Search PubMed⌕ Search

Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 343 records · Page 19Linked to original sources
PubMed1991

Discrete association of CD3 and CD4 molecules in T-cell stimulation acting through the autologous mixed lymphocyte reaction and the CD3/T-cell receptor complex in human autoreactive T-cell clones.

To investigate autologous antigen recognition, we developed two autoreactive CD4+ T-cell clones, A2 and A10, maintained with non-T cells and IL-2. Autologous non-T-cell stimulation of the T-cell clones resulted in a decrease in cell surface expression of CD4, whereas the expression of CD2, CD3, and WT31 was unchanged. Activation of the autoreactive T-cell clones by cell surface binding anti-CD3 MoAb, as a specific antigen stimulator of the T-cell receptor complex, induced cell surface antigen comodulation of CD3, CD4, and WT31. These data suggest a discrete association of CD3 and CD4 molecules in T-cell stimulation, acting through the autologous mixed lymphocyte reaction and the CD3/T-cell receptor complex. PMA treatment resulted in concomitant down-regulation of CD3 and CD4 but calcium ionophore treatment did not. Thus, it appears that phosphorylation of CD3 leads to the down-regulation of surface antigens of CD4.

Antibodies, Monoclonal↗
PubMed1991

Comparison of endothelium-dependent responses of monkey cerebral and temporal arteries.

1. Endothelium-dependency of vasodilator responses was compared in helical strips of monkey cerebral and superficial temporal arteries contracted with prostaglandin F2 alpha. Acetylcholine produced an endothelium-dependent relaxation in the temporal arteries, but did not consistently alter the tone of cerebral arteries. 2. Adenosine 5'-triphosphate (ATP) produced a transient contraction followed by a relaxation in the temporal and cerebral arteries; removal of the endothelium partially attenuated the relaxation of the cerebral arteries and markedly suppressed the relaxation in the temporal arteries. The dependency of adenosine 5'-diphosphate (ADP)-induced relaxations on the endothelium was also greater in temporal arteries than in cerebral arteries. 3. Histamine-induced relaxations in the temporal arteries were independent of the endothelium and were reversed to contractions by cimetidine. Cerebral arterial relaxations induced by histamine were partly dependent on the endothelium. Relaxations caused by substance P were reversed to contractions by removal of the endothelium in the temporal arteries, whereas the peptide did not consistently alter the tone of cerebral arteries. 4. The Ca2+ ionophore, A23187, relaxed the temporal and cerebral arteries to a similar extent; removal of the endothelium abolished these relaxations. Glyceryl trinitrate elicited similar relaxation of cerebral and temporal arteries, and these were independent of the endothelium. 5. These findings clearly indicate heterogeneity in the endothelium-dependency of several vasodilator responses in monkey intra- and extracranial arteries, although the ability of these arteries to respond to A23187 and glyceryl trinitrate does not appear to differ. The heterogeneous responses observed so far could therefore be due to different distributions of receptors or to variation in receptor-effector coupling in endothelial cells.

Acetylcholine↗
PubMed1991

Production of intracellular and extracellular interleukin-1 alpha and interleukin-1 beta by peripheral blood monocytes from patients with connective tissue diseases.

An enzyme linked immunosorbent assay (ELISA) was used to estimate the production of intracellular and extracellular interleukin-1 (IL-1) alpha and beta by peripheral blood monocytes from 26 patients with various connective tissue diseases (CTD), including 19 with systemic lupus erythematosus, four with progressive systemic sclerosis, two with mixed connective tissue disease, and one with Sjögren's syndrome. Monocytes obtained from patients with CTD with serum antibodies to nuclear ribonucleoprotein (nRNP) released significantly higher concentrations of extracellular IL-1 alpha and IL-1 beta, whereas intracellular IL-1 alpha and IL-1 beta production was similar to that by monocytes from patients with CTD without antibodies to nRNP. Furthermore, the concentrations of extracellular IL-1 alpha correlated significantly with those of extracellular IL-1 beta. There was no significant correlation between the concentrations of extracellular and intracellular IL-1 alpha, and those of extracellular and intracellular IL-1 beta, indicating that synthesis and secretion of IL-1 by human monocytes may be two distinct biological events. It seems that enhanced extracellular release of both IL-1 alpha and IL-1 beta contributes to the excessive anti-nRNP production in CTD.

Adult↗
PubMed1991

Constrictor action of oxyhemoglobin in monkey and dog basilar arteries in vivo and in vitro.

