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Biomedical subjects

K Okawa

Publications and source records attributed to K Okawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

Encephalopathy and cytomegalovirus colitis in an AIDS child.

A 2-year-old girl, who had prolonged thrush and spastic diplegia, was found to have a mother-to-child vertical transmission of human immunodeficiency virus type-1 (HIV). A brain computed tomography scan revealed a symmetrical calcification on the bilateral basal ganglia and periventricular white matter. She had an acquired immune deficiency syndrome (AIDS) encephalopathy of pure dominant pyramidal tract disorder without an intellectual deficit. Helper cell lymphocyte count (CD4) increased with the beginning of zidovudine (ZDV, also known as AZT) monotherapy but began to decrease after the 4th week to reach the baseline at 20th week. Zidovudine plus didanosine combination therapy was started at the 68th week, but because of intolerance, the combination was changed to ZDV plus lamivudine at the 98th week. By the 80th week, neither severe opportunistic infection nor deterioration of the neurological status was recognized, but chronic diarrhea appeared. The diarrhea advanced to the wasting syndrome at the age of 4 years and cytomegalovirus genome was confirmed in a biopsied specimen of the colon. Ganciclovir treatment was effective in stopping the diarrhea and increasing her bodyweight, but after the age of 5, resumption of diarrhea was followed by progressive emaciation and weakness. This work may provide some clues in treating children's AIDS.

AIDS Dementia Complex↗
PubMed1998

Ulcerative colitis with skip lesions at the mouth of the appendix: a clinical study.

OBJECTIVE: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. METHODS: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. RESULTS: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. CONCLUSION: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis.

Adult↗
PubMed1998

Systemic and pulmonary responses of inflammatory cytokines following esophagectomy.

Inflammatory cytokines in plasma and bronchoalveolar lavage fluid (BALF) from 16 post-esophagectomy patients with and without preoperative methylprednisolone administration were studied. Interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations in plasma and BALF were measured by ELISA immediately after surgery (0-POD) and on the postoperative day 1 (1-POD). In patients without methylprednisolone treatment, IL-8 levels in BALF were 362 +/- 67 pg/ml on 0-POD and 948 +/- 359 pg/ml on 1-POD, and were approximately 10 times higher than those in plasma levels. IL-6 levels in plasma were significantly higher than those in BALF. The TNF-alpha concentration was similarly low in plasma and BALF. The patients with preoperative methylprednisolone treatment had significantly lower IL-8 levels in BALF and plasma compared with the patients without the treatment. Immunocytochemically, each cytokine was identified in the cytoplasm of bronchoalveolar macrophage. The percentage of polymorphonuclear cells (PMN) among BAL cells was significantly increased on 1-POD when compared with that of 0-POD, and tended to be decreased by preoperative methylprednisolone treatment. These results suggest that IL-6 was markedly increased in the peripheral circulation and that increased pulmonary IL-8 might be related to an accumulation of PMN in the lung under surgical stress. Further, methylprednisolone administration could possibly reduce postoperative cytokine responses at the local and systemic levels.

Adult↗
PubMed1998

[A case report of esophageal carcinoma with grade 3 response by preoperative chemotherapy using CDDP/5-FU/LV].

A 67-year-old man was diagnosed as having a type 3 advanced esophageal carcinoma by barium swallow and endoscopy. Biopsy specimens showed well-differentiated squamous cell carcinoma with positive immunostaining for p53, C-erb B-2 and negative for bcl-2. Two courses of chemotherapy using 5-FU, leucovorin and CDDP were performed before operation. Because no cancer cells were present in the surgical specimens, the effect was evaluated as grade 3. This neoadjuvant chemotherapy may be effective for esophageal carcinoma with a possible apoptosis mechanism.

Aged↗
PubMed1997

Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42.

