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Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 775 records · Page 43Linked to original sources
PubMed1997

Disease stage of chronic hepatitis C assessed by both peritoneoscopic and histologic findings and its relationship with response to interferon therapy.

BACKGROUND: Disease stage in patients with chronic hepatitis C was assessed by both peritoneoscopy and histology and correlated with responses to interferon therapy. METHODS: The subjects were 105 patients with chronic hepatitis C treated with interferon who were classified into 28 sustained responders, 34 transient responders, and 43 nonresponders according to alanine aminotransferase normalization. The influence of various patient's characteristics on responses to interferon therapy was investigated by multivariate analysis. RESULTS: Patients were categorized into 21 patients who exhibited a "smooth liver" on peritoneoscopy and did not demonstrate histologic bridging fibrosis (group I) and 84 patients who exhibited a "granular" or "nodular liver" on peritoneoscopy and/or had histologic bridging fibrosis (group II). Multivariate analysis showed that genotype 2a/2b (p = .0002), low viremia (p = .0048), and early disease stage (group I) (p = .0290) were significant independent factors contributing to sustained response, and that early disease stage (group I) (p = .0010) and genotype 2a/2b (p = .0085) were those contributing to sustained or transient response. Neither peritoneoscopic nor histologic findings alone were a significant factor influencing responses to interferon therapy. CONCLUSION: Disease stage assessed by both peritoneoscopic and histologic findings may serve as a reliable marker for predicting responses to interferon therapy in chronic hepatitis C.

Adult↗
PubMed1997

Combined hepatocellular carcinoma and cholangiocarcinoma in a mare.

A hepatic malignant tumour composed of both hepatocellular and cholangiocellular elements was studied histologically, immunohistochemically and electron microscopically in an 18-year-old Thoroughbred mare. Bile canaliculi and alpha-fetoprotein were useful in identifying the hepatocellular element, and mucin and keratin were good markers of biliary differentiation. The simultaneous presence of bile canaliculi and mucin-producing cells in most of the neoplastic lesions suggested that this tumour arose from a stem cell with capacity to differentiate into hepatocytes and biliary epithelium.

Animals↗
PubMed1997

Calcium-evoked insulin release from insulinoma cells is mediated via calcium-sensing receptor.

BACKGROUND: We have previously reported that high extracellular calcium ([Ca2+]o) levels elicited rapid increases in the cytosolic free calcium ([Ca2+]i) and insulin release from human insulinoma cells. In this study we further investigated the mechanism for stimulus-secretion coupling of insulinoma cells exposed to high levels of [Ca2+]o. METHODS: Insulinoma tissues were surgically obtained for primary culture. The changes of [Ca2+]i level in response to various agents were monitored by fluorometry. Total RNA was extracted from tissues and subjected to reverse transcription-polymerase chain reaction (RT-PCR) with calcium-sensing receptor (CaR)-specific primers. PCR products were subcloned and sequenced. RESULTS: When [Ca2+]o level was elevated, [Ca2+]i in insulinoma cells was immediately increased. Application of neomycin abolished the increase in [Ca2+]i level, although extracellular nifedipine and lanthanum chloride did not affect it. The depletion of intracellular calcium stores with thapsigargin or carbachol eliminated the increase in [Ca2+]i level. RT-PCR analysis identified the 682 bp product, of which the sequence was identical to the corresponding regions of human parathyroid CaR. CONCLUSIONS: Intracellular Ca2+ release might be important in insulin release from insulinoma cells after exposing to high level of [Ca2+]o. CaR could be involved in this mechanism.

Adult↗
PubMed1997

Serotonin elevates the c-wave of the electroretinogram of the rabbit eye by increasing the transepithelial potential.

