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Biomedical subjects

T Murase

Publications and source records attributed to T Murase.

At least 235 records · Page 13Linked to original sources

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.

We have discovered a novel compound, NO-1886, which possesses a powerful lipoprotein lipase (LPL) activity-increasing action. Administration of NO-1886 increased LPL activity in the postheparin plasma, adipose tissue, and myocardium of rats, and produced a reduction in plasma triglyceride levels with concomitant elevation of HDL cholesterol levels. Administration of NO-1886 increased LPL enzyme mass in postheparin plasma and mRNA activity in epididymal adipose tissue, and it was concluded that the mode of action of this compound is stimulation of tissue LPL synthesis. We also conducted long-term studies to assess the impact of increases in LPL activity and HDL levels on the development of atherosclerotic lesions in rats. Administration of NO-1886 for as long as 90 d significantly decreased the degree of atherosclerotic changes in the coronary arteries of vitamin D2-treated, cholesterol-fed rats. Statistical analysis indicated that increased concentration of HDL is the factor contributing mostly to the prevention of coronary artery sclerosis. In summary, the results of our study indicate that compound NO-1886 increases LPL activity, causing an elevation in HDL levels, and that long-term administration of NO-1886 to rats with experimental atherosclerosis provides significant protection against the development of coronary artery lesions.

Adipose Tissue↗

Evoked spinal cord potentials for diagnosis during brachial plexus surgery.

We used evoked spinal cord potentials (ESCP) for intraoperative diagnosis in 17 cases of traumatic brachial plexus palsy. Forty spinal nerves were directly stimulated during exploration of the brachial plexus and ESCP recorded from the cervical epidural space were compared with simultaneously observed somatosensory evoked potentials (SEP) and myelographic findings. Both SEP and ESCP could be evoked in 21 spinal nerves but ESCP were always more distinct and five to ten times greater in amplitude than SEP. In four nerves, ESCP but no SEP were produced, suggesting that there was continuity from the nerves to the spinal cord. ESCP were obtained from two spinal nerves which appeared to be abnormal on the myelogram. The results show that intraoperative electrodiagnosis by epidural ESCP recordings can provide useful information on the lesions of traumatic brachial plexus palsy.

Adolescent↗

Reduction of serum lipoprotein (a) by estrogen in men with prostatic cancer.

The catabolism of lipoprotein(a), Lp(a), remains unclear. Very recently we observed that estrogen, a hormone known to increase low-density lipoprotein (LDL) receptor activity, reduced serum Lp(a) levels in a man with familial hypercholesterolemia (FH) (JAMA 267: 2328, 1992). In the present study, we attempted to further evaluate this Lp(a)-lowering action of estrogen in men without FH. Seven men, aged 61-84 yr, treated with estrogen for prostatic cancer were the subjects and seven men who underwent surgical treatment without estrogen therapy served as controls. Fasting blood was collected before and 1-3 months after estrogen therapy, and serum Lp(a) levels and lipoprotein profiles were determined. Estrogen treatment caused significant changes in serum lipoproteins, i.e., decreases in LDL-cholesterol, and increases in high-density lipoprotein (HDL)-cholesterol. Serum triglyceride levels tended to increase. Serum apo A-1 underwent a two-fold increase, while apo B did not change. Serum Lp(a) levels ranged from 8 to 62 mg/dl. After estrogen treatment serum Lp(a) was reduced markedly, with a mean reduction of 81% (71-95%). Serum lipids, lipoproteins and Lp(a) did not change significantly in the controls. The results demonstrated a regulating effect of estrogen on serum Lp(a) levels, and the findings further suggested that Lp(a) is removed via LDL receptors. However, previous studies have shown that maneuvers causing a decrease in LDL-cholesterol do not always cause a reduction in serum Lp(a). Thus, our findings suggested the possible presence of a receptor which is estrogen-inducible and different from the LDL receptor.

