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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 451 records · Page 25Linked to original sources

[Intermittent methylprednisolone pulse therapy for myasthenia gravis in childhood].

We studied the effects of the intermittent methylprednisolone pulse (IMP) therapy without the maintenance steroid therapy for 6 children with myasthenia gravis; 3 cases with generalized type and 3 with ocular type. None of them was controlled satisfactorily by oral steroid therapy or anti-choline esterase agents. Two cases with generalized type and the other two with ocular type achieved remission by the initial pulse therapy, and were kept under good control by subsequent IMP therapy performed periodically or at the time of relapse. The other two cases could not be introduced to complete remission by the initial pulse therapy, but improved gradually by subsequent periodical IMP therapy. The IMP therapy without maintenance of oral steroid therapy is more useful as compared with oral administration of steroids, in controlling myasthenia gravis and also in preventing side effects due to steroid therapy.

Adolescent↗

Gelsolin is localized in neuronal growth cones.

Gelsolin, a Ca(2+)-sensitive actin filament-severing protein, is involved in actin turnover. Immunocytochemical study with anti-gelsolin antibody revealed that the protein is localized in both filopodia and the body part of growth cones of differentiated PC12 cells with nerve growth factor (NGF) and of rat dorsal root ganglion neurons. Here, we identified gelsolin as one of the molecular bases for the Ca(2+)-dependent movement of growth cones.

Animals↗

Regulation of activity levels of glycolipid sulfotransferases by transforming growth factor alpha in renal cell carcinoma cells.

Accumulation of sulfolipids associated with markedly elevated levels of glycolipid sulfotransferase activities was previously demonstrated in human renal cell carcinoma cells. To explore the regulation mechanisms of sulfoglycolipid synthesis in renal cancer, effects of various growth factors on the metabolic enzymes of sulfoglycolipids were investigated by using a human renal cell carcinoma cell line, SMKT-R3. Among the growth factors tested, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to increase the sulfotransferase activity markedly (about 300%), but did not change that of arylsulfatase A, which hydrolyzes sulfoglycolipids. The augmented effects of TGF-alpha was abolished by cycloheximide. Since TGF-alpha is known to bind to the same receptor as EGF, SMKT-R3 cells were investigated for the EGF receptor by affinity cross-linking with 125I-EGF. A radiolabeled protein with a molecular mass of 175 kDa corresponding to the ligand-receptor complex was immunoprecipitated with a monoclonal anti-EGF receptor antibody. When production of the growth factors was examined immunochemically, the cells were found to secrete TGF-alpha at a low level and retain it in a membrane-bound form, whereas EGF was not detected. These observations suggest that the sulfotransferase activities are regulated through the autocrine, paracrine, and/or juxtacrine modes of intercellular stimulation by TGF-alpha in human renal cancer cells.

Carcinoma, Renal Cell↗

Phosphorylation of a 62 kd porcine alpha-internexin, a newly identified intermediate filament protein.

A 62 kd protein was purified from the Triton-insoluble fraction of porcine brain white matter. This protein formed 10nm filaments, in vitro. The phosphorylation of the 62 kd protein by cAMP-dependent protein kinase caused electrophoretic mobility to shift to 66 kd on SDS-PAGE and a complete loss of the filament forming ability ensued. Amino acid sequences of four peptide fragments obtained from the 62 kd protein by lysylendopeptidase were identical with that of a 66 kd rat brain alpha-internexin. Amino acid analyses of the phosphopeptide fragment derived from phosphorylated porcine alpha-internexin revealed that the phosphorylation sites by cAMP-dependent protein kinase located in the amino-terminal head domain of this protein. These results strongly suggest that alpha-internexin polymerizes into 10nm filaments in vitro and that phosphorylation of the amino-terminal domain of alpha-internexin controls its polymerizability.

Amino Acid Sequence↗

Effects of discrimination learning on the rat amygdala dopamine release: a microdialysis study.

Extracellular levels of dopamine (DA) and its metabolites were monitored with the in vivo microdialysis method in the amygdala of rats while and after they performed a discrimination learning task or a non-discrimination task. A group of rats was trained to discriminate between lamp-on and lamp-off states under an operant-type learning procedure. After a stable discriminative behavior was established, a dialysis probe was inserted into the basolateral amygdaloid nucleus of each rat. The concentrations of DA and its metabolite 3,4-dihydroxyphenylacetic acid significantly increased during the learning sessions as compared to their basal levels. In contrast, another group of rats trained on a similar, but non-discriminative task showed no such increases. These results suggest that the dopaminergic neural systems in the basolateral amygdaloid nucleus are activated during ongoing behavior maintained under the discrimination learning situation.

