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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 361 records · Page 20Linked to original sources
PubMed1996

MIB-1 immunostaining and DNA flow cytometry in meningiomas.

The correlation between S- and G2/M-phase fractions and MIB-1 index in meningiomas was investigated. Flow cytometric analyses were performed on cell suspensions from 81 samples of paraffin-embedded tissue from 29 patients with a total of 28 meningiomas and 1 hemangiopericytoma using the modified Hedley's method. Sections from the paraffin-embedded tissues were stained with anti-MIB-1 monoclonal antibody after microwave oven processing. Five hundreds cells were scored. Correlations between data were estimated using linear regression. DNA aneuploidy was present in 4/29 tumors. Mean S- and G2/M-phase fractions in the 25 nonrecurrent tumors were 1.77 and 4.76%, and in the recurrent tumors were 2.41 and 5.81%, respectively. The proliferative index (PI = S + G2/M fraction) was 6.52% in the nonrecurrent tumors and 8.29% in the recurrent tumors. The mean MIB-1 score in the nonrecurrent tumors was 1.25% and in the recurrent tumors was 2.69%. There was a linear correlation between percentage of S-phase fraction or PI and the MIB-1 score. Both methods are useful to assess the proliferative activity in meningioma.

Antibodies, Monoclonal↗
PubMed1996

Clinical significance of abnormal postexercise systolic blood pressure response in patients with hypertrophic cardiomyopathy.

The clinical significance of abnormal postexercise systolic blood pressure (SBP) response in patients with hypertrophic cardiomyopathy (HCM) was assessed by treadmill exercise testing in 30 normal subjects and 96 patients with HCM. SBP recovery ratios were derived by dividing the SBP at 1 and 3 min after exercise by the peak exercise SBP. The upper normal limit of the SBP ratio was defined by two standard deviations (SD) from the mean in 30 normal subjects. A postexercise SBP ratio that exceeded the upper normal limits of the SBP ratio was considered to be an abnormal SBP response in patients with HCM. Twenty-seven (28%) of 96 patients with HCM showed an abnormal SBP response. Compared with the normal SBP response group (69 cases) among patients with HCM, the abnormal SBP response group had lower SBP response during exercise (22 +/- 25 vs 62 +/- 26 mmHg : mean +/- 1 SD, p < 0.05), more prolonged QRS width (110 +/- 21 vs 92 +/- 20 msec, p < 0.05), higher incidences of ventricular tachycardia (12 vs 7 cases, p < 0.001), and sudden death (7 vs 0 cases, p < 0.0001). The defect area of Tl-201 myocardial scintigraphy was more extensive in the abnormal SBP response group (2.9 +/- 1.7 segments) than in the normal SBP response group (1.1 +/- 1.3 segments, p < 0.05). During atrial pacing (120/min), pulmonary artery wedge pressure was slightly elevated from 10 +/- 2 (at rest) to 14 +/- 3 mmHg (during pacing) (p<0.001), cardiac index showed no significant changes, and time constant T was shortened from 58 +/- 13 to 48 +/- 10 msec (p < 0.001) in the normal SBP response group, but in the abnormal SBP response group pulmonary artery wedge pressure was highly elevated from 12 +/- 5 to 20 +/- 3 mmHg (p < 0.0001), cardiac index was decreased from 2.5 +/- 0.7 to 2.1 +/- 0.6 l/min/m2 (p < 0.05), and the time constant T had no significant changes. These observations suggest that patients with HCM and abnormal postexercise SBP response have an abnormal cardiac response during exercise and extensive myocardial damage.

Blood Pressure↗
PubMed1995

Septo-hippocampal cholinergic system under the discrimination learning task in the rat: a microdialysis study with the dual-probe approach.

To investigate regulation of the septo-hippocampal cholinergic system by dopaminergic inputs to the septum in rats which performed a discrimination learning task, an in vivo microdialysis method with the dual-probe approach was used. Rats were trained to discriminate between lamp-on and -off states under an operant-type learning procedure. After stable discriminative behavior was established, dialysis probes were implanted into the hippocampus and the lateral septum area of each rat. The concentration of dopamine (DA) in the septum rapidly increased within 20 min after the beginning of a learning session. However, another group of rats trained on a similar but non-discriminative task showed no such increase. The concentration of acetylcholine (ACh) in the hippocampus was significantly enhanced during the learning session and rapidly returned to the basal value after the session, but showed a delayed and diminished increase in the non-discrimination group. These results suggest that DAergic inputs to the septum may be involved in control of the septo-hippocampal cholinergic system which is of importance for discrimination learning behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Spontaneously immortalized adult mouse Schwann cells secrete autocrine and paracrine growth-promoting activities.

