[A case of IDDM in sixteenth-week pregnancy].
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Adult↗
Biomedical subjects
S Ikeda
Publications and source records attributed to S Ikeda.
Characterization of amyloid fibril protein from a case of cerebral amyloid angiopathy showing immunohistochemical reactivity for both beta protein and cystatin C.
We isolated and carried out a chemical analysis of the amyloid fibril protein from the leptomeningeal vessels of a case with non-hereditary cerebral amyloid angiopathy (CAA) showing dual immunohistochemical reactivity with antibodies to both beta-protein and cystatin C. A crude amyloid fibril fraction reacted only with anti-beta-protein antibody, and cystatin C immunoreactivity was observed in the first PBS supernatant. Complete amino acid sequence of this cystatin C-immunoreactive protein showed a homologous structure to that of normal cystatin C. It is concluded that cystatin C is not an intrinsic component of the amyloid fibril in this type of CAA.
Aged↗
Identification of a novel transthyretin variant (Val30----Leu) associated with familial amyloidotic polyneuropathy.
A novel variant transthyretin which contains a leucine-for-valine substitution at position 30 was isolated and identified in the serum of a patient with familial amyloidotic polyneuropathy (FAP). The amino acid substitution was proven to result from a guanine-to-cytosine change at the first base of codon 30 located in exon 2 in the mutated transthyretin gene by restriction fragment length analysis on the amplified transthyretin gene using Cfr13 I. The study indicates that the point mutation of the transthyretin gene is a cause of the disorder.
Amino Acid Sequence↗
Study of low molecular weight heparin effect on the relation between anticoagulant activity and antithrombin III affinity.
Low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) were fractionated by rabbit antithrombin III (AT III)-Sepharose, and the effects of each affinity fraction on the coagulation and fibrinolytic activities were investigated. FR-860 was fractionated to no-affinity, low-affinity (LA) and high-affinity (HA) fractions, and UF-heparin to LA and HA fractions. The HA fractions showed higher activities regarding the prolongation of activated partial thromboplastin time, anti-factor Xa activity and antithrombin activity compared with those of LA. The HA and LA fractions exhibited the enhancement of heparin cofactor II (HC II) activity and fibrinolytic activity in a dose-dependent manner. These results suggest that the antithrombotic activity of FR-860 is exerted through AT III and other mechanism such as HC II-mediated system.
Animals↗
Hematoporphyrin derivative photodynamic therapy in roentgenographically occult carcinoma of the tracheobronchial tree.
From July 1981 to July 1987, hematoporphyrin derivative photodynamic therapy (HpD-PDT) was administered to 36 patients admitted to the National Cancer Center Hospital with roentgenographically occult lung cancer in whom biopsy showed 39 malignant lesions of the trachea and bronchus, although all the lesions could not be localized by the plain chest radiography and computed tomography scanning. The patients received an injection of HpD (2.5 mg/kg body weight) intravenously 72 hours before laser photoirradiation, and all patients underwent at least one session of PDT through a fiberoptic bronchoscope. Among the 39 malignant lesions of the trachea and bronchus, apparent complete responses were obtained in 11 patients with 12 lesions and less than complete responses in 27 lesions. Those with less than complete responses subsequently were treated with surgical or radiation therapy. Of the 36 patients, 16 patients are alive 37 to 109 months after therapy (mean, 65.1 months) with no apparent recurrence or metastasis, and 20 patients have died. Five of the 20 patients died of recurrent lung cancer, and the other 15 died of secondary causes. Regarding treatment complications, only a small amount of excessive airway secretions were observed, and there was no abscess formation in any patient.
Adult↗
Differences between solid and duct-ectatic types of pancreatic ductal carcinomas.
Macroscopically, 45 pancreatic ductal carcinomas were classified into two types: solid type (36 tumors) and duct-ectatic type (9 tumors). To disclose the biologic differences between these two types, they were compared by incidence, primary site, histologic types and grades, and biologic behavior. Although 20 solid type carcinomas arose from the branch duct, the duct-ectatic type carcinoma originated in the branch duct in three tumors, in a cyst in one, and in the main duct in one. The major component of the solid type was tubular (glandular) adenocarcinoma with high nuclear atypia and slight mucous secretion. The major component of the duct-ectatic type was papillary adenocarcinoma with low nuclear atypia and abundant mucous secretion. Thirty-four solid type carcinomas showed pancreatic stromal invasion, and 28 showed metastasis. Nine duct-ectatic type carcinomas spread intraductally and had not metastasized. It is concluded that the biologic differences between the two macroscopic type carcinomas are induced by the histologic types and grades.