Amygdala↗

Increase in ubiquitin conjugates dependent on ischemic damage.

Insoluble ubiquitin conjugates (UC) in the mitochondrial fraction of the gerbil cortex were analyzed following transient forebrain ischemia. At 1 h of reperfusion after 2-10 min of ischemia, UC increased as the duration of ischemia was prolonged. Pre-treatment with pentobarbital, rather than post-treatment immediately after recirculation, reduced the increase of UC at 1 h of reperfusion following 5 min of ischemia. Pentobarbital had no effect on in vitro ubiquitination of heat-denatured lysozyme by the extract of gerbil cortex. These results suggest that increase in UC is dependent on ischemic damage and pentobarbital attenuates the increase of UC by relieving injury during ischemia.

Adenosine Triphosphate↗

[Effect of arotinolol on insulin secretion and insulin clearance rate in patients with Graves' disease].

Glucose-induced insulin secretion, 24-h urinary C-peptide (CPR) and euglycemic clamp were examined in five patients with hyperthyroid Graves' disease before and 2 weeks after treatment with arotinolol (20 mg/day, p.o.). Plasma glucose and insulin responses to oral administration of 75 g glucose were not changed by arotinolol treatment. 24-h urinary CPR and basal posthepatic insulin delivery rate (BPIDR) as an indicator of insulin secretion were significantly suppressed by arotinolol. Glucose infusion rate (GIR) as an indicator of insulin sensitivity and glucose clearance rate (GCR) were not influenced by arotinolol therapy. Insulin clearance rate (ICR) was significantly suppressed by arotinolol. These findings suggest that arotinolol inhibits insulin secretion by decreasing ICR but does not attenuate insulin release induced by glucose in hyperthyroid patients, and that insulin sensitivity and GCR are not affected by arotinolol.

Adrenergic beta-Antagonists↗

Responses of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to hemorrhage.

The activity of subfornical organ (SFO) neurons that were antidromically identified by electrical stimulation of the rat hypothalamic paraventricular nucleus (PVN) was tested for a response to microiontophoretic application of angiotensin II (ANG II) or hemorrhage (10 ml/kg b.w.t.). Microiontophoretically (MIPh) applied ANG II caused an increased excitability in 24 out of 28 neurons tested and the excitation was blocked by MIPh-applied saralasin (Sar), a specific ANG II antagonist. Of these neurons that responded to ANG II, 14 displayed an increase in neuronal firing in response to hemorrhage, while 10 were unresponsive. The excitatory response to hemorrhage in 5 out of 14 neurons tested was prevented by MIPh-applied Sar, whereas the response of the remaining neurons was not affected. These results show that part of SFO neurons projecting to the PVN may receive neural inputs from the peripheral baroreceptors, and suggest that the inputs may be partially attributable to the involvement of central angiotensinergic circuits.

Action Potentials↗

Median preoptic neurons projecting to the hypothalamic paraventricular nucleus are sensitive to blood pressure changes.

Twenty-one neurons in the median preoptic nucleus (MnPO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. The activity of these identified neurons was tested for a response to activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous administration of the alpha-agonist metaraminol. Of the neurons tested, 14 displayed a reduction and 2 exhibited an increase in neuronal excitability that accompanied a 30- to 50-mmHg elevation in mean arterial pressure, while 5 were unresponsive. The results show that efferent pathways from the MnPO to the PVN may receive neural inputs from the peripheral baroreceptors, suggesting the involvement of the pathways in the control of cardiovascular function.

Action Potentials↗

Neural cell adhesion molecule (NCAM) and perineural invasion in bile duct cancer.

Perineural invasion is associated with tumor spreading and an unfavorable prognosis in a variety of cancers. Recently, neural cell adhesion molecule (NCAM) has been reported to be affinitive to neural tissues, which suggests some relationship between NCAM and perineural invasion. This study was designed to elucidate the role of the expression of NCAM on the development of perineural invasion in bile duct cancer. A histopathologic study was performed on 24 patients with bile duct carcinoma who underwent resections. The overall incidence of NCAM expression in the resected specimen was 66.7% and that of perineural invasion was 87.5%. Furthermore, NCAM expression was shown to be positive in 16 (76%) out of 21 cases in whom perineural invasion was observed. A significant positive correlation was found between the expression of NCAM and perineural invasion in bile duct cancer. These results highlight an important role of NCAM in the development of perineural invasion in bile duct cancer.

