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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 451 records · Page 25Linked to original sources
PubMed1995

[Mucopolysaccharidoses].

Mucopolysaccharidoses (MPS) are a lysosomal storage disorders caused by deficiency of several enzymes needed for degradation of mucopolysaccharides (glycosaminoglycans). Undegraded glycosaminoglycans accumulate in the cell, part of which are excreted into the urine. There are 10 known enzyme deficiencies that give rise to six distinct MPS. Despite the different enzyme defect, there is clinical similarity between different deficiencies and conversely, wide phenotypic variety among even one enzyme deficiency. Most of the cDNAs corresponding the defect enzyme as well as genomic DNA have been cloned. Mutational analyses of the patient gene have revealed the molecular basis of the disease, correlation of the genotype and phenotype and made the accurate heterozygote diagnosis feasible. Supportive management can greatly improve the quality of life and moreover, development of therapies, such as BMT, administration of recombinant enzyme and gene transfer are in progress for the patients suffering from MPS.

Animals↗
PubMed1995

[Effects of carbon monoxide produced during laparoscopic surgery].

One of the complications of laparoscopic surgery is carbon monoxide (CO) production under the use of electro-cautery. We studied 11 patients undergoing laparoscopic urological surgery. The concentrations of CO in peritoneal cavity and carboxyhemoglobin (HbCO) in arterial blood were measured before the operation under laparoscopy, during the use of electro-cautery and after the operation. The concentration of CO in peritoneal cavity reached 78 ppm during the use of electro-cautery but the HbCO level was unchanged. In the study on laparoscopic cholecystectomy (LC) performed previously, we had found no change of HbCO. The increase of CO on LC was more pronounced than in the present study. The concentration of CO in peritoneal cavity might be more dependent on the intensive use of electro-cautery than on operation time. Additionally the frequency of the insertion and extraction of the instruments through the trocar could have influenced it. CO could also be produced in the carbon dioxide cylinder. It should be investigated since it might contaminate the operating room.

Adult↗
PubMed1995

Natural human interferon-alpha enhances the expression of intracellular adhesion molecule-1, integrin alpha 2 and beta 1 by a mucosal epithelial cell line.

We have found that pretreatment of a human oral mucosal epithelial cell line KB with natural human interferon-alpha (IFN-alpha) augments the expression of intercellular adhesion molecule-1 (ICAM-1), and the complex of CD29 and CD49b, which is known as very late antigen (VLA)-2, in a dose-dependent manner, whereas the expression of other adhesion molecules such as CD44 leukocyte function associated antigen-3 (LFA-3), VLA-4 and endothelial leukocyte adhesion molecule-1 (ELAM-1) did not show any significant changes under the same conditions. The pretreatment of KB cells with IFN-alpha also induces the adhesion of these cells to the human leukemia T cell line MOLT-16 and to peripheral T lymphocytes in a dose-dependent manner. However, the adhesion of the above-mentioned T cells to KB cells was not inhibited by specific antibodies against ICAM-1, CD29, and CD49b. The results thus show that adhesion molecules other than ICAM-1, CD29, AND CD49b are responsible for the induced adhesion between T cells and IFN-alpha-pretreated KB cells.

Antigens, CD↗
PubMed1995

[The inferior epigastric artery as a coronary artery bypass graft].

From January 1992 through December 1993, 31 patients underwent myocardial revascularization with the inferior epigastric artery (IEA) graft. There were one emergency case and four coronary reoperation cases. IEA grafts were taken down through the left side paramedian incision and dilated with papaverine hydrochloride solution. The distal anastomoses were made to left anterior descending (3 cases), diagonal (14 cases), obtuse marginal (9 cases), postero-lateral (I case) and right coronary artery (4 cases). The proximal anastomoses were made to the aorta (22 cases), the hood of a new vein graft (4 cases) and the hood of an old vein graft (4 cases). When IEA was not long enough to reach the ascending aorta, it was anastomosed to the internal thoracic artery (2 cases) or the gastroepiploic artery (1 case) graft. There was one hospital death, and early patency rate (within one month) was 90% (19/21). The postoperative angiography performed at 1.3 years or 2 years showed excellent IEA graft patency. These results suggested that the IEA is suitable as a coronary artery bypass graft. Further long-term patency must be evaluated.

Adult↗
PubMed1994

Molecular cloning of the second major allergen, Cry j II, from Japanese cedar pollen.

Cloning of a cDNA from Cry j II, the second major allergen from Japanese cedar (Cryptomeria japonica) pollen, is described. An isolated Cry j II cDNA contained an open reading frame coding for 514 amino acid residues. The mature Cry j II protein consisted of 388 amino acid residues (R46-S433). According to a homology analysis, no amino acid sequence homology was observed between Cry j II and Cry j I, another major allergen. But Cry j II showed homology with polygalacturonase (PG) derived from tomato (40% identity) at the amino acid level. The sequence information can potentially be used to devise an effective course of immunotherapy for Japanese cedar pollinosis.

Allergens↗
PubMed1994

Overexpression rescues the mutant phenotype of L176F mutation causing beta-glucuronidase deficiency mucopolysaccharidosis in two Mennonite siblings.

