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Biomedical subjects

A Kubota

Publications and source records attributed to A Kubota.

At least 73 records · Page 4Linked to original sources
PubMed1999

Diversity of NK cell receptor repertoire in adult and neonatal mice.

Murine NK cytotoxicity is regulated by two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2. We developed a single-cell RT-PCR method to analyze expression of all known Ly49 and NKG2A genes in individual NK cells and determined the receptor repertoires of NK cells from adult and neonatal (1-wk-old) C57BL/6 mice. In adult mouse NK cells, up to six different receptors were coexpressed in random combinations. Of 62 NK cells examined, 42 different patterns of receptor expression were observed. Most of them expressed at least one Ly49, whereas NKG2A was detected in 32% of the cells. Over 75% of them expressed Ly49C, I, or NKG2A, which are thought to recognize self-class I MHC (H-2b). Coexpression of multiple Ly49 receptors and NKG2A was stochastic. In contrast, very few neonatal NK cells expressed any Ly49, but almost 60% of them expressed NKG2A. These results demonstrate that adult NK cells are quite heterogeneous and have diverse receptor repertoires. They also suggest that the expression of NKG2A precedes Ly49 expression in NK cell ontogeny, and NKG2A is a major inhibitory receptor in neonatal NK cells.

Aging↗
PubMed1999

Inhibition of NK cells by murine CMV-encoded class I MHC homologue m144.

Murine cytomegalovirus (CMV)-encoded protein m144 is homologous to class I MHC heavy-chain and is thought to regulate NK-cell-mediated immune responses in vivo. To examine the effects of m144 on NK cytotoxicity in vitro, various cell lines were transfected with wild-type m144 or a chimeric construct in which the cytoplasmic domain of m144 was replaced with green fluorescence protein. Burkitt lymphoma line Raji expressed a significant level of m144 as determined by anti-m144 mAb binding or the green fluorescence of the fusion protein. The level of m144 expression was relatively low compared with that of transfected murine class I MHC Dd. However, m144 on Raji cells partially inhibited antibody-dependent cell-mediated cytotoxicity of IL-2-activated NK cells. NK cells from the CMV-susceptible BALB/c as well as those from the resistant C57BL/6 mice were inhibited by m144. Antibodies against the known murine NK inhibitory receptors Ly-49A, C, G, and I did not affect the inhibitory effect of m144. These results suggest that the murine CMV class I MHC homologue m144 partially inhibits NK cells by interacting with a novel inhibitory receptor.

Animals↗
PubMed1999

The MH1 domains of smad2 and smad3 are involved in the regulation of the ALK7 signals.

The biological responses of the transforming growth factor beta (TGF-beta) superfamily are induced by activation of a receptor complex and Smad proteins. We surveyed the TGF-beta superfamily receptors using the degenerate PCR strategy, and found activin receptor-like kinase 7 (ALK7) to be abundantly expressed in fetal rat pancreatic islets. ALK7 is also expressed in adult rat islets and pancreatic beta-cell-derived MIN6 cells. The constitutively active form of ALK7, ALK7(T194D), activated Smad3 and a chimeric Smad protein, Smad3-2, containing the MH1 domain of Smad3 and the MH2 domain of Smad2, and translocated them to nuclei and then induced activation of the human PAI-1 promoter. However, neither Smad2 nor Smad2-3 protein, containing the MH1 domain of Smad2 and the MH2 domain of Smad3 were activated. These results indicate that the ALK7 signal regulates nuclear localization and activation of Smad2 and Smad3, and the MH1 domain of Smad2 has inhibitory effects on the nuclear localization.

Activin Receptors↗
PubMed1999

Handlebar hernia: case report and review of pediatric cases.

The authors describe a rare case of handlebar hernia in a 9-year-old-boy. All layers of his abdominal wall were disrupted by a fall on a bicycle; however, his skin and intra-abdominal organs were completely intact. Computed tomography demonstrated subcutaneous intestinal loops protruding through the rent. Surgical repair was performed, and his postoperative course was uneventful.

