Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 847 records · Page 47Linked to original sources

PubMed1990

Sulfhydryl drug-induced eruption: a clinical and histological study.

Sulfhydryl drug-induced skin eruptions were studied clinically and histologically in 23 patients. In this study, tiopronin, D-penicillamine, captopril and gold sodium thiomalate were considered to be sulfhydryl drugs, because they have a thiol group or release sulfhydryl compounds. The clinical features included skin eruptions that were maculopapular, erythema multiforme-like, eczematous, psoriasis-like, seborrheic dermatitis-like, Gibert-like, lichen planus-like, and pemphigus-like. These clinical findings were reminiscent of the wide variety of eruptions seen in cutaneous graft-versus-host reactions (GVHR). Histologically, areas of vacuolation and eosinophilic necrosis with a satellite infiltrate of lymphoid cells were seen in the epidermis, and perivascular infiltrates were noted in the dermis. These findings were similar to the histological picture of cutaneous GVHR. In skin tests with sulfhydryl compounds, 19 out of 20 subjects showed positive reactions, and autoantibodies were found in 8 out of 12 subjects tested. Sulfhydryl drugs seem likely to induce immunologic changes in the host and to produce a distinctive reaction similar to that of cutaneous GVHR.

Adult↗

PubMed1990

Generalized rash induced by sulfhydryl drug in guinea pigs--a comparative study on it with cephalothin-induced rash in guinea pigs.

Adverse reactions produced by sulfhydryl compounds with active thiol groups have generally formed a distinctive pattern in man when they are viewed as a class. It has been reported that cutaneous SH-induced drug eruptions have a wide variety of clinical presentations; histologically, they show a pattern of eosinophilic necrosis and/or satellite necrosis similar to that seen in cutaneous graft vs host reactions. In the present experiments, guinea pigs were sensitized with cephalothin (CET) and thiol compounds such as tiopronin (TP), D-penicillamine, gold sodium thiomalate or thiomalate, using a method similar to that described previously. In lymphocyte stimulation tests, lymph node cells from the sensitized animals responded positively to spleen cells pulsed with each thiol compound. Intracutaneous tests revealed some positive reactions to each thiol compound; there was a tendency to produce a tuberculin type reaction with indurated erythema rather than the Jones-Mote type seen in CET-induced reactions. The dose-requirements for positive intracutaneous tests and generalized rash (GR) due to thiol compounds were lower than for CET, which required relatively large doses. Histologically, infiltration of basophilic cells was prominent in the skin lesions induced by intracutaneous tests with CET and in those of CET-induced GR. On the other hand, intracutaneous tests with TP following the induction of TP-induced GR revealed eosinophilic degeneration of epidermal cells, which was similar to the eosinophilic necrosis seen in cutaneous GVHR. Intracutaneous tests after the induction of CET-GR did not show any eosinophilic changes in the epidermal cells. These findings are reminiscent of the characteristics of eruptions induced by thiol compounds in man, which differ from the eruptions induced by CET.

Animals↗

PubMed1990

Evaluation of skin test reactions in patients with non-immediate type drug eruptions.

Skin test reactions were evaluated in 242 patients who appeared to develop delayed type drug eruptions from the clinical course. The patch testing was positive in 62 (31.5%) of 197 patients tested and the intradermal testing in 105 (89.7%) of 117 patients. The positive ratios of intradermal testing were higher in maculopapular (MP), erythema multiforme (EM), and erythrodermic (ED) types than in eczematous (Ecz) type drug eruptions, while those of patch testing were comparatively high in ED, Ecz type, and anticonvulsant-induced drug eruptions. It is considered that the combination of patch testing and intradermal testing is useful for determination of causative drugs in delayed type drug eruptions.

Adolescent↗

PubMed1990

Gold sodium thiomalate (GTM) induces hypersensitivity to thiomalate, the thiol carrier of GTM.

