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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 577 records · Page 32Linked to original sources

Muscle cramps and elevated serum creatine phosphokinase levels induced by beta-adrenoceptor blockers.

We have assessed the propensity of beta-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a beta-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a beta-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all beta-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK = 96 vs 133 IU.ml-1, CPK-MB = 14 vs 18 IU.ml-1) or carteolol (CPK = 117 IU.ml-1, CPK-MB = 18 IU.ml-1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Three-dimensional-MRI of neurovascular compression in patients with hemifacial spasm.

We prospectively studied 30 patients to assess the usefulness of three-dimensional (3D) contrast-enhanced MRI in patients with hemifacial spasm. In all patients neurovascular compression of the facial nerve could be detected. Microvascular decompression was performed in 14, and vascular compression of the root exit zone of the facial nerve and the offending artery were exactly as predicted by MRI in all but 2. We also retrospectively studied whether the symptomatic side could be defined only by enhanced 3D MRI in 55 randomised individuals (30 with and 25 without hemifacial spasm). All symptomatic sides were correctly identified, and the false-positive rate was 13.8%.

Adult↗

Microcephaly and early-onset nephrotic syndrome--confusion in Galloway-Mowat syndrome.

We report a 2-year-old girl with nephrotic syndrome, microcephaly, seizures and psychomotor retardation. Histological studies of a renal biopsy revealed focal glomerular sclerosis with mesangiolysis and capillary microaneurysms. Dysmorphic features were remarkable: abnormal-shaped skull, coarse hair, narrow forehead, large low-set ears, almond-shaped eyes, low nasal bridge, pinched nose, thin lips and micrognathia. Cases with this rare combination of microcephaly and early onset of nephrotic syndrome with various neurological abnormalities have been reported. However, clinical manifestations and histological findings showed a wide variation, and there is a lot of confusion in this syndrome. We therefore reviewed the previous reports and propose a new classification of this syndrome.

Child, Preschool↗

Characterization of tumor-necrosis-factor-gene-transduced tumor-infiltrating lymphocytes from ascitic fluid of cancer patients: analysis of cytolytic activity, growth rate, adhesion molecule expression and cytokine production.

We characterized tumor-infiltrating lymphocytes (TIL) from ascites of patients with ovarian or pancreatic cancer in which the human tumor necrosis factor (TNF) gene was successfully transduced with retrovirus vector. The TNF-gene-transduced TIL (TNF-TIL) from these patients showed a higher level of TNF production and higher cytotoxic activity against K562 and Daudi cells than did neomycin-phosphotransferase-gene-transduced TIL (neo-TIL). Of these TIL preparations, only that from pancreatic cancer was further characterized since it was collected in a relatively large amount. In spite of the fact that the autologous tumor cells showed resistance to soluble TNF, the TNF-TIL clearly demonstrated enhanced cytotoxicity against them as compared with neo-TIL. The enhanced cytotoxicity was ascribed to autocrine effects of secreted TNF on TIL, which included augmentation of adhesion molecule (CD2 and CD11a) and interleukin-2 receptor expression, and elevation of production of interferon gamma, lymphotoxin and granulocyte/macrophage-colony-stimulating factor and its paracrine effect on target cells to facilitate them to be more susceptible to TIL.

Ascites↗

A case of Werner's syndrome associated with systemic lupus erythematosus.

The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.

Adult↗

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats.

The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200, and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 micrograms/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats.

Acute Disease↗

Concurrent detection of cholecystocolic fistula and hepatic abscess by hepatobiliary scintigraphy.

We report the case of a 58-year-old male with cholecystocolic fistula and hepatic abscess that were not diagnosed by routine radiologic examinations, but concurrently detected by hepatobiliary scintigraphy with 99mTc-PMT, and confirmed at operation. Hepatobiliary scintigraphy is noninvasive and useful in the detection of a biliary enteric fistula and lesions about related organs. Concurrent detection of cholecystocolic fistula and hepatic abscess on hepatobiliary series is of great clinical value in planning surgical intervention.

