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Biomedical subjects

T Kuwabara

Publications and source records attributed to T Kuwabara.

At least 91 records · Page 5Linked to original sources
PubMed1995

Novel colorectal adenocarcinoma-associated 40- and 47-kDa protein antigens recognized by anti-60-kDa heat shock protein antibody.

Expression of 40- and 47-kDa proteins recognized by anti-60-kDa heat shock protein antibody was investigated in colorectal adenocarcinoma tissue. In all cases of colorectal adenocarcinoma tissue (n = 9), 40- and 47-kDa proteins were detected by immunoblot analysis. However, expression of these two proteins was extremely low or was not expressed in control tissue. There was no correlation between the quantity of these two bands and histologic type or the location of the tumors. Our results first demonstrate the accumulation of structurally altered 60-kDa heat shock protein-associated antigens in carcinoma tissue and suggest that these two proteins could be a possible candidate for tumor-specific 60-kDa heat shock protein-related protein antigens.

Adenocarcinoma↗
PubMed1995

Receptor-mediated clearance of G-CSF derivative nartograstim in bone marrow of rats.

To clarify the role of the granulocyte colony-stimulating factor (G-CSF) receptor in the nonlinear elimination of a recombinant human G-CSF derivative, nartograstim (NTG), the accompanying changes in the in vivo NTG total body clearance at steady state (CLss) or the early-phase tissue uptake clearance (CLuptake) in rats were compared with the change in the number of G-CSF receptors in bone marrow. The infusion rate-dependent decrease in CLss in control rats confirmed the existence of a saturable elimination mechanism for NTG. The Michaelis-Menten constant (Km) and maximal velocity for this saturable process were estimated to be 107 pM and 15.5 pmol.h-1.kg-1, respectively. The Km for this saturable process was comparable with the dissociation constant (Kd) for the specific binding of NTG to bone marrow cells. After administration of excess NTG, the CLuptake of tracer amounts of 1251-NTG by bone marrow and spleen, which corresponds to the receptor density in the tissues, was reduced at 2 h but gradually recovered. This change in CLuptake corresponds well to the change in the in vitro NTG-binding capacity in each isolated cell. This reduction in CLuptake might be due to the downregulation of G-CSF receptors on the cell surface. On the other hand, the saturable CLss in cyclophosphamide-treated rats was 17% of that in control rats, whereas the saturable CLss in rats given NTG repeatedly was twofold greater than in controls, which is associated with the upregulation of G-CSF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Saturable uptake of a recombinant human granulocyte colony-stimulating factor derivative, nartograstim, by the bone marrow and spleen of rats in vivo.

Kinetic analysis of the in vivo tissue distribution of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) derivative, nartograstim (NTG; nartograstim is an international nonproprietary name of KW-2228, Kyowa Hakko Kogyo, Tokyo, Japan) was studied in rats to determine the mechanism of the growth factor's nonlinear pharmacokinetic properties. The early-phase tissue uptake clearance (CL(uptake)) by each tissue was determined within 5 min after the i.v. administration of 125I-NTG. Coadministration of various amounts (0.6-150 microgram/kg) of unlabeled NTG did not produce any significant change in CL(uptake) by kidneys and liver. The hepatic and renal extraction ratios of NTG were low, 0.10 to 0.15, which suggests that there is no saturable uptake system in either of these organs. CL(uptake) by the kidneys was comparable to the glomerular filtration rate of unbound NTG. By contrast, a dose-dependent reduction in CL(uptake) by bone marrow and spleen was clearly observed with increasing doses of unlabeled NTG, i.e., at the maximal dose, these values were 14% and 20%, respectively, of those after a tracer dose. A saturable process was, therefore, involved in the tissue uptake of 125I-NTG by bone marrow and spleen. The intrinsic clearance (Vmax/Km) of this saturable uptake by bone marrow, 1.4 ml min-1 kg-1, was greater than that by the spleen, 0.09 ml min-1 kg-1. The sum of the intrinsic clearances of the saturable process was comparable with the value for the clearance of the saturable elimination process of NTG obtained previously by nonlinear pharmacokinetic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Functional magnetic resonance imaging of the human primary visual cortex during visual stimulation].

Signal changes in the human primary visual cortex during visual stimulation were evaluated using non-invasive functional magnetic resonance imaging (fMRI). The experiments were performed on 10 normal human volunteers and 2 patients with homonymous hemianopsia, including one who was recovering from the exacerbation of multiple sclerosis. The visual stimuli were provided by a pattern generator using the checkerboard pattern for determining the visual evoked potential of full-field and hemifield stimulation. In normal volunteers, a signal increase was observed on the bilateral primary visual cortex during the full-field stimulation and on the contra-lateral cortex during hemifield stimulation. In the patient with homonymous hemianopsia after cerebral infarction, the signal change was clearly decreased on the affected side. In the other patient, the one recovering from multiple sclerosis with an almost normal visual field, the fMRI was within normal limits. These results suggest that it is possible to visualize the activation of the visual cortex during visual stimulation, and that there is a possibility of using this test as an objective method of visual field examination.