We have previously shown that IQGAP1, a recently identified target for Cdc42 and Rac1 small GTPases, showed a distribution similar to that of cortical actin cytoskeleton at the membrane ruffling area induced by insulin and Rac1(val12) (Kuroda, S., Fukata, M., Kobayashi, K., Nakafuku, M., Nomura, N., Iwamatsu, A., and Kaibuchi, K. (1996) J. Biol. Chem. 271, 23363-23367). Here we identified an IQGAP1-interacting molecule with molecular mass of 43 kDa (p43) from bovine brain cytosol, using glutathione S-transferase (GST)-IQGAP1 affinity column chromatography. The amino acid sequencing of the protein revealed that p43 was identical to beta- and gamma-actin. IQGAP1 was cosedimentated with filamentous actin (F-actin). The amino-terminal domain (amino acids 1-216) of IQGAP1 was responsible for the interaction with F-actin. Falling ball viscometry assay revealed that IQGAP1 cross-linked the F-actin. This IQGAP1 activity was further enhanced by guanosine 5'-(3-O-thio)triphosphate (GTPgammaS).GST-Cdc42 but not by GDP.GST-Cdc42. The gel filtration analysis of IQGAP1 revealed that IQGAP1 appeared as oligomers and that GTPgammaS.GST-Cdc42 but not GDP.GST-Cdc42 enhanced the oligomerization of IQGAP1. These results strongly suggest that IQGAP1, acting downstream of Cdc42, can cross-link the actin filament through its oligomerization.

Actins↗
PubMed1997

Endoscopic dexamethasone injection following balloon dilatation of anastomotic stricture after esophagogastrostomy.

BACKGROUND: Anastomotic stricture is common after esophagogastrostomy. Recent advances in nonsurgical treatment include the silicon bougie and balloon dilatation. However, simple dilatation alone with a silicon bougie or endoscopic balloon dilator was repeated a mean of 4.7+/-5.4 times to control anastomotic stricture because of its temporary effect. METHODS: For 11 patients, endoscopic injection of dexamethasone (8 mg) around the anastomosis was done immediately after balloon dilatation (40 psi for 5 minutes). RESULTS: This method significantly reduced the number of the dilatations to 1.1+/-0.3 (P < 0.05). Ten of the 11 patients did not need any further treatment. There were no side effects or complications of dexamethasone injection. CONCLUSION: A combination of endoscopic balloon dilatation and dexamethasone injection provided an easy and safe method for preventing the recurrence of anastomotic stricture.

Anastomosis, Surgical↗
PubMed1997

Cytotoxin genes of Helicobacter pylori in chronic gastritis, gastroduodenal ulcer and gastric cancer: an age and gender matched case-control study.

Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA). Both host factors and H. pylori strain differences may contribute to differences in the diseases. Thus, we conducted an age and gender matched case-control study of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and gastric cancer (GCA) to examine the role of strain differences of the H. pylori cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain reaction to examine the gastric juice for H. pylori DNA. The test was positive for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients, showing no statistically significant difference among the diseases (P = 0.84). cagA and vacA genes (picked up by using a vacA1 + vacA2 primer pair which detected non-variable regions of the vacA gene) were detected by PCR in the H. pylori DNA-positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%; DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically significant differences were found in the frequencies of these cytotoxin genes in H. pylori-positive cases among the various gastric diseases (P = 0.39 for cagA and P = 0.64 for vacA).

Adult↗
PubMed1996

Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)

The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP.RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase.

3T3 Cells↗
PubMed1996

Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.

The small GTP binding protein Rho is implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid to form stress fibers and focal contacts. Here we have purified a Rho-interacting protein with a molecular mass of approximately 164 kDa (p164) from bovine brain. This protein bound to GTPgammaS (a non-hydrolyzable GTP analog).RhoA but not to GDP.RhoA or GTPgammaS.RhoA with a mutation in the effector domain (RhoAA37).p164 had a kinase activity which was specifically stimulated by GTPgammaS.RhoA. We obtained the cDNA encoding p164 on the basis of its partial amino acid sequences and named it Rho-associated kinase (Rho-kinase). Rho-kinase has a catalytic domain in the N-terminal portion, a coiled coil domain in the middle portion and a zinc finger-like motif in the C-terminal portion. The catalytic domain shares 72% sequence homology with that of myotonic dystrophy kinase and the coiled coil domain contains a Rho-interacting interface. When COS7 cells were cotransfected with Rho-kinase and activated RhoA, some Rho-kinase was recruited to membranes. Thus it is likely that Rho-kinase is a putative target serine/threonine kinase for Rho and serves as a mediator of the Rho-dependent signaling pathway.

