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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 505 records · Page 28Linked to original sources

[Mutagenicity studies of iodixanol, a new non-ionic isotonic contrast medium].

A new non-ionic isotonic contrast medium, iodixanol (a diastereomeric mixture of 5,5'-[(2-hydroxytrimethylene) bis (acetylimino)] bis [N, N'-bis (2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzene-dicarboxamide]) was studied for mutagenicity by using the Ames method, in vitro cytogenetics and micronucleus test. Iodixanol had no mutagenic effect on S. typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) or E. coli (WP2uvrA) in the reverse mutation assay with or without metabolic activations. In the cytogenetic study, iodixanol had no effect on the Chinese hamster cells with or without metabolic activations. Intravenous injections of iodixanol for two times at a dose of 800, 1,600 or 3,200 mgI/kg in the mouse micronucleus test did not increase the incidence of micronucleated polychromatic erythrocytes. These results show that iodixanol has no mutagenic potential.

Animals↗

Sodium-coupled neutral amino acid cotransporter inhibited by the volatile anesthetic, halothane, in megakaryocytes.

We have studied the effects of halothane, a popular volatile anesthetic, on Na(+)-coupled L-alanine cotransporters using rat bone marrow megakaryocytes subjected to patch-clamp whole-cell recordings. L-Alanine applied externally induced an immediate current response which was abolished by the elimination of external NaCl. The optical isomer, D-alanine, induced no such response. A ligand probe for the Na(+)-dependent amino-acid cotransporter (A-system), 2-methylaminoisobutyrate, induced a response comparable to that of L-alanine. The response was fitted by a Michaelis-Menten equation with a Km of 2.5 and 58.5 mM for L-alanine (with 120 mM Na+) and external Na+ (with 10 mM L-alanine), respectively. The volatile anesthetic, halothane, acutely and reversibly inhibited the inward current responsible for the Na(+)-coupled L-alanine cotransporter. Complete inhibition was attained at 1 mM, and 50%-inhibition at 0.35 mM. Halothane in a clinically relevant concentration reduced nutrient uptake via the cotransporter A-system. The sensitivity of the A-system to halothane is comparable to or greater than that of Na+/K+/Cl- cotransporter, sodium/proton exchange, stimulus-secretion coupling, and of many ion channels in nerve cells.

Amino Acid Transport Systems↗

[A case of Sjögren's syndrome complicated with cryoglobulinemia, nephrogenic diabetes insipidus, and renal tubular acidosis].

A 68-year-old woman had been complained of xerostomia since she was 30 years old. Further symptoms of polyuria, polyposia and insomnia had been developed since she was 35 years old. The biopsy material from a minor salivary gland demonstrated the infiltration of lymphocytes into mesenchyme which was compatible with Sjögren's syndrome. She admitted to our hospital because of myalgia in bilateral gastrocnemius and petechiae in both lower extremities in addition to the complaints described above. Complete blood cell counts on admission revealed hemoglobin 9.7 g/dl, platelet count 12.5 x 10(4)/microliters, and white blood cell count 3,300/microliters. Marked polyuria, polyposia (more than 5,000 ml/day, respectively) and low urine gravity (1.005) were observed, although the serum creatinine level showed normal value. Serologic examination showed that the elevation of total serum protein concentration (9.5 g/dl) with marked elevation of serum IgG level (6,190 mg/dl). Her immunoglobulins contained cryoglobulin (cryocrit 20%), and immunoelectrophoresis demonstrated the existence of IgG-kappa monoclonal protein. A positive anti-nuclear antibody at 1:320 dilution, a positive rheumatoid factor and a positive antibody to SS-A (Ro) were also observed. The serial studies of blood gas analysis could not demonstrated the presence of metabolic acidosis. Together with the result of elevated plasma antidiuretic hormone level and results of vasopressin test, Fishberg's concentrating test and the tests of the overload of NH4Cl or bicarbonate, she was diagnosed Sjögren's syndrome with both diabetes insipidus and subclinical renal tubular acidosis. She was initially medicated with prednisolone (40 mg/day, orally), then she was given six courses of intravenous cyclophosphamide (750 mg/body/month).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗

[IgD-lambda type multiple myeloma associated with IgG-kappa type benign monoclonal gammopathy].

