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Biomedical subjects

T Chiba

Publications and source records attributed to T Chiba.

At least 325 records · Page 18Linked to original sources

Sensory innervation to the anterior portion of lumbar intervertebral disc.

STUDY DESIGN: The level of dorsal root ganglia that receives sensory afferent nerves from the anterior portion of the lower lumbar intervertebral disc was investigated in rats using a retrograde transport method. OBJECTIVES: Sometimes patients with lower lumbar disc lesions complain of inguinal pain that does not correspond to the dermatome of the injured nerve roots. To investigate the origin of the pain, the authors studied the sensory innervation to the anterior portion of the lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA: The innervation to the posterior portion of the lumbar disc has been extensively investigated and has been reported to be segmental. However, little is known about the nerve supply to the anterior portion of the lumbar disc. METHODS: The retrograde transport method was used in rats. As tracers, horseradish peroxidase and choleratoxin B subunit were used. Horseradish peroxidase crystals were placed on the anterior portion of the L5-L6 disc, and choleratoxin B subunit was injected into the L5-L6 disc. The bilateral dorsal root ganglia were histologically examined. RESULTS: Labeling of L1 and L2 dorsal root ganglia neurons was recognized. No neurons were labeled in dorsal root ganglia of other levels, including the segmentally corresponding L5. CONCLUSIONS: Using the retrograde transport method, the authors demonstrated that the anterior portion of the L5-L6 lumbar intervertebral disc was innervated from L1 or L2 spinal nerves in rats. These results appear to explain the reason why patients with lower lumbar disc lesions sometimes complain of inguinal pain corresponding to the L1-L2 dermatome.

Animals↗

Inhibition of cholesterylester accumulation by 17 beta-estradiol in macrophages through activation of neutral cholesterol esterase.

Premenopausal women are at a lower risk of coronary heart disease relative to age matched men. However, the underlying mechanisms are not clearly understood. This article studies the effects of 17 beta-estradiol (17 beta-E2) at physiological concentrations on the cholesterylester metabolism in macrophages (J774 A.1 cells) with a particular focus on neutral cholesterol esterase (N-CEase). Cells were incubated with beta-VLDL, [1-14C]oleic acid and 17 beta-E2 (0.25 and 2.5 nM). 17 beta-E2 dose-dependently reduced cholesteryl-[1-14C]oleate (14C-CO) at 36 h and 48 h relative to the control. It also stimulated hydrolysis of 14C-CO in foam cells on 36 h and 48 h incubation. In addition, 17 beta-E2 markedly increased N-CEase activity at 24 h and 36 h. This increase preceded the enhanced hydrolysis of cholesterylester, 17 alpha-E2 (inactive isomer), estrone and estriol had no stimulatory action on N-CEase, whereas progesterone and testosterone inhibited it. 17 beta-E2-treatment (24 h) increased the activity of cyclic AMP-dependent protein kinase (A-kinase). DEAE-cellulose column chromatography revealed that an isoform (type II) of A-kinase appeared in 17 beta-E2-treated cells in addition to type I of A-kinase found in the control cells. These results suggest that inhibition of cholesterylester accumulation in macrophages by 17 beta-E2 is mediated by an enhancement of N-CEase activity possibly through an increase in A-kinase.

Animals↗

Recruitment order and dendritic morphology of rat phrenic motoneurons.

The detailed morphology of rat phrenic motoneurons (PMs) was studied in 40 electrophysiologically identified cells with intracellular injection of Neurobiotin. In 15 cells, the dendritic trees were fully analyzed by using path-distance analysis, and total surface area and volume were estimated. Based on their relative onset times (ROT; i.e., the time of firing onset relative to the onset of whole phrenic activity), PMs were classified into three types; early recruited (type E; ROT < 10%), late recruited (type L; ROT > 12.5%), and quiescent (type Q; not recruited under normal conditions). Dendrites constituted 93.3% of the surface area of cells and 38.9% of the cell volumes. The number of primary dendrites (nPD) averaged 10.1, and the mean number of terminations was 38.8. The combined diameters of primary dendrites of PMs correlated well with the total dendritic surface area and the number of dendritic terminations. Comparisons among cell types revealed that type Q cells had greater dendritic surface areas and volumes than type E or type L cells. With path-distance analysis, this difference was found to be due to differences between the cell types in the numbers of their dendrites, their combined dendritic lengths, and the number of their branches. The differences between these data and those available for cat motoneurons are discussed. The input resistance of PMs correlated with their total surface area but did not correlate with their somal surface area, indicating that, in rat, PM input resistance is a function of the entire neuronal membrane rather than of the somal surface alone.

