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Biomedical subjects

K Kamata

Publications and source records attributed to K Kamata.

At least 145 records · Page 8Linked to original sources

[Clinical characteristics of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in adult].

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) were originally described as separate disease entities. Recently, HUS and TTP have been considered a single disease, because of the identical microangiopathic lesion. In the present study, we investigated the clinical and histological characteristics of HUS/TTP. Eleven patients with a definite diagnosis of HUS/TTP were found from a cohort of adult patients who were admitted to Kitasato University Hospital in the past two decades. Their clinical and histological characteristics were retrospectively analyzed. All of the 11 patients with HUS/TTP were sporadic and non-diarrheal cases with a mean age of 49 years +/- 10. Preceding episodes of flu-like syndrome and the administration of mitomycin C were observed in 3 and 5 patients, respectively. On admission, two of 10 patients with renal dysfunction required dialysis treatment, while none developed nephrotic syndrome. Six patients showed CNS manifestation, such as consciousness disturbance and convulsion. Three patients with severe hypertension did not show consciousness disturbance. As for the final outcome, 6 patients recovered and the remaining 5 died. Two died after 60 hospital days. In the histopathological investigation, renal biopsy specimen showed narrowing of the capillary loops in the glomeruli due to swelling of the endothelial cells, double contour of the glomerular basement membrane, or mesangial cell necrosis and sclerosis. In the autopsy specimen, internal organ infarction with fibrin thrombi in small arteries was observed in multiple organs, such as brain, kidneys, hearts, lungs, jejunum, liver, pancreas, adrenal glands and pituitary gland. A circumferential myocardial infarction with hyaline thrombi in the medial layer of myocardium was characteristic of HUS/TTP. In conclusion, microangiopathic lesions with infarction spread widely throughout various organs in HUS/TTP. Involvement of internal organs, not to mention kidneys and brain, is lethal and their prognosis remains poor.

Adult↗

[Surgical treatment and long-term results of congenital heart disease in adults: early and late follow-up studies in 231 cases].

In a past one decade from January 1981 to August 1991, 231 patients over 18 years old with congenital heart disease (CHD) including 65 patients with cyanotic (C) and 166 with acyanotic (AC) diseases, were surgically treated. There were one operative death (0.6 percent mortality) and three late deaths (1.9%) in 166 patients with AC diseases, whereas there were four operative (6.1%), and four late deaths (6.1%) in 65 patients with C. These patients were followed for 3 to 124 months (the mean of 46.4 +/- 11.9) after the operation. Compared with group AC, group C showed a high rate of early postoperative deaths or late deaths. Group AC comprised patients in their forties (95 patients with ASD and 15 with PDA) and those in their thirties (26 with VSD and 13 with ECD) at the operation. On the contrary, except 5 patients with Ebstein disease, a mean age of patients of group C at the operation lay in their twenties. Surgical outcomes for adult patients of group C still pose much problems compared with AC group in terms of decreased heart function, development of collateral circulatory pathway, and impaired hepatic and renal functions by long lasting hypoxemia. In group C decreased heart function or association of abscess of the brain might be the main cause of postoperative LOS. These findings indicate that early diagnosis, recent advanced operative procedure and appropriate postoperative care can provide symptomatic remission for even adult patients with severe CHD with a low mortality.

Adolescent↗

Stabilization of microtubules by dynein-binding in vitro. Stability of microtubule-dynein complex.

We have studied the effects of dynein binding on the stability of microtubules in vitro, using Tetrahymena ciliary dynein and microtubules (three-cycled purified microtubules: 3 X-Mts and phosphocellulose-column purified microtubules: PC-Mts). To determine the relative stability of the microtubules, we first prepared the microtubules bound with dynein (Mts--dynein complex) and subjected the Mts-dynein complex to treatments that depolymerize the microtubules, such as dilution to below critical concentration of tubulin, calcium ions and lower temperature. Dark-field microscopy revealed that the microtubules in the Mts--dynein complex appeared intact under conditions which otherwise result in microtubule depolymerization. However, when dynein was dissociated from the Mts--dynein complex with addition of ATP, no microtubule was found in the specimens under the same conditions. That is, the microtubules in the Mts--dynein complex did not depolymerize upon dilution with the buffer solution to below critical concentration of tubulin. However, addition of ATP to the diluted specimen caused dynein to become separated from the Mts, resulting in complete depolymerization of the microtubules. Stability of the microtubules was also studied by the turbidity changes and was confirmed by the patterns of stained gel bands in electrophoresis. With the addition of calcium ion, the Mts--dynein complex decomposed into separate molecules dynein and tubulin. At the lower temperature of 0 degrees C, the 3 X-Mts--dynein complex was decomposed into dynein and tubulin, while the microtubules in the PC-Mts--dynein complex did not depolymerize. Although we have not yet studied the effects of cytoplasmic dynein binding on the microtubules, the results suggest that the stabilizing effect of dynein binding to the microtubules is one of the important functions of dynein in vivo.

