgery may be useful for predicting prognosis in patients with esophageal carcinoma.

Adult↗
PubMed2001

Urokinase receptor and vascular endothelial growth factor are synergistically associated with the liver metastasis of colorectal cancer.

Considering recent findings that the urokinase plasminogen activation (PA) system is involved in invasion and vascular endothelial growth factor (VEGF) is involved in angiogenesis of colorectal cancer, we evaluated these factors in the liver metastasis of primary colorectal cancer. Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2), and were also assayed immunohistochemically for expression of VEGF protein. Among the PA system factors, both the levels of uPAR and PAI-1 were significantly higher in larger tumors than in smaller ones, and were also significantly higher in tumors that invaded subserosa, serosa or adjacent organs than in mucosal, submucosal tumors or in tumors that invaded the muscle layer. The uPAR levels were significantly higher in tumors with liver metastasis than in those without. VEGF overexpression was significantly more frequent in tumors with lymph node involvement or liver metastasis than in those without. Among the PA system factors, the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis. The combination of high uPAR level and overexpression of VEGF was associated with the worst prognosis in patients with colorectal cancer. These results suggest that uPAR and VEGF might contribute synergistically to the liver metastasis of colorectal cancer.

Colorectal Neoplasms↗
PubMed2001

Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.

Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.

Animals↗
PubMed2001

Inhibitory effects of small-molecule CCR5 antagonists on human immunodeficiency virus type 1 envelope-mediated membrane fusion and viral replication.

We established a human immunodeficiency virus type 1 (HIV-1) envelope (Env)-mediated membrane fusion assay and examined the small-molecule CCR5 antagonist TAK-779 and its derivatives for their inhibitory effects on HIV-1 Env-mediated membrane fusion and viral replication. The membrane fusion assay is based on HIV-1 long terminal repeat-directed beta-D-galactosidase reporter gene expression in CD4- and CCR5-expressed HeLa (MAGI-CCR5) cells after cocultivation with effector 293T cells expressing HIV-1 Env. Inhibition of HIV-1 replication was also determined in MAGI-CCR5 cells infected with the corresponding cell-free HIV-1. TAK-779 effectively suppressed R5 HIV-1 (strain JR-FL) Env-mediated membrane fusion as well as viral replication. Its 50% inhibitory concentrations (IC(50)s) for membrane fusion and viral replication were 0.87 +/- 0.11 and 1.4 +/- 0.1 nM, respectively. These values corresponded well to the IC(50) for (125)I-RANTES (regulated on activation, T cell expressed, and secreted) binding to CCR5 (1.4 nM). The inhibitory effects of 18 TAK-779 derivatives on membrane fusion differed from one compound to another. However, there was a close correlation among their inhibitory effects on membrane fusion, viral replication, and RANTES binding. The correlation coefficient between their IC(50)s for membrane fusion and viral replication was 0.881. Furthermore, since this assay depends on Env expressed in the effector cells, it is also applicable to the evaluation of CXCR4 antagonists. These results indicate that the HIV-1 Env-mediated membrane fusion assay is a useful tool for the evaluation of entry inhibitors.

Amides↗
PubMed2001

Colonization with Schizophyllum commune of localized honeycomb lung with mucus.

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.

Aged↗
PubMed2001

Alveolar macrophages that phagocytose apoptotic neutrophils produce hepatocyte growth factor during bacterial pneumonia in mice.

Hepatocyte growth factor (HGF) is postulated to play an important role in the repair of pulmonary epithelium in acute lung injury. To evaluate the role of HGF in bacterial pneumonia, the kinetics of HGF production and the cellular sources of HGF have been examined in the lungs of mice that had been intratracheally challenged with Pseudomonas aeruginosa. Neutrophil accumulation in the airway occurred immediately, reached a peak at 36 h, and then progressively declined by 14 d after infection. We found a biphasic pattern of HGF messenger RNA expression and protein synthesis in the lung after bacterial infection. The first peak for HGF production was found at 6 h after infection, and the primary source of HGF was shown to be bronchial epithelial cells. Interestingly, the second peak for HGF production, which was found around 48 to 72 h after infection, was closely associated with the increase in the percentage of alveolar macrophages (AMs) that became positive for myeloperoxidase, indicating phagocytosis of apoptotic neutrophils. The cellular source of the second peak was found to be AMs. Further, murine AMs which phagocytosed apoptotic neutrophils induced higher levels of HGF production in vitro. These results strongly indicate a novel mechanism of HGF production by AMs, which are phagocytosing apoptotic neutrophils, and the pivotal role of AMs in the healing and repair of damaged pulmonary epithelium through the production of HGF.