Action Potentials↗

Ultrastructural localization of nerve terminals containing nitric oxide synthase in rat adrenal gland.

Immunoelectron microscopy was performed to localize immunoreactivity for nitric oxide synthase (NOS) in rat adrenal gland. NOS-immunoreactive (NOS-ir) nerve fibers were observed around blood vessels and endocrine cells in the zona glomerulosa of the cortex. Electron microscopy showed that NOS-ir axon varicosities were in close contact with the smooth muscles of blood vessels and with the cytolemma of endocrine cells. In the adrenal medulla, several NOS-ir ganglion cells were found. Synaptic contacts between non-immunoreactive axons and dendrites of NOS-ir neurons were observed. NOS-ir nerve fibers were distributed among chromaffin cells. Positive axon varicosities were in close contact with the catecholamine-storing chromaffin cells. These results suggest that NOS-ir nerve cells control directly the secretion of corticosteroid and catecholamine in addition to the vascular tone.

Adrenal Cortex↗

Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells.

Fas antigen is a member of the tumor necrosis factor receptor family that transduces a lethal signal to the Fas-sensitive cells. We previously established the Fas-resistant variant cell lines LAC2D1R and JKT2D1R from the parental Fas-sensitive cell lines, SUPT13 and Jurkat, respectively. Recently, we isolated the Fas-resistant variant CEM2D1R from CCRF-CEM. All of the variants were Fas+ but resistant to Fas-mediated apoptosis. Further biochemical analysis revealed that the intracellular glutathione (GSH) content of the Fas-resistant variants was higher than in the original cells. When the Fas-resistant variants were incubated with buthionine sulfoximine (BSO) or in GSH-free/cysteine-free medium to deplete GSH, Fas resistance was reversed. Incubation of the cells with cycloheximide also decreased intracellular GSH and reversed the Fas resistance. Furthermore, incubation of activated peripheral blood lymphocytes with BSO enhanced Fas-mediated apoptosis. When the Fas-sensitive cells were incubated with N-acetylcysteine (NAC), intracellular GSH was increased and Fas-mediated apoptosis was blocked. In contrast, Fas-resistant variants, as well as Fas-sensitive cells pre-treated with NAC remained susceptible to allogeneic lymphokine-activated killer cells, most likely due to perforin-dependent killing. The results suggest that Fas-mediated apoptosis, but not perforin-dependent killing, is modulated by intracellular GSH in human T lymphocytes.

Acetylcysteine↗

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis.

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P < 0.001), habitual heavy drinking (P < 0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc, P < 0.05), and age greater than 60 years (P < 0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80-9.78) in male patients, 3.27 (95% CI, 1.46-7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01-3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00-4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively, P < 0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4 +/- 4.4 years vs 28.4 +/- 3.9 years; P < 0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis.

Age Factors↗

Severe acute hepatitis A associated with acute pure red cell aplasia.

A rare case of severe acute hepatitis A complicated by pure red cell aplasia (PRCA) is reported. A 60-year-old man with jaundice and hepatomegaly was diagnosed as having acute hepatitis A by positive IgM anti-hepatitis A antibody (anti-HAV). Severe anemia rapidly developed 3 weeks after admission, and the patient was diagnosed with PRCA by both bone marrow smears and erythrocyte survival study. The anemia was transient and bone marrow recovered within 1 week. However, concomitant with bone marrow recovery, the hepatitis worsened. He became drowsy and disoriented and severe jaundice, ascites, prolonged prothrombin time, increased transaminase levels, and abnormal electroencephalogram (EEG) were exhibited. Plasma exchange transfusion and glucagon-insulin (GI) therapy improved the consciousness level, but bilirubin, transaminase levels, and IgM anti-HAV titer remained high. Intravenous administration of lipophilized prostaglandin E1 (lipo-PGE1) was added to the GI therapy. Bilirubin and transaminase levels were normalized in the 8th week after the initiation of this combination therapy (17 weeks after admission). The combined use of lipo-PGE1 with plasma exchange and GI therapy appeared to be useful for the prolonged severe hepatitis in this patient.

Acute Disease↗

Changes in the distribution of cells expressing tumour-associated antigen in lymph nodes during the progression of enzootic bovine leukosis.

