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Biomedical subjects

K Okawa

Publications and source records attributed to K Okawa.

At least 19 recordsLinked to original sources

Developing corticorubral axons of the cat form synapses on filopodial dendritic protrusions.

Developing neurons transiently grow numerous spine- or filopodium-like dendritic protrusions (SLDPs). Electron microscopy on identified input and intracellular staining of postsynaptic cells were performed to gain insight into their significance. Newborn kitten-corticorubral axons, labelled with biocytin, commonly made synapses on SLDP, often multiply invaginated by the SLDPs. Correspondingly, intracellularly labelled kitten rubrospinal cells had numerous SLDPs. Taking into account that corticorubral synapses are largely formed on dendritic shafts in adult cats, it is likely that the SLDPs play some important role in the development of corticorubral synapses. We hypothesize that rubrospinal cells elongate SLDPs searching for corticorubral axons to form synapses.

Aging

New treatment of ulcerative colitis with K-76.

The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease.

Adolescent

Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16 or aclarubicin followed by recombinant human granulocyte-colony stimulating factor.

We developed an effective method for harvesting large numbers of peripheral blood stem cells (PBSC) for use in autotransplantation. Twenty patients with hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP-16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The optimal time for starting PBSC collection was determined by monitoring the CD34-positive stem cells in blood using immunomagnetic beads. PBSC were collected with a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was processed in each apheresis. Under these conditions, a total of 64 apheresis procedures was performed in the 20 patients. The mean numbers of mononuclear cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x 10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So far, 11 patients have been transplanted with PBSC and obtained rapid hematopoietic recovery. The median time to recover neutrophils more than 0.5 x 10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method for harvesting large numbers of PBSC allows safer autotransplantation in patients with chemoradiosensitive tumors, and is applicable to older patients.

Aclarubicin

Blue rubber bleb nevus syndrome with disseminated intravascular coagulation and thrombocytopenia: successful treatment with high-dose intravenous gammaglobulin.

A 63-year-old woman was diagnosed as having blue rubber bleb nevus syndrome (BRBNS) with disseminated intravascular coagulation (DIC). Hematological data showed typical DIC: PT 13.2 sec, activated PTT 55.3 sec, fibrinogen 20 mg/100 ml, FDP-E 928 ng/ml, D-dimer 3,477 ng/ml, platelet count 25 x 10(3)/microliters. Although hypofibrinogenemia was successfully controlled by the continuous infusion of heparin, 10,000 units/day, thrombocytopenia has continued. Based on shortened platelet life span, high level of platelet associated IgG, and increased number of megakaryocyte in the bone marrow, the thrombocytopenia was thought to be due to antiplatelet antibody. Her platelet count returned to normal after intravenous infusion of high-dose gamma globulin (IVIg, Sandoz) at the dose of 400 mg/kg for 2-5 days, while corticosteroid, Gabexate mesilate, synthetic thrombin inhibitor MD-805, urinastatin and warfarin had no effect. Thus, DIC or thrombocytopenia may become a serious complication in some patients with BRBNS and IVIg may be useful for correcting thrombocytopenia in the patient.

Disseminated Intravascular Coagulation

Predictive factors for the response of ulcerative colitis patients during the acute-phase treatment.

Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2-microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase.

Acute Disease

Intracellular predominance of the pyridoxal 5'-phosphate form of aspartate aminotransferase in Escherichia coli B and reversible transformation of this form by extracellular substances.

The intracellular proportion of the pyridoxal 5'-phosphate form of aspartate aminotransferase to the total enzyme in E. coli B cells was determined by a newly devised method, dependent on selective inactivation of the intracellular pyridoxal 5'-phosphate form of the enzyme by extracellularly added sodium borohydride. A large portion (80-99%) of the intracellular aspartate aminotransferase was in pyridoxal 5'-phosphate form in both natural and synthetic medium-grown bacterial cells. The intracellular predominancy of pyridoxal 5'-phosphate did not vary during the growth of bacteria and during incubation of bacterial cells in various kinds of buffers with different pH values. In contrast, the saturation levels generally used to describe in vivo the proportions of the apo and holo vitamin B6-dependent enzymes did not reflect the intracellular amount of the pyridoxal 5'-phosphate (holo) form of aspartate aminotransferase probably because the intracellular pyridoxal 5'-phosphate form was changed to an apo form by the disruption of bacterial cells for preparing crude extract. Various extracellularly-added vitamin B6 antagonists decreased the intracellular amount of pyridoxal 5'-phosphate without decrease in the total intracellular activity of the enzyme. The modified forms were stable in E. coli B cells and reversed into pyridoxal 5'-phosphate form by incubation of the antagonist-treated cells in the buffer containing pyridoxal. The present results showed that the sodium borohydride reduction method can be used for further analysis of the in vivo interaction of pyridoxal 5'-phosphate and apoaspartate aminotransferase. The fact that about 50% of the intracellular pyridoxal 5'-phosphate form was changed to a modified form without impairment of cell growth in the presence of 4-deoxypyridoxine, and that about 50% of intracellular modified aspartate aminotransferase was reversed to pyridoxal 5'-phosphate by the removal of antagonist followed by incubation suggested that there exists characteristically 2 different fractions of pyridoxal 5'-phosphate forms of aspartate aminotransferase in E. coli cells.

