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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 217 records · Page 12Linked to original sources

Epileptic falling spells after epidural haematoma in adult Down's syndrome.

A 35-year-old man with Down's syndrome showed epileptic falling spells. He had suffered from a traumatic right-sided epidural haematoma 3 years before. It had been neurosurgically treated, but MRI taken 5 days later had revealed a small contracoup contusion at the left temporal lobe. His falling spell was a brief tonic seizure without disturbance of consciousness. Background activities of EEG consisted of slow alpha waves interspersed with sporadic theta waves and the amplitude at the left temporal area was lower than the opposite one. Interictal EEG showed sharp waves or sharp and slow wave complexes predominantly at the right temporo-centro-parietal area as well as diffuse, though predominantly at frontal areas, bursts of slow waves with high amplitude. The EEG suggested focal epileptic activities evolving into secondary generalization. SPECT of the brain showed the hypoperfusion at the left temporal area and at the right posterotemporo-parietal area, where the hypoperfusion was somewhat reduced after the improvement of seizures. Seizures were well controlled with phenytoin combined with phenobarbital. The incidence of epilepsy in the Down's syndrome has been reported to increase after the middle age in association with the development of Alzheimer's neuropathology. When those people would sustain head injuries, it was necessary to follow carefully using SPECT and EEG.

Adult↗

Stimulation of haematogenous liver metastases by ischaemia-reperfusion in rats.

OBJECTIVE: To find out whether hepatic ischaemia-reperfusion stimulates hepatic tumour metastases using a cell line of rat ascitic hepatoma (AH130). DESIGN: Prospective experimental study. SETTING: University laboratories, Japan. MATERIALS: 118 male Donryu rats. INTERVENTION: After laparotomy alone (group 1, n = 35) or laparotomy and 20-minutes ischaemia (group 2, n = 34) or laparotomy and 30-minutes ischaemia (group 3, n = 34) of the median and left hepatic lobes, the animals were given either an intraportal injection of 1 x 10(5) or an intravenous injection of 1 x 10(6) viable AH130 cells. MAIN OUTCOME MEASURES: 10 days after inoculation of tumour cells the number of nodules on the surface of the right lobe and of the median plus left lobes were separately counted for each liver. RESULTS: Irrespective of the route of tumour inoculation in group 1, there was no significant difference in the number of tumours/g liver between the right and the median plus left lobes. However, in groups 2 and 3, the number of tumours/g liver in the median plus left lobes was significantly higher than in the right lobe (p < 0.05). Furthermore, in the median plus left lobes, animals who had had 30 minutes of ischaemia had significantly more tumours than those in the other two groups (p < 0.01). CONCLUSION: Hepatic ischaemia-reperfusion may increase the risk of development of haematogenous liver metastases, by stimulating tumour cell-endothelial cell interactions.

Analysis of Variance↗

Comparative evaluation of procedures with a Baxter CS-3000 cell separator for collecting peripheral blood cells from children.

The safety and efficacy of apheresis using a newly developed procedure with a small volume separation container holder (SVSCH, Baxter) for the collection of PBSC from children with cancer were retrospectively compared with our historical experience with other procedures using different equipment and the CS-3000 plus cell separator. The procedures tested included the application of (a) specialized collection protocol 4 using the combination of an SVSCH and a small volume collection chamber (SVCC) (group A: 6 collections in 4 patients), (b) standard lymphocyte collection protocol 3 with GRANULO separation (G) and A-35 collection chambers (group B: 9 collections in 5 patients), and (c) modified collection procedure 1-120 with G and SVCC (group C: 7 collections in 3 patients). Although the retrospective nature of this study and the differences in the cohorts tested prevent a reliable analysis, the percent decrease in the peripheral platelet count after collection tended to be minimum in group A (11% +/- 5% versus 23% +/- 4% [B] or 17% +/- 4% [C]). Moreover, the largest number of CD34+ cells was collected in group A (8.7 +/- 9.4 x 10(5)/100 ml processed blood) compared with groups B (5.5 +/- 7.5 x 10(5)/100 ml processed blood) and C (4.0 +/- 2.8 x 10(5)/100 ml processed blood). These data suggest that a procedure incorporating SVSCH can be safely and effectively applied to small children and enables the selective collection of PBSC with less contamination by platelets, which is useful for subsequent cell processing.