Biliary Fistula↗

Postgastrectomy osteomalacia with pseudofractures assessed by repeated bone scintigraphy.

A patient with osteomalacia secondary to vitamin D deficiency after gastrectomy for gastric cancer is presented. Initial bone scintigrams showed both asymmetric and symmetric focal areas of intense uptake due to pseudofractures reminiscent of bone metastases. Radiographs only confirmed the presence of pseudofractures at some, but not all, of the abnormal sites demonstrated by bone scintigraphy. At first, metastatic bone disease was suspected. However, the appearance of repeated bone scintigram was normalized after treatment with vitamin D. A diagnosis of osteomalacia was established. The present case serves to illustrate that symmetric focal lesions are important features of pseudofractures secondary to osteomalacia, and comparison with radiographs and repeated bone scintigraphy are necessary in distinguishing between bone metastases and pseudofractures.

Bone Neoplasms↗

The value of combined 99mTc-Sn-colloid and 99mTc-RBC scintigraphy in the evaluation of a wandering spleen.

Wandering spleen is the term commonly applied to splenic hypermobility that results from laxity or maldevelopment of its suspensory ligaments. It comes to medical attention usually as an abdominal mass, or when the spleen undergoes torsion. Diagnosis on clinical grounds alone is rarely made, and ultrasonography, CT and MRI findings have no specific characteristics for this condition. 99mTc-labeled colloid taken up by the spleen may provide a specific diagnosis. We report a case of wandering spleen, in which the preoperative diagnosis was made on the basis of sequential liver-spleen scintigraphy with 99mTc-Sn-colloid and blood-pool scintigraphy with 99mTc-RBC. This is a rare case, in which hypermobility was assessed by sequential 99mTc-Sn-colloid scintigraphy, and to our knowledge, is the first case in which 99mTc-RBC scintigraphy provided useful information on splenic blood volume and its location.

Adult↗

Sequential subtraction scintigraphy with 99mTc-RBC for the early detection of gastrointestinal bleeding.

To improve the early detectability of gastrointestinal (GI) bleeding, we have developed a new subtraction scintigraphic technique using in vivo labeled 99mTc red blood cells (RBC). Use of this new sequential subtraction method every 5 min makes it possible to detect early the bleeding site and calculate the bleeding rate. In phantom experiments, focal activity was detected on subtraction images at pump rates of more than 0.20 ml/min at any urethane thickness, but was negative on conventional scintigrams. The calculated pump rate by the subtraction method correlated well with the actual syringe pump rate (y = 1.07x - 0.02, r = 0.99, p < 0.01) in the case of an 8-cm urethane board as an abdominal wall. Twenty-four of 50 patients with suspected GI bleeding were confirmed to be positive within 24 hr. The subtraction method showed 15 true positive and 2 false positive cases within 60 min. On the other hand, the conventional scintigraphic method showed only 7 true positive and 1 false positive cases. Sensitivity of the subtraction method was 62.5%, which was significantly higher (p < 0.05) than that of the conventional scintigraphic method (29.2%). These results suggest that sequential subtraction scintigraphy with 99mTc-RBC is an effective method for the early detection of GI bleeding and shortening the examination time as compared with conventional scintigraphy.

Adolescent↗

T-cell mediated polyclonal B-cell activation in a case of B-cell lymphoma associated with polyclonal hypergammaglobulinemia.

The mechanism of abnormal immunoglobulin production in non-Hodgkin's lymphoma is still poorly understood. We report a case of B-cell type non-Hodgkin's lymphoma associated with marked elevated polyclonal hyper-gammaglobulinemia (serum IgG was 7598 mg/dl; IgM, 455 mg/dl). We conducted a mixed lymphocyte culture test using peripheral lymphocytes obtained from the patient and a healthy volunteer. After co-culture with the patient's CD3+ cells, not only the patient's CD3- cells but also control CD3- cells produced greater amounts of IgG and IgM. Elevated IL-6 was also detected from the patient's CD3+ cells. This strongly suggests that B-lymphoma cells stimulate CD3+ cells to produce IL-6 and hence activate normal CD3- cells.