A 76-year-old man was admitted to Kisen hospital because of lumbago and chest pain. Laboratory examinations revealed a chronic renal failure with marked elevation of the serum BUN (48.8 mg/dl) and creatinine levels (8.2 mg/dl). The serum electrophoresis demonstrated a hypergammaglobulinemia with M peaks. An immunoelectrophoresis demonstrated monoclonal IgD-lambda and IgG-kappa proteins in the serum, and lambda-type Bence Jones protein in the urine (0.4 g/day). Bone marrow smears revealed an abnormal proliferation of atypical plasma cells (43%). A systemic X-ray examination of the skeletal system showed systemic osteoporosis without punched out lesion. The patient was diagnosed as having IgD-lambda type multiple myeloma and IgG-kappa type benign monoclonal gammopathy by quantifying concentration of two M proteins (1,160 mg/dl in IgD, 1,179 mg/dl in IgG, respectively). A combination chemotherapy with melphalan and prednisolone was administered monthly for multiple myeloma, and hemodialysis for the renal failure was performed 3 times a week. A marked improvement of his laboratory findings including a diminution of the serum IgD-lambda M-protein was obtained. On the other hand, IgG-kappa M-protein level was unchanged. Two M-protein levels showed a different behavior after the combination chemotherapy. Although the patient died of congestive heart failure, the partial remission of multiple myeloma has been maintained for 16 months with chemotherapy.

Aged↗

Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity in rats during repeated cis-diamminedichloroplatinum administrations.

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD. Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administration of DDP. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.

Animals↗

Changes in prevalence of anti-HCV antibodies associated with preventive measures among hemodialysis patients and dialysis staff.

The latest prevalence of hepatitis C virus (HCV) infection was evaluated in 548 Japanese patients undergoing hemodialysis, and 216 members of the hospital dialysis staff. An assay of anti-HCV antibodies was performed using both first- and second-generation immunoenzymatic tests, and anti-HCV specificity was confirmed with a second-generation recombinant immunoblot assay. Of 548 hemodialysis patients, 90 (16.4%) were positive with first-generation, and 166 (30.3%) with second-generation tests. These rates were significantly higher than those for either hospital staff members (0.5% and 2.3%; p < 0.01) or healthy blood donors (0.98% and 1.30%; p < 0.001). Patients with a history of blood transfusion tended to have a higher positivity rate for anti-HCV than did the non-transfused group (35.4% vs. 25.7% with second generation tests; p < 0.05). Positivity for anti-HCV was related to the duration of hemodialysis. Only a few patients seroconverted during the 2-year, 5-month period between the previous and present studies. Although hemodialysis patients remain a high-risk group for HCV infection, the prevalence of anti-HCV antibodies has decreased recently thanks to the use of erythropoietin for renal anemia, the universal screening of blood donors for anti-HCV antibodies, and improvements in infection control measures for this virus.

Adult↗

[Massive and progressive hepatosplenomegaly caused by disseminated nontuberculous mycobacteriosis in a patient with acquired immunodeficiency syndrome].

A 28-year-old hemophilia A patient was admitted to our hospital in July, 1991 because of high fever, chronic diarrhea and anemia. The patient had been recognized as a asymptomatic carrier of human immunodeficiency virus (HIV) in 1985 and had developed Pneumocystis carinii pneumonia and had been diagnosed as acquired immunodeficiency syndrome (AIDS) in 1990. Hematologic laboratory examinations on admission revealed pancytopenia and a CD4+ cell count of 3/mm3. X-ray findings of chest and abdomen were normal and bacterial cultures of sputum, urine, blood, stool, cerebrospinal fluid and bone marrow yielded no pathogenic microorganisms. Microscopical examination of the stained specimens showed no acid-fast bacilli. On his fifth hospital day, his liver and spleen enlarged markedly and an abdominal CT scan obtained on the 13th day revealed high-grade hepatosplenomegaly. Administration of several kinds of antibiotics, antifungal agents, antiviral agents, antituberculous agents and gamma-globulin medicines did not relieve the symptoms. On the 28th day the patient had developed a subarachnoid hemorrhage and died five days later. Retrospectively all cultures for acid-fast bacilli of the specimens on his admission yielded nontuberculous mycobacteria. The bacteria were identified as Mycobacterium avium by polymerase chain reaction and his disease was eventually diagnosed as disseminated Mycobacterium avium complex (MAC) infection. The liver and spleen weighed 2,660 g and 1,840 g respectively at autopsy. Although hepatosplenomegaly is commonly recognized in AIDS patients with disseminated MAC infection, such massive and rapid enlargement has been rarely observed. This case study emphasize the importance of diagnosis and rapid treatment at the early stage of MAC infection.

AIDS-Related Opportunistic Infections↗

[Experience in intra-hepatic-arterial chemotherapy and hepatic resection for metastatic colorectal cancer].

