Biomedical subjects

A Kubota

Publications and source records attributed to A Kubota.

At least 55 records · Page 3Linked to original sources

PubMed2000

Reduction in excessive muscle tone by selective depletion of serotonin in intercollicularly decerebrated rats.

Intercollicular decerebration in animals induces sustained facilitation of muscle tone of the limbs and this animal model has been used to assess centrally acting muscle relaxants. We have examined the involvement of central and spinal cord serotonergic pathways in the onset of excessive muscle tone in an intercollicularly decerebrated rat. Descending serotonergic pathways are known to modulate, directly or indirectly, the excitability of spinal cord motoneurons and it is inferred that serotonin (5-HT) plays an important role in locomotion. Alteration of muscle tone has been investigated in 5-HT-depleted rats with a neurotoxin, 5, 7-dihydroxytryptamine (5,7-DHT) after pretreatment with desipramine. Intracerebroventricular (i.c.v.) administration of 5,7-DHT reduced 5-HT content in the forebrain to 50.5% and that in the spinal cord to 10.5%, while intrathecal (i.t.) administration of 5,7-DHT decreased 5-HT content in the spinal cord to 8.9% without causing any change in the forebrain. In contrast, noradrenaline or dopamine content was not affected by the neurotoxin in both tissues. These treatments significantly attenuated the muscle tone in the animal models. Moreover, the measurement of 5-HT and 5-hydroxyindoleacetic acid content in intact rats after decerebration showed that facilitation of the 5-HT turnover in the spinal cord, but not in the forebrain, was enhanced compared with sham-operated rats. These findings suggest that the descending serotonergic pathways are essential to induce excessive muscle tone in the intercollicular decerebrated rats and that 5-HT antagonists might be candidates for centrally acting muscle relaxants.

5,7-Dihydroxytryptamine↗

PubMed2000

Congenital ileal atresia presenting as a single cyst-like lesion on prenatal sonography.

A routine prenatal sonographic examination at 37 weeks' menstrual age revealed a large sonolucent lesion with peristaltic movement in the abdomen of a fetus. After birth, the female infant showed progressive abdominal distention, and radiography showed a bubble-like dilatation of the small intestine. Exploratory laparotomy revealed ileal atresia with nearby partial torsion of the dilated small bowel. The incomplete torsion may have functioned as a check valve, inducing segmental dilatation of the ileum without proximal dilatation.

Female↗

PubMed2000

Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression.

In the mouse, two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2, have been identified on NK cells. Individual NK cells can express several Ly49 molecules as well as members of the CD94/NKG2 family. The expression of multiple receptors with different specificities for MHC class I is thus thought to generate NK cells with diverse recognition patterns. To delineate the mechanism by which NK cells begin to express different patterns of Ly49 and CD94/NKG2 molecules, we developed a clonal assay in which NK1.1(-), IL-2/ IL-15 receptor beta+ NK precursors generated by culture of multipotential Lin(-), c-kit+ progenitors in IL-7, stem cell factor and flt3 ligand are induced to differentiate into NK1.1+ , Ly49+ NK cells. Examination of the clonal populations thus generated revealed heterogeneity in the pattern of Ly49 and CD94/NKG2 gene expression. In addition, a distinct kinetic pattern of expression was observed. CD94, NKG2A, NKG2C and Ly49B were expressed first followed by Ly49G, then Ly49C and I and finally, Ly49A, D, E and F. The data suggest a stochastic but ordered acquisition of class I receptors on NK cells in which developing NK cells become capable of expressing distinct receptors at different times but show no absolute prerequisite to express the receptors that are acquired early in NK development for the expression of those that are acquired later.

Animals↗

PubMed2000

Amsler grid examination and optical coherence tomography of a macular hole caused by accidental Nd:YAG laser injury.

PURPOSE: To compare a macular hole from accidental Nd:YAG laser injury with idiopathic macular holes. METHODS: Case report. In a 24-year-old man with accidental Nd:YAG laser injury, right eye, Amsler grid testing and optical coherence tomography were performed. RESULTS: Nd:YAG laser injury was responsible for a macular hole about 700 microm in diameter. The visual acuity was 20/100. Amsler grid testing displayed a central scotoma with no surrounding distortion. Optical coherence tomography showed a defect in all retinal layers at the macula. CONCLUSION: The scotoma caused by Nd:YAG laser injury is not surrounded by distortion; the hole is produced by the defect of all retinal layers. In contrast, idiopathic macular holes generally produce a pincushion pattern on Amsler grid testing and have no tissue loss.