B-Lymphocytes↗

Suicide in later life in Japan: urban and rural differences.

It is estimated that in the year 2020, approximately 25% of the Japanese population will be over 65 years of age. Moreover, suicide is a significant public health problem in Japan, where more than 6,000 elders take their lives each year. The authors compare late-life suicide in urban Kawasaki with suicide among the elderly in rural Higashikubiki over a 12-year period, from 1979 through 1990. The suicide rates in Kawasaki were lower than for Japanese elders as a whole, whereas those in rural Higashikubiki were extraordinarily high. The most frequent method used in both areas was hanging, and none of the victims died of gunshot wounds. In Higashikubiki, almost two thirds of victims lived in a three-generation family and none lived alone. The change of the family system from the traditional extended family to the nuclear family is accelerating, especially in rural areas. The authors suggest that the greatly elevated suicide rates among the elderly in Higashikubiki, and in rural regions of Japan more generally, results from these rapidly occurring changes in traditional social structure.

Aged↗

O-glycosylation of a precursor to a sweet potato vacuolar protein, sporamin, expressed in tobacco cells.

Sporamin, a vacuolar protein of the sweet potato, is synthesized as a precursor that contains signal peptide and an N-terminal propeptide that functions as a vacuolar targeting determinant. Sporamin, when expressed in tobacco cells, migrated as smeared bands on an SDS-polyacrylamide gel. The smearing was due to O-glycosylation of the precursor to sporamin. The smeared bands were stained by a glycan-specific stain but no N-glycosylation site was found in the amino acid sequence of the precursor to sporamin. The glycan attached to sporamin contained galactose and arabinose as major sugar components. Mutations that altered the Pro36 or Ser39 residue of the precursor to sporamin prevented glycosylation of the protein, and analysis by semiquantitative Edman degradation suggested that a glycan moiety was attached to Pro36 and, possibly, to Ser39. Pulse-labeling and cell-fractionation experiments revealed that the O-glycosylation of the precursor to sporamin occurred in the Golgi apparatus. Thus, this modification serves as a good marker of the transport from the endoplasmic reticulum (ER) to the Golgi apparatus of the precursor to sporamin. Treatment of transformed tobacco cells with brefeldin A (BFA) caused the intracellular accumulation of prosporamin that did not migrate as smeared bands. Thus, it appeared that BFA inhibited the transport of the precursor to sporamin to the Golgi apparatus. This result provides the first biochemical evidence that BFA inhibits transport from the ER to the Golgi apparatus in plant cells.

2,2'-Dipyridyl↗

Inhibitory effects of bisbenzylisoquinoline alkaloids on induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha.

Bisbenzylisoquinoline alkaloids are known to affect immune responses as well as inflammatory responses, and have been used for the treatment of inflammatory symptoms in China. This study is aimed at elucidating the inhibitory effects of two alkaloids, fangchinoline and isotetrandrine, on the induction of the proinflammatory cytokines, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha), by Staphylococcus aureus Cowan 1 (SAC)-stimulated human peripheral blood mononuclear cells. These two alkaloids inhibited cytokine production in a dose-dependent manner, and they inhibited it by more than 90% at 10 micrograms/ml at every time point examined. Of note was that these two alkaloids appeared to inhibit IL-1 beta production more effectively than IL-1 alpha production. When the levels of cytokine mRNA were measured by semiquantitative RT-PCR, these alkaloids reduced the levels of the mRNAs of IL-1 beta and TNF-alpha, but not that of beta 2-microglobulin, suggesting that these alkaloids may suppress cytokine transcription selectively.

Alkaloids↗

Comparison of reactivity of monoclonal antibody (3F2) to trimeric tumor necrosis factor (TNF-alpha) with that to monomeric TNF-alpha.