The influence of serotonin (5-hydroxytryptamine, 5-HT) and serotonin analogues on the direct current electroretinogram (d.c. ERG) and the standing potential of the albino rabbit eye (SP) was studied. After unilateral vitrectomy, corneal recordings were obtained during simultaneous intravitreal perfusion with a control solution alternating with 5-HT at concentrations of 25, 120 and 200 microM. The c-wave increased at 25 and 120 microM when changing from control solution to test solution (P < 0.05) but did not decrease significantly when changing back to control solution (P > 0.05). The c-wave was reversibly elevated at 200 microM (PHS-5-HT, P < 0.01; 5-HT-PHS, P < 0.05). To analyse further the influence on the c-wave, in vivo intraretinal microelectrode recordings were obtained during intravitreal perfusion with 5-HT. The transepithelial potential (TEP) increased (P < 0.01), while the slow PIII was not significantly affected (P > 0.05). The serotonin receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, 5-methoxytryptamine, alpha-methyl-5-hydroxytryptamine and 2-methyl-5-hydroxytryptamine, caused a significant reversible elevation of the c-wave, whereas 5-carboxyamidotryptamine did not. Tropisetron did not block the serotonin effect and LY53857 had an effect of its own on the c-wave. The results seem to indicate that the influence of serotonin on the c-wave is mainly due to an effect on the retinal pigment epithelium (RPE) and that more than one type of serotonin receptor may be involved.

5-Methoxytryptamine↗
PubMed1997

Differential sensitivities to hyperbaric oxygen of lymphocyte subpopulations of normal and autoimmune mice.

We studied the effect of exposure to hyperbaric oxygen (HBO): 2.8 atm absolute 100% oxygen for 4 h daily over 3-7 days, on the immune system of normal (BALB/c and MRL- +/+) and autoimmune MRL-lpr/lpr) mice. In HBO exposed BALB/c mice, we observed a remarkable decrease in the cell population of the spleen and thymus. We found that the sensitivity to HBO varied among subpopulations of lymphocytes. For example, CD4+ CD8+ double positive cells in the thymus and B220+ B cells in the spleen were more sensitive than CD4+ or CD8+ single positive T cells in the thymus, and Thy-1+ T cells in the spleen, respectively. Accordingly, despite the decrease in total cell number in the spleen, the proliferative response of T cells from the spleen to Con A was not impaired in the HBO exposed mice. Exposure of MRL-lpr/lpr mice to HBO caused a marked reduction of weight and cell population of the otherwise enlarged spleen and lymph nodes, and amongst others of percentages of B220+Thy-1+ double positive abnormal cells. These results suggest the HBO therapy may be applicable for the treatment of some autoimmune diseases.

Animals↗
PubMed1997

Congo red reverses amyloid beta protein-induced cellular stress in astrocytes.

An amyloid-binding dye Congo red has been reported to prevent the neurotoxic effect of Alzheimer's amyloid beta protein (Abeta). In the present study, we investigated the effect of Congo red in cultured rat cortical astrocytes. Abeta (1 nM-10 microM) did not cause cell death, but potently inhibited the cellular redox activity as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Congo red (0.2-20 microM), when added together with or prior to Abeta, significantly blocked Abeta-induced inhibition of redox activity. Furthermore, when Congo red was added after treatment with Abeta, the inhibited redox activity was restored to normal, indicating that Congo red can reverse Abeta-induced cellular stress. The reversing effect of Congo red cannot be explained by the inhibition of Abeta fibril formation and suggests a novel aspect of the interaction of Congo red with Abeta.

Amyloid beta-Peptides↗
PubMed1997

In vivo voltammetric studies of the effects of intrathecal morphine on noxious heat stimuli-induced serotonin release in the nucleus raphe magnus of anesthetized rats.

The effects of cutaneous noxious heat stimuli and intrathecal administration of morphine on the oxidation current of 5-hydroxytryptamine (serotonin: 5-HT) in the nucleus raphe magnus (NRM) were examined in anesthetized rats. An oxidation current of 5-HT was seen at 320-340 mV using differential normal pulse voltammetry with nafion-coated carbon fiber electrodes. The signal was decreased by 28.5 +/- 5.7 and by 12.7 +/- 4.1% after cutaneous noxious heat stimuli of 52 and 45 degrees C, respectively. These decreases lasted for 5-10 min. Non-noxious stimuli (37 degrees C) did not affect the 5-HT signal. Intrathecal administration of morphine (2.5, 5.0, 10.0 and 15.0 microg) in the absence of cutaneous stimulation did not change the signal significantly. However, low doses of morphine (2.5 or 5.0 microg, i.t.) potentiated the decrease in the 5-HT signal induced by noxious stimuli, and high doses (10.0 or 15.0 microg, i.t.) attenuated it. Both effects of morphine at low and high doses were antagonized by naloxone (0.5 mg/kg, i.p.). These results indicate that the intrathecal administration of morphine affects the cutaneous noxious heat stimulus-induced decrease of serotonin release in the NRM.