A case of the gold sodium thiomalate (GTM)-induced eruptions with thiomalate (TM) hypersensitivity was reported. A 61-year-old Japanese woman developed lichenoid and seborrheic dermatitis (SD)-like eruptions with alopetia, when the total dosage of GTM administered for rheumatoid arthritis became 110 mg. The eruptions slowly disappeared with pigmentation after discontinuance of the GTM therapy, and the resumption resulted in the development of similar eruptions. She showed a positive reaction to GTM in an intradermal test. She also showed a positive response to TM, which is the thiol carrier of GTM, in the patch test, but a negative one to metallic gold. After administration of auranofin (AF), she also developed the SD-like eruptions with hypersensitivity to metallic gold as well as AF on patch testing, but did not develop the lichenoid ones. Our animal experiments revealed an almost complete cross reaction between GTM and TM, but only a partial one between GTM and aurothioglucose, which have dissmilar structures in the carrier part for gold. Probable roles of hypersensitivity to TM and metallic gold, which are metabolites of GTM, were discussed, respectively, in the genesis of the GTM-induced lichenoid eruptions and the AF-induced SD-like eruptions.

Animals↗

PubMed1990

Perioperative blood transfusion and gastric cancer: adverse effects or unfavourable conditions of pretreatment?

The use of perioperative blood transfusion (PBT), the immunological status pre-operatively and at discharge from hospital, and the clinical course were examined retrospectively in 124 patients who underwent 'curative' resection for gastric cancer at Shinkokura Hospital, Japan from 1979 to 1988. The general condition of patients with PBT was worse than that of those without PBT and the pre-operative immunological status of patients with PBT was less favourable than that of those without PBT. At the time of discharge from hospital the immunological condition remained worse for patients who had been given PBT. The clinical course of patients with PBT was significantly worse. A dose-response relationship was evident but the types of blood products did not influence the outcome. Cox regression analysis adjusting for potentially confounding prognostic factors revealed that the clinical course was not altered by perioperative blood transfusion itself. These observations do not support the idea of adverse effects of perioperative blood transfusion on outcome of patients undergoing 'curative' resection for gastric cancer.

Actuarial Analysis↗

PubMed1990

Expression of a novel transcript of the myelin basic protein gene.

A cDNA (M41) corresponding to a mouse myelin basic protein (MBP) mRNA with a longer 5'-untranslated region than predicted from earlier studies of MBP gene structure has been isolated and characterized. The additional 5'-untranslated region is encoded by two previously unidentified exons upstream of the major transcription start site of the gene. Using a DNA probe specific for M41-MBP mRNAs, Northern blot analysis indicated that expression of this transcript follows a developmental course in mouse brain similar to that of the majority of MBP mRNAs, but that the level of expression varies between brain and spinal cored. Expression of MBP mRNAs similar to the mouse M41-MBP also was identified in rat brain. The results suggest that the structure of the MBP gene is more complex than originally thought, containing at least two more exons. There appears to be at least one more MBP gene promoter that directs the synthesis of a subset of MBP mRNAs with a unique 5'-untranslated region.

Animals↗

PubMed1990

Phosphorylation of P0 glycoprotein in peripheral nerve myelin.

The P0 protein in mammalian PNS myelin is known to undergo several posttranslational modifications, such as glycosylation, acylation, sulfation, and phosphorylation. Phosphorylation of purified P0 protein in vitro was studied comparatively using three enzymes, i.e., calcium/phospholipid-dependent protein kinase (protein kinase C), calcium/calmodulin-dependent protein kinase II (CaM kinase II), and the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase). The phosphorylation of P0 protein by CaM kinase II was the greatest, followed by that by protein kinase C; phosphorylation by A kinase, however, was much lower. In order to identify phosphorylation sites, P0 protein was phosphorylated with [32P]ATP and each kinase and then digested with lysylendopeptidase. The resulting phosphopeptides were isolated by HPLC. Subsequent amino acid sequence analysis and comparison with the known sequence of P0 protein revealed that Ser181 and Ser204 were strongly phosphorylated by both protein kinase C and CaM kinase II. In addition, Ser214 was also phosphorylated by protein kinase C, but not by CaM kinase II. Because all of these sites are located in the cytoplasmic domain of P0 protein, phosphorylation may be important for maintenance of the major dense line of PNS myelin.

