Three cases of GAD65 antibody-positive diabetes with ketosis and abrupt onset resulting in non-insulin-dependent state.
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Biomedical subjects
Publications and source records attributed to R Iwasaki.
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To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.
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A 54-year-old male was admitted for loss of appetite lasting for about 3 months. The patient was diagnosed as malignant lymphoma in the stomach invading directly the pancreas, spleen and transverse colon. Chemotherapy, two cycles of VEPA.M, was selected as the initial treatment. After the first cycle of chemotherapy, the patient was discharged temporarily. During the second cycle, on an ambulant basis, the patient suddenly complained of severe pain and distension in the abdomen. Through the X-ray examination of the chest, free air was demonstrated in the bilateral subphrenic spaces. The patient was diagnosed as perforation of the gastrointestinal tract. Subsequently, total gastrectomy was performed. Pathological examination revealed no malignant cells in the stomach wall. It is suggested that the perforation was caused by weakening of the stomach wall following chemotherapy.
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A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.
The synthesis of N-acetylcysteine conjugates of 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1) is described. The reaction of estrone 2,3-quinone with N-acetylcysteine provided 2-OHE1 and its C-4 and C-1 thioether conjugates in a ratio of 1:1, while estrone 3,4-quinone with N-acetylcysteine gave 4-OHE1 and its C-2 thioether conjugate as a sole product. Their structures were characterized by inspection of NMR spectra, chemical derivatization (methylation and acetylation), and comparison with the reactivity of 4-bromoestrone 2,3-quinone or 2-bromoestrone 3,4-quinone toward N-acetylcysteine.
The authors present 3 cases of osteochondritis and 2 cases of osteochondral fracture of the knee. These cases were treated with a bioabsorbable ultra high strength poly (L-lactide) pin, which has the highest mechanical strength value of any nonfiber reinforced poly (L-lactide) reported previously. Three of the patients were male, and 2 were females; their ages ranged from 12 to 21 years. The followup period ranged from 2 years to 7 years 9 months (mean, 4.1 years). Two to 4 poly (L-lactide) pins with a diameter of 2 mm were used to fix the osteochondral fragments or the transplanted autogenous osteochondral grafts. In all cases, satisfactory bone union was obtained, and no inflammatory reaction was observed during the entire followup periods. The ranges of motion were normal, and there was no pain in any of the cases. It is concluded that the poly (L-lactide) pin is safe and useful in the repair of osteochondral fractures of the knee and in fixing grafted osteochondral fragments.
Alterations of the Bruton's tyrosine kinase (Btk) gene are responsible for X-linked agammaglobulinemia (XLA). Although mutations in various regions were reported mainly in the Caucasian population, correlation between the locations of mutation and the clinical phenotypes remains unclear. We report 12 abnormalities of the Btk gene found in 12 unrelated families out of 14 XLA families in Japan and their clinical features. We utilized Southern blotting and single-strand conformation polymorphism (SSCP) analysis. Gene rearrangement in the kinase domain was identified in two patients by Southern blotting. Seven point mutations, two small deletions, and one small insertion were detected by SSCP and sequencing. The SSCP analysis also provided information about the carriers in these families. We found some clinical heterogeneity in the affected family members with the same gene mutation. Moreover, there is considerable inconsistency between the locations of gene aberrations and the immunological phenotypes. Some patients with a nonsense mutation, which may result in the lack of kinase domain, have detectable B cells and immunoglobulins. These identified alterations will provide valuable clues to the Btk protein function and the pathogenesis of XLA.
A part of caseinphosphopeptides (CPP) formed during the digestion of casein in the small intestine of rats fed casein was not hydrolyzed in the digestive tract, but was excreted into the feces. Amino acid compositions of CPP fraction of feces for wk 1 and 2 were almost identical. The residual CPP in the feces expressed by the rate of bound phosphoserine in the CPP fraction of feces to bound phosphoserine ingested (phosphoserine-CPP/phosphoserine-ingested rate) in the ileum was the highest 4 h after the start of feeding of casein but decreased significantly after 10 h. No significant difference was observed in the rats of contents in jejunum, cecum, and colon between 4 h and 10 h after the start of feeding. No significant difference was observed in the phosphoserine-CPP/phosphoserine-ingested rate in contents of any part of the digestive tract between 50% casein and 50% CPP I (a commercial CPP product with nearly the same amino acid composition as that of casein) 4 h and 10 h after the start of feeding, except for the cecum 4 h after the start of feeding. No significant difference in phosphoserine-CPP/phosphoserine-ingested rate was observed in the contents of any part of digestive tract between the groups fed 50% casein and 5% CPP III +45% soybean protein isolate (SPI) 4 h or 10 h after the start of feeding (CPP III is a commercial CPP product containing nearly 8 times the concentration of phosphoserine as CPP I).(ABSTRACT TRUNCATED AT 250 WORDS)
A 76-year-old diabetic woman with non-obese Cushing's syndrome developed poor glycemic control with glibenclamide. She presented with a slight weight loss while bedridden due to a fall. Cushing's syndrome in this patient was suspected because of hypercortisolemia with eosinopenia, and adrenal Cushing's syndrome was diagnosed by endocrine and radiological examinations. A right adrenal adenoma was confirmed by autopsy. In this patient, progressive obesity and other common features of Cushing's syndrome may have been concealed by aging itself and coexisting diabetes mellitus.