Adenocarcinoma↗

Neurotoxic effects of 2,5-hexanedione on rapidly growing unmyelinated peripheral nerve axons of a rat fetus: dose-effect relationship.

To investigate the potential neurotoxicity of 2,5-hexanedione (2,5HD) on developing axons we examined peripheral nerves of rat fetuses. Pregnant female Sprague-Dawley rats were injected subcutaneously with 680 mg/kg of 2,5HD once a day from Day 12 of gestation (GD12) to GD16 in one group and with 340 mg/kg of 2,5HD once a day from GD12 to GD20 in the other group. On GD20 live fetuses were removed from the uteri and their sciatic nerves were examined morphologically. By electron microscopical observations, affected nerves revealed axons which were aggregated and fused together, but there were no axons aggregated with neurofilaments. The diameter distributions of axons revealed an increase in the number of small-size axons in the nerves of the 340 mg/kg group and showed an enlargement of part of the axons in the nerves of the 680 mg/kg group, suggested by the appearance of a second peak at a diameter larger than that of the first peak.

Animals↗

Involvement of neurons sensitive to angiotensin II in the median preoptic nucleus in the drinking response induced by angiotensin II activation of the subfornical organ in rats.

The involvement of neurons sensitive to angiotensin II (ANG II) in the median preoptic nucleus (MnPO) in mediating the drinking response caused by administration of ANG II either directly into the subfornical organ (SFO) or intravenously was examined in the conscious rat. In all rats (n = 16) having correct injector placement in both of these brain sites, injections of ANG II (10(-12) M) into the SFO elicited drinking. Previous injections of saralasin (10(-10) M), a specific ANG II antagonist, but not saline vehicle, into the MnPO significantly attenuated the drinking response to ANG II administration directly into the SFO. Intravenous infusions of ANG II (75 ng/kg) produced a drinking response in 12 of the 16 rats, and the response was significantly reduced by pretreatment with saralasin (10(-10) M), but not by saline, in the SFO. These results show the importance of MnPO neurons responsible for ANG II in mediating the dipsogenic response to ANG II acting at the SFO and suggest that the response may be implicated in angiotensinergic neural circuits from the SFO to the MnPO.

Angiotensin II↗

Chemical mediators released from hepatic macrophages in primary culture--basic characteristics of human hepatic macrophages and changes in liver cirrhosis.

Chemical mediators released from human hepatic macrophages (HHM phi) in primary cultures were analyzed for their secretory function and probable contribution to the modulation of the host defense system and metabolism in liver cirrhosis. In our basic studies, HHM phi increased dose dependently the release of superoxide (O2-) and interleukin-1 (IL-1) when stimulated by opsonized zymosan, up to 1000 micrograms/dish. PGE2 production showed a relatively narrow range of dose dependency, and larger doses led to a reduction of PGE2 yield in some samples. Next, we compared the mediator release from the HHM phi of patients with liver cirrhosis with that from HHM phi in normal liver. O2- released from HHM phi of 8 patients with liver cirrhosis was significantly decreased (controls, n = 20) (P < 0.01). IL-1 released from the HHM phi of 6 cirrhotic patients tended to be higher than that from the HHM phi of 10 control patients, but the difference was not statistically significant (P < 0.10). PGE2 production, however, was about the same in the two groups. These results suggest that cultured HHM phi have certain basic characteristics in releasing mediators with highly potent specific activities and also that these secretory abilities may change in liver cirrhosis. In conclusion, the analysis of cultured HHM phi may be a very practical way to clarify their inherent abilities and participation in the complicated clinical features of liver cirrhosis.

Carcinoma, Hepatocellular↗

Altered fluidity of liver plasma membranes following partial hepatectomy in rats.

The fluidity of liver plasma membranes was assessed during regeneration following partial hepatectomy in rats. Fluorescence polarization was measured using 1,6-diphenyl-1,3,5-hexatriene to evaluate the fluidity of liver plasma membranes. The fluorescence polarization value of liver plasma membranes of control rats was 0.189 +/- 0.005 (mean +/- SEM). The fluorescence polarization values decreased initially after a 70% hepatectomy [0.176 +/- 0.003 at 3 hr and 0.174 +/- 0.004 at 6 hr (P < 0.01)] at 3 and 6 hours, but then recovered to preoperative levels (0.181 +/- 0.004, 0.189 +/- 0.004, 0.189 +/- 0.003, 0.193 +/- 0.003, 0.200 +/- 0.002, 0.208 +/- 0.007, and 0.190 +/- 0.003 at 12, 24, 36, 48, 72, 96 hr, and 7 days, respectively). Flow cytometric analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody was used to investigate the cell kinetics of the regenerating liver after 70% hepatectomy. The proportion of S-phase incorporating BrdU was not increased at 6 or 12 hr, but it then increased to peak of 27.9 +/- 1.9% at 24 hr. Subsequently, at 48, 72, and 168 hr, the proportion decreased to 8.5 +/- 0.6, 5.9 +/- 0.3, and 1.0 +/- 0.1%, respectively. The ratio of phospholipid to cholesterol contents of liver plasma membranes following partial hepatectomy did not significantly change in spite of markedly altered membrane fluidity. Thus, the alteration of membrane function occurs in conjunction with the initiation of the regeneration process following partial hepatectomy. It is suggested that the alteration of membrane fluidity plays an important role in the homeostatic response for cell proliferation.