Out of 213 consecutive cases of colorectal cancer patients, 39 patients had liver metastasis (31 synchronous metastases and 8 metachronous metastases). One-and 3-year survivals of these patients with liver metastases were 46.5% and 30.1%, respectively. Twenty-four patients who were treated with intra-hepatic-arterial chemotherapy had better survival rates of 54.7% at 1 year, and 36.5% at 3 years than non-treated patients. Fifteen patients who underwent curative hepatic resection had better survival rates of 83.1% at 1 year, and 48.5% at 3 years than non-resected patients. Thirteen patients who underwent curative hepatic resection followed by intra-hepatic-arterial chemotherapy had good survival rates of 80.8% at 1 year, and 53.9% at 3 years. Seven patients who had multiple metastases to both lobes, were treated with intra-hepatic-arterial chemotherapy. These patients had a better survival rate of 22.9% at 1 year than non-treated patients.

Adenocarcinoma↗

Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease.

A 21-year-old male developed massive proteinuria and microscopic hematuria, 1 year after allogeneic BMT for acute lymphoblastic leukemia. These symptoms occurred during an exacerbation of chronic cutaneous graft-versus-host disease (GVHD). Renal biopsy revealed granular deposits of IgG and IgM along the glomerular basement membrane, and subepithelial electron dense deposits. A diagnosis of membranous nephropathy was made. With prednisolone therapy proteinuria decreased gradually, and amelioration of cutaneous lesions was also noted. It was speculated that the disordered immune regulation of chronic GVHD resulted in the development of immune complex nephritis.

Adult↗

Absorption of indomethacin from nasal cavity in rats.

AIM: To investigate if identical bioavailability, rapid Tmax, and Cmax of indometacin (Ind) could be achieved when Ind is administered in rats via intranasal (ina) route. METHODS: The pharmacokinetics of Ind solution at a dosage of 3 mg.kg-1 was studied after i.v., ina, and po in rats using HPLC. RESULTS: It showed that the time to peak (Tmax) of ina Ind 3 mg.kg-1 solution was 0.08 h, approached that after i.v. route the peak concentration (Cmax) following ina was 20.0 mg.L-1, 2.4 times higher than po dosing. CONCLUSION: It demonstrated that the ina administration of Ind was superior to po in rats, and that Ind absorption through nasal mucosa was a reasonable approach at lower doses.

Absorption↗

Introduction of DNA into sea urchin eggs by particle gun.

We have applied the particle gun method, which was developed to introduce DNA into plant cells, to sea urchin eggs and have obtained excellent expression of the introduced DNA in the embryos. The expression can be normalized by concomitantly-introducing a reference construct. The method provides a new approach to quantitative analysis of cis-regulatory elements in sea urchin embryos.

Animals↗

[Clinical usefulness of urinary anti HIV antibody test--a large scale study from 11 institutes in Japan].

An enzyme immuno assay kit has been developed to detect anti-HIV antibody in urine. In order to examine the clinical utility of the kit, 1333 urine samples were assayed. These samples consisted of 233 urine samples from HIV infected patients, 472 samples from HIV uninfected patients including 203 samples from patients with urogenital diseases, and 628 samples from normal subjects. Anti-HIV antibodies were detected in all the urine samples from HIV infected patients, and the diagnostic sensitivity for HIV infection was 100% with no false negative cases. A variety of anti-HIV antibody titers were found in the urine samples from HIV infected patients. However, no significant differences were found in the distribution patterns of urinary anti-HIV antibody titers among AC, ARC and AIDS patients. False positives were determined in only five samples in 628 healthy subjects (0.8%), one in 19 patients with hepatitis (5.3%), one in 45 patients with hemophilia (2.2%) and two in 105 pregnant women (1.9%). The antibody titers of all the false positive samples in these groups were less than the cut-off index multiplied by two. However, relatively high positive rates were demonstrated in the samples from urogenital diseases (11.8%), diabetes mellitus (20.0%) and auto-immune diseases (7.3%). False positive results were found to be directly correlated to the protein concentration of urinary protein, especially the immunoglobulin concentration in urine. The assay system was also evaluated by various reproducibility tests performed by different operators at different laboratories. The test results were satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Surgery for Crohn's anal fistulas.

The aim of this study was to analyze the features of Crohn's anal fistulas and to evaluate the efficacy of seton treatment. In 119 patients with Crohn's disease, the incidence of anal fistula was 56% (67/119), with no significant difference in the incidence among patients with ileitis, colitis, and ileocolitis. "Intractable" anal fistulas were found in 17% of patients with ileitis, compared to 64% of those with colitis (P = 0.051) and 68% of those with ileocolitis (P = 0.014). Seton treatment, i.e., non-cutting, long-term seton drainage, was performed for 21 patients (5 with intersphincteric, and 16 with transsphincteric fistulas). In the 16-month follow up, 9 patients required redrainage for recurrent fistulous abscess, mainly because of progressive colorectal disease. Finally, a good result was obtained in 17 of the 21 patients (81%) and no recurrent fistulous abscess developed in the 8 patients in whom all setons were removed. Anal continence was preserved in all the patients. These results indicate that anal fistulas with Crohn's ileitis were cured more easily than those with colitis or ileocolitis, and that seton treatment was effective for intersphincteric fistula with multiple fistula openings and for transphincteric fistulas in patients exhibiting remission of intestinal Crohn's disease.