Animals↗

Simultaneous measurement of vasodilation and changes in cyclic nucleotides in the perfused mesenteric arterial bed of the rat.

We examined the relationship between relaxation responses of the mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 microM acetylcholine, 0.1 microM calcium ionophore A23187, and 1 microM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 microM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 microM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 microM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 microM methylene blue, and both the cAMP and cGMP levels were decreased. L-NG-Monomethyl arginine (L-NMMA) (100 microM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 microM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 microM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.

Acetylcholine↗

[Ankylosing spondylitis with acute anterior uveitis--correlation between HLA-B27 and clinical and radiologic findings].

Six cases of ankylosing spondylitis (AS) complicated with acute anterior uveitis (AAU) were reviewed. Clinical and radiologic findings of these cases were correlated with HLA-B27. All the patients were men; four of them were HLA-B27 positive, and two were B27 negative. The average age of onset was younger in B27+ patients than in B27- patients. Ophthalmologic study showed no definite difference in inflammatory change of AAU between B27+ patients and B27- patients. AAU in B27+ patients was completely cured in three months. A history of low back pain was more apparent in B27+ than in B27- patients. Three out of four B27+ patients showed complete bony ankylosis in sacroiliac joints, whereas no ankylosis was seen in B27- patients. CT scan was useful to demonstrate sacroilitis in cases with equivocal radiologic findings. Spondylitic changes were more extensive in B27+ than in B27- patients. The results support the concept that HLA-B27+ AS and B27- AS are different entities with similar phenotypic expression, and HLA-B27 is an arthritogenic gene in the Japanese population as well.

Acute Disease↗

Transbronchial lung biopsy in the diagnosis of suspected ocular sarcoidosis.

We conducted clinical research using transbronchial lung biopsy in 60 patients with suspected ocular sarcoidosis who showed no bilateral hilar lymphadenopathy and sparse contributory evidence for sarcoidosis. The patients had a combination of granulomatous iritis with mutton-fat keratic precipitates or iris nodules, trabecular nodules, tent-like peripheral anterior synechiae, snowball or string-of-pearls vitreous opacities, retinal perivasculitis, and spotty retinochoroidal exudates. The transbronchial lung biopsy specimen showed noncaseating epithelioid granuloma in 37 patients (61.7%); these patients were diagnosed as having sarcoidosis. Bronchoalveolar lavage showed a high percentage of patients with an increased lymphocyte fraction among those with positive transbronchial lung biopsy results. The present results may serve as a basis for a clinical diagnosis of sarcoidosis in patients with suspected sarcoidosis without apparent extraocular manifestations.

Adolescent↗

Electrical stimulation of tooth pulp increases the expression of c-fos in the cat supraoptic nucleus but not in the paraventricular nucleus.

Immunoreactivity to Fos protein was detected in the supraoptic (SON) and para-ventricular (PVN) nuclei of the cat using immunohistochemical methods. In the intact animal group, only a few Fos-positive neurons were observed in the PVN, but the SON did not contain any positive neurons. Intraperitoneal injection of pentobarbital sodium (Nembutal: 35 mg/kg) induced c-fos expression in the SON, but not in the PVN. Electrical stimulation of tooth pulp with an intensity that was 3 times the threshold of the jaw-opening reflex (200-600 microA) increased the number of Fos-positive neurons in the SON by up to 388% as compared with those of the Nembutal group, whereas the stimulation did not alter the number in the PVN. The increase was observed throughout the extent of the SON. In addition, morphine treatment (2 mg/kg, i. p.), 5 minutes before tooth pulp stimulation, considerably inhibited the increase in the SON. There were no significant differences among the 3 groups (intact, Nembutal, morphine) in the number of positive neurons in the PVN. These findings suggest that these hypothalamic nuclei have different functional roles and that the SON is involved in nociception and/or the consequent emotional and visceral reactions.

Animals↗

Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats.

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.

Animals↗

Endothelium-dependent vasodilator effects of the extract from Salviae Miltiorrhizae radix. A study on the identification of lithospermic acid B in the extracts.