Adult↗
PubMed1995

Functional magnetic resonance imaging of the primary visual cortex: evaluation of human afferent visual system.

The authors evaluated signal changes in the human primary visual cortex during visual stimulation using functional magnetic resonance imaging (MRI) scanner at 1.5 Tesla. Experiments were performed on 10 normal volunteers and 2 patients with homonymous hemianopsia. In the normal volunteers, a signal increase was observed on the bilateral primary visual cortex during hemifield stimulation. In one patient with homonymous hemianopsia after cerebral infarction, the signal change was clearly decreased on the affected side. In the other patient, who was recovering from multiple sclerosis to an almost normal visual field, the fMRI results were within normal limits. These results suggest that it is possible to map noninvasively the activation of the visual stimulation with a clinical MRI system, and that this test might be useful as an objective method of visual field examination.

Adult↗
PubMed1995

Characterization of an HDV ribozyme which consists of three RNA oligomer strands.

Properties of a mutant hepatitis delta virus (HDV) ribozyme which consists of three RNA oligomer strands (Fig. 1c) are described. Effects of the MgCl2 concentration, pH and temperature on the cleavage reaction were examined. The dependence on these conditions did not resemble those of the published data for other HDV ribozymes (the parent) which consist of single-strand RNA of about 90 nt. The highest cleavage for the mutant was observed at 35-40 degrees C, while the parent ribozymes show higher activity at around 60 degrees C than at 40 degrees C. Thus we suppose that the most of the parent ribozymes are in inactive conformation at 40 degrees C and high temperature is needed to change the equilibrium between the inactive and active conformations. Since the Tm of the mutant was around 50 degrees C, these results suggest that the most of the mutant ribozyme complex molecules are in active conformation at 40 degrees C.

Base Sequence↗
PubMed1994

Regulation of 60-kDa heat shock protein expression by systemic stress and 5-hydroxytryptamine in rat colonic mucosa.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that 5-hydroxytryptamine (5-HT) mediates alteration of bowel motility. In this study, the effects of water-immersion stress and the administration of 5-HT on the expression of a 60-kDa heat shock protein (HSP60) in rat colonic mucosa were investigated. The effect of YM-060, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, on the expression of this protein was also studied. Water-immersion stress and the administration of 5-HT induced synthesis of HSP60 in rat colonic mucosa. The induction of HSP60 and the number of defecations were clearly inhibited by the oral administration of YM-060. Our results suggest that the induction of HSP60 in rat colonic mucosa by water-immersion stress may be associated with gastrointestinal motility mediated by 5-HT, especially via 5-HT3 receptors.

Animals↗
PubMed1994

Induction of heat shock protein and prevention of caerulein-induced pancreatitis by water-immersion stress in rats.

Water-immersion stress is known to be involved in the development of hemorrhagic pancreatitis in caerulein-induced pancreatitis, when the stress is given following caerulein injection. The effects of pre-treatment with water-immersion to caerulein-induced pancreatitis were investigated in this study. 1. A 60-kDa heat shock protein was induced by pre-treatment with water-immersion stress in the pancreas. 2. Intra-peritoneal injection of caerulein (40 micrograms/kg) induced acute pancreatitis in rats without pre-treatment with water-immersion. However, when the rats were pre-treated with water-immersion, acute pancreatitis was not developed and no change of serum amylase levels was observed by i.p. injection of caerulein.

Amylases↗
PubMed1994

A prolyl endoproteinase that acts specifically on the extrinsic 18-kDa protein of photosystem II: purification and further characterization.

An endoproteinase, which specifically cleaves the Pro12-Leu13 bond of the extrinsic 18-kDa protein of PSII, was purified from PSII membranes of spinach. The presence of 0.05% (w/v) Tween 20 and 1 M NaCl was essential for maintenance of proteolytic activity during the purification. The molecular mass of the enzyme was estimated to be 95 kDa by gel-filtration chromatography. Active fractions contained a polypeptide of 165 kDa that was converted into diffusely stained polypeptides of 54 kDa upon reduction with dithiothreitol. The Km of the 18-kDa protein in the proteolytic reaction was 0.3 microM. Inhibition of the proteolysis by compounds that contain prolyl bonds revealed that both a prolyl bond and a positive charge are necessary for interaction with the proteinase, but some other structural factor(s) must also be involved in the high-affinity interaction between the proteinase and the 18-kDa protein. Reconstitution of NaCl-treated PSII membranes with the 23-kDa protein and/or the 18-kDa protein revealed that the 18-kDa protein was not cleaved by the proteinase when the substrate protein was functionally associated with the membranes. A comparison of the properties of the proteinase with those of a proline-specific endopeptidase from Flavobacterium suggests that these enzymes are quite different in terms of substrate specificity.