Accidents, Occupational↗

PubMed2000

Successful closure of recurrent traumatic csf rhinorrhea using the free rectus abdominis muscle flap.

BACKGROUND: We present two patients in whom a free rectus abdominis muscle flap was used to close recurrent traumatic CSF rhinorrhea. CASE DESCRIPTION: CT scan of both patients showed frontal lobe atrophy and porencephaly after contusional hematoma. In the first patient, because the site of CSF leakage was not identified and the patient underwent three unsuccessful attempts to close the fistula using the fascia lata, we treated the patient by unifying all paranasal sinuses and by filling them with a free rectus abdominis muscle flap. In the second patient, CSF rhinorrhea recurred 6 years after closure of the fistula using the fascia lata. The patient underwent separation of a porencephalic cyst from the paranasal sinus and a free muscle flap was placed extradurally, because the CSF pulse pressure in the enlarged left anterior horn eroded the previously repaired fascia lata, resulting in the recurrence of CSF leakage. CONCLUSION: Although duraplasty is the primary procedure for repairing dural fistulas, the vascularized free muscle flap is an alternative method when the location of the fistula is not identified or the patient with recurrent CSF rhinorrhea has severe frontal lobe atrophy and porencephaly.

Adult↗

PubMed2000

Investigation of TTV by in situ hybridization in patients with chronic hepatitis.

To clarify whether TT virus (TTV) was present in liver tissues, 12 liver tissue samples from patients with chronic hepatitis positive for TTV in their serum and 11 samples from serum-negative patients were obtained by needle biopsies and investigated using in situ hybridization. Positive staining was observed in nine (75%) of 12 cases positive for TTV (serum-positive group) and three (27.3%) of 11 cases negative for TTV (serum-negative group) (P=0.061). Three kinds of staining patterns were observed: nuclear, cytoplasmic and both. In 58.3% (7/12) of the patients positive for TTV staining, the stained areas were found in both the nucleus and cytoplasm. Only cytoplasmic staining was observed in three cases from the serum-positive group. Only nuclear staining was observed in two cases from the serum-negative group. No significant differences were found in the clinical background between the in situ hybridization-positive and -negative groups, and between the serum-positive and -negative groups. The present study shows that TTV exists in the liver tissue, especially in hepatocytes, of chronic hepatitis patients and that the localization of TTV in the cell is different from case to case, although why this is so remains to be clarified.

Journal Article↗

PubMed2000

Two cases of persistent hyperinsulinemic hypoglycemia that showed spontaneous regression and maturation of the Langerhans islets.

Near-total pancreatectomy has been recommended as the treatment for persistent hyperinsulinemic hypoglycemia (PHH) in infants. However, recently there has been a report described that one third of 95% pancreatectomy failed to prevent hypoglycemia and more than two thirds had diabetes ultimately. The authors experienced 2 cases of PHH, which raise a query about the extensive pancreatectomy. Case 1: A female patient who manifested PHH shortly after birth underwent less extensive pancreatectomy twice at age 2 months and 8 years. After each operation, her clinical symptoms regressed, and she became free from the disease eventually. Histologic findings showed nesidioblastosis in which the islets clearly matured. Case 2: A male infant with PHH had an absolute indication for pancreatectomy. However, after a meticulous control of the blood glucose level with parenteral nutrition followed by continuous enteral nutrition feeding combined with medication, he became free from the disease. The current cases show there exist cases of PHH in which the islets mature and symptoms regress spontaneously. Therefore, we conclude near-total pancreatectomy is not always the treatment of choice. As an alternate strategy, long-term controlled feeding and medication combined with or without less extensive pancreatectomy should be considered with the expectation of spontaneous regression.

Adenoma, Islet Cell↗

PubMed2000

Surgical intervention for emphysematous pulmonary regions in a postoperative infant with congenital diaphragmatic hernia.