Animals↗
PubMed2001

Three-drug combinations of emivirine and nucleoside reverse transcriptase inhibitors in vitro: long-term culture of HIV-1-infected cells and breakthrough viruses.

Emivirine (EMV) is a non-nucleoside reverse transcriptase inhibitor currently undergoing Phase III clinical trials in HIV-1-infected patients. In this study, the anti-HIV-1 activity of EMV in combination with two nucleoside reverse transcriptase inhibitors was examined in cell cultures. The combinations EMV plus stavudine (d4T) plus lamivudine (3TC) and EMV plus d4T plus didanosine (ddI) synergistically inhibited HIV-1 replication in MT-4 cells. Although not statistically significant, EMV plus d4T plus 3TC appeared to be more synergistic than EMV plus d4T plus ddI. Synergism was also observed with any two-drug combinations, such as EMV plus d4T, EMV plus 3TC, EMV plus ddI, d4T plus 3TC, or d4T plus ddI. The three-drug combinations completely suppressed HIV-1 replication for at least 40 days after virus infection. Except for d4T, virus emerged in the presence of every compound alone or some combinations at lower concentrations. Susceptibility tests of the breakthrough viruses to each compound showed that the viruses obtained in the presence of EMV alone and 3TC alone were significantly less susceptible to EMV and 3TC, respectively. These viruses had specific amino acid mutations in their reverse transcriptase.

Anti-HIV Agents↗
PubMed2001

Anti-HIV-1 activity and structure-activity relationship of cepharanoline derivatives in chronically infected cells.

Cepharanthine (12-O-methyl cepharanoline) is a plant alkaloid and has been shown to inhibit tumour necrosis factor-alpha- or phorbol 12-myristate 13-acetate-induced HIV-1 replication in the chronically infected promonocytic cell line, U1. Its mechanism of action is considered to be the inhibition of nuclear factor kappaB, a potent inducer of HIV-1 gene expression. In this study, we have synthesized 96 derivatives of cepharanoline, including cepharanthine, and examined their inhibitory effects on HIV-1 replication in U1 cells. Among the 12-O-alkyl derivatives, cepharanthine proved to be the most active, and the activity decreased as the length of the alkyl chain increased. All of the 12-O-acyl derivatives were totally inactive, while a few 12-O-carbamoyl derivatives displayed modest activity. Since 12-O-ethyl derivatives were found to be as active as cepharanthine against HIV-1 replication, we further synthesized various 12-O-ethyl derivatives of cepharanoline. Among the derivatives, five proved to be more active inhibitors than cepharanthine, and the most active compound was 12-O-ethylpiperazinyl cepharanoline. The 50% effective concentrations of this compound and cepharanthine were 0.0041 and 0.028 microg/ml (0.0060 and 0.046 microM), respectively.

Alkaloids↗
PubMed2001

Rapid and reversible changes in dendrite morphology and synaptic efficacy following NMDA receptor activation: implication for a cellular defense against excitotoxicity.

Postsynaptic neuronal dendrites undergo functional and morphological changes in response to pathologically excessive synaptic activation. Although rapid formation of segmental focal swelling (varicosity) is the most prominent hallmark in such excitotoxic injury, little is known about the pathophysiological function of these structural alterations. We used cultured rat hippocampal slices to evaluate the relationship between the formation of varicosities and subsequent neuronal death. Substantial numbers of segmental dendritic varicosities were observed all over the hippocampus within 5 minutes of exposure to 30 microM NMDA, although neuronal death was detected only in the CA1 region 24 hours after NMDA exposure. Sublethal NMDA concentrations (1-10 microM) induced reversible focal swelling in all hippocampal subregions. NMDA-induced neuronal death was prevented either by NMDA receptor antagonists or by the use of Ca(2+)-free medium, whereas varicosity formation was virtually independent of Ca(2+) influx. Rather, the Ca(2+)-free conditions per se produced dendritic focal swelling. Also, NMDA-induced varicosity formation was dependent on extracellular Na+ concentration. Thus, we believe that varicosity formation is not causally related to neuronal injury and that the two phenomena are separable and involve distinct mechanisms. Interestingly, dendrite swelling was accompanied by AMPA receptor internalization and a rapid, long-lasting depression in synaptic transmission. Moreover, low Na+ conditions or treatment with ethacrynic acid or proteinase inhibitors, which effectively prevent varicosity formation, aggravated NMDA-induced excitotoxicity, and eliminated the regional specificity of the toxicity. Therefore, the pathological changes in dendrite morphology and function may be associated with an early, self-protective response against excitotoxicity.

Animals↗
PubMed2001

Sudden death due to cardiovascular disorders: a review of the studies on the medico-legal cases in Tokyo.