Aspartate Aminotransferases

Clinical and prognostic features of rectal sparing in ulcerative colitis.

Thirty patients with ulcerative colitis who had been followed clinically for more than 5 years were studied. Patients with total or left-sided colitis were investigated to evaluate the significance of rectal sparing in the prognosis of the disease. Patients were divided into two groups, one with complete or relative sparing of the rectum and the other with homogeneous lesions ranging from the rectum to the proximal colon based on endoscopic findings. The administration of topical corticosteroids seemed to have little effect on rectal sparing. However, the relapse index was significantly higher in patients with rectal sparing. The intractability index, representing the ratio of the duration of the active stage to the investigation period, was also higher, though not significantly so, in this group. The results suggest that rectal sparing may give information about intractability or a tendency to relapse.

Administration, Topical

[Immunocytochemical characterization of the DNA-polymerase alpha-positive colonic mucosal epithelial cells in patients with ulcerative colitis].

Colonic mucosal epithelial cells (EpC) in patients with ulcerative colitis (UC) have been shown to express HLA-DR antigen. In the present study, we observed the characteristics of HLA-DR-positive EpC using immunoperoxidase technique. In the control group, colonic EpC expressed HLA-ABC, but not HLA-DR. Only the EpC at the base of glands revealed positive for DNA-polymerase alpha (DNA-P). On the other hand, in actively inflamed mucosa of UC, about 80% of glands strongly expressed HLA-DR. Furthermore, most of EpC in the HLA-DR-positive glands showed positive nuclear stainings for DNA-P. This indicates that these EpC are not in the resting stage. It is strongly suggested that there are close relationships between the regeneration or proliferation of the EpC and class II MHC (HLA-DR) expression on the EpC in UC.

Adolescent

Possible role of vascular endothelial cells in immune responses in colonic mucosa examined immunocytochemically in subjects with and without ulcerative colitis.

Phenotypic characteristics of vascular endothelial cells of the colonic mucosa in patients with ulcerative colitis and healthy controls were studied with immunoperoxidase staining by light and electron microscopy. The cells could be classified into two groups according to their phenotypes; one was positive for von Willebrand factor and the other had an antigen detected by a monoclonal antibody, OKM5. The endothelial cells positive for von Willebrand factor were usually in relatively large blood vessels, and OKM5-positive cells were mostly located in small capillaries along the glandular epithelium. OKM5-positive endothelial cells also expressed HLA-DR and interleukin-1 (IL-1). In patients with ulcerative colitis, OKM5-positive endothelial cells and spindle-shaped cells that might be precursors of endothelial cells were more numerous in the lamina propria than in the other subjects. Thus, OKM5-positive endothelial cells may be important as antigen-presenting cells and immunoregulatory cells in the intramucosal immune system. Furthermore, colonic epithelial cells in patients with ulcerative colitis synthesized HLA-DR and IL-1, and may have a close relation to immune responses, such as antigen processing and presentation to immunocompetent cells. It was suggested that these cells have a close relation to the pathogenesis of the impaired immune responses in situ in ulcerative colitis.

Colitis, Ulcerative

Glycoprotein Ib has a partial role in platelet-von Willebrand factor collagen interaction.