Adenocarcinoma↗
Study of anticoagulant mechanism of low molecular weight heparin.
The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and AT III was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and AT III with stronger affinity to AT III than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and AT III with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, AT III did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between AT III and FR-860, but not that between AT III and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, AT III and thrombin.
Animals↗
Survival for clinical stage I lung cancer not surgically treated. Comparison between screen-detected and symptom-detected cases. The Japanese Lung Cancer Screening Research Group.
To assess the extent of overdiagnosis bias in lung cancer screening, clinical Stage I lung cancer cases detected by chest radiograph examination, with histologic or cytologic evidence of malignancy and not treated by surgical operation, were followed up for more than 10 years. Of 1297 screen-detected and 1297 symptom-detected cases collected from 20 institutions, 42 screen-detected and 27 symptom-detected cases satisfied the study criteria. In about half of the cases, the patients had no contraindication for surgical treatment, but they refused surgical procedure. All such patients from the screen-detected and symptom-detected groups died within 122 and 67 months, respectively, of diagnosis. Among the screen-detected and symptom-detected cases, 80% and 81%, respectively, of the patients died of lung cancer. The median survival time was 25 and 13 months for those in the screen-detected and symptom-detected groups, respectively. The difference in survival was statistically significant between the two groups, which indicated the effect of lead time and length-biased sampling. Analysis of the causes of death other than lung cancer showed that there was no difference in the observed cumulative rates of deaths of other causes between the two groups, and these figures were almost the same as those expected from the general population. This indicates that overdiagnosis bias would be minimal in screen-detected lung cancer cases detected by chest radiograph examination.
Aged↗
Spinal cord vascular and leptomeningeal amyloid beta-protein deposition in a case with cerebral amyloid angiopathy.
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid fibrils on leptomeningeal and cortical blood vessels, and the incidence of this disorder increases with age. However, this form of vascular amyloid deposition rarely involves tissues outside of the brain. A 71-year-old woman first developed some deterioration in memory, and soon afterwards suffered from recurrent episodes of subcortical hemorrhage. Histopathological examination of this case revealed typical pathology of Alzheimer's disease with an extensive appearance of beta-protein type CAA, and additionally, the spinal leptomeningeal vessels and the pia-arachnoid membranes were also affected by amyloid beta-protein deposits. The spinal cord involvement associated with CAA and Alzheimer's disease is unusual, and the present case provides additional important information on the pathogenesis of disorders with beta-protein deposition including Alzheimer's disease.
Aged↗
Characterization of a transthyretin-related amyloid fibril protein from cerebral amyloid angiopathy in type I familial amyloid polyneuropathy.
Recently, it has been reported that transthyretin (TTR)-immunoreactive amyloid deposition with cerebral amyloid angiopathy in central nervous system is a common pathological finding in type I familial amyloid polyneuropathy (FAP). In the present study, we performed isolation and sequence analysis of TTR-related amyloid fibril protein from the meninges of a patient with type I FAP. Purified major amyloid fibril protein had a molecular weight of 15 kDa. Complete sequence analysis revealed that this amyloid fibril protein was a variant TTR with a single amino acid substitution of methionine for valine at position 30. This variant TTR is a previously unrecognized as cerebrovascular amyloid fibril protein. Furthermore, the patients with type I FAP are well known to have the variant TTR in the serum. These suggest that cerebrovascular amyloid fibril protein in type I FAP may derive from a serum precursor.
Amino Acid Sequence↗
Phenotypic diversity and prognosis of adult T-cell leukemia.
We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double-negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4-.CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant.
Antigens, CD↗
Epitope mapping of the carcinoembryonic antigen with various related recombinant proteins expressed in Chinese hamster ovary cells and 25 distinct monoclonal antibodies.