Adolescent↗

Cytocidal activity of PBL, LAK, and IDEC-C2B8 and expression of HLA class 1, ICAM-1, and CD20 in vincristine-resistant hematologic cell lines.

This study was designed to determine whether the cytocidal activity of immunotherapy such as cytotoxic peripheral blood lymphocytes (PBL), lymphokine-activated killer (LAK) cells, and chimeric anti-CD20 mouse/human monoclonal antibody, IDEC-C2B8, overcome vincristine (VCR) resistance in cultured cell lines derived from human leukemia/lymphoma. In addition, the relation between the susceptibility to these immunotherapies and the expression levels of HLA class 1 and ICAM-1 as well as CD20 on the cell surface was analyzed. Three of six VCR-resistant cell lines were less susceptible to PBL cytotoxicity compared with wild-type cells, whereas the susceptibility was kept in the other three VCR-resistant cell lines. Four of six VCR-resistant cell lines were less susceptible to LAK activity and the other two cell lines were as sensitive to LAK cells as their wild-type counterparts. There was no correlation between the susceptibility for PBL cytotoxicity and the expression of HLA class 1 in both wild and VCR-resistant cells. In contrast, ICAM-1 in the two cell lines that showed decreased susceptibility for LAK cytotoxicity disappeared, although that in one cell line increased. IDEC-C2B8 was effective only against B-cell lines expressing CD20. One cell line in which the expression of CD20 increased was nearly six times more sensitive to IDEC-C2B8 than wild type. Thus, we concluded that the resistance to VCR in some tumor cell lines is associated with modified susceptibility for immunotherapies by the different expression of target molecules from those of wild-type counterparts.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells.

Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, inactivates urokinase-type plasminogen activator (uPA) and regulates degradation of the extracellular matrix; whether it functions for or against tumor progression, however, has been the subject of controversy. To assess the role of PAI-1 in invasion and proliferation of hepatocellular carcinoma (HCC) cells, HLE cells were transfected with a vector capable of expressing an antisense PAI-1 transcript. Analysis of seven stably transfected clones (PAI-1-) showed reductions of 81% in PAI-1 mRNA by northern blot analysis and 63% in the cellular PAI-1 antigen level by enzyme-linked immunosorbent assay (ELISA). There was no change in the levels of secreted PAI-1 or PAI-2. The activity of cellular uPA increased by 54%, without change in the protein level or the secreted uPA activity evaluated by ELISA. Morphologically, PAI-1 antisense induced a spindle shape with narrower cytoplasmic processes in HLE cells. The forced inhibition of PAI-1 increased the invasion and the growth of PAI-1- cells by 75% and 82%, respectively. These results suggest that PAI-1 plays a role in inhibiting invasion and proliferation, and the balance between uPA and PAI-1 expression is important to assess the invasiveness of HCC cells.

Carcinoma, Hepatocellular↗

Vasculitis confined to the peripheral nerve and skin: a variant of non-systemic vasculitic neuropathy.

We describe a patient presenting with vasculitic neuropathy associated with cutaneous vasculitis in the absence of other clinical or laboratory evidence of the underlying systemic vasculitis, and showing a favourable prognosis. Although the early proposed criteria for the diagnosis of non-systemic vasculitic neuropathy (NSVN) exclude the involvement of extraneural tissues, the condition observed in our patient might represent a variant of NSVN, with the vasculitis confined to the small vessels in both the peripheral nerve and the skin.

Aged↗

Spinocerebellar ataxia type 6 in relation to CAG repeat length.

UNLABELLED: The purpose of the present study was to assess the relationship between clinical characteristics of spinocerebellar ataxia type 6 (SCA6) and CAG repeat length. MATERIALS AND METHODS: We examined clinical symptoms of 54 patients with SCA6. CAG repeat length was compared among subgroups divided by clinical manifestations. RESULTS: The major symptom was progressive cerebellar ataxia. Truncal or limb ataxia, dysarthria, and nystagmus were observed in more than 80% of the patients. In analysis of CAG repeat length in patients with different types of nystagmus, CAG repeat length was the longest when both upbeat and downbeat nystagmus existed (P < 0.01). In addition, CAG repeat length was longer when the initial symptom was ataxic gait and was shorter when the initial symptom was dysarthria or ocular symptom (P < 0.05). CONCLUSION: Clinical features of SCA6 might be influenced by the length of abnormal CAG repeat.