We established spontaneously immortalized Schwann cell lines from long-term cultures of adult mouse dorsal root ganglia and peripheral nerves. One of the cell lines, designated IMS32, responded to mitogenic stimuli by platelet-derived growth factor (PDGF)-BB, acidic and basic fibroblast growth factors (aFGF, bFGF), and transforming growth factors (TGF)-beta 1 and -beta 2, as determined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. Furthermore, conditioned media (CM) obtained from IMS32 cells showed mitogenic activity for both IMS32 cells and long-term cultured Schwann cells. Western blot analysis revealed TGF-beta-like molecule in the CM, and the activity was absorbed with anti-TGF-beta neutralizing antibody. Reverse transcription followed by polymerase chain reaction (RT-PCR) of IMS32 RNA revealed that these cells expressed TGF-beta 1, -beta 2, and -beta 3 transcripts. When rat pheochromocytoma PC12 cells were incubated with the CM, they developed neurite growth. Coculture of PC12 and IMS32 cells also showed neurite growth of PC12 cells. RNA transcripts of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), ciliary neurotrophic factor (CNTF), and glial cell line-derived neurotrophic factor (GDNF) were detected from IMS32 cells by RT-PCR. In these, we sequenced the mouse GDNF cDNA coding region and observed 97% and 90% homologies to corresponding rat and human cDNA sequences, respectively. These results indicate that the immortalized Schwann cell line mitotically responds to various growth factors and secretes autocrine and paracrine growth-promoting activities in vitro.

Animals↗
PubMed1995

Responses of median preoptic neurons projecting to the hypothalamic paraventricular nucleus to osmotic stimulation in Wistar-Kyoto and spontaneously hypertensive rats.

Twenty-one median preoptic nucleus (MnPO) neurons in normotensive Wistar-Kyoto rats (WKY) and 18 MnPO neurons in spontaneously hypertensive rats (SHR) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) under urethane anesthesia. No significant differences in the latency, conduction velocity, or threshold of antidromic activation were observed between WKY and SHR. The spontaneous discharge rate was significantly higher in SHR than in WKY. The activity of these identified MnPO units was examined for response to intracarotid injections of isotonic (0.15 M NaCl solution, 0.05 ml) or hypertonic (0.3 M NaCl solution, 0.05 ml) saline. All the units did not change their activity to the injections of isotonic saline. Of these units, 14 units in WKY and 12 units in SHR displayed and 3 units in WKY and 4 units in SHR exhibited a reduction in neuronal activity following the injections of hypertonic saline, while the remaining 4 units in WKY and 2 units in SHR were unresponsive. The duration and frequency of excitatory response, but not the inhibitory response, caused by the osmotic stimulation was much greater in SHR than in WKY. These results show that MnPO neurons projecting to the PVN may carry the information from osmosensitive elements and that there is a difference between WKY and SHR in the responsivity of these MnPO neurons to the osmotic stimulation.

Animals↗
PubMed1995

Possible involvement of vasoactive intestinal polypeptide in the central stimulating action of pituitary adenylate cyclase-activating polypeptide on prolactin secretion in the rat.

Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on prolactin (PRL) secretion was studied in Wistar strain male rats in vivo. Intravenous injection of PACAP-38 and PACAP-27 resulted in a dose-related increase in plasma PRL levels both in conscious rats and in urethane-anesthetized rats. In anesthetized animals, i.c.v. injection of PACAP-38 and PACAP-27 also elicited a dose-related increase in plasma PRL. The PRL secretion induced by i.c.v. injection of PACAP-38 was attenuated by pretreatment with rabbit antiserum to vasoactive intestinal polypeptide (VIP). These findings suggest that PACAPs stimulate PRL secretion in the rat by acting not only directly on the pituitary but also indirectly through the central nervous system, at least partly, via hypothalamic VIP.