Antigenic epitopes of carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen (NCA) were analysed in relation to their domain structures [domains N, I (A1-B1), II (A2-B2), III (A3-B3) and M for CEA and domains N, I (A1-B1), and M for NCA]. We reconstructed cDNAs for CEA-N, CEA-N-I, CEA-N-I-II, CEA-N-I-II-III-M (CEA-whole), NCA-N, NCA-N-I and NCA-N-I-M (NCA-whole), which were expressed in Chinese Hamster Ovary (CHO) cells. The recombinant proteins were purified by immunoadsorption and gel filtration. Their mol. wts judged from Western blotting were 17,000-26,000 for CEA-N, 70,000 for CEA-N-I, 150,000 for CEA-N-I-II, 165,000 for s-CEA-whole which was spontaneously released from cells into culture medium, 180,000 for p-CEA-whole which was solubilized with phosphatidylinositol specific phospholipase C (PI-PLC) from cells, 18,000-25,000 for NCA-N, 63,000 for NCA-N-I, and 96,000 for p-NCA-whole which was solubilized with PI-PLC from cells. The divergence of the observed mol. wts from those calculated from cDNA sequences seems to indicate that these recombinant proteins are highly N-glycosylated. By enzyme immunoassays, the immunoreactivities of the purified recombinant proteins were tested with 25 distinct anti-CEA monoclonal antibodies (MAbs), each representative of 25 different subgroups within five groups (Groups 1-5) previously classified by us in terms of the reactivity with CEA and CEA-related antigens. Twenty-one MAbs previously shown to react with different protein epitopes of the CEA molecule allow to define six groups (A-F) of epitopes according to their expression by different domains of the CEA and NCA molecules. Among four epitopes common to CEA and NCA, two were found to be present on domain N (Group A) and two on domain I (Group B). Among 15 epitopes absent from NCA but expressed by CEA and normal fecal antigens (NFAs), four were on domain N (Group C), five on domain I (Group D) and six on domain II (Group E). Two epitopes were previously described as "CEA distinctive", because they were recognized by MAbs reacting with CEA but not with the NFAs. These two epitopes (Group F) were found to be expressed by p-CEA-whole but not by s-CEA-whole. The latter results suggest that the Group F epitopes are located on a part of the domain III close to the anchoring device of the CEA molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Hepatic resection is not enough for hepatocellular carcinoma. A follow-up study of 92 patients.
We followed up 92 patients who underwent curative hepatic resection for hepatocellular carcinoma between 1982 and 1991. The long-term survival rates for these 92 patients for 1, 3, and 5 years were 98.8, 81.6, and 57.3%, respectively. As of May 1991, the carcinoma had recurred in 52 patients (56.5%). Recurrent tumors usually occurred in the residual liver within 3 years after surgery but were not always located near the primary lesion. The biologic characteristics of the primary tumors, such as serum alpha-fetoprotein, tumor size, number of tumors, and portal involvement, were closely related to recurrence and long-term survival. However, the type of hepatectomy performed on the primary tumor had little influence on recurrence or long-term survival. We conclude that recurrence cannot be avoided by hepatic resection alone, much less with limited resection; postoperative positive adjuvant therapy is required to prevent recurrence for patients with satellite nodule and/or portal involvement.
Adolescent↗
Novel complications with HTLV-1-associated myelopathy/tropical spastic paraparesis: interstitial cystitis and persistent prostatitis.
Lower urinary symptoms associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are common, but have been regarded as 'neurogenic' due to spinal involvements. However, in some cases, these symptoms are persistent, progressive, and not directly correlated with the severity of other neurologic symptoms of the lower spinal cord. These findings prompted us to locate organic lesions in the lower urinary tract and to correlate them with HTLV-1 infection. Among 35 HAM patients with lower urinary symptoms, we found 4 cases with the symptoms persistent and progressive: 3 with contracted bladder and another with persistent prostatitis. Histological or cytological examinations indicated local lymphocytic infiltrations in the lower urinary tract in all cases: 3 by the infiltration in the bladder and the other by a high concentration of lymphocytes in expressed prostatic secretions. Of 3 cases whose urinary samples were available, 2 showed significant increase in the concentration of urinary anti-HTLV-1 antibody of IgA class. The urinary IgA antibody of the third case was not elevated, but the sample had been obtained after resection of the affected bladder. None of the control cases showed significant anti-HTLV-1 IgA antibody in urine except for a case of gross hematuria due to chemotherapy directed against adult T-cell leukemia. We suggest inclusion of these processes into the spectrum of complications for HAM/TSP. The elevated excretion of anti-HTLV-1 of IgA class in urine may be an indicator of these complications.
Adult↗
Increase of sensitivity to aminoglycoside antibiotics by polyamine-induced protein (oligopeptide-binding protein) in Escherichia coli.