Amino Acid Sequence↗
PubMed1994

Argon laser treatment of trichiasis: a clinical and histopathologic evaluation.

Trichiasis is a common condition of multiple etiologies. Cryosurgery has been advocated as an effective means of treatment but may be associated with serious complications, including scar, skin depigmentation, and lid notching. We treated eight consecutive eyelids with the argon laser. At the end of a 3-month follow-up period, no recurrence was noted. The only observed complication was mild eyelid notching in one eyelid. Histopathologic evaluation of two specimens obtained 10 days and 5 weeks after laser treatment confirmed the highly localized coagulative effect of the laser with minimum destruction of adjacent tissues. Orientation of the eyelid so that the laser beam and the lash follicle are coaxial and careful measurement of the depth of vaporization of the lash follicle are important in confirming complete treatment and minimizing recurrence.

Adult↗
PubMed1994

Mitochondrial encephalomyopathy: elevated visual cortex lactate unresponsive to photic stimulation--a localized 1H-MRS study.

We used localized H-magnetic resonance spectroscopy (MRS) to study the metabolic changes in the visual cortex of patients with mitochondrial encephalomyopathy. Measurement of metabolite levels in the occipital visual cortex obtained in the dark with seven normal subjects and with four patients (all four of whom had Kearns-Sayre syndrome [KSS]) showed high lactate levels in the patients. Photic stimulation (PS) in four normal volunteers showed that lactate increased immediately after the start of PS and that it decreased to the baseline level with continued PS. Lactate in the resting state was higher in the KSS patients than in the controls, and, unlike the controls, the KSS patients showed no significant elevation of lactate with PS.

Humans↗
PubMed1994

Nonlinear pharmacokinetics of a recombinant human granulocyte colony-stimulating factor derivative (nartograstim): species differences among rats, monkeys and humans.

NTG is a human G-CSF derivative produced by Escherichia coli using gene-engineering techniques. The dose dependency of NTG pharmacokinetics in rats and monkeys was examined and compared with that previously reported for humans. In all species, the total clearance decreased and the mean residence time was prolonged as the intravenously administered dose of NTG was increased. At higher doses, the clearance in each species approached a constant value. This suggests that both saturable and nonsaturable processes are involved in NTG elimination. At the lowest dose, the saturable process accounted for 57% to 76% of total clearance. The plasma concentration-time profiles of NTG in rats and monkeys were analyzed by nonlinear pharmacokinetic models which contained both linear and Michaelis-Menten type elimination from the central compartment. The Km and Vmax values in rat, about 240 pM and 40 pmol/hr/kg, respectively, were comparable to those in the monkey. On the other hand, the values in humans were smaller, about 17% and 7%, respectively, than those in experimental animals. Therefore, the intrinsic clearance of saturable process (Vmax/Km) in humans was about one-half that in monkeys. To clarify the mechanism of the saturable clearance of NTG, the in vitro metabolic activities in rat bone marrow, spleen cells and peripheral leukocytes, which possess the G-CSF receptor, were determined. The metabolic activity of bone marrow cells was five-fold greater than that of the other cells. The in vitro metabolic and binding studies with bone marrow cells, demonstrated that the Im in NTG metabolism and Kd for NTG binding were 94 and 142 pM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Elevation of cerebral lactate detected by localized 1H magnetic resonance spectroscopy in a patient with migraine].

Localized 1H magnetic resonance spectroscopy was performed in a 45-year-old woman with migraine. She developed throbbing headache attacks without aura since thirteen years ago and the attack was accompanied with right hemiplegia since seven years ago. Brain MRI showed no abnormalities and 123I-IMP SPECT revealed mild frontal dominant decrease of cerebral blood flow. It seemed that her condition was positioned between migraine with prolonged aura and migrainous infarction of complicated migraine in the classification of International Headache Society. Spectra obtained from bilateral frontal lobe interictally showed elevation of lactate at left side. Choline, creatine, and N-acetyl-aspartate were almost equal on both side. The above results suggest that slight ischemia which is not detected by MRI is present or there is a disturbance of oxidative glycolysis, which is induced by mitochondrial dysfunction.

Brain↗
PubMed1993

Assessment of high-energy phosphorus compounds in the rat kidney by in situ 31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide.

31P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed. 31P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the 31P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of beta-ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than beta-ATP and Pi. In conclusion, according to the findings of 31P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and beta-ATP should be examined further.

Animals↗