3T3 Cells↗
PubMed1996

The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.

The small GTP-binding protein Rho functions as a molecular switch in the formation of focal adhesions and stress fibers, cytokinesis and transcriptional activation. The biochemical mechanism underlying these actions remains unknown. Using a ligand overlay assay, we purified a 160 kDa platelet protein that bound specifically to GTP-bound Rho. This protein, p160, underwent autophosphorylation at its serine and threonine residues and showed the kinase activity to exogenous substrates. Both activities were enhanced by the addition of GTP-bound Rho. A cDNA encoding p160 coded for a 1354 amino acid protein. This protein has a Ser/Thr kinase domain in its N-terminus, followed by a coiled-coil structure approximately 600 amino acids long, and a cysteine-rich zinc finger-like motif and a pleckstrin homology region in the C-terminus. The N-terminus region including a kinase domain and a part of coiled-coil structure showed strong homology to myotonic dystrophy kinase over 500 residues. When co-expressed with RhoA in COS cells, p160 was co-precipitated with the expressed Rho and its kinase activity was activated, indicating that p160 can associate physically and functionally with Rho both in vitro and in vivo.

Amino Acid Sequence↗
PubMed1996

Identification of a putative target for Rho as the serine-threonine kinase protein kinase N.

Rho, a Ras-like small guanosine triphosphatase, has been implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid (LPA) to form stress fibers and focal contacts. The form of RhoA bound to guanosine triphosphate directly bound to and activated a serine-threonine kinase, protein kinase N (PKN). Activated RhoA formed a complex with PKN and activated it in COS-7 cells. PKN was phosphorylated in Swiss 3T3 cells stimulated with LPA, and this phosphorylation was blocked by treatment of cells with botulinum C3 exoenzyme. Activation of Rho may be linked directly to a serine-threonine kinase pathway.

3T3 Cells↗
PubMed1996

Effect of bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis.

Salicylazosulphapyridine and corticosteroids are the only remedies for inflammatory bowel disease currently in clinical use. They do not, however, necessarily bring about satisfactory therapeutic benefits, so that new agents are needed. In this study, we evaluated the effect of bucillamine, a new antirheumatic agent, in experimental rat colitis induced by trinitrobenzene sulfonic acid enema. Wistar rats were given vehicle alone (n = 16) or treated with 50 (n = 20) or 150 (n = 20) mg/kg of bucillamine daily for three weeks after induction of colitis. Conventional histological sections of the colon stained by haematoxylin and eosin were prepared and observed under a light microscope to determine colonic damage scores. The determinations were significantly lower in the group treated with 50 mg/kg of bucillamine and tended to be lower in the group treated with 150 mg/kg of bucillamine than in the untreated group, which implied that the experimentally induced colonic inflammatory changes and ulcerations were alleviated by bucillamine. Blood tests showed no abnormal values at the end of the treatment. The present observations suggest that bucillamine should be developed further as a possible therapy for inflammatory bowel disease.

Animals↗
PubMed1996

Distribution and anti-inflammatory effect of mesalazine on carrageenan-induced colitis in the rabbit.

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.

Aminosalicylic Acids↗
PubMed1996

Changes in urinary nitrate and nitrite during treatment of ulcerative colitis.

The urinary excretion rates of nitrate (NO3) and nitrite (NO2) were monitored in 14 patients with active ulcerative colitis during treatment using hydrocortisone and sulfasalazine. During the active phase of the disease, the NO3 excretion was significantly higher in the patients than in healthy controls (n = 6, p < 0.05), although it varied considerably among the patients. During the healing phase, the NO3 excretion decreased concurrently with improvement of symptoms and colorectal ulceration, but the NO2 excretion increased. During the inactive phase of the disease, the NO3 and NO2 excretions were significantly lower than during the active phase, and the NO2/NO3 ratio resembled that in the healthy controls. In contrast, a patient who failed to respond to treatment showed continuously high NO3 and NO2 excretion rates. These results indicate that urinary NO3 and NO2 excretions vary with the disease state in ulcerative colitis.