Angiographic studies on anesthetized dogs and Japanese monkeys showed that oxyhemoglobin (HbO2) injected into the cisterna magna produced a constriction of the basilar artery; the maximal constriction was attained 2-4 h later. Intracisternal injections of autologous blood, prostaglandin (PG) E2 and PGF2 alpha also constricted the artery to a similar extent, although the peak response was obtained much later (approximately 1 wk) with blood and was earlier (approximately 20 min) with PGs. The vasoconstrictor action of HbO2 was almost abolished by treatment for 5 h with aspirin in dogs and monkeys, whereas treatment of dogs with OKY 046, a thromboxane A2 synthesis inhibitor, did not significantly alter the action. In isolated monkey basilar arteries, HbO2 elicited a concentration-related contraction, which was suppressed by treatment with aspirin and by endothelium denudation. The basilar arteries responded to PGE2 and PGF2 alpha with contractions comparable to those caused by elevated external K+. Levels of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha in the nutrient solution bathing dog and monkey cerebral arteries were increased by HbO2; the increment was depressed by endothelium denudation and by treatment with indomethacin. These findings suggest that cerebral artery constriction caused by HbO2 in vivo and in vitro is associated mainly with the release of vasoconstrictor PGs, such as PGE2 and PGF2 alpha. Endothelium appears to play an important role in the release of PGs. Cerebral vasospasm elicited by intracisternal injections of HbO2 may be a useful model for the analysis of mechanisms underlying the provocation of delayed vasospasm after subarachnoid hemorrhage.

Animals↗
PubMed1991

Endothelin-1-like immunoreactivity in human urine.

By using a radioimmunoassay specific for endothelin-1 (ET-1), we studied whether ET-1-like immunoreactivity (LI) is present in human urine. Significant amounts of ET-1-LI were present in human urine, and the daily urinary excretion of ET-1-LI in 30 normal subjects was 67.6 +/- 35.5 ng/day. The mean urinary excretion of ET-1-LI determined in spot urine was 82.8 +/- 38.2 pg/mg creatinine (n = 30), while the mean plasma concentrations of ET-1-LI in the same individuals were 1.1 +/- 0.5 pg/ml. There was no significant correlation between urinary ET-1-LI excretion and its plasma levels. Reverse-phase high-pressure liquid chromatography of human urine extract revealed a major ET-1-LI component coeluting with standard ET-1. The present study demonstrates the presence of ET-1-LI excreted in human urine, although its exact source and physiological significance in renal tissues remain to be determined.

Adult↗
PubMed1991

Studies on the synthesis of condensed pyridazine derivatives. IV. Synthesis and anxiolytic activity of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-ones and related compound.

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.

Animals↗
PubMed1991

Effects of a depressor on cochlear blood flow and perilymphatic oxygen tension.

To clarify the characteristics of the blood circulation in the cochlea, we investigated the relationship between cochlear blood flow and perilymphatic oxygen tension in guinea pigs with trimetaphan camsilate induced hypotension. Cochlear blood flow was measured by laser Doppler flowmetry, and perilymphatic oxygen tension by a polarographic method. Cochlear blood flow generally paralleled systemic blood pressure, while perilymphatic oxygen tension showed a slower response to the decrease of systemic blood pressure. Although there were individual differences in the changes of systemic blood pressure, cochlear blood flow and perilymphatic oxygen tension, they were found to be dose dependent. Since hypotension induced by trimetaphan camsilate is fairly reproducible in the dose range of this experiment, this drug can be used as a ganglion blocking agent in experiments on cochlear blood flow and perilymphatic oxygen tension during systemic hypotension. The change of perilymphatic oxygen tension with a slower response could be considered to be a factor in the homeostasis in the inner ear fluid.

Animals↗
PubMed1991

Feasibility of pulse oxymetry to measure arterial O2 saturation in studies on cochlear blood circulation.

To understand the characteristics of oxygen transport to the inner ear, the relationship between arterial O2 saturation and cochlear microcirculation was investigated under different respiratory condition in guinea pigs. To monitor arterial O2 saturation a pulse oxymeter instead of an arterial blood gas analyzer was used. When the arterial O2 saturation was measured in the foot pad by a pulse oxymeter under different respiratory conditions, the data showed a close correlation with the results of blood gas analysis. For the measurement of cochlear microcirculation, a pulse oxymeter was found to be a feasible respiratory monitor for animal experiments. With this apparatus our study demonstrated a slower reaction in the decrease of perilymphatic oxygen tension than of cochlear blood flow during stepwise induction of hypoventilation monitored by a pulse oxymeter. Under certain conditions of hyperventilation in which arterial O2 saturation and perilymphatic oxygen tension increased gradually, cochlear blood flow was found to decrease. This decrease of cochlear blood flow could be attributed to chemical controls which are regulated, as in the cerebral blood circulation, by the content of CO2 and H+ in the vascular bed in the cochlea.