Biologically active TNF-alpha is a trimer. Our newly developed monoclonal antibody against recombinant human TNF-alpha (3F2) bound to TNF-alpha immobilized on a solid phase precoated with the same monoclonal antibody, 3F2. We therefore examined the possibility that 3F2 preferentially recognized trimeric TNF-alpha, and obtained the following results. (i) Treatment of TNF-alpha with 1% NP40 enhanced the dissociation from the trimer to the monomer. The treatment also reduced the reactivity of 3F2 to TNF-alpha immobilized on a solid phase precoated with either 3F2 or a rabbit anti-TNF-alpha antibody (PT50). (ii) When trimeric and monomeric TNF-alpha, obtained by gel filtration of NP40-treated TNF-alpha, were assayed with either PT50 (solid phase)/3F2 (fluid phase) or PT50/PT50, PT50/3F2 showed a higher response to trimeric TNF-alpha than to monomeric TNF-alpha, while PT50/PT50 showed the opposite result. (iii) The values for two fractions containing only trimeric TNF-alpha obtained on ELISA with PT50/3F2 fitted the standard curve for ELISA with PT50/3F2 which was made by using unseparated TNF-alpha. Taken together, these findings suggested that 3F2 preferentially recognizes trimeric TNF-alpha.

Antibodies, Monoclonal↗

Permeability change of liposomal membrane induced by interleukin-1 alpha.

Interleukin-1 (IL-1) is produced and released by various cells, including activated macrophages, and plays important roles in inflammation as well as immune responses. Since the precursor of IL-1 has no signal peptide, the mechanism of IL-1 release has been an enigma. To investigate the possibility of direct interaction of IL-1 with the lipid bilayer, the interleukin-1 alpha (IL-1 alpha)- or beta (IL-1 beta)-induced permeability change of the liposomal membrane was determined. IL-1 alpha, but not IL-1 beta, caused an increase in the permeability of liposomes composed of phosphatidylserine (PS), at neutral and acidic pHs, as demonstrated by measuring the efflux of calcein. On the other hand, liposomes composed of phosphatidylcholine (PC) showed no increase in permeability when incubated with IL-1 alpha, suggesting the importance of acidic phospholipids in the interaction of IL-1 alpha with the membrane. Furthermore, permeability of liposomal membrane was markedly increased by IL-1 alpha in the presence of 1 microM calcium ions, although a permeability change was observed even in the absence of calcium ions. IL-1 alpha also induced the efflux of fluorescent dextran (average M(r) of 39,600), raising the possibility of translocation of IL-1 alpha through the cell membrane.

Calcium↗

Therapeutic effects of the angiogenesis inhibitor TNP-470 against carcinomatous peritonitis in mice.

The therapeutic effects of the new anti-angiogenesis factor TNP-470 were examined against carcinomatous peritonitis in mice. In the first experiment using carcinomatous peritonitis caused by i.p. inoculation of 10(6) M5076 tumor cells, TNP-470 solution was injected i.p. in a bolus of 50 mg/kg body weight into two groups of 10 mice either 1 or 8 days after the i.p. inoculation. The administration of TNP-470 on day 1 extended the survival time of the mice compared with 10 control mice receiving no treatment, whereas TNP-470 given on day 8 did not affect the survival time. In the next experiment on the M5076 tumor, TNP-470 solutions at 100 or 300 mg/kg were injected i.p. in a bolus into two groups of 20 mice 1 day after the inoculation 10(6) tumor cells, respectively. The administration of TNP-470 at 100 mg/kg also had an inhibitory effect. However, TNP-470 at 300 mg/kg caused toxic death in half of the mice. Next, we examined the effects of TNP-470 on another type of carcinomatous peritonitis model, which was caused by i.p. inoculation of 10(6) B16 melanoma cells. In this experiment, TNP-470 solutions in a bolus of 150 mg/kg were injected i.p. into six groups of 10 mice each on day 1 only (group 1), on days 1 and 4 (group 2), on days 1, 4 and 7 (group 3), on day 8 only (group 4), on days 8 and 11 (group 5), or on days 8, 11 and 14 (group 6), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