Animals↗
PubMed1995

Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates growth hormone release from GH3 cells through type II PACAP receptor.

Effect of pituitary adenylate cyclase activating polypeptide (PACAP) on growth hormone (GH) release from GH3 cells was studied in a dynamic superfusion system. PACAP-38 and PACAP-27 stimulated GH release from superfused GH3 cells. The stimulatory effect of PACAP-38 was comparable to those of vasoactive intestinal polypeptide (VIP) and PACAP-27 at a concentration of 1 nM, but the duration of action was more prolonged in PACAP-38 than in the other two peptides. PACAP(6-38), a selective antagonist of PACAP, as well as a VIP antagonist blunted the GH release induced by PACAP-38 and VIP. An antagonist of GH-releasing factor (GRF) at a concentration of 1 microM, however, did not affect the GH release induced by PACAP-38. These findings suggest that PACAP and VIP stimulate GH release from GH3 cells through type II PACAP receptor but not through the GRF receptors.

Animals↗
PubMed1995

Caldesmon and low Mr isoform of tropomyosin are localized in neuronal growth cones.

Neuronal growth cones move actively, accompanying changes in intracellular Ca2+ concentration. The movement of growth cones may partly depend on the actomyosin system, considering the presence of actin and myosin II. Yet, Ca(2+)-sensitive regulatory proteins for the actomyosin system have not been identified in growth cones. In the present study, caldesmon, an inhibitory protein on actin-myosin interaction, was detected in the growth cone fraction isolated from embryonic rat brain, using immunoblotting with the antibody to chicken gizzard caldesmon. Morphological evidence of caldesmon in growth cones of cultured rat neurons was obtained using the indirect immunofluorescence method. Since inhibition of caldesmon on actin-myosin interaction can be overcome by calmodulin and Ca2+, caldesmon may be involved in the Ca(2+)-dependent regulation in growth cone motility. Tropomyosin is another member of the actomyosin system whose function may be regulated by caldesmon in smooth and nonmuscle cells. A low Mr isoform of tropomyosin was distributed in the growth cone fraction. Using specific antibodies against tropomyosin isoforms, we further clarified morphologically that the low Mr isoform was localized in growth cones, but not the high Mr isoform. High Mr isoforms of tropomyosin were present in nonneuronal cells. Actin filaments in growth cones may be unstable, since low Mr tropomyosin binds to actin filaments with a lower affinity than high Mr isoforms. The instability of actin filaments may be suitable for the rapid movement and shape changes of growth cones.

Actins↗
PubMed1995

Modification of rectal absorption of morphine from hollow-type suppositories with a combination of alpha-cyclodextrin and viscosity-enhancing polysaccharide.

An attempt was made to optimize the rectal delivery of morphine, using cyclodextrins as an absorption enhancer and polysaccharides as a swelling hydrogel in Witepsol H-15 hollow-type suppositories, and this was tested in rabbits. alpha- and beta-cyclodextrins enhanced the rate and extent of bioavailability, the former being more effective; gamma-cyclodextrin decreased the absorption of morphine. The in-vitro membrane permeation studies using excised rectal sacs revealed that alpha-cyclodextrin enhanced the permeation of morphine through the rectal membranes. In contrast, viscous polysaccharides such as xanthan gum retarded the plasma morphine levels after the rectal administration, reflecting in-vitro slow release characteristics. A combination of alpha-cyclodextrin and xanthan gum produced sustained plasma profiles of morphine along with an increased rectal bioavailability (more than 4 times). From the observation of the distribution behavior of suppositories in rabbit rectum and colon after the rectal administration, xanthan gum was found to prevent the upward spread of the drug. Gross and microscopic observations suggested that this preparation was less irritating to the rectal mucosa.

Animals↗
PubMed1995

Neural cell adhesion molecule and perineural invasion in gallbladder cancer.

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer.

Adenocarcinoma↗
PubMed1995

Effect of dibutyryl cyclic AMP on the cell cycle of human pancreatic cancer inoculated in nude mice.