A postoperative infant with congenital diaphragmatic hernia (CDH) developed extrinsic obstruction of the trachea by the innominate artery that ensued from unequal expansion of the lungs followed by left mediastinal shift. Septation of the anterior mediastinum prevented unequal expansion of the lungs, and elongation of the innominate artery improved proximal airway obstruction. Prolonged artificial ventilation, however, resulted in the emphysematous bullae in the left lung. Lung volume reduction surgery (LVRS), at 3 years of age, ameliorated the respiratory distress and resulted in good weight gain. Surgical intervention, including LVRS, should be considered to improve respiratory disturbance caused by difference in compliance of the lungs in children.

Hernia, Diaphragmatic↗

PubMed2000

Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience.

BACKGROUND/PURPOSE: There are few long-term chronological reviews examining the incidence of total parenteral nutrition (TPN)-associated intrahepatic cholestasis (TPNAC) in infants. The authors therefore reviewed TPNAC in their 25-year series, and also looked at the current problems associated with TPN in infants. METHODS: Two hundred seventy-three surgical neonates who received TPN for more than 2 weeks were divided into 3 groups chronologically: group A (1971 through 1982, n = 77), group B (1983 through 1987, n = 72), and group C (1992 through 1996, n = 124). TPNAC was defined as serum direct bilirubin (DB) level greater than 2.0 mg/dL during the neonatal period. RESULTS: The incidence of TPNAC in groups A, B and C was 57%, 31%, and 25% (P< .01), respectively, and the mortality rate from TPN-associated complications was 13%, 3%, and 3% (P< .05), respectively. Over the last 5 years, severe TPNAC developed in 20 patients (16%). Four of 20 died of TPN-associated sepsis with hepatic failure; 2 had hypoganglionosis with intractable stagnant enteritis and subsequent sepsis, and 2 had fatal respiratory or cardiac disease. CONCLUSIONS: The incidence of TPNAC in surgical neonates and TPN-associated mortality rates have decreased significantly. The mortality rate, however, still remains at 3%. Two of 4 fatal cases had hypoganglionosis, which were totally dependent on TPN. In patients who require long-term TPN, TPN still has unsolved problems, and small bowel transplantation may be indicated.

Cholestasis, Intrahepatic↗

PubMed2000

Effect of liposome-mediated macrophage depletion on Schwann cell proliferation during Wallerian degeneration.

The axolemma is considered a well-established mitogen, responsible for Schwann cell proliferation during Wallerian degeneration in the peripheral nerve. However, very little is known about the role of macrophages in Schwann cell proliferation. To test the possible influence of macrophages on Schwann cell proliferation during Wallerian degeneration, macrophages were depleted by dichloromethylene diphosphonate (CI2MDP)-containing liposomes in two-month old C57BL/6J mice. CI2MDP-containing liposomes were injected into the mice intravenously prior to inducing Wallerian degeneration. The injection was repeated every other day to maintain macrophage depletion. Physiologic saline was injected into the control mice. To assess macrophage depletion in vitro, cells were isolated from sciatic nerves at 1, 2, 3, 5, and 7 days post-transection (DPT) and Mac-1 positive cells attached to coverslips were counted. In an in vivo study, Mac-1 positive cells were counted on sciatic nerve sections at the same time points. Throughout the course, the number of Mac-1 positive cells in macrophage-depleted mice was less than that in the control mice both in vivo and in vitro. Schwann cell proliferation was assessed by an in vitro system that reflects in vivo status at the time of cell isolation. Schwann cells were isolated from sciatic nerves at the same time points and proliferation rate was measured by thymidine autoradiography. The proliferation rate was mildly suppressed in macrophage-depleted mice, especially for the initial 3 DPT; however, the pattern of proliferation was not significantly different from controls. These results suggest that macrophages contribute to Schwann cell proliferation during Wallerian degeneration however, their contribution may be relatively limited.

Analgesics, Non-Narcotic↗

PubMed2000

Infiltration of hematogenous lineage cells into the demyelinating central nervous system of twitcher mice.