Aged↗

Association of HLA-A24 with complete beta-cell destruction in IDDM.

A sensitive C-peptide immunoreactivity radioimmunoassay demonstrated the presence of subtle, but definite residual beta-cell function in patients with IDDM of long duration. Although HLA antigens are known to influence susceptibility to IDDM, their contribution to the extent of pancreatic beta-cell destruction has not yet been examined extensively. We studied the relationship between residual beta-cell function and HLA class I and class II antigens in 111 unrelated Japanese IDDM patients. Using the sensitive C-peptide immunoreactivity radioimmunoassay, the presence or absence of residual beta-cell function was evaluated by the C-peptide immunoreactivity response to a 100-g oral glucose load. DNA typing for HLA-DQA1 and HLA-DQB1 antigens was performed in addition to serological typing of HLA-A, HLA-B, HLA-C, and HLA-DR antigens. A C-peptide immunoreactivity response > 0.033 nM was regarded as an indication of the presence of residual beta-cell function, not the assay error. Surprisingly, 35 of 37 (94.6%) patients without residual beta-cell function had HLA-A24, whereas only 39 of 74 (52.7%) patients with residual beta-cell function had this antigen (corrected P = 9.795 x 10(-6). Any other HLA antigens, including the DR and DQ loci, showed no difference in the frequency with regard to residual beta-cell function. The duration of diabetes was similar between the groups with and without residual beta-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunogenetic and clinical characterization of slowly progressive IDDM.

OBJECTIVE: To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS: We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (< 3 mo, acute clinical-onset group, n = 134), group B (3-12 mo, intermediate group, n = 31), and group C (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS: The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C than in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects. CONCLUSIONS: These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved beta-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe beta-cell destruction in group A patients.

Adolescent↗

Carpal-tunnel syndrome in hemodialysis. Syndrome diagnosed in 8 of 60 patients.

Clinical and electrophysiological examination for carpal-tunnel syndrome was performed in 60 consecutive hemodialysis patients. The syndrome was diagnosed in 8 patients, 6 of whom had had hemodialysis for more than 10 years. Cystic radiolucency in the carpal bone, possibly a sign of amyloid deposition, was observed more frequently in carpal-tunnel patients and amyloid-induced tenosynovitis in the carpal-tunnel had formed in 4 cases.

Adult↗

[Antibiotic prophylaxis for transurethral resection of the prostate--comparison of oral administration therapy with intravenous administration therapy].

To compare the prophylactic effect of oral and intravenous antibiotics against postoperative fever and urinary tract infection (UTI) after transurethral resection of the prostate (TUR-P), we conducted a multi-center prospective randomized study. The incidence of pyrexia over 38 degrees C was defined as the primary endpoint. One hundred and fifty patients with sterile urine before TUR-P were entered into this study. The patients were allocated randomly into the two arms; arm A cefotiam 4 g a day for 7 days, arm B tosufloxacin 300 mg a day for 7 days, based on the stratification into the 4 groups determined with/without preoperative indwelling catheters and with/without the history of preoperative UTI. Of these patients, 143 were eligible. We divided 124 patients without preoperative UTI and without indwelling catheters as the "low risk group", and the other 19 patients with preoperative UTI and/or with indwelling catheters as the "high risk group". In the low risk group, 9 patients out of 63 (14.3%) in arm A and 6 out of 61 (9.8%) in arm B had pyrexia during 7 postoperative days. The incidence of fever in arm B was 4.4% less than that in arm A and the 95% confidence limit was from -7% to 16%. In the high risk group, 4 out of 11 (36.4%) patients in arm A and none of 8 in arm B had fever but the difference was not significant. The incidence of post operative UTI in the low risk group on the 4 to 5, 9 to 12, 23 to 26 and 37 to 40 postoperative days was 8.3, 16.4, 25.0 and 23.9% in arm A and 6.7, 16.7, 29.6 and 36.7% in arm B, respectively. The prophylactic effect of oral administration of tosufloxacin is equivalent to that of the intravenous administration of cefotiam. The use of oral antibiotics is beneficial to reducing the cost of medication.