Animals↗
PubMed1991

Interleukin 1 and tumor necrosis factor-alpha synergistically increase the production of interleukin 6 in human synovial fibroblast.

We have previously reported that synovial cells could participate in B cell differentiation processes in rheumatoid arthritis (RA) by producing interleukin-6 (IL-6) spontaneously or in response to interleukin-1 (IL-1) stimulation. In this paper, we examined the effects of tumor necrosis factor-alpha (TNF-alpha) on IL-6 production by human synovial fibroblasts. TNF-alpha, as well as IL-1, is a putative relevant molecule in the inflammatory process and in articular destruction in RA. Both IL-1 and TNF-alpha induced IL-6 production by synovial fibroblasts in a dose dependent manner. When synovial fibroblasts were stimulated by IL-1 and TNF-alpha in combination, IL-6 production increased synergistically after 48 hr of a 72 hr culture period. Kinetic studies revealed that the presence of both cytokines at the early phase of stimulation was required for the synergistic effect. These results suggest that TNF-alpha could be involved in a cytokine network in the affected joints of RA and could contribute synergistically with IL-1 to the IL-6 production by synovial fibroblasts in vivo.

Arthritis, Rheumatoid↗
PubMed1991

[A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid].

A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.

Adult↗
PubMed1991

[Studies on plasma immunoreactive human brain natriuretic peptide (hBNP) levels in patients with congestive heart failure and present forms of hBNP in human cardiac ventricle].

By using a specific radioimmunoassay (RIA) for human brain natriuretic peptide (hBNP), we measured immunoreactive hBNP (ir-hBNP) in plasma from patients with congestive heart failure (CHF). There appeared to be relationship between the enhanced ir-hBNP secretory activity and the severity of the failing heart as well as that of immunoreactive human atrial natriuretic peptide (ir-hANP). However, the secretion of ir-hBNP was augmented much more than that of ir-hANP in sever CHF patients. Gel permeation chromatography coupled with the RIA revealed that ir-hBNP in human ventricle is composed with gamma-hBNP and hBNP (1-32) as well as that of human atrium. However, we found differences of the gamma-hBNP/hBNP (1-32) ratio in atrial and ventricular tissues. These findings suggest that the hBNP secretion mechanism differ in the two areas of human heart.

Adult↗
PubMed1991

Suppression of lipoprotein lipase in 3T3-L1 cells by a mediator produced by SEKI melanoma, a cachexia-inducing human melanoma cell line.

Production of a cachexia-inducing factor(s) by the SEKI melanoma cell line, established from a human melanoma, has been well documented. Conditioned medium from cultures of this melanoma cell line contains a factor(s) that inhibits the activity of lipoprotein lipase (LPL) in fully differentiated 3T3-L1 adipocytes. The mode of inhibition of this enzyme by the factor, i.e. its dose-dependency and time course, is very similar to that of LPL-inhibition by a macrophage-derived cachexia-inducing factor, cachectin/tumor necrosis factor (cachectin/TNF). However, the conditioned medium of SEKI melanoma cells does not contain any immuno-reactive substances reactive in enzyme-linked immunosorbent assay (ELISA) with anti-cachectin/TNF antibody, or with anti-interleukin 1 alpha or beta antibodies. This LPL-suppression factor present in the conditioned medium seems to be a peptide because of its heat-lability and apparent molecular weight of more than 25,000. The conditioned media from cultures of four other different cell lines were found to show no significant suppression of LPL activity. These results imply that SEKI melanoma cells produce a cachexia-inducing factor(s) similar to cachectin/TNF but that the molecule involved is different.

Animals↗
PubMed1991

Cardiopulmonary function values before and after heartworm removal in dogs with caval syndrome.