Amino Acids↗

PubMed1990

Endothelin augments unitary calcium channel currents on the smooth muscle cell membrane of guinea-pig portal vein.

1. The effects of endothelin (ET) on the Ca2+ channel current in smooth muscle cells of the guinea-pig portal vein were investigated using the patch-clamp technique with whole-cell and cell-attached configurations. 2. ET augmented the macroscopic Ba2+ current in a dose-dependent manner; this effect was inhibited by nifedipine or Cd2+. Augmentation of the inward current by ET did not depend on the amplitude of the depolarizing pulse. Further, when the membrane potential was held at -60 mV, ET increased the amplitude of the Ba2+ inward current measured at the peak and end of the depolarizing pulse to the same extent. 3. By contrast, when the membrane potential was held at -80 mV, depolarizing pulses to potentials more negative than 0 mV produced greater augmentation of the inward current than did those more positive than 0 mV. Moreover, when a depolarizing pulse to below 0 mV was applied, ET increased the peak amplitude of the inward current more than the amplitude measured at the end of pulse. 4. Using the patch-clamp technique with cell-attached configuration, two types of unitary Ba2+ current with conductances of 22 and 12 pS were obtained in 50 mM-Ba2+ solution. Nifedipine inhibited both types of unitary channel current, but the sensitivity of the 22 pS Ca2+ channel to nifedipine was 20-fold higher than the 12 pS Ca2+ channel. 5. Bath application of ET prolonged the mean open time, reduced the number of sweeps in which no Ca2+ channel was opened ('blank' sweep), and increased the number of channel openings evoked by each depolarizing pulse without changes of conductance. As a consequence, ET increased the open probability of both channels. 6. Augmentation of the 12 pS channels by ET was seen only in the early phase of a depolarizing pulse (57 ms from the onset of 170 ms pulse), while augmentation of the 22 pS channels was seen during the entire period of a depolarizing pulse. 7. When ET was added to the pipette solution, the activity of both Ca2+ channels was increased. However, this effect was less frequently observed than when ET was applied in the bath. 8. These results suggest that ET augments both the nifedipine-sensitive and resistant Ca2+ channels in the smooth muscle cell membrane of the guinea-pig portal vein, but in different ways. Presumably, ET acts indirectly on the voltage-dependent Ca2+ channel.

Animals↗

PubMed1990

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of internal medicine].

A novel human native immunoglobulin liquid preparation for intravenous injection, C-425, was used in combination with antibiotics to study its efficacy, safety, and usefulness in 262 patients with severe infections which had not responded to antibiotic therapy of 3-day or more duration. As a result of the Committee judgement, 12 of the 262 patients were excluded from this study; 87 were included only in safety analysis; 163 (62.2%) were included in efficacy, safety, and usefulness analyses (complete inclusion). The complete analysis of 163 patients consisted of 93 patients (57.1%) with suspected septicemia, 33 (20.2%) with pneumonia, and 18 (11.0%) with septicemia. Eighty percent or more of the patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of C-425 was judged by the doctors in charge to be "excellent" or "good" in 49.1% of the total cases. The rate of effectiveness was calculated at 74.8% when "excellent", "good" and "fair" cases were all included. Similarly, the rate of effectiveness calculated from the results of Committee judgment was 53.4% when "excellent" and "good" cases were included, and 68.7% when "excellent", "good" and "fair" cases were included. Microbiological assessment was conducted in 19 patients. Causative organisms were eliminated in 11 patients, decreased in number in 1, persisted in 5, and replaced in 2. The rate of elimination was 57.9%. Side effects appeared in 6 of 250 patients (2.4%). It was judged that 3 patients (1.2%) of the 6 were affected by the drug or suspected to be affected, but they were not considered clinically important. Hepatic disfunction was found in 4 patients (1.6%) of the 250; but it was not clarified whether this was related to the drug. From these results, C-425 was considered to be an effective and very safe drug for treating severe internal infections.