A newly developed 99mTc-labeled renal scintigraphic and renographic agent, 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) was studied clinically and compared with 131I-OIH in 16 patients with various renal and urinary tract disorders. The abdominal aorta and the common iliac artery were clearly visualized in the vascular phase. The renogram patterns showed the same pattern in all cases. The parameters on the renogram such as Tmax, T2/3, T1/2 were compared. The highly significant correlations of Tmax, T2/3 and T1/2 were observed between 99mTc-MAG3 and 131I-OIH with correlation coefficient of 0.982, 0.907, 0.990, respectively. In all cases, excretion of 99mTc-MAG3 was slower than that of 131I-OIH and the ratios of Tmax, T2/3 and T1/2 between 99mTc-MAG3 and 131I-OIH were 1.113 +/- 0.121, 1.277 +/- 0.247, 1.179 +/- 0.075, respectively. It is concluded that 99mTc-MAG3 is useful renal imaging agent as an alternative to 131I or 123I-OIH.
A 56 year old female patient had acute myocardial infarction which was confirmed by autopsy. However the patient showed no elevation of CK activity in the serum. We proved the deficiency of CK-MM protein in her serum as well as in the myocardial tissues. To further elucidate the molecular mechanism we isolated and characterized genomic DNA and cDNA of CK-MM from the myocardial tissue of the patient and demonstrated the depression of mRNA of CK-MM which might be related with the deficiency of CK-MM protein. Point mutation at codon 54 [Exon 2, GAC (Asp)-->GGC(Gly)] was also demonstrated on the beta-sheet of CK-MM. Association of point mutation with depressed CK-MM is to be clarified.
BACKGROUND: The angiotensin I-converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular disease. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been investigated in the Japanese population. METHODS AND RESULTS: A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 100 healthy subjects and 178 patients with coronary artery disease (CAD) (70 angina pectoris, 108 myocardial infarction), whose serum ACE levels were concomitantly measured. Polymorphism of the ACE gene was characterized by three genotypes: two deletion alleles (genotype DD), two insertion alleles (genotype II), and heterozygous alleles (genotype ID). No differences could be detected among the three genotypes for total cholesterol, HDL cholesterol, and body mass index. Serum ACE levels were 11.4 +/- 2.7, 14.5 +/- 3.5, and 16.6 +/- 4.6 IU/mL for genotypes II, ID, and DD, respectively. In the study population, the genotype DD was more closely associated with CAD than the other two genotypes (ID and II). The frequency of deletion alleles was higher (0.58) in the CAD group than in healthy control subjects (0.42) (P < .05). Furthermore, multivessel disease was more strongly associated with deletion alleles than with insertion alleles (P < .05). CONCLUSIONS: A deletion polymorphism of the ACE gene is associated with serum ACE activity and increased risk for CAD in the Japanese.
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Squalene inhibited the effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), such as increased 32Pi incorporation into phospholipids of HeLa cell membrane, induction of Epstein-Barr-virus early antigen in Raji cell and induction of ornithine decarboxylase in mouse skin. Squalene also markedly suppressed the promoting activity of TPA on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.
METHODS: The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS: As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION: These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.
Although the value of surgical decompression and stabilization for solitary spinal metastasis is well documented, indication for surgery for advanced multiple metastatic tumors of the spine is controversial. In this study, the clinical effect of posterior decompression and stabilization was investigated in 11 patients with advanced multiple spinal metastases with unfavorable conditions. Mean blood loss during surgery was 3000 g. Disseminated intravascular coagulation occurred in three patients. Neurologic improvement was observed in nine patients. There was no neurologic deterioration due to surgery in any patients. A measure of pain relief was obtained in all patients. However, the postoperative longevity was short and the patients died 2.5 months (on average) after operation, except in cases of breast cancer. The effect of the posterior surgery on multiple spinal metastases depended on primary diseases. In cases of short life expectancy, the effect of the surgery was limited only to the short duration of neurologic improvement, pain relief, and ease of nursing care while confronted with grave surgical morbidity. In cases of long life expectancy with tumors like breast cancer, however, posterior decompression and stabilization were expected to exert long-term therapeutic effect. Therefore, the posterior surgery for multiple spinal metastases is cautiously indicated considering the nature of the primary tumor.