A monoclonal antibody (MAb), c143, that recognizes a tumour-associated antigen that is "upregulated" on neoplastic B cells in cattle with enzootic bovine leukosis (EBL), was used as a marker to study disease progression. An immunohistochemical examination of neoplastic tissue and superficial cervical lymph nodes from 14 animals with EBL revealed three morphologically definable stages of change in the structure of lymph nodes, associated with the distribution of c143-positive cells: (1) the presence of c143-positive cells at the marginal sinus with no apparent changes in lymph node structure; (2) the presence of positive cells extending into and distorting the architecture of the lymph node, with clear evidence of proliferation before overt changes (enlargement of lymph nodes) were evident; and (3) the presence of positive cells throughout the lymph node with total disruption of lymph node structure when clinical signs of lymph node enlargement were evident. The results indicated that the bovine leukaemia virus-transformed lymphocytes or neoplastic cells in peripheral blood accumulate in the marginal sinus area at the earliest stages, and subsequently proliferate and infiltrate into follicles, leading to the development of clinical signs of lymphosarcoma.

Animals↗

Antinociceptive activity of deltorphin analogs in the formalin test.

Two deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogs, [N alpha-n-butyl-Gly6]DLT ([nBuG6]DLT) and [N alpha-iso-butyl-Gly6]DLT ([isoBuG6]DLT), were examined for their antinociceptive activities by a formalin test in mice after subcutaneous (s.c.) injection. [nBuG6]DLT exhibited potent dose-dependent antinociceptive activities at doses of more than 0.02 mumol/kg at the first and second phases, while morphine similarly inhibited of the pain responses at doses more than 0.01 mumol/kg in the formalin test. [isoBuG6]DLT showed potent antinociceptive activity at the second phase, but did not inhibit the pain response at the first phase. This phenomenon may be caused by a mu-antagonist/delta-agonist property of this compound. The antinociceptive effects of these analogs were antagonized by delta-antagonist naltrindole, but not by the mu-antagonist naloxone. These findings suggest that the antinociceptive effects were mediated via delta-receptors. These compounds may be useful as delta-agonists for clarifying the mechanism of analgesia mediated by delta-opioid receptors.

Analgesics, Opioid↗

Ovarian small cell carcinoma with K-ras mutation: a case report with genetic analysis.

A rare case of ovarian small cell carcinoma is reported. Laboratory examination of a 46-year-old woman with a lower abdominal tumor showed marked hypercalcemia. Her condition deteriorated progressively, and she died one month after admission. A right ovarian tumor, 8 cm in diameter, metastases to multiple organs, and intraperitoneal bleeding were confirmed by autopsy. Microscopically, the small tumor cell had rounded nuclei with small distinct nucleoli and a scanty cytoplasm. Small cell carcinoma was diagnosed from these histological features and the clinical course associated with hypercalcemia. Immunohistochemical studies showed positive staining of neuron specific enolase (NSE) and keratin. Genetic analysis using DNA extracted from paraffin sections of metastatic lesions revealed mutation of K-ras codon 12. Loss of heterozygosity of the p53 and adenomatous polyposis coli (APC) genes was not informative. Previous reports have shown that ras gene mutations occur in 30% of epithelial ovarian tumors and significantly more frequently in mucinous than in other types of ovarian tumors. These results suggest that small cell carcinoma is of epithelial origin and may have a genetic alteration similar to that of mucinous tumors.

Base Sequence↗

Clearance of parenchymal tumors following radiotherapy: analysis of hepatocellular carcinomas treated by proton beams.

Clearance of a parenchymal tumor following radiotherapy was determined by using follow-up CT scans of 18 hepatocellular carcinoma tumors treated with focused proton beams. Regression analysis of the daily decrement (DD) and the diameter (D) of a tumor mass in each CT observation interval, DD = a*Db, showed that the exponent b was 3.0 or larger in early periods and 2.0 or smaller in late periods. This suggests that the clearance depends initially on the tumor volume, subsequently on the tumor surface area, and then it becomes much more moderate, possibly due to radiation damage to the parenchymal tissues.

Aged↗

Two district alpha(1)-adrenoceptor subtypes in the human prostate: assessment by radioligand binding assay using 3H-prazosin.

1. We showed that there were two distinct alpha(1)-adrenoceptor subtypes (alpha(1H) and alpha(IL)) in the human prostate which show different affinities for 3H-prazosin. 2. WB4101, tamsulosin, 5-methylurapizil, phentolamin, and terazosin, but not nifedipine, had significantly higher pKi values for the alpha(1H)-subtype than for the alpha(IL)-subtypes. 3. There was good correlation (r = 0.92, P < 0.05) between the pKi values obtained for the alpha(1H)-receptors in membrane fractions and the cloned human alpha(1c)-adrenoceptor subtype.