The Tokyo Metropolitan Government has a medical examiner system, in which all cadavers classified as "unusual death" in the city of Tokyo should be examined, and if necessary, autopsied to determine the cause of death. Of about 10,000 unusual deaths examined per year, two thirds are usually determined to have died of natural causes. The most common cause of sudden natural death is ischemic heart disease, especially acute myocardial infarction. Pathological examination, however, proves acute myocardial ischemia in only one third of autopsies. Subarachnoid hemorrhage and intracerebral hemorrhage, acute myocarditis and cardiomyopathies and aortic dissection/aneurysm as well as pulmonary thromboembolism are frequent causes of death in medical examiner cases. Both pathological and socio-medical problems associated with these diseases are discussed.

Aortic Aneurysm↗
PubMed2001

Cancer chemoprevention by ginseng in mouse liver and other organs.

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.

Animals↗
PubMed2001

[The causes of death in patients with non-MDR pulmonary tuberculosis in our hospital].

We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently.

Adult↗
PubMed2001

Preserved Smad4 expression in the transforming growth factor beta signaling pathway is a favorable prognostic factor in patients with advanced gastric cancer.

The signals of the transforming growth factor beta (TGF-beta) superfamily are conveyed through cell surface serine/threonine kinase receptors to the intracellular mediators known as Smads. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function to control gene expression. The present study analyzed the expression of Smad4 and TGF-beta1 to determine their prognostic significance in advanced gastric cancer. Of 249 cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF-beta1 antibodies were used for immunohistochemical staining. Reduced expression of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric cancer. Smad4 expression was related to the depth of tumor invasion (P < 0.05), and TGF-beta1 expression correlated with tumor gross type (P < 0.05). Postoperative survival analysis indicated that patients who had a tumor with reduced Smad4 expression had a poorer clinical outcome than those with preserved expression (P < 0.05). Furthermore, in patients with TGF-beta1-positive tumors, survival rate was significantly better in patients with preserved Smad4 expression than in those with reduced Smad4 expression (P < 0.05). According to multivariate analysis, Smad4 expression acted as an independent prognostic factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective predictor of outcome for patients with advanced gastric cancer.

Adult↗
PubMed2001

[Effective combination chemotherapy for a recurrent case of carcinoma of the remnant stomach].

A 69-year-old-man underwent distal gastrectomy for gastric carcinoma in 1988. Another gastric carcinoma was discovered in the remnant stomach in March 1995. Total gastrectomy and lymph node dissection were performed. CEA was up and we detected a big left suprarenal mass by abdominal CT. Suprarenalectomy was performed in June 1997. The swelling of lymph nodes was detected by CT and CEA was up to 1,000. Combination chemotherapy with intermittent 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) was performed. CEA suddenly decreased and lymph node swelling was reduced.

Adenocarcinoma↗
PubMed2001

[A case of acute sensory neuropathy associated with cytomegalovirus infection].

We report a non-compromised patient with acute sensory neuropathy (ASN) developed following cytomegalovirus (CMV) hepatitis. A 67-year-old man admitted to a hospital because of acute hepatic dysfunction accompanying fever and skin eruption. One month later, when hepatic function normalized, numbness and clumsiness started acutely first in the right upper limb next to all the extremities. He found difficulty in walking in a couple of weeks. One month after the commencement of neurological illness, he was referred to us. On examination, he had sensory limb ataxia. His gait was wide-based, and Romberg sign was positive. Position sense was severely diminished in the extremities. Skin sensation was also attenuated distally, while no motor weakness was noted. Tendon reflexes were almost absent. Nerve conduction studies revealed absent sensory potentials in all but the left median nerve, in which amplitude was 5.5 microV with sensory conduction velocity of 40.7 m/s. Motor conduction studies, on the other hand, appeared normal except for a slight focal delay in the right ulnar nerve across the elbow. Mild increase in F-wave latencies was noted. A sural nerve specimen taken two months after the neurological onset showed a marked decrease in myelinated fiber density and active fiber degenerations accompanying axonal sproutings. Sjögren syndrome and paraneoplastic neuropathy were excluded serologically and by comprehensive imaging techniques. Although IgM anti-CMV antibody was not detected, serum IgG anti-CMV antibody was positive and significantly increased during the neurological illness. The intrathecal antibody synthesis of IgG anti-CMV antibody was suggested by a low serum/cerebrospinal fluid (CSF) antibody ratio and a high CSF IgG index. From these observations, it was strongly suggested that acute hepatitis and subsequent ASN were associated with CMV infection in this patient. Although some cases with post-infectious ASN have been previously reported, this is the first report of ASN preceded by CMV infection.

Acute Disease↗