Adolescent↗

PubMed1990

Fluctuating hearing loss in lipoma of the cerebellopontine angle.

Two cases of lipoma of the cerebellopontine angle are presented. Both of them showed fluctuating hearing loss, and one case exhibited Menière-like symptoms. In one of the cases, continued clinical surveillance is considered in view of a high chance of postoperative morbidity.

Adult↗

PubMed1990

Dual action of FRC8653, a novel dihydropyridine derivative, on the Ba2+ current recorded from the rabbit basilar artery.

Actions of FRC8653 on the macroscopic and unitary Ba2+ currents were studied using the rabbit basilar artery. Application of (+/-)-FRC8653 (less than 1 microM) increased the amplitude of the inward current when depolarization pulses more negative than -10 mV were applied but inhibited it when depolarization was more positive than 0 mV (in each case from a holding potential of -80 mV). At a holding potential of -40 mV, (+/-)-FRC8653 (greater than 0.1 nM) consistently inhibited the inward current. (-)-FRC8653 (greater than 1 nM) inhibited the amplitude of the inward current evoked by a depolarizing pulse more positive than -10 mV (the holding potential being -80 mV). At the holding potential of -80 mV, but not at -40 mV, (+)-FRC8653 (1 microM) enhanced the current amplitude evoked by a depolarizing pulse more negative than -10 mV but inhibited the current evoked by a pulse more positive than 0 mV. (+/-)-FRC8653 shifted the voltage-dependent inhibition curves to the left, and the slope of the curve became steeper (test pulse of +10 mV). Two types of single Ca2+ channel currents (12 and 23 pS) were recorded from the basilar artery by the cell-attached patch-clamp method. Opening of the 12-pS channel occurred with a depolarizing pulse (-20 mV) from a holding potential of -80 mV, but not from one of -60 mV. (+)-FRC8653 activated, and (-)-FRC8653 inhibited, the 23-pS channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Stability and localization of biotin-labeled murine monoclonal antibody to human gastric cancer in normal mice and nude mice-human tumor models.

We examined the tissue localization of biotin-labeled murine monoclonal antibody (MAb) S202 directed against the human scirrhous gastric carcinoma cell line MK-01 in normal and tumor-bearing mice after intravenous (IV) administration. The biotin-labeled MAb proved to be stable in vivo under normal conditions, antibody titer being 1:256 at 4 hr after IV injection. At 24 hr after injection, the tumor was stained by the avidin-biotin-peroxidase complex (ABC) method. Biotin-labeled MAb was found to be suitable for detection of the xenografted tumor of nude mice. This study provides new information concerning the dynamics of the distribution of biotin-labeled MAb in vivo.

Adenocarcinoma, Scirrhous↗

PubMed1990

Molecular dynamics simulation of papain-E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine) complex.

To investigate the possible binding mode of E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine), a potent cysteine protease inhibitor, to papain active site, molecular dynamics simulations were applied to two complex forms: R- and S- configurational forms of E-64 C2 atom for the covalent bond formation with the papain Cys-25 SH group. The tertiary structures of the papain-E-64 complexes were built by visual interactive modelling and the energy minimization technique, and were subjected to the dynamics simulations of 10 ps. Although no significant difference was observed between the potential energies of energy-minimized R- and S-complex forms, the molecular dynamics simulations suggested that the hydrogen bonding mode of the former form is more advantageous than that of the latter one. Comparing with the hydrogen bonds observed in the papain-E-64 complex crystal, it could be concluded that the present molecular dynamics simulation reflects well the three-dimensional structure concerning the interaction of E-64 with the papain active site. The conformational characteristics of E-64 and its possible interaction mode with papain were also discussed.

Computer Simulation↗

PubMed1990

[Morphine hydrochloride suppositories. II. Bioavailability of morphine hydrochloride suppositories in dogs].