Infiltration of hematogenous lineage cells into the central nervous system (CNS) was investigated in the twitcher mouse, a murine model of globoid cell leukodystrophy in human. The hematogenous cells were selectively labeled following intraperitoneal injection of rhodamine isothiocyanate (RhIc). The frequency of detecting Rhlc-labeled cells (Rhlc+ cells) in the twitcher CNS varied with age. RhIc+ cells were hardly detected when injection was made prior to the postnatal day (PND) 30. The number of Rhlc' cells increased thereafter peaked at PND 35-38 and declined drastically at PND 40-45. The majority of RhIc+ cells were distributed in white matter of the CNS that correlated well with the areas of demyelination and of increased microglia/macrophage population described in our earlier studies. Almost all Rhlc+ cells were double-labeled with antibody for Mac-1 and also with MHC class II. Some small cells double-labeled with RhIc and antibodies for CD4, CD8, or IL-2R were also identified. By RT-PCR, the expression of monocyte chemoattractant protein- (MCP-1) mRNA increased drastically at PND 30, peaked at PND 35, and decreased gradually after PND 40. This pattern of mRNA changes correlated well with the dynamic pattern of the infiltration of hematogenous cells into the CNS, suggesting a role of chemokine(s) in the cellular infiltration in the twitcher brain. The expression of IL-10 mRNA also increased gradually. IL-10 is a cytokine inhibitory factor and a major regulator in suppressing the inflammatory response. Thus, our results indicated that hematogenous lineage cells infiltrated in the CNS of twitcher mice, and that MCP-1 and IL-10 may play an important role in regulating the cellular recruitment.

Animals↗

PubMed2000

[Effects of low concentration of styrene monomer vapor on pregnancy].

To investigate the effects of exposure to styrene vapor on pregnancy, mice proved to be pregnant were exposed to 0, 2, 20 and 100 ppm styrene continuously for 24 hours during the period from day 0 to day 15 of gestation. A special small exposure chamber which can accurately maintain a constant low concentration of styrene vapor was made and used in the experiment. 1) In the 100 ppm group, hyperkinesis was presented in the chamber during the exposure period and inhibition of body weight gain was found (p < 0.01). No deaths occurred in any of the groups. 2) At necropsy of dams, no significant difference was found between the styrene exposed groups and the control group in any of the fertility indices, number of implantations, number of live fetuses, percentage of resorptions, or in the percentage of dead fetuses. The 100 ppm group showed lower fetal and placental weights (p < 0.01). 3) Gross necropsy of dams in the 100 ppm group showed significantly decreased adipose tissue. The liver, kidney and spleen weights were also low (p < 0.01). 4) When exposed to 100 ppm, which corresponds to 5 times the permissible concentration, i.e., 20 ppm, for 24 hours, non-pregnant dams showed no abnormality, while pregnant dams showed inhibition of body weight gain and significantly lower fetal and placental weights and maternal organ weights. Therefore, careful consideration should be given to exposure of women of childbearing age to styrene.

Animals↗

PubMed2000

Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.

Activating Transcription Factor 2↗

PubMed2000

[Cervical lymph node metastasis from an unknown primary tumor].

Between June/1986 and June/1999, we treated 18 cases of previously untreated metastatic carcinoma in cervical lymph nodes from an unknown primary tumor. Among them, 15 cases were squamous cell carcinoma, 2 were adenocarcinoma, and one was undifferentiated carcinoma. The dose of radiotherapy, which was planned only for the cervical lymph nodes, was 60-70 Gy at the metastatic sites. Preventive radiotherapy at possible primary sites was performed only in one case. After these treatments, a primary lesion appeared in only two cases: in one case a tumor was found in the hypopharynx, and the other, which had been diagnosed as undifferentiated carcinoma, proved to be malignant lymphoma. Outcomes were analyzed except for these two cases. The five-year survival rate was 31%. The loco-regional control rate was 57% after radiation treatment limited to the affected cervical lymph nodes. Distant metastasis appeared more often in open-biopsy cases than in those receiving fine-needle aspirations (FNA). According to these results, treatment of possible primary sites may not be necessary, and for initial pathological diagnosis, FNA is recommended, while open biopsy should be avoided, if possible.