The prognosis of pancreatic cancer is very poor because of its high malignant potential. To improve the prognosis of pancreatic cancer, a decrease in the grade of malignancy by dibutyryl cyclic AMP (db-cAMP), a differentiation inducer, was attempted using human pancreatic cancer cell line inoculated to nude mice. In this study, 0.1 or 5.0 mumol/animal/day of db-cAMP was administered for 7 consecutive days in short-term group animals and for 28 consecutive days in long-term group animals. Animals in both groups are sacrificed 28 days after first administration of db-cAMP, and tumor size, histology, and cell cycle analysis using flow cytometry (FCM) were studied. Tumor size and histology showed no significant changes by db-cAMP. However, in cell cycle analysis, 5.0 mumol/animal/day of db-cAMP brought significant block of the cell cycle phases between G1 and S in the short-term group and the phase between S and G2/M in the long-term group, indicating a decrease in cell cycle speed and, consequently, a decrease in the proliferation of tumor cell. The results show that db-cAMP may be useful in decreasing the grade of malignancy of pancreatic cancer.

Animals↗
PubMed1995

Differences in electrophysiological properties of angiotensinergic pathways from the subfornical organ to the median preoptic nucleus between normotensive Wistar-Kyoto and spontaneously hypertensive rats.

Electrophysiological properties of angiotensinergic pathways from the subfornical organ (SFO) to the median preoptic nucleus (MnPO) were investigated in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) under urethane anesthesia. The activity of SFO neurons that were antidromically activated by electrical stimulation of the MnPO was compared between WKY (n = 28) and SHR (n = 27). No significant differences were observed between WKY and SHR in the latency, conduction velocity, or threshold of antidromic activation. The firing rate was significantly shorter in SHR. The activity of MnPO neurons was tested for a response to microiontophoretic application of angiotensin II (ANG II) and electrical stimulation of the SFO. Sixteen of 46 MnPO neurons tested in WKY and 15 of 47 MnPO neurons tested in SHR were excited by both ANG II applied iontophoretically and SFO stimulation, and the excitatory responses were prevented by iontophoretically applied saralasin, a specific ANG II antagonist. In these MnPO neurons that demonstrated the excitation to both SFO stimulation and ANG II, the firing rate was significantly higher and the threshold current required to evoke the SFO stimulus-induced excitation was significantly lower in SHR. The sensitivity to SFO stimulation was much greater in SHR than in WKY. These results provide evidence that there are marked alterations in the physiological properties of the angiotensinergic circuit from the SFO to the MnPO between WKY and SHR and imply that a disorder in the neural circuit may contribute, in part, to hypertension.

Angiotensin II↗
PubMed1995

Specificity of androgenic regulation of input to sexually dimorphic motoneurons in male rat lumbar spinal cord.

Averaged antidromic field potentials were recorded near motoneuronal somata of the spinal nucleus of the bulbocavernosus (SNB) after stimulation of their axons, in intact, castrated, and testosterone-treated castrated male rats under urethane anesthesia. When the SNB motoneurons were antidromically activated with double pulses to the bulbocavernosus (BC) nerve, the first pulse inhibited the antidromic response caused by the second pulse at interstimulus intervals of 5-40 ms, implying the presence of recurrent or other inhibition activated by BC nerve stimulation. Castration and androgen treatment had no significant effect on the amplitude of the suppression. In this regard this pathway differs from other pathways that synapse onto SNB motoneurons, in which activity is highly sensitive to androgen, indicating that androgen exerts its effects only on specific neural circuits that influence SNB motoneurons.

Androgens↗
PubMed1995

Significance of altered fluidity of plasma membranes of the liver and kidney in rats with sepsis.