Animals↗

Androgenic modulation of the activity of lumbar neurons involved in the rat bulbocavernosus reflex.

The bulbocavernosus (BC) reflex, produced in the BC motor nerve in response to electrical stimulation of the contralateral pudendal sensory nerve, was investigated in intact, castrated, and testosterone-treated castrated male rats under urethane anesthesia. No significant group differences in the reflex latency, sensory or motor conduction velocity, or central delay were observed. A conditioning pulse to the pudendal sensory nerve caused suppression of the averaged antidromic field potential recorded in the contralateral spinal nucleus of the bulbocavernosus (SNB) after stimulation of the SNB axons in the BC motor nerve. The suppression occurred at 6- to 35-ms intervals between shocks to pudendal sensory nerve and BC motor nerve, and was markedly smaller in castrated males than in the other two groups. In contrast, a conditioning pulse to the contralateral BC motor nerve had no effect on the SNB antidromic field potential. These results indicate that androgen modulates the efficacy of synaptic transmission onto SNB motoneurons or other neurons involved in the BC reflex.

Animals↗

An electrophysiological study of descending projections to the lumbar spinal cord in adult male rats.

Recent anatomical evidence suggests that descending projections from the lateral vestibular nucleus (LVe) and gigantocellular reticular nucleus (Gi) innervate areas of the lumbar spinal cord near the spinal nucleus of the bulbocavernosus (SNB). To confirm this finding electrophysiologically, we recorded and mapped averaged field potentials within the lumbar spinal cord of male rats in response to electrical stimulation of the LVe or Gi and compared these with the location of averaged field potentials evoked at the same levels by stimulation of SNB axons in the bulbocavernosus (BC) nerve. Stimulation of the LVe or the Gi produced negative field potentials that were largest at sites 200-450 microns dorsolateral to SNB somata. In an attempt to verify that this region innervates SNB motoneurons, the BC motor nerve volley was recorded in response to microstimulation at various depths within the spinal cord. Stimulation of sites dorsolateral and lateral to the SNB somata elicited volleys in the BC nerve that had two components. The onset latency of the earlier component was similar to the antidromic latency of SNB motoneurons to BC nerve stimulation, and the threshold for eliciting this component was lowest at sites in the electrode track near SNB somata. Thus, the earlier component may be evoked by direct stimulation of the SNB motoneurons. The threshold for evoking the later component was lowest at the sites 230-380 microns dorsolateral to SNB somata, suggesting that this component involves activation of other neurons. These results indicate that the LVe and Gi may modulate the activity of SNB motoneurons through interneurons located in a region several hundred microns away from SNB somata.

Animals↗

An appraisal of segmental pancreatectomy for benign tumors of the pancreatic body: a report of two cases.

To preserve pancreatic and splenic function, segmental pancreatectomy with pancreatojejunostomy was performed on two patients with benign pancreatic tumors, and a 3-year follow-up study was conducted. The pancreatic endocrine functions assessed by 75 g oral glucose tolerance test were normal 3 years after surgery, and the exocrine functions returned to within the normal range 1 month after surgery according to a pancreatic function diagnostant (PFD) test. The platelet count increased transiently to 48.9 x 10(4)/mm3, and 70.5 x 10(4)/mm3, in the two patients, respectively, but returned to the preoperative value 1 month postoperatively. The operative times were 7 h 51 min and 5 h 3 min, which included the time taken for intraoperative ultrasonography and frozen section diagnosis, and the blood losses were 183 ml and 212 ml. The postoperative hospitalization period averaged 39 days and no complications developed in either patient. The method of performing segmental pancreatectomy, initially reported by Letton and Wilson for cases of pancreatic trauma, was evaluated and successfully applied to benign pancreatic tumors.

Adenoma, Islet Cell↗