Adenocarcinoma↗

PubMed2000

[Evaluation of hepatic toxicity following high-dose 5-FU arterial infusion chemotherapy: analysis of 42 cases of colorectal liver metastases].

The regional toxicity of an anticancer agent for normal liver tissue following hepatic arterial infusion chemotherapy (HAI) was evaluated in terms of morphology, function, and histopathology. Forty-two patients(M:F = 30:12; mean age, 59.9 years) with liver metastases from colorectal cancer were treated with HAI using a totally implantable vascular access port system from July 1994 to March 1999. The regimen used here was so-called weekly high-dose 5-fluorouracil(5-FU) infusion(5-FU, 1,000 mg/m2/week). Volume measurement of the liver demonstrated not only whole liver atrophy including the tumor but also volume reduction of the non-tumorous lobe. Atrophic change of the liver was seen in patients who were administered over 20 g/m2 of 5-FU(p < 0.01). The CT attenuation values of the liver were examined, and fatty infiltration was seen in six patients. Histologic examination of liver biopsies from the non-tumorous part revealed steatosis and infiltration of inflammatory cells in the portal triad, which were not seen in specimens prior to HAI. On clinical laboratory findings, enzymes representing bile duct, including alkaline phosphatase, leucine amino peptidase, and gamma-glutamyltranspeptidase, were increased in 22 patients. In terms of regional toxicity for long-term HAI, 20 g/m2 of 5-FU, is the key dose at which to consider temporary cessation or dose reduction.

Adult↗

PubMed1999

Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice.

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.

Administration, Oral↗

PubMed1999

IFN-gamma production and cytotoxicity of IL-2-activated murine NK cells are differentially regulated by MHC class I molecules.

Activation of NK cells by target cells leads to cytotoxicity as well as production of various cytokines including IFN-gamma. MHC class I molecules on target cells regulate NK cytotoxicity. However, little is known about the regulation of IFN-gamma production by NK cells. We examined the production of IFN-gamma in individual murine NK cells stimulated with tumor cell lines by flow cytometric analysis of intracellular IFN-gamma. Among several tumor lines tested, the rat basophilic leukemia line RBL-1 induced particularly high level of IFN-gamma production in IL-2-activated NK cells, whereas other lines, including the prototypic NK target YAC-1, induced very low or no IFN-gamma production. Transfection of murine classical MHC class I molecules into RBL-1 cells substantially inhibited IFN-gamma production. This inhibition of IFN-gamma production by MHC class I was independent of Ly-49 or CD94/NKG2A expression on NK cells. These results indicate that some target cells directly stimulate IL-2-activated NK cells and induce IFN-gamma production, but the requirements for the induction of IFN-gamma production seem different from those for NK cytotoxicity. Furthermore, similar to NK cytotoxicity, induction of IFN-gamma production is inhibited by MHC class I on stimulating cells. However, the MHC class I-specific receptors inhibiting IFN-gamma production are different from those for NK cytotoxicity.

Animals↗

PubMed1999

The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID.

We analyzed a mechanism of transcriptional regulation of the human insulin gene by cyclic AMP response element modulator (CREM) through four cyclic AMP response elements (CREs). We isolated two novel CREM isoforms (CREMDeltaQ1 and CREMDeltaQ2), which lack one of the glutamine-rich domains, Q1 and Q2 respectively, and six known isoforms (CREMtaualpha, CREMalpha, inducible cyclic AMP early repressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and the RINm5F pancreatic beta-cell line. CREM isoforms functioned as efficient transcriptional activators or repressors to modulate insulin promoter activity by binding to all of the insulin CREs. The binding activity of repressors is higher than that of activators and suppressed not only basal activity but also activator-induced activities. Furthermore, CREM activator interacted directly with the transcription factor IID components hTAF(II)130 and TATA box-binding protein (TBP). These results suggest that the activation of the insulin gene transcription by CREM activator is mediated by not only direct binding to the CREs but also by recruiting transcription factor IID to the insulin promoter via its interaction with hTAF(II)130 and TBP. On the other hand, the CREM repressor ICER competitively interrupts the binding of the activators to CREs and does not interact with either TBP or hTAF(II)130; therefore, it might fail to stabilize the basal transcriptional machinery and repress transactivation.

Animals↗