Abdominal Muscles↗
PubMed1999

Tracheal agenesis in a child who survived for 6 years.

The authors report on a child with tracheal agenesis who survived for 6 years and 10 months. A female infant was born with respiratory distress and an absence of audible cry. With mask ventilation, gastrostomy and division of the esophagus was performed just after birth. She was well ventilated with an endotracheal tube inserted through the cervical esophagostomy after thoracic esophageal banding. An accidental extubation caused her anoxic encephalopathy at 9 months of age. She had been alive without artificial ventilatory support until she died of acute esophageal bleeding.

Abnormalities, Multiple↗
PubMed1999

Benign mesenchymoma of the cheek: report of a case and review of the literature.

Benign mesenchymoma is a soft tissue neoplasm that contains 2 or more differentiated mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the cheek in a 6-year-old boy is presented. The literature pertaining to mesenchymoma in the head and neck region is reviewed and discussed.

Cheek↗
PubMed1999

Functional ileus in neonates: Hirschsprung's disease-allied disorders versus meconium-related ileus.

Sixty-eight neonates with functional ileus were reviewed. Twelve required laparotomy; in seven, histological studies revealed decreased ganglia and ganglion cells of the myenteric plexus (MP) (Group A), and in five, MP was normal (Group B). In the remaining 56 cases, obstructive symptoms were relieved following conservative therapy (Group C). All Group A cases except one had normal birth weight, while Group B and C cases showed significantly lower birth weights. A marked caliber change of the small intestine and/or small-caliber distal intestine with meconium stagnation in the proximal intestine was commonly demonstrated at operation in Group A and B, or on contrast enema in Group C. Four Group A cases died of enteritis, and three survivors suffered from prolonged obstructive symptoms. The grade of histological abnormality of MP correlated with the clinical outcome. In Group B, three died of sepsis shortly after surgery, but two survivors have been free from symptoms. Group A can be categorized as Hirschsprung's disease-allied disorders (HAD). Group B and C can be categorized as meconium-related ileus (MRI). The similarity of the macroscopic findings of HAD and MRI, and the occurrence of MRI exclusively in low birth weight neonates, strongly suggest that functional immaturity of MP plays a role in the etiology of MRI.

Ganglia↗
PubMed1999

Genetic vulnerability of cortical neurons isolated from stroke-prone spontaneously hypertensive rats in hypoxia and oxygen reperfusion.

Severe hypertension and cerebrovascular diseases develop in stroke-prone spontaneously hypertensive rats (SHRSP). Cortical neurons from SHRSP are more vulnerable than those from Wistar Kyoto rats (WKY) to the effects of nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, idebenone, and nilvadipine (a Ca2+ channel blocker) can reduce neuronal damage caused by hypoxia or neurotoxic agents. This study was designed to determine 1) whether cortical neurons from SHRSP are more vulnerable than those from WKY and 2) whether neuronal damage is minimized by the so-called neuroprotective agents in cells exposed to hypoxia and oxygen reperfusion. We demonstrated that 6 to 24 h of hypoxia did not increase cell death in either WKY or SHRSP, whereas 36 h of hypoxia significantly increased cell death in SHRSP (p < 0.01). Furthermore, 6 to 36 h of hypoxia and 1.5 to 5 h of reperfusion heavily damaged cells from both strains of rats, and most cells became apoptotic or necrotic. We also verified that the ability to protect neurons in hypoxia and oxygen reperfusion was as follows: idebenone > insulin-like growth factor-1 (IGF-1) > nilvadipine. These data indicate that oxygen radical generation occurs and the free radicals heavily damage neurons in hypoxia and oxygen reperfusion. SHRSP neurons are weaker than WKY neurons in these conditions. Furthermore, we surmise that idebenone, an antioxidant, decreases free radicals, and IGF-I attenuates p53-mediated apoptosis and thereby prevents cell death. We conclude that antioxidants are more potent than IGF-1 in protecting cortical neurons from damage caused by hypoxia and oxygen reperfusion, although both are very useful in minimizing damage to cortical neurons.