The adhesion of human fixed washed platelets (FWP) to collagen was decreased after treatment with Serratia marcescens protease (SP), which removed 95% of the glycocalicin from platelet membrane glycoprotein (GP) Ib. However, the diminished adhesion of SP treated FWP to collagen could still be increased in the presence of purified von Willebrand factor (vWF). This ability to vWF to increase FWP adhesion to collagen is defined as collagen cofactor (CCo). The adhesion of FWP to collagen was not affected by a monoclonal antibody (MAb) to GP IIb/IIIa (10E5), that inhibits ADP and collagen induced platelet aggregation. On the other hand, it was decreased by 50% by a MAb to GP Ib (6D1), that inhibits ristocetin induced platelet aggregation. Adhesion of FWP in buffer to collagen was completely inhibited by Ricinus communis agglutinin I or concanavalin A, while Lens culinalis agglutinin and wheat germ agglutinin showed 50% inhibition. The FWP adhesion to collagen in the presence of vWF (normal plasma) was unaffected by MAbs to GP IIb/IIIa (10E5, P2, HPL1) but was decreased to 32-38% by MAbs to GP Ib (6D1, AN51, HPL11). A MAb to vWF (CLB-RAg 35), that inhibits ristocetin induced binding of vWF to platelets, decreased the CCo of normal plasma by 70%. The MAb, CLB-RAg 201, that inhibits the binding of vWF to collagen, completely inhibited the CCo of normal plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

Immunoglobulin-containing cells in the colonic mucosa of rabbits with carrageenan-induced colitis.

Immunohistochemical analysis of immunocompetent cells in the colonic mucosa was performed with carrageenan-induced experimental colitis in rabbits. Colitis was induced by seven months of oral administration of lambda-degraded carrageenan following immunization with the same substances containing Freund's complete adjuvant. In the colonic mucosa with colitis, IgG- and IgM-containing cells were significantly increased in number (IgG: 540 +/- 94/mm2 in experimental group, vs. 120 +/- 54/mm2 in control, P less than .05, IgM: 55.0 +/- 19.7/mm2 in experimental group, vs. 6.7 +/- 2.4/mm2 in control, P less than .05). There was no significant increase of IgA-containing cells either in number or in proportion to the total mononuclear cells. These changes, induced by carrageenan in rabbits, had resembled those in human ulcerative colitis well. These observations suggested an impairment of the IgA-regulated local immune system and an abnormality in the differentiation process of immunoglobulin-secreting cells.

Animals

Dissociation between the functional activity and immunoreactive concentration of C1 esterase inhibitor in active and quiescent Crohn's disease.

The plasma immunoreactive concentration and the functional activity of C1 esterase inhibitor (C1INH) were measured in 17 samples from 15 patients with Crohn's disease (CD) and 10 samples from healthy volunteers. C1INH activity was measured by the chromogen substrate method and the immunoreactive concentration by the single radial immunodiffusion method. The functional activity was 95.7 +/- 4.6% in the controls. In CD it was 60.8 +/- 7.5% in the active stage (CDAI greater than 100) and 113.4 +/- 4.9% in the quiescent stage (CDAI less than or equal to 100). There were significant differences between the controls and both the active and quiescent stages (p less than 0.05). The activity was significantly lower in the active than in the quiescent stages (p less than 0.01). However, the difference in the immunoreactive concentration of C1INH in the active and quiescent stages was not significant; it was 27.8 +/- 3.5 mg/dl in the active stage and 33.7 +/- 2.0 mg/dl in the quiescent stage. This difference in the pattern of change between the immunoreactive concentration and the functional activity of C1INH might arise from the mode of C1INH action, with stoichiometric binding to substrates, giving rise to irreversible complexes. These results showed the functional consumption of C1INH in active CD, which may be an aggravating factor in the pathogenesis of the inflammatory process in the patient.

Adult

[Neonatal hyperbilirubinemia of inadequately breast-fed infants and the effect of formula supplementation].

One hundred and fifty full-term breast-fed infants were analysed for their oral intake in the first 6 days. Fifty infants with less than 330 ml/kg/6 days breast feeding were defined as inadequately breast-fed infants. Twenty inadequately breast-fed infants without formula supplementation had significantly lower total fluid intake, lower total calorie intake, more body weight loss and significantly higher rates of hyperbilirubinemia and requirement of phototherapy when compared with the control group of 100 infants with more than 330 ml/kg/6 days breast feeding. On the other hand, 30 inadequately breast-fed infants with formula supplementation had significantly higher total fluid intake, higher total calorie intake, lower body weight loss and requirement of phototherapy than those without formula supplementation. From these data, we suggest that (1) Inadequate feeding may be a factor responsible for the higher prevalence of early neonatal jaundice in breast-fed infants reported in the literature. (2) Lower fluid intake, lower calorie intake and greater body weight loss may be associated with the higher incidence of hyperbilirubinemia and requirement of phototherapy. (3) Formula supplementation may be helpful in decreasing the risk of hyperbilirubinemia in inadequately breast-fed infants.

Breast Feeding