Animals↗
PubMed1997

Visual evoked potentials in the vicinity of the optic tract during stereotactic pallidotomy.

We recorded visual evoked responses in eight patients with Parkinson's disease, using a depth electrode either at or below the stereotactic target in the ventral part of the globus pallidus internus (GPi), which is located immediately dorsal to the optic tract. Simultaneously, scalp visual evoked potentials (VEPs) were also recorded from a mid-occipital electrode with a mid-frontal reference electrode. A black-and-white checkerboard pattern was phase reversed at 1 Hz; check size was 50 min of arc . Pallidal VEPs to full field stimulation showed an initial positive deflection, with a latency of about 50 ms (P50), followed by a negatively with a mean latency of 80 ms (N80). The mean onset latency of P50 was about 30 ms. P50 and N80 were limited to the ventralmost of the GPi and the ansa lenticularis. Left half field stimulation evoked responses in the right ansa lenticularis region while right half field stimulation did not, and vice versa. These potentials thus seemed to originate posterior to the optic chiasm. The scalp VEPs showed typical triphasic wave forms consisting of N75, P100 and N145. The location of the recording electrode in the ansa lenticularis region did not modify the scalp VEP. These results suggest that P50 and N80 are near-field potentials reflecting the compound action potentials from the optic tract. Therefore, N75 of the scalp VEPs may represent an initial response of the striate cortex but not of the lateral geniculate nucleus.

Aged↗
PubMed1997

Different effects of cholinergic agents on responses recorded from the cat visual cortex and lateral geniculate nucleus dorsalis.

We investigated the effect of cholinergic agents on the cat visual evoked potentials (VEPs) recorded from the primary visual cortex (V1) and lateral geniculate nucleus dorsalis (LGNd) to determine on which level of the visual pathway the cholinergic system acts. VEPs to the alternation of 0.1 cycles per degree sinusoidal gratings at 1 and 4 Hz were recorded from N2O-anesthetized cats directly from the surface of V1 and LGNd. The depth of recording in LGNd was determined by the site where the maximal response was obtained by 1 Hz stimulation. VEPs to 4 Hz stimulation, which showed sinusoidal waveforms and were analyzed by fast Fourier transforms, were used as indicators for modulation by cholinergic agents. Physostigmine, an acetylcholinesterase inhibitor, 0.7 mg/kg i.v., suppressed the amplitude of the responses more at V1 (suppression ratio: mean +/- SD, 85.4 +/- 9.3%) than at LGNd (32.4 +/- 30.7%) (P < 0.05). Conversely, scopolamine, a muscarinic receptor blocker, 0.7 mg/kg i.v., increased the amplitude of the responses more at V1 (enhancement ratio: mean +/- SD, 60.3 +/- 22.3%) than at LGNd (-22.2 +/- 22.5%) (P < 0.05). These results indicate that the V1 changes reflect a direct cortical cholinergic effect, probably by modulating the cholinergic projection from the nucleus basalis of Meynert to V1.

Animals↗
PubMed1997

Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response.