Animals↗
PubMed1999

Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.

Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen radicals were involved in reoxygenation injury after hypoxia in hippocampal slices. Vitamin E inhibited the reoxygenation injury in cultured cortical neurons. In addition, the temporal cortices in Alzheimer's disease have increased sensitivity to oxygen radicals, and Vitamin E slowed the progression of the disease. Thus we fed Wistar Kyoto and SHRSP rats either a normal diet or a high Vitamin E diet for 3 weeks. We measured Vitamin E concentrations of plasma and brain by applying the HPLC method. Vitamin E increased its concentration in plasma, cerebral cortex, and hippocampus (p < 0.01) during a 3-week pretreatment. In addition, we clipped both common carotid arteries in these rats for 30 minutes. After the blocking, the rats were reperfused for 6 and 9 days, respectively, and then killed. We cut the brains coronally, removed the hippocampal CA1 regions, and examined the neurons using an electron microscope. SHRSP rats with normal cerebral circulation had 30.4+/-8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by 6 and 9 days of reperfusion, respectively, increased apoptotic neurons in SHRSP rats fed a normal diet (6 days: 542.5+/-154.1 per 1000 neurons; 9 days: 657.5+/-110.2 per 1000 neurons). In contrast, apoptotic neurons in SHRSP rats fed a high Vitamin E diet were significantly (p < 0.01) small in number (6 days: 41.3+/-27.5 per 1000 neurons; 9 days: 35.5+/-19.7 per 1000 neurons) even though the rats were treated in the same way. These data demonstrate that oxygen radical generation occurs after reperfusion and that free radicals heavily damage the neurons in SHRSP rats. Vitamin E reacts with the radicals and prevents neuronal apoptosis caused by cerebral ischemia and reperfusion. Therefore, Vitamin E seems to be an important agent in lowering radical damage to hippocampal neurons.

Animals↗
PubMed1999

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗
PubMed1998

Transcriptional repressors are increased in pancreatic islets of type 2 diabetic rats.

To further clarify the mechanism of impaired insulin gene transcription in the diabetic state, we investigated the expression and function of the transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM gene generates both transcriptional activators and repressors by alternative splicing and an intronic promoter. We isolated a novel alternatively spliced CREM isoform, CREM-17X, which efficiently represses insulin gene transcription, in addition to the three previously reported repressors. We also compared mRNA levels of insulin and the CREM repressors in pancreatic islets of Wistar and GK (Goto-Kakizaki) rats, the well-characterized spontaneous animal model of type 2 diabetes. The CREM repressor levels are increased, and the expression of insulin mRNA is decreased in GK rats, suggesting that increased CREM repressor expression in pancreatic islets could contribute to the decreased insulin gene transcription that results in impaired insulin secretion in type 2 diabetes.

Animals↗
PubMed1998

Effect of macrophage suppression with silica on the proliferation of Schwann cells during Wallerian degeneration.

Effects of macrophage suppression on Schwann cell proliferation in Wallerian degeneration was investigated in vitro with thymidine autoradiography. Sciatic nerves of C57BL mice were transected shortly after an intraperitoneal injection of silica dust and Schwann cells were harvested at 1, 2, 3, 5, 7, and 10 days post-transection. In silica treated mice, Schwann cells from post-transected nerve stumps proliferated despite marked suppression of macrophages, although there was some initial delay. The results of this study suggest that the mechanism of Schwann cell proliferation is multifactorial and in addition to the influence of growth factors mediated and released by macrophages, other factor(s) such as degenerated axolemma may play a more pivotal role in Schwann cell proliferation in vivo.

Animals↗