The present study was conducted to investigate changes in plasma membrane fluidity of the liver and kidney in sepsis, which is the main cause of multiple organ failure. Male Wistar rats weighing 200-250 g were used in all experiments. Sepsis was induced by cecal ligation and puncture. As a control, a sham operation was performed. The time course of plasma membrane fluidity of the liver and the renal cortex in septicemic rats or in controls was studied. To evaluate the fluidity, fluorescence polarization was measured using 1,6-diphenyl-1,3,5-hexatriene. The fluorescence polarization values of liver plasma membranes increased after cecal ligation and puncture: 0.183 +/- 0.004 (mean +/- SEM), 0.194 +/- 0.008, 0.206 +/- 0.003, and 0.210 +/- 0.002 at 0, 24, 48, and 72 hr, respectively. Corresponding values for membranes of the renal cortex increased in a similar fashion. To determine whether factors involved in cell membrane damage exist in blood, the direct effects of lipopolysaccharide (LPS), platelet-activating factor (PAF), and serum from normal rats or from septicemic rats on membrane fluidity were studied. The fluorescence polarization of plasma membranes of the liver or renal cortex to which septicemic rat serum was added was higher than that of plasma membranes to which normal rat serum was added. The fluorescence polarization of liver plasma membranes was increased by LPS, but that of plasma membranes of the renal cortex was slightly decreased. In addition, the fluorescence polarization of liver plasma membranes was increased by PAF, but that of plasma membranes of the renal cortex was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Monoethylglycinexylidide formation as an independent measure of warm hepatic ischemia and reperfusion injury.

An accurate serologic measure of hepatic function would be clinically useful in selecting donors for liver transplantation. An experimental model that incorporates varying lengths of total hepatic warm ischemia with reperfusion injury was utilized to compare serologic parameters and mitochondrial performance of oxidative phosphorylation in predicting hepatocellular injury. Monoethylglycinexylidide (MEGX) formation following bolus intravenous lidocaine injection was found to be significantly decreased (P < 0.0001) at all periods of ischemia when compared to that in nonischemic controls. A serum MEGX level of < 50 micrograms/liter suggested severe hepatic damage. No correlation was found between MEGX level and liver viability as measured by animal survival. Serum transaminase (AST and ALT) levels demonstrated progressive, nonsignificant elevations with increasing length of ischemia (P = 0.0779 at the maximum ischemic time). Polarographic measurements of mitochondrial oxidative phosphorylation did not reveal a significant alteration in subcellular metabolism with prolonged ischemic time. These data highlight the comparative sensitivity of MEGX formation as an early quantitative measurement of hepatocellular injury during warm ischemia, although it was not predictive of organ viability.

Adenosine Triphosphate↗
PubMed1995

Alteration in the fluorescence polarization of rat plasma and liver cell membranes following bile duct ligation in rats.

The fluorescence polarization levels of liver cell membranes and plasma were analyzed to determine membrane fluidity following bile duct ligation (BDL) in rats. Fluorescence polarization was measured with a spectrofluorophotometer equipped with polarizers, using 1,6-diphenyl-1,3,5-hexatrien (DPH) as a probe. After bile duct ligation, liver cell membrane fluidity decreased significantly for up to 14 days after surgery (P < 0.001 on 3rd and 7th days). The polarization of the plasma in rats with BDL slightly but significantly increased compared to the levels in the control animals over the 14-day period following BDL. In addition, a small but significant correlation in the polarization levels between plasma and liver cell membranes (r = 0.362, P < 0.02) was observed. The co-incubation of BDL plasma with normal liver cell membranes resulted in a decrease in membrane fluidity, which suggested that BDL rat plasma had a direct effect on membrane fluidity. After a 70% hepatectomy, the polarization of the membranes from remnant livers in the BDL rats remained elevated relative to the sham-operated controls. It is thus concluded that the membrane fluidity of the livers in BDL rats decreases following bile duct ligation and does not increase after a 70% hepatectomy, presumably due to the increased plasma level of bilirubin.

Animals↗
PubMed1995

Clinical application of allogeneic peripheral blood stem cells transplantation.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for autologous transplantation to provide hematopoietic stem cells after intensive chemoradiotherapy. However, PBSC which contain a large number of T cells represent a potential risk for graft-versus-host disease (GVHD) in allogeneic (allo) transplantation. There are about 50 case reports of clinical trials of rhG-CSF-mobilized allo PBSC transplantation (PBSCT) with relatively rapid hematological recovery, without severe acute GVHD except in a few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected when allo PBSCT began. However, whether allo PBSCT will increase the risk of chronic GVHD is not clear, because the period of observation has been too short. Also, it will be of interest to determine the clinical effect of allo PBSCT on relapse of hematological malignancy post-transplant. Whether allo PBSCT will increase life-threatening acute and chronic GVHD, and whether PBSC allografting will result in permanent hematological and immunological reconstitution has to be determined by prospective randomized clinical trials.

Graft vs Host Disease↗