BACKGROUND/AIMS/METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determinant of extracellular matrix deposition and breakdown. We measured serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels using the respective one-step sandwich enzyme immunoassays in 98 patients with chronic hepatitis C treated with interferon beta to examine their clinical significance for assessment of liver histology and to determine whether they can be useful as predictors of the interferon response. RESULTS: Serum TIMP-1 levels showed a positive correlation with the degree of fibrosis (r(s)=0.30, p= 0.004). Serum MMP-2 levels revealed positive relationships with the degree of periportal necrosis (r(s)= 0.32, p=0.002), the degree of fibrosis (r(s)=0.26, p= 0.01) and total score of histological activity index (r(s)=0.24, p=0.02). Serum MMP-2 levels were significantly higher in patients with no response than in those with sustained and transient response (p<0.01 and p<0.05, respectively), while serum MMP-1 levels did not differ among the three groups. Compared with the levels in sustained responders, the total amounts of serum TIMP-1 were significantly lower in transient responders and non-responders (p<0.01 and p<0.001, respectively). As for serum TIMP-2 levels, a significant decrease was found in transient responders and non-responders (p<0.01). The ratios of serum MMP-2 to TIMP-1 levels were significantly higher in transient responders and non-responders than in sustained responders (p<0.001, respectively) even when HCV RNA levels were low in patients with HCV genome subtype 1b or when the HCV genome subtype was 2a or 2b. Sustained response was never found in type 1b patients with ratios of serum MMP-2 to TIMP-1 levels of over 6.0. In logistic multivariate regression analysis, the ratios of serum MMP-2 to TIMP-1 level (p=0.0001), HCV genome subtype (p=0.005) and serum TIMP-2 level (p=0.03) were the independent predictors for sustained response, while serum MMP-2 level (p=0.0006) was the only predictor for no response. CONCLUSIONS: Serum MMP-2 and TIMP-1 levels might be useful for estimating the degree of liver fibrosis. The ratio of serum MMP-2 to TIMP-1 levels may serve as a new predictor of interferon response in patients with chronic hepatitis C.

Alanine Transaminase↗
PubMed1997

Production of bioactive salmon calcitonin from the nonendocrine cell lines COS-7 and CHO.

To produce bioactive salmon calcitonin from the conventional nonendocrine cell lines, COS-7 and CHO, we devised a salmon calcitonin expression vector by combining the amino-terminus of human calcitonin precursor with a salmon calcitonin sequence, inserting the efficient furin-cleavable processing sequence Arg-X-Arg-X-Lys-Arg before salmon calcitonin, and deleting the carboxyl-terminal extension peptide. This chimeric calcitonin precursor terminates at glycine to easily receive an amidation reaction. COS-7 and CHO produced a high level of bioactive calcitonin by the resorption pit formation assay. Although amidating activity is highly expressed in CHO, but only a little in COS-7 cells, both cells produced a similar level of bioactive calcitonin. Thus, the engineered salmon calcitonin expression vector enables nonendocrine cells even with low amidation activity to produce bioactive calcitonin.

Animals↗
PubMed1997

Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor during and after major abdominal surgery.

STUDY OBJECTIVE: To evaluate the influence of major abdominal surgery on the plasma levels of inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 10 ASA physical status I and II patients undergoing upper abdominal surgery. INTERVENTIONS: All patients received combined general-epidural anesthesia with isoflurane and nitrous oxide, after insertion of an epidural catheter at T7-T9 dosed with 1.5% lidocaine. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine (IL-6, IL-8, G-CSF) levels were determined with an enzyme-linked immunosorbent assay (ELISA) at pre-anesthesia, 0, 2, and 4 hours during surgery, and at the end of surgery, followed by sampling on the morning of postoperative days 1 (POD1) and 3 (POD3). Plasma cortisol levels were also determined. The plasma levels of IL-6 increased gradually after skin incision and reached the maximal value at the end of surgery (p < 0.001). IL-8 levels also increased from the baseline value to their maximum at the end of surgery (p < 0.05). G-CSF levels were elevated from the pre-anesthesia value to their maximum by the end of operation (p < 0.005). Plasma cortisol levels were increased after skin incision (p < 0.001). Postoperative cytokine levels correlated significantly with each other (r = 0.68, p < 0.05 for IL-6 vs. IL-8; r = 0.81, p < 0.005 for IL-6 vs. G-CSF; and r = 0.84, p < 0.005 for IL-8 vs. G-CSF). Postoperative IL-6 levels and intraoperative blood loss correlated significantly (r = 0.64, p < 0.05). CONCLUSIONS: These results suggest that major upper abdominal surgery stimulates the release of inflammatory cytokines presumably from the operation site. Further study is warranted to evaluate the modulation of inflammatory responses in the perioperative period.

Abdomen↗
PubMed1997

New serine protease inhibitors with leukotriene B4 (LTB4) receptor binding affinity.

A series of new trypsin-like serine protease inhibitors, 1, 2 and 7-23, containing amidinobenzene moiety was found to show potent LTB4-receptor affinity. Among them, compounds 1 and 2 were found to be LTB4 receptor antagonists based on an inhibition assay of human polymorphonuclear neutrophil (PMN) intracellular calcium mobilization induced by LTB4. Compounds 1 and 2, which satisfy the reported structural requirements for good oral activity, are expected to show a balanced dual mode of action, i.e., protease inhibitory activity and LTB4 receptor antagonist activity, in vivo.