Cardiopulmonary function values were determined before and after surgical removal of adult heartworms in 25 dogs with spontaneous and 4 dogs with drug-induced caval syndrome (CS). Fifteen dogs with spontaneous CS (recovery group) and 4 dogs with drug-induced CS (drug-induced CS group) recovered after removal, and 10 dogs with spontaneous CS were euthanatized or died (nonsurviving group). Before heartworm removal, injected radiographic contrast medium was regurgitated from the right ventricle to the right atrium. Mean pulmonary arterial pressure and total pulmonary resistance were not statistically different between the recovery and nonsurviving groups of dogs, but the end-diastolic right ventricular pressure (mean +/- SD, 6.9 +/- 9.1 mm of Hg) and the a (8.7 +/- 9.2 mm of Hg)- and v (6.3 +/- 8.5 mm of Hg)-waves of the right atrial pressure curve in the recovery group were less, respectively, than the end-diastolic right ventricular pressure (17.3 +/- 6.0 mm of Hg) and the a (15.8 +/- 6.1 mm of Hg)- and v (21.4 +/- 6.9 mm of Hg)-waves in dogs of the nonsurviving group. After heartworm removal, contrast medium regurgitation disappeared, and cardiac output of the right ventricle increased in dogs of the recovery (from 2.08 +/- 0.72 to 2.38 +/- 0.68 L/min; P less than 0.05) and drug-induced CS (from 1.42 +/- 0.19 to 1.88 +/- 0.26 L/min, P less than 0.05) groups. However, regurgitation remained, and cardiac output did not increase in some dogs of the nonsurviving group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Experimental study on destruction of the third ventricle floor in the midline:--examination for the trans-third ventricle approach].

Surgery of a basilar bifurcation aneurysm is a very difficult operation in neurosurgery. For the treatment of this lesion, two methods are widely used at present: one is the subtemporal approach developed by Drake and the other is the pterional approach by Yasargil. With either approach, however, the treatment of a basilar bifurcation aneurysm accompanied by megadolichobasilar anomaly is difficult and hazardous due to the necessity for excessive retraction of the brain, nerves and vessels. Recently we successfully treated two cases of ruptured basilar bifurcation aneurysm complicated with megadolichobasilar anomaly by the trans-third ventricle approach. The floor of the third ventricle was already partly destroyed by aneurysmal rupture in both cases. It was required to make a small split in the third ventricle floor in order to get a wider operative field. Postoperatively, however, no influence from the splitting of the floor was seen. An experimental study was carried out in dogs to determine the influence from the destruction of the floor of the third ventricle. Using microsurgical techniques, the third ventricle floor was opened along the midline. Dogs were sacrificed 30 days after surgery. The following items were evaluated before, during, and after surgery: clinical symptom, blood pressure, pulse, body temperature, serum electrolytes, serum osmotic pressure, pituitary hormones (anterior lobe), cortisol, ADH (2.5mol NaCl loading test), electroencephalogram, cerebral blood flow and pathological change. No significant abnormalities could be detected in endocrine and metabolic functions, and no histological changes were seen around the hypothalamus. In conclusion, it is justified to split the third ventricle floor along the midline if it is indicated.

Animals↗
PubMed1991

[A specific and highly sensitive radioimmunoassay of human brain natriuretic peptide].

We established specific and highly sensitive radioimmunoassay (RIA) for the detection of human brain natriuretic peptide (BNP), and confirmed the presence of BNP-like immunoreactivity (BNP-LI) in human circulating blood and the heart. The antibody used in this RIA did not react any known human atrial natriuretic peptide (ANP). Gel permeation chromatography coupled with the RIA revealed that BNP-LI in atrium is composed with high molecular BNP and low molecular BNP. Furthermore, dominant form of BNP-LI in human plasma was thought to be low molecular BNP. Mean concentration of BNP-LI in plasma from normal subjects was 5.9 pg/ml, which was about 5 times lower than that of ANP-LI. Mean concentration of BNP-LI in human cardiac atrium was 45.6 ng/mg protein, which was about 40-fold lower than that of ANP-LI. Furthermore, concentration of BNP-LI in human cardiac ventricle was in a range of 0.1-4.8 ng/mg protein, being about 1/20 that of cardiac atrium. These data suggest that BNP synthesized in human heart and secreted into circulation.

Heart Atria↗
PubMed1990

Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblasts.

We have investigated the effects of recombinant human tumor necrosis factor (TNF)/cachectin on the cellular binding of human low density lipoprotein (LDL) to human skin fibroblasts. When recombinant TNF was added to cultured cells, LDL binding doubled after 24 h of incubation. The effect of TNF was dose-dependent and its maximal effect was observed at concentrations of 1-10 ng/ml. TNF also stimulated the growth of human skin fibroblasts 1.6-fold. These results indicate that TNF increases LDL-receptor activity, which might be related to its stimulatory effect on cell growth.

Dose-Response Relationship, Drug↗
PubMed1990

Levels of serum granulocyte colony-stimulating factor in patients with infections.

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age-matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

Acute Disease↗