Adult↗
PubMed1996

Katanin, the microtubule-severing ATPase, is concentrated at centrosomes.

The assembly and function of the mitotic spindle involve specific changes in the dynamic properties of microtubules. One such change results in the poleward flux of tubulin in which spindle microtubules polymerize at their kinetochore-attached plus ends while they shorten at their centrosome-attached minus ends. Since free microtubule minus ends do not depolymerize in vivo, the poleward flux of tubulin suggests that spindle microtubules are actively disassembled at or near their centrosomal attachment points. The microtubule-severing ATPase, katanin, has the ability actively to sever and disassemble microtubules and is thus a candidate for the role of a protein mediating the poleward flux of tubulin. Here we determine the subcellular localization of katanin by immunofluorescence as a preliminary step in determining whether katanin mediates the poleward flux of tubulin. We find that katanin is highly concentrated at centrosomes throughout the cell cycle. Katanin's localization is different from that of gamma-tubulin in that microtubules are required to maintain the centrosomal localization of katanin. Direct comparison of the localization of katanin and gamma-tubulin reveals that katanin is localized in a region surrounding the gamma-tubulin-containing pericentriolar region in detergent-extracted mitotic spindles. The centrosomal localization of katanin is consistent with the hypothesis that katanin mediates the disassembly of microtubule minus ends during poleward flux.

Adenosine Triphosphatases↗
PubMed1996

[Percutaneous microwave coagulation therapy for hepatocellular carcinoma--study on its therapeutic effect in surgical cases].

Six patients with hepatocellular carcinoma were subjected to percutaneous microwave coagulation therapy (PMCT) by ultrasonic guiding. The size of the main tumor in the present cases was limited to not more than 2 cm. From 18 to 48 days after PMCT, each patient was subjected to surgery and pathological examination. By macroscopic observation, the PMCT area including both non-tumor and tumor regions looked yellowish white, and the boundary was clearly recognized. In the histological examination, the coagulation area surrounded by fibrous capsule was found, and deletion of nuclei and changes in stainability were observed in the marginal region. These changes indicated obvious coagulation necrosis, but the changes became less intense toward the center in the area, and in some portions, the tissue was indistinguishable from viable cells by light microscopy. In 2 cases out of the 6, part of the tumor remained outside the coagulation area. Since only the area determined by the microwave electrode is coagulated to cause necrosis on PMCT, sufficient safety margin should be required.

Aged↗
PubMed1995

Perinatal development of action potential propagation in cat rubrospinal axons.

1. The development of action potential conduction was studied by intracellular recording of antidromic spikes in cat rubrospinal cells. 2. The distance between the C1 and L1 spinal segments increased linearly from 5.6 cm at embryonic day (E) 59 to 9.8 cm at postnatal day (P) 30. 3. The conduction time from the C1 segment to the rubrospinal neuron soma, estimated from antidromic spike latency evoked by stimulation of the C1 segment, decreased rapidly prior to birth and then slowly thereafter. This coincided with a reduction in conduction time variation between cells. 4. The conduction time from the red nucleus to the L1 segment followed a similar time course during development. The conduction time reached the adult value by P30, at which time the spinal cord is only half the adult length. 5. The conduction velocity between the C1 and L1 segments increased monotonically between E59 and P30, from a low of 1 m s-1 to a maximum of 34 m s-1. 6. The rise time of rubrospinal neuron somadendritic spikes followed a developmental time course similar to that for conduction time. 7. Myelination of rubrospinal axons, as judged by the presence of myelinated segment spikes, began to occur prior to E59. 8. These findings suggest that development of action potential propagation in rubrospinal cells can be divided into an early and a late stage: conduction time reaches the adult value during the early stage, i.e. by the first postnatal month, and is maintained during the late stage. We propose that myelination, axon diameter increase and maturation of membrane properties act to reduce conduction time to adult values during the early stage, while a proportional increase in fibre diameter with axonal length results in a constant conduction time during the late stage.

Action Potentials↗