Administration, Oral↗

Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency.

To study the metabolic abnormalities in familial lecithin-cholesterol acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and LCAT replacement therapy on plasma lipids and apolipoproteins were investigated in a patient with LCAT deficiency. The patient had elevated triglycerides (TG, 543.7 mg/dl) and phospholipids (PL, 350.3 mg/dl) and normal total cholesterol (TC, 206.9 mg/dl). Change to a low-fat diet reduced TC and TG by 20% and 75%, respectively. These reductions occurred mainly in the d < 1.006 fraction. At baseline, the patient had normal apolipoprotein B (apo B), low apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) and elevated apolipoprotein E (apo E). Long-term treatment with a low-fat diet increased plasma apoA-I and decreased apo E. However, urinary protein excretion did not change throughout the observed period. LCAT replacement with fresh frozen plasma (FFP) after the low-fat diet further reduced plasma apo E to the normal range. These results indicate that the elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT in the plasma, but also to fat intake. A low-fat diet may be effective in correcting lipid abnormalities. Moreover, plasma apo E may be a good indicator of the efficacy of diet therapy.

Apolipoproteins E↗

[Adenocarcinoma of colon 19 years after ureterosigmoidostomy: a case report].

A 65-year-old man underwent total cystectomy in 1972 for a bladder tumor. Ureterosigmoidostomy was performed in this case. A physical examination in 1983 revealed occult blood in the feces, and colon fiberscopic examination disclosed a polyp in this patient, who then underwent polypectomy. Histology confirmed hyperplasia. In 1985, colon fiberscopic examination revealed a polyp in the sigmoid, resulting in another polypectomy. Adenoma was established by histology. In April 1991, fresh blood was found in the feces, and a Borrmann II tumor was confirmed by colon fibrerscopic examination. Sigmoidectomy, colostomy, and right ureterostomy were performed. Histology confirmed moderately differentiated adenocarcinoma.

Adenocarcinoma↗

Bilineage hematopoietic inhibitor and T lymphocyte dysfunction in a patient with pure red cell aplasia, myasthenia gravis and thymoma.

The case history, laboratory findings and clinical course of a patient with pure red cell aplasia (PRCA) combined with myasthenia gravis and thymoma are reported herein. In vitro study revealed bilineage complement-dependent IgG inhibitor(s) in both the granulocyte-macrophage and erythroblastic progenitor cells. His serum showed high anti-acetylcholine receptor antibody levels associated with activity of myasthenia gravis as well as PRCA. Patient history of thymectomy 7 years previously followed by extensive cutaneous candidiasis with abnormal T lymphocyte subsets (decreased T4/T8 ratio and increased number of activated T lymphocytes) in both the bone marrow and peripheral blood suggested primary T lymphocyte dysfunction, whereas the erythropoiesis was not inhibited by T lymphocytes. This case is of interest in the context of a possible immunological pathogenesis for other hematopoietic disorders, including some cases of aplastic anemia.

Antibodies↗

Marked islet amyloid polypeptide-positive amyloid deposition: a possible cause of severely insulin-deficient diabetes mellitus with atrophied exocrine pancreas.

An insulin-deficient 51-year-old man was put on dietary therapy and sulfonylurea (SU). Although there was good glycemic control for 2 years, the fasting blood glucose (FBG) level increased gradually over the subsequent 4-year period, and there was a marked increase in body weight. Secondary failure of SU therapy 20 years after the initial diagnosis led to insulin therapy. The FBG became unstable, and the C-peptide response disappeared. The patient died of nonketotic hyperosmolar coma and pneumonia at the age of 87. At autopsy, the pancreas showed marked atrophy (32 g) with extensive fatty degeneration. Islets replaced by islet amyloid polypeptide (IAPP)-positive amyloid (IAPP-AM) amounted to 77% in the tail, 74% in the body, and 73% in the head of the pancreas. All islets were positive for IAPP-AM throughout the pancreas, except for a pancreatic polypeptide-rich lobe, where none were positive. IAPP-AM-positive islets had also undergone fatty change of the surrounding pancreatic acinar cells. beta-Cells decreased remarkably in number and were displaced to the periphery of the islets by the IAPP-AM deposits. These findings suggest that IAPP-related diabetes could have a progressive course, with secondary oral hypoglycemic agent failure and the subsequent development of severe insulin deficiency similar to that seen in insulin-dependent diabetes mellitus.