1. The aqueous extract of Salviae Miltiorrhizae radix (Chinese crude drug named "dan-shen") relaxed the noradrenaline-precontracted aorta with endothelium. 2. Vasodilation by the extract disappeared in aorta without endothelium, and was inhibited by pretreatment with 10(-4) M NG-monomethyl-L-arginine (L-NMMA) or 10(-5) M methylene blue. 3. The inhibition of the extract-induced vasodilation by L-NMMA was reversed by L-arginine (3 x 10(-4) M). 4. The component of the extract was analyzed by chromatography, fast atom bombardment mass spectroscopy (FAB-MS) and 1H-NMR. 5. An active component of the extract, which showed endothelium-dependent vasodilation, was found to be identical with lithospermic acid B.

Acetylcholine↗

Changes in contractile responses of the urinary bladder to substance P in streptozotocin-induced diabetic rats.

1. Functional changes in the urinary bladder obtained from streptozotocin-induced diabetic rats were investigated by determining the responsiveness of bladder strips to capsaicin or substance P (SP). 2. Contractile responses of detrusor strips of the urinary bladder in response to capsaicin were almost abolished in both diabetic rats and capsaicin-pretreated rats. 3. Maximal contractions of diabetic detrusor strips induced by SP were significantly increased when compared to age-matched controls. 4. In contrast to the contractile responses to SP, the density of SP receptors was significantly decreased in diabetic rats. 5. The increased contractile responses to SP were markedly decreased by treatment with indomethacin, OKY-046 or quinacrine, but not with nordihydroguaiaretic acid. 6. Contractile responses of detrusor strips to prostaglandin F2 alpha and E2 were unchanged in the diabetic state. 7. These results suggest that the increased contractile responses of detrusor strips of the bladder to SP in the diabetic state are due to increased synthesis of prostaglandins and/or thromboxane A2 via the increased activity of phospholipase A2 on the smooth muscle of the diabetic bladder.

Animals↗

Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. I. PAF-induced contractile response and calcium mobilization.

1. Platelet-activating factor (PAF) caused contraction of the rat stomach fundus in a concentration-dependent manner in the presence of atropine, guanethidine, chlorpheniramine, methylsergide, indomethacin, nordihydroguaiaretic acid and tetrodotoxin. 2. PAF produced phasic contraction followed by tonic contraction. The PAF-induced tonic contraction was significantly reduced by treatment with CV-6209, an antagonist of PAF, but phasic contraction induced by PAF was rather resistant to CV-6209. 3. The contraction induced by PAF was markedly reduced when tissues were previously exposed to PAF (desensitization). 4. Nicardipine reduced the PAF-induced phasic contraction but not of the tonic contraction. 5. PAF-induced contractions were almost abolished in Ca(2+)-free medium. 6. The Ca(2+)-contraction in Ca(2+)-free solution was significantly augmented by PAF, whereas the Ca(2+)-contraction in Ca(2+)-free, isotonic high K+ (60 mM) medium was unaffected by PAF. 7. These results suggest that PAF-induced contractile response in the rat stomach fundus is due to an influx of Ca2+ through voltage-dependent Ca(2+)-channels (VDC) and receptor-operated Ca(2+)-channels (ROC). It is further suggested that PAF may depolarize the stomach fundus and this depolarization may open the VDC, whereas PAF may not act directly on the VDC.

Animals↗

Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. II. PAF-induced phosphatidylinositol turnover and desensitization.

1. Accumulation of [3H]-inositol phosphates (IPs) was slightly enhanced by PAF in a concentration-dependent manner, but the accumulation was very small as compared with that induced by carbachol. 2. The levels of [32P]-phosphatidic acid which is transformed from diacylglycerol (DAG) were increased by treatment with PAF or with carbachol. 3. PAF-induced contraction was significantly reduced by treatment with phorbol 12-myristate 13-acetate (PMA). 4. These results suggest that while PAF slightly stimulates the turnover of phosphatidylinositol (PI) in the rat stomach fundus, this response may not be responsible for the PAF-induced contractile response, and that the desensitization induced by repeated application of PAF may be due to the activation of protein kinase C.

Animals↗

Involvement of nitric oxide pathway in non-adrenergic non-cholinergic (NANC) relaxation in the rat stomach: differential innervation of NANC nerves in the longitudinal and circular muscle of the fundus.