Adult↗

The 14-3-3 protein detectable in the cerebrospinal fluid of patients with prion-unrelated neurological diseases is expressed constitutively in neurons and glial cells in culture.

The 14-3-3 protein belongs to a family of 30-kD proteins originally identified by two-dimensional analysis of brain protein extracts. Recently, the detection of the 14-3-3 protein in the cerebrospinal fluid (CSF) is utilized as a highly reliable test for the premortem diagnosis of prion diseases such as Creutzfeldt-Jakob disease. For the initial step, to clarify the biological implication of the CSF 14-3-3 protein in these diseases, its expression was investigated in neural tissues and cultures and CSF samples from patients with a variety of neurological diseases by Western blot analysis and immunocytochemistry. The constitutive expression of the 14-3-3 protein was identified in all neural and nonneural tissues examined. It was expressed in all neurons, astrocytes, oligodendrocytes, and microglia in culture with its location in both cytoplasmic and nuclear regions. The 14-3-3 protein was detected in the CSF of 8 out of 71 patients, including 1 Gerstmann-Sträussler-Scheinker disease patient and 7 patients with prion-unrelated neurological diseases, such as meningoencephalitis of viral, bacterial, or tuberculous origin, multiple sclerosis, and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These results suggest that the 14-3-3 protein expressed constitutively at substantial levels in both neurons and glial cells might be released into the CSF as a disease-nonspecific consequence of the extensive brain damage and indicate that the analysis of the 14-3-3 protein in the CSF is not useful as a screening test for prion diseases.

Animals↗

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Aged↗

Dynamic changes in serum leptin concentrations during the fetal and neonatal periods.

We investigated the dynamics of the leptin concentration throughout the perinatal period. Serum leptin concentrations in venous cord blood at different gestational ages were measured in 20 preterm and 139 term newborns, as well as in 143 pregnant women and 24 term newborns at approximately 6 d of life. Leptin concentrations in preterm newborns (mean 4.6+/-6.9 ng/mL) were lower than those in term newborns (mean 19.6+/-14.3 ng/mL) and tended to increase according to gestational age and birth weight, especially from the late stage of gestation. Leptin concentrations in pregnant women increased from the first trimester and then remained higher than those in non-pregnant women throughout the remainder of pregnancy even after controlling for body mass index. The leptin concentrations of newborns declined rapidly and were extremely low by approximately 6 d of life (mean 1.9+/-1.1 ng/mL). These results suggest that fetuses might produce a part of circulating leptin in their own adipocytes and that the relatively high leptin concentrations at birth and their rapid decline in the early neonatal period might reflect the dramatic changes of the hormonal and nutritional state during the perinatal period.

Body Mass Index↗

Development changes in long-form leptin receptor expression and localization in rat brain.

The expression and localization of long-form leptin receptor (OB-Rb) were studied immunocytochemically in the brain of fetal and adult rats using a polyclonal antibody that specifically recognized OB-Rb. At 14 days of gestation, immunoreactive cells were observed in the ventricular layer, which contains premature neuronal cells. At 18 days of gestation, they were weakly stained but obvious in the paraventricular nucleus (PVN), and ependymal cells also showed immunoreactivity. At birth, the immunoreactivity of OB-Rb in the PVN seemed to be much lower than that in adult rats and remained low during the suckling period. Considering the presence of neuroendocrine and structural neuronal abnormalities in Lepob/Lepob mice with genetic leptin deficiency, these results suggest that the expression of OB-Rb in premature neuronal cells may have some function, and that the regulation of energy balance by leptin through hypothalamic regions, such as PVN, may not yet be developed in the perinatal period.

Aging↗

An epidemic of parapoxvirus infection among cattle: isolation and antibody survey.