Crohn Disease↗

Antibody to ras proteins in patients with colon cancer.

The current study examined sera from 160 colon cancer patients and 60 normal individuals to determine whether antibody to mutated p21 ras protein was present. Studies focused on the aspartic acid substitution at amino acid position 12 (denoted D12), one of the most common mutations in colon adenocarcinoma. IgA antibodies directed against mutated p21 ras-D12 protein were detected in 51 (32%) of 160 colon cancer patients, but only in 1 (2.5%) of 40 normal individuals. The greater incidence of antibody in cancer patients provides presumptive evidence that immunization to the ras proteins occurred as a result of the malignancy. Examination of sera for antibody reactivity to wild-type p21 ras protein (denoted p21 ras-G12) as well as p21 ras proteins bearing the D12, V12, S12, or L61 mutations showed that antibody detected was largely to normal segments of the p21 ras protein. Epitope mapping, using peptide neutralization assays with mutated or normal ras peptides as competitors, demonstrated that in 10 (67%) of 15 sera examined the antibody reactivity to p21 ras-G12 protein was neutralized by peptides near the carboxyl terminus of p21 ras protein, but not by peptides spanning the specific point mutation region. Antibody reactivities correlated with peripheral blood lymphocyte count, but did not correlate with patient age, sex, histology, stage, tumor locus, lymph node metastasis, or serum carcinoembryonic antigen.

Antibodies, Neoplasm↗

One hundred neuroblastomas detected through a mass screening system in Japan.

BACKGROUND: In Japan, a nationwide mass screening (MS) program for preclinical detection of neuroblastoma in infants was done by measuring urinary vanillylmandelic acid and homovanillic acid at the age of 6 months. In this study, clinical, histopathologic, and biologic features of 100 neuroblastomas detected through the Japanese MS are presented. METHODS: Clinical data of the MS cases were collected and histologic and biologic studies performed on the surgically resected neuroblastomas. Histopathologic evaluation was done including the Shimada classification (all tumors), N-myc oncogene status (58 tumors), and ploidy analysis (31 tumors). The serum ferritin level was measured before surgical intervention in 27 cases. RESULTS: The primary tumor sites of these cases were adrenal (69), retroperitoneum (21), and mediastinum (10). The tumors were clinical Stage I (31), II (31), III (19), IV (8), and IV-S (9); two children had bilateral primary adrenal tumors. Ninety-three percent (93/100) had favorable histology; 100% (58/58) had nonamplified N-myc oncogene expression; 81% (25/31) showed a favorable ploidy pattern, and 96% (26/27) had normal serum ferritin levels. To date, all children in this series are alive and well, although a total of 13 tumors were associated with one or two poor risk factors; 6 had unfavorable histology (UH), 5 had an unfavorable ploidy (UP) pattern, one had UH and UP, and one had an elevated ferritin level. CONCLUSIONS: The majority of neuroblastomas detected through the MS showed favorable biologic factors (biologically favorable group). However, there was a small group with histopathologic and/or biologic unfavorable factors. Patients with unfavorable factors apparently benefit most from early surgical intervention.

Ferritins↗

Sciatic nerve regeneration navigated by laminin-fibronectin double coated biodegradable collagen grafts in rats.

Biodegradable type I collagen tube grafts filled longitudinally with laminin and fibronectin double coated collagen fiber bundles (L-F grafts) were implanted to promote sciatic nerve regeneration in rats. Grafts filled with uncoated collagen fibers were used as control. A 1 cm defect on the right sciatic nerve was filled with a graft in the manner of bridging. Thirty days after implantation, several newly developed nerve fasciculi were found at the middle portion of the L-F grafts in contrast to no developed nerves in the controls. After 60 days, the middle and distal portions of both grafts included well-developed nerve tissues with prominent myelinated and unmyelinated nerve fibers surrounded by perineural cells, but the control distal portion showed fewer nerve fibers. All artificial collagen elements were completely degraded and absorbed at 30 days, and new nerve tissues surrounded by an epineurium successfully connected the proximal stump to the distal stump of the initially separated nerve. Descending and ascending action potentials were evoked in all grafts at 60 days. These results indicated that laminin and fibronectin may promote the growth of axons in biodegradable collagen grafts, which guided nerve regeneration well and allowed the formation of epineurium.

Animals↗