Amidines↗
PubMed1997

Two forms of hemitonic seizure in patients with infantile hemiplegia and epilepsy.

Two forms of unilateral tonic (hemitonic) seizure were observed in two adult epileptic patients with infantile hemiplegia. Their ictal EEGs showed diffuse bilaterally synchronous spike bursts without focal features. In one case, a 31-year-old male, the VTR/EEG recording clearly demonstrated hemitonic seizure which simultaneously involved his paretic limbs and body and were associated with loss of consciousness and autonomic signs. In the other case, a 33-year-old male, partial seizures with secondary unilateral generalization were demonstrated by VTR/EEG recording. The reason why these cases do not exhibit motor seizure activity on the unaffected side despite diffuse bilateral EEG changes, a lower motor threshold in the paretic limbs and inhibitory effect in the brain-stem on undamaged side are postulated. These two cases suggest that hemitonic seizures include heterogeneous characteristics of partial and generalized epilepsy. In patients with diffuse brain damage, such as those with infantile hemiplegia, seizures appear to exhibit complicated patterns, with characteristics of partial and generalized seizures. There is a gradiation of expression of unilateral seizure, range from clearly partial seizures to those with mostly features of generalized seizures, except for an asymmetry of motor expression.

Adult↗
PubMed1997

Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.

To clarify the pathogenesis of ossification of the ligamentum flavum (OLF), we examined the expression and localization of bone morphogenetic proteins (BMPs) and their receptors (BMPRs) in the ligamentum flavum of the patients with OLF by immunohistochemical staining and compared them with staining patterns in control patients. The BMPRs appeared extensively in mature and immature chondrocytes around the calcified zone and in spindle-shaped cells and round cells in the remote part from ossified foci in examined tissue of OLF. The ligands for BMPRs, BMP-2/-4 and osteogenic protein-1 (OP-1)/BMP-7, colocalized in OLF patients. In the control cases, expression of BMPs and BMPRs was observed around the calcified zone at the insertion of the ligamentum flavum to the bone, and limited expression was found in the smaller range. Thus, the expression profile of BMPs and BMPRs in OLF patients was entirely different from the control patients, suggesting that BMPs may be involved in promoting endochondral ossification at ectopic ossification sites in OLF, and that ossification activity is continuous in these patients.

Activin Receptors↗
PubMed1997

Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology.

Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3+HLADR+ subset in three cases and the CD3- CD56+ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber- or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remission, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.

Bone Marrow Diseases↗
PubMed1997

The polymeric immunoglobulin receptor (secretory component) in a human intestinal epithelial cell line is up-regulated by interleukin-1.

Secretory component (SC or polymeric immunoglobulin receptor) on mucosal epithelial cells mediates transcytosis of polymeric immunoglobulin into external fluids and functions as a receptor for polymeric immunoglobulin. SC expression in a human colonic adenocarcinoma cell line, HT-29 has been reported to be up-regulated by various cytokines, such as interferon-gamma, tumour necrosis factor-alpha and interleukin-4 (IL-4). However, up-regulation of SC by IL-1 is controversial. In this study, we investigated the effect of human recombinant IL-1 alone on SC expression in HT-29 cells in detail. Immunocytochemistry and Northern blot analysis revealed that IL-1 beta increased both the number of SC-positive cells and SC mRNA expression. Enzyme-linked immunosorbent assay revealed that IL-1 beta enhanced secretion by HT-29 cells in both time- and dose-dependent manners. IL-1 alpha had the same effects on HT-29 cells. Northern blot analysis demonstrated that cycloheximide and actinomycin D abolished the effect of IL-1. Moreover, we detected IL-1 receptor (IL-1R) type I mRNA in HT-29 cells by polymerase chain reaction (PCR) and sequenced the PCR-amplified product. We think that it reflects the possibility of the presence of IL-1R in HT-29 cells. From these data, we concluded that IL-1 beta and IL-1 alpha play regulatory roles in SC expression, and their effects depend on de novo protein synthesis and transcription.

Blotting, Northern↗