A disease characterized by papules, nodules, vesicles and, rarely, pustules and ulcers on teats was seen among cattle on a farm in Chiba Prefecture, Japan. A virus was isolated by inoculation of fetal bovine lung cell cultures from a vesicle on a teat of an infected cow. The virus was subsequently passaged in fetal bovine lung and muscle cells in which it produced complete cytopathic changes. The virus was identified by physicochemical examinations and electromicroscopic observation as a parapoxvirus. A seroepidemiological survey was performed on antibody to the isolated virus by the agar gel immunodiffusion test. The isolated virus formed a precipitation line which cross reacted with other parapoxviruses isolated previously in Japan. The positive rate was more than 50% among cattle in the Kanto district. The positive rate increased with age. It was suggested that parapoxvirus infection might have already been prevalent among cattle in Japan.

Age Factors↗

Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factor-beta and platelet-derived growth factor-BB.

Pathologic remodeling of mesangial matrix after glomerular injury is the central biologic feature of glomerular scarring (sclerosis). Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated in the development of glomerular scarring in rat and human glomerulonephritis. To clarify molecular and cellular mechanisms involved in abnormal mesangial remodeling, this study focused on the role of alpha1beta1 integrin, a collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction as an experimental model of in vivo collagen matrix remodeling and scar formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell (MC)-mediated collagen gel contraction in association with the alpha1beta1 integrin expression was evaluated. Integrin function blocking studies using anti-alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is essentially required not only for collagen-dependent adhesion/migration, but also for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin in mesangial cells cultured on plastic surface and in collagen gels. The upregulation of alpha1beta1 integrin expression by TGF-beta correlated with increases in gel contraction and collagen-dependent adhesion but not migration of mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction and migration without affecting cell adhesion to collagen I. Growth factor-induced collagen-dependent adhesion, migration, and gel contraction were significantly attenuated by incubation with anti-alpha1, beta1 subunit antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen matrix remodeling can be modulated by TGF-beta and PDGF-BB via different mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF-beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.

Animals↗

Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

We investigated the effect of stabilized Fab oligomerization by disuccinimidyl suberate on tumor uptake in a pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A10, which was previously shown to react specifically with gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in tumors than Fab or F(ab')2 but lower than IgG. However, oligomers with C-C bonds maintained higher tumor to normal tissue specificity ratios than IgG 24 h post-infusion. In conclusion, tumor uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab')2, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose radionuclides with reduced radio-uptakes in normal tissues for the radioimmunotherapy of gastrointestinal carcinomas.

Animals↗

Proliferating cell nuclear antigen as a predictor of therapeutic effect of continuous 5-fluorouracil administration in gastric cancer.

The change of proliferating cell nuclear antigen (PCNA) expression was examined in three gastric cancer cell lines, MKN28, MKN45 and MKN74, during continuous or bolus exposure to 5-fluorouracil (5-FU). The cytotoxic effect of 5-FU was almost the same in all the cells. PCNA expression was higher at 24 and 72 h after continuous 5-FU treatment than before treatment. Continuous 5-FU treatment of cells revealed higher expression of PCNA protein and mRNA than did bolus treatment. Flow cytometry revealed that 5-FU increased cell population at the late G1 or S phase 24 and 72 h after treatment. PCNA values at the late G1 and S phase were significantly higher than those at other phases 24 h after treatment. These results suggest that PCNA expression increased due to cell cycle accumulation at late G1 and S phases. Thus PCNA values just after chemotherapy of gastric cancer may be useful in predicting the therapeutic effects of continuous 5-FU administration.

Antimetabolites, Antineoplastic↗

[Clinical results and prognostic factors of radiotherapy for bone metastases from breast cancer].

The purpose of this study was to analyze the results of initial radiotherapy for bone metastases (BM) from breast cancer and to investigate the prognostic factors. Between 1981 and 1995, 65 women (109 lesions) received initial radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG score. The control rates of pain including the prevention of pathological fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median survival time of all patients was 11 months, and the survival rates were 56% at 1 year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long-term survivors. Univariate analysis showed that a normal state of LDH, no other metastatic organs, a disease-free interval longer than two years, good performance status (0 or 1), BM limited to the axial bones, maintenance chemo-hormonal therapy and an age of more than 55 years were good prognostic factors. Multivariate analysis showed that LDH, age and performance status were significant predictors of prognosis. It is important to note the prognostic factors at the initial treatment of BM from breast cancer. We consider that further prospective studies are needed to determine the optimal treatment schedule, including radiotherapy and its combination with chemohormonal therapy, for BM.

Adult↗