1. The effects of NG-nitro-L-arginine (L-NNA) on non-adrenergic, non-cholinergic (NANC) relaxation elicited by transmural nerve stimulation (TNS) or high K+ were studied in the rat stomach fundus in order to investigate the mode of innervation of NANC nerves in the longitudinal and the circular muscle of the fundus. 2. Relaxation responses of the fundus to TNS were larger in circular than in longitudinal muscle strips. 3. Treatment with L-NNA (10(-5) M) reduced slightly but significantly the relaxation induced by TNS in both circular and longitudinal muscle strips of the fundus. The inhibitions of the TNS-induced relaxation by L-NNA were reversed partly by L-arginine (10(-3) M). 4. Although K+ produced concentration-dependent contraction in longitudinal muscle strips of the fundus, low concentration of K+ (20 mM) produced rapid and long-lasting relaxation in circular muscle strips of the fundus. 5. The 20 mM of K(+)-induced relaxation in circular muscle strips was significantly inhibited by L-NNA (10(-5) M) or oxyhemoglobin (2 x 10(-5) M). The inhibition of the K+ (20 mM)-induced relaxation by L-NNA was reversed by L-arginine (10(-3) M). 6. These results suggest that NO is one of mediators or transmitters in the NANC relaxation of the rat fundus, and that the density of NO-containing NANC nerves in the stomach fundus is richer in circular than in longitudinal muscle.

Animals↗

High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand black/white F1 hybrid mice, and low-dose combination may be synergistic.

To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybrid (B/W) mice, and also to study the possible synergistic effect of both drugs, B/W mice were heminephrectomized at 32 weeks of age, and were divided into six groups. Each group of mice was treated with 50 microliters phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylprednisolone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein venipuncture), as well as renal tissue specimens, were taken at 32 and 40 weeks of age. The degree of proteinuria, and serum anti-DNA activity (by ELISA) were determined. Renal specimens were evaluated with light- and immunofluorescence (C3)-microscopy, the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immunofluorescence (IF) scores. The survival rate at 40 weeks of age was significantly elevated in 0.6 mg DSP, 6 mg DSP, and methylprednisolone + DSP groups of mice compared with the control group. The appearance rate of significant post-treatment proteinuria was comparable among all groups. The difference (post-treatment titre--pretreatment titre) of serum anti-DNA activity in the 6 mg DSP and methylprednisolone + DSP groups were significantly less, while that of the 3 mg methylprednisolone group was greater compared with the control level. As for the total LM score, the levels significantly decreased in the 6 mg DSP, methylprednisolone + DSP and 3 mg methylprednisolone groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3).

A randomized trial with OKT3, an anti-T cell monoclonal antibody or with 15-deoxyspergualin against methylprednisolone-resistant rejection crisis was performed in 25 posttransplant patients immunosuppressed with prednisolone and cyclosporine. At least temporary reversal of rejection was observed in 58.3% of patients treated with 15-deoxyspergualin. This reversal rate may be quite comparable to 61.5% seen in patients treated with OKT3. Adverse effects with 15-deoxyspergualin were related to bone marrow suppression, while those with OKT3 were pyrexia, gastrointestinal symptoms, and herpes infection. In contrast to OKT3, which may act by modulating T cell surface antigen, 15-deoxyspergualin may be effective somewhere in the later stages of the rejection cascade.

Adult↗

Phorbol ester (PMA)-induced biphasic contraction of the rat aorta and effects of sodium nitroprusside and forskolin on the contraction.

Effects of sodium nitroprusside (SNP) and forskolin on the contractile responses of aortic strips to phorbol 12-myristate 13-acetate (PMA) were investigated in the present study. PMA produced biphasic contraction in the rat aorta, i.e. sustained, slowly developing contraction followed by phasic contraction superimposed on the sustained contraction. Both sustained contraction and phasic response were completely abolished by treatment with staurosporine. Phasic contraction was completely inhibited by nicardipine or removal of external Ca2+, whereas sustained contraction was not affected by nicardipine. Both SNP and forskolin inhibited sustained contraction. Ca(2+)-induced contraction of the aorta which had been treated with PMA in Ca(2+)-free medium was completely inhibited by nicardipine and was partially inhibited by forskolin, but SNP had no effect on the Ca(2+)-contracture. These results suggest that 1) PMA contacts the rat aorta through stimulation of protein kinase C and activation of voltage-dependent Ca2+ channels; 2) there may be great differences in the effects of cyclic GMP and cyclic AMP on the protein kinase C-induced sustained and phasic contractions.

Adenylyl Cyclases↗