The sensitivity of Escherichia coli to several aminoglycoside antibiotics was examined with E. coli DR112 transformed by the gene for polyamine-induced protein (oligopeptide-binding [OppA] protein) or polyamine transport proteins. The results clearly showed that sensitivity to aminoglycoside antibiotics (gentamicin, isepamicin, kanamycin, neomycin, paromomycin, and streptomycin) increased due to the highly expressed OppA protein. When the gene for OppA protein was deleted, sensitivity to aminoglycoside antibiotics was greatly decreased. It was also shown that isepamicin could bind to OppA protein with a binding affinity constant of 8.5 x 10(3) M-1 under the ionic conditions of 50 mM K+ and 1 mM Mg2+ at pH 7.5, and isepamicin uptake into cells was greatly stimulated by the OppA protein. These results, taken together, show that the OppA protein increases the uptake of aminoglycoside antibiotics. In addition, the OppA protein increased the transport of spermidine and an oligopeptide (Gly-Leu-Tyr). The uptake of isepamicin into cells was partially inhibited by spermidine, suggesting that the binding site for isepamicin overlaps that for spermidine on the OppA protein. Spermidine uptake activity by the OppA protein was less than 1% of that of the ordinary spermidine uptake system. Aminoglycoside antibiotics neither stimulated the synthesis of OppA protein nor increased spermidine uptake.
Amino Acid Sequence↗
Asymptomatic homozygous gene carrier in a family with type I familial amyloid polyneuropathy.
Type I familial amyloid polyneuropathy (FAP) is a molecular disorder with a mutation of the transthyretin (TTR) gene, and most patients previously examined were reported to be heterozygous for this mutant gene. In the present study a rapid and easy DNA diagnostic method employing the polymerase chain reaction revealed an asymptomatic homozygous TTR gene carrier in a Japanese family with type I FAP. The level of the variant TTR (methionine instead of valine at position 30) in his serum was much higher than that usually found in type I FAP patients. However, the histological findings of the biopsied rectum and abdominal fat tissues failed to demonstrate amyloid deposits, and the autonomic nerves from his rectal mucosa were normally preserved. Moreover, his 72-year-old mother (a TTR gene heterozygote) was supposed to start amyloid deposition in her late sixties. It is suggested that in addition to the mutant TTR gene some other factors control the development of the disease.
Aged↗
Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy.
The pathogenesis of diabetic nephropathy relative to the changes in the glomerular extracellular matrices was investigated. Renal tissues from 10 diabetic patients were immunostained with antibodies directed against heparan sulfate proteoglycans (HS-PGs), laminin, type IV collagen and fibronectin. Seven patients were nephrotic and had advanced glomerulosclerosis with nodular lesion, while the other 3 had no renal manifestations or minor glomerular tissue alterations. Controls included kidneys removed from patients with renal tumors and specimens obtained by renal biopsy from patients with IgA nephropathy. Relationships among proteinuria, intensity of fluorescence and glomerular changes were studied. In diabetes 3 patients with minor glomerular lesions were found to have no changes in various components of extracellular matrices. A marked reduction in the intensity of staining with anti-HS-PG antibodies was observed in renal specimens from patients with nodular glomerulosclerosis and proteinuria, while a mild decrease in the intensity of fluorescence was observed in tissues stained with antilaminin antibodies. An increase compared to normal control sample findings in type IV collagen and fibronectin was observed in the mesangium of sclerosing glomeruli. No loss of HS-PG was observed in patients with IgA nephropathy. These results indicate that glomerular extracellular matrix HS-PG is lost in association with diabetic nephropathy; this loss results in alteration of the charge-selective properties of glomerular capillaries. This alteration may, in part, be the cause of the proteinuria associated with diabetic nephropathy.
Adult↗
Homozygosity for the transthyretin-Met30 gene in three Japanese siblings with type I familial amyloidotic polyneuropathy.
We report the cases of three siblings homozygous for a mutated transthyretin (TTR) gene that causes type I familial amyloidotic polyneuropathy (FAP), in whom we made the diagnosis by identifying both the mutated TTR gene and a variant TTR in their sera. Their serum levels for the variant TTR are twice those of patients heterozygous for the gene, but two have late-onset FAP and the third is an elderly asymptomatic carrier. TTR abnormality is a necessary condition for the development of FAP, but there may be other factors that retard or prevent its clinical development.
Aged↗