Adrenergic alpha-1 Receptor Antagonists↗

Reg gene expression is increased in rat gastric enterochromaffin-like cells following water immersion stress.

BACKGROUND & AIMS: Reg gene has been isolated from regenerating rat pancreatic islets, and subsequent studies have shown a trophic effect of Reg protein on islet cells. However, little is known about the role of Reg protein in the stomach. The aim of this study was to clarify the localization of Reg messenger RNA (mRNA) and its product in the stomach and to examine changes in the level of their expression during regeneration of gastric mucosal cells. METHODS: Gastric lesions were experimentally induced in Sprague-Dawley rats by water immersion stress. Northern blot analysis and in situ hybridization studies were performed to examine changes in mRNA levels. Immunohistochemical studies were performed to identify the cellular localization and to investigate the change in Reg protein level. RESULTS: Reg mRNA and its product were distributed in the basal part of the oxyntic mucosa and were expressed mainly in enterochromaffin-like cells. Levels of both Reg mRNA and its product were markedly increased in the water immersion-induced gastric lesions. CONCLUSIONS: Reg mRNA and its product are expressed in gastric enterochromaffin-like cells, and their levels are increased during the healing process of water immersion-induced gastric lesions.

Animals↗

D-mannose dimer introduced human recombinant interleukin- 1 alpha, NEO IL-1 alpha, exhibits altered tissue distribution in mice.

Previous studies have demonstrated that the carbohydrate-introduced recombinant human IL-l alpha exhibited impairment in both biologic activities in all the experiments in vitro and receptor binding capacity compared with intact IL-l alpha. However, the glycosylated IL-l alpha exhibited selective activities in vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice were injected by intravenous and intraperitoneal routes with 2.0 mu g radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2 alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha exhibited higher levels than IL-l alpha in blood, heart, and liver. No significant difference was observed in brain at each time point. IV injection demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha increased twofold over that of IL-l alpha in liver at 1 h after dosing. These findings are consistent with the result of IP injection. There was no significant difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV administration. These differences in tissue distribution may contribute to the selective activities of glycosylated IL-l alpha in vivo. The results also suggest that by coupling with mannose dimer, it is possible to develop neocytokines prone to liver distribution.

Animals↗

Presence of prostaglandin EP4 receptor gene expression in a rat gastric mucosal cell line.

RGM-1 is an epithelial cell line established from gastric mucosa of adult Wistar rats. In this study, we characterized this newly established cell line by Northern blot analysis. We also investigated deoxyribonucleic acid (DNA) synthesis and hexosamine production in RGM-1 by PGE2. Northern blot analysis did not detect any transcript of proton pump, gastrin receptor, histidine decarboxylase, somatostatin and pepsinogen 1, indicating the absence of characteristics of parietal, ECL, D and chief cells in RGM-1 cells. However, this periodic acid-Schiff (PAS)-positive cell line expressed prostaglandin EP4 receptor mRNA but not EP1 and EP3 receptor mRNAs. [3H]-thymidine incorporation into DNA of the cells was not increased by PGE2. In contrast, PGE2 increased hexosamine content in RGM-1 cells. These results suggest that RGM-1 may be a useful model of gastric mucosal cells and that PGE2 plays a role on mucin synthesis in RGM-1 cells possibly via EP4 receptors.

Animals↗

Erythropoietin stimulates proliferation of rat-cultured gastric mucosal cells.

Most anemic patients with chronic renal failure have gastric mucosal lesions. However, these gastric lesions are often improved after the administration of recombinant human erythropoietin (rHuEPO). We have used the rat gastric mucosal cell line RGM-1, to examine the possibility that rHuEPO might directly stimulate the growth of gastric mucosal cells in vitro. Our results show that rHuEPO dose-dependently increased [3H]thymidine incorporation into RGM-1 cells and their expression of c-myc gene. In addition, 125I-rHuEPO specifically bound to RGM-1 cells, and moreover, erythropoietin receptor gene expression was detected by RT-PCR. We conclude that rHuEPO has a direct growth-promoting effect on RGM-1 cells, suggesting possible usefulness of rHuEPO administration for the treatment of gastric mucosal damage in patients with chronic renal failure.

Animals↗