Bioavailabilities of morphine after rectal administration of three different morphine.HCl suppositories were evaluated in dogs, whose rectum was lavaged or non-lavaged. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The release of morphine from the suppositories was examined after stored for two weeks at 30 degrees C. The plasma concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine++.HCl solution. In the case of rectal lavaged dogs, the plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration of morphine.HCl solution. The release of morphine from Witepsol H-15 suppository was more rapid than those from other suppositories. Morphine after rectal administration of Witepsol H-15 suppository was rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller than those of other suppositories. In rectal non-lavaged dogs, the bioavailabilities of morphine after rectal administration of morphine.HCl solution and suppositories decreased more than those of rectal lavaged dogs. Although the bioavailability of morphine after rectal administration of morphine.HCl was decreased by the influence of contents in the rectum, morphine from Witepsol H-15 suppository was more rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller. These results indicate that, among their suppositories, Witepsol H-15 suppository is available for the terminal care of malignant disease.

Administration, Oral↗

PubMed1990

Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of disease activity in sarcoidosis.

We investigated the clinical value of measuring serum concentrations of soluble IL-2R in monitoring sarcoidosis. Serum concentrations of soluble IL-2R were measured in 70 patients with sarcoidosis. The mean value for active untreated sarcoidosis was 1,143 +/- 509 U/ml, while the normal range in 97 healthy control subjects was 80 to 300 U/ml. The mean value for active untreated sarcoidosis was significantly higher than that for dormant disease (353 +/- 183 U/ml) or that for corticosteroid-treated patients (380 +/- 151 U/ml). Serial changes in serum soluble IL-2R level were studied in cases of spontaneous remission or in corticosteroid-treated patients; a good correlation was noted between the changes in serum level of soluble IL-2R and clinical status. A positive correlation was noted between serum concentration of soluble IL-2R and serum ACE activity. These data confirmed that measurement of serum concentration of soluble IL-2R could be used in monitoring the disease activity in sarcoidosis.

Adult↗

PubMed1990

Binding, internalization and the cytotoxicity of monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS) in target cells.

To study the mechanism of action of the monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS), the internalization of the antibody and its conjugate into target cells was examined. The incubation of radiolabeled A7 and A7-NCS with target cells revealed that both were taken up by target cells in a time dependent fashion. The immunocytochemical study using anti-NCS also revealed the intracellular localization of the conjugates. The cytotoxicity of the conjugate was markedly reduced when the binding sites were occupied by an excess of antibody on the cell surface. These results showed that A7-NCS was internalized into target cells and that its cytotoxicity was mediated through specific binding and internalization.

Animals↗

PubMed1990

Familial pituitary adenoma--report of four cases from two unrelated families.

The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.

Adenoma↗

PubMed1990

Spinal cord glioblastoma multiforme with intracranial dissemination--case report.

A case of spinal cord glioblastoma multiforme with intracranial dissemination is reported. A 23-year-old female was admitted to a local hospital complaining of lumbago. Myelography revealed an intramedullary thoracic tumor. The tumor was partially removed through a laminectomy at Th11-L1. The histological diagnosis was glioblastoma multiforme, and focal irradiation (total 50 Gy) was given. Eight months after the operation, symptoms of increased intracranial pressure appeared. Computed tomographic (CT) scans showed marked hydrocephalus, and multiple tumors at anterior horns of bilateral lateral ventricles. A ventriculoperitoneal shunt and an Ommaya reservoir into the left lateral ventricle were emplaced. Three months later, she was transferred to our hospital. CT scans showed enhanced lesions in the fourth ventricle, anterior horn of the left lateral ventricle, septum pellucidum, and pituitary gland. Suboccipital craniectomy was performed, and the mass around the fourth ventricle was partially removed. Histological examination of the tumor specimens showed glioblastoma multiforme. Postoperatively, she received whole brain irradiation (total 50 Gy), and intrathecal injection of beta-interferon via the Ommaya reservoir. However, she died of respiratory insufficiency. It is considered that the spinal cord glioblastoma multiforme disseminated into the intracranial space.

Adult↗