Amyloid↗

Treatment of lead poisoning in wild geese.

Twenty-seven wild geese (Anser albifrons) suffering from lead poisoning caused by ingestion of lead shot were treated with disodium calcium ethylenediaminetetraacetate. The concentration of lead in blood ranged from 0.4 to 23.0 micrograms/ml, with a mean concentration of 5.6 micrograms/ml. In 22 of the birds, 1 to 48 lead pellets (mean, 10.5 pellets/bird) were seen on radiographs of their gizzards. Eleven of 27 birds recovered 3 to 8 weeks after the initiation of treatment. In the birds that recovered, the lead pellets were rapidly eroded as the birds recovered their appetites in response to treatment, and disappeared radiographically between treatment days 17 and 52. The birds that did not survive died within 4 weeks, despite decreased concentrations of lead in blood. Of these 16 birds, 15 had radiographic evidence of impaction of the proventriculus at the first examination and no evidence of resolution of the impaction at the time of death. In contrast, only 2 of the 11 geese that recovered had impaction of the proventriculus at the time of admission. Thus, the condition of the proventriculus seems to be the first consideration to evaluate in the prognosis of lead poisoning in geese.

Animals↗

A newly identified null allelic mutation in the human lipoprotein lipase (LPL) gene of a compound heterozygote with familial LPL deficiency.

In a Japanese patient with familial LPL deficiency, a new null allelic mutation, one base pair deletion at nucleotide position 916 was identified in exon 5 of one allele. In exon 3 of the other allele, we found the same nonsense mutation as we described previously in other Japanese kindreds. For the deletional mutant allele, we developed a simple detection method and constructed the DNA haplotype.

Alleles↗

Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia.

Apolipoprotein E (apoE) has a high affinity to cell-surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma lipoprotein metabolism, transgenic mouse lines with integrated rat apoE gene under the control of the metallothionein promoter were established. We found that a high expressor line produced rat apoE mainly in the liver, and the gene product was almost entirely associated with plasma lipoproteins. The plasma level of rat apoE in homozygotes for the transgene was 17.4 mg/dl after zinc induction (vs. 4.56 mg/dl of mouse apoE in controls). In this group, plasma cholesterol and triglyceride levels were 43% and 68% reduced as compared with controls, respectively. Heterozygotes showed decreases in both lipids to a lesser extent. Gel filtration chromatography showed that lipid reduction was mainly due to decreased very low density lipoproteins (VLDL) and LDL. Especially in zinc-treated homozygotes, VLDL had almost disappeared, and a remarkable decrease in LDL and a slight decrease in high density lipoprotein were also observed. Consistently, the plasma level of apoB, a structural protein of VLDL and LDL, was 78% lower than that of controls, indicating a marked reduction in lipoproteins containing apoB. Furthermore, the transgenic mice, in contrast to controls, did not develop hypercholesterolemia when fed a high cholesterol diet. These results demonstrated that overexpression of apoE reduces plasma cholesterol and triglyceride levels and prevents diet-induced hypercholesterolemia. From dramatic and dose-related decreases in plasma lipoproteins in transgenic mice, we conclude that apoE plays a key role in plasma lipoprotein metabolism.

Animals↗

Superficial bladder cancer treated by total cystectomy: tumour characteristics and patient survival.

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.

Adult↗