Two beta-glucuronidase-deficient Mennonite siblings were found to be homozygous for a mutation in exon 3 of the beta-glucuronidase gene that produces a Leu-->Phe substitution (L176F). The siblings also have the previously described benign polymorphism, P649L. Although their cultured fibroblasts contained 1.5-2.2% of normal beta-glucuronidase activity, transient expression of the L176F/P649L cDNA in COS cells produced nearly as much enzyme activity as the wild-type control cDNA. The L176F/P649L enzyme was as stable as wild-type enzyme following endocytosis by fibroblasts and delivery to lysosomes, but was more labile to heat inactivation at 65 degrees C. To study the mutant enzyme at lower levels of expression, we stably transfected mouse mucopolysaccharidosis type VII cells with the L176F/P649L cDNA and selected single-copy cell lines. Metabolic labeling with [35S]methionine revealed that cell lines expressing the mutant enzyme activity at low levels (7-10% of the wild type) actually produced the same amount of enzyme protein as the cell lines expressing the more active wild-type enzyme. However, the cell lines expressing four times this much mutant enzyme protein produced 150-200% as much enzyme activity as the cell line expressing the single-copy wild-type cDNA. These data suggest that overexpression can drive the folding reaction or the self-association of mutant monomers to form active tetramers and, at least partially, correct the beta-glucuronidase deficiency seen at low levels of expression with certain missense mutations.

Alleles↗
PubMed1994

A high-level and regulatable production system for recombinant glycoproteins using a human interferon-alpha promoter-based expression vector.

A novel expression vector for human cells, pIFP, which expresses a cloned gene under the control of the human interferon-alpha-encoding gene (IFN-alpha) promoter (pIFN) was constructed. As a model of glycoprotein production, a human erythropoietin-encoding cDNA (EPO) inserted downstream from pIFN in pIFP was introduced into human B-cell leukemia-derived BALL-1 cells, and EPO-producing cells were established. Upon stimulation with Sendai virus, the cells produced human EPO at high levels. The highest production level and the highest inducibility were 872 IU/ml and 67-fold, respectively. Simultaneously, the transformed cells also produced IFN-alpha and tumor necrosis factor-alpha (TNF-alpha), as the parental BALL-1 cells did. Comparing the amounts of the substances produced, activity of the exogenous pIFN introduced seemed much higher than that of the endogenous one. Further, the transformed cells could be obtained in a large quantity by being applied to the 'in vivo cell proliferation method (hamster method)'. Human EPO produced by the transformed cells had a molecular mass range of 35 to 42 kDa, similar to that of EPO produced by CHO cells. The processing of EPO seemed to occur properly. The combination of the human pIFN, BALL-1 cells and the hamster method provides us with a useful production system for bioactive glycoproteins of human origin.

Animals↗
PubMed1994

Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5'-flanking region.

Mucopolysaccharidosis IV A (MPS IV A) is the result of a genetic deficiency in a lysosomal hydrolase, N-acetylgalactosamine-6-sulfatase (GALNS). To investigate MPS IV A patients at the level of the genome, we analyzed the structure of the human GALNS-encoding gene. From the genomic library of a normal subject in lambda EMBL3, we isolated five overlapping clones covering the coding region of the GALNS cDNA and determined the structural organization. The gene is about 50 kb long and contains 14 exons. The 5'-flanking region lacks a canonical TATA box and CCAAT sequences, but is G+C-rich (70.5%), with four GC boxes, characteristic of a housekeeping gene promoter. The transcription initiation site was determined by primer extension analysis, using RNA from human liver and HeLa cells. Transcription was found to initiate at a few sites, the major ones being 58 and 22 bp upstream of the translation initiation codon. The 5'-flanking region had promoter activity by transient expression, determined using a CAT assay. In addition, this region retained promoter activity, even in reverse orientation. The region -98 to -1 upstream of the ATG codon was defined by deletion analysis to be a minimal promoter. One GC box in this region is likely to be a binding site of a regulatory element.

Base Sequence↗
PubMed1994

Case of 46,XX/47,XY, +21 chimerism in a newborn infant with ambiguous genitalia.

We describe whole-body chimerism in a newborn infant with small phallus, pseudo-vaginal perineal hypospadias, and a bifid scrotum containing gonads. The human testis determining factor gene (SRY) was detected by PCR amplification. GTG-banding chromosome analysis in peripheral blood lymphocytes and cultured fibroblasts derived from right cubital skin showed a 46,XX/47,XY, +21 karyotype. Their ratios in each cell line were 294:5 and 178:7, respectively. QFQ-banding chromosome analysis documented 3 heteromorphic satellites on trisomic chromosomes 21 in the 47,XY, +21 cell line and a homozygous satellite pattern in the 46,XX cell line. Heteromorphic patterns of chromosomes 4, 13, 14, and 22 were also different between the two cell lines. To our knowledge, such disomy/trisomy chimeras have not been described previously.

Cells, Cultured↗
PubMed1994

Clinical study of biological response modifiers as maintenance therapy for hepatocellular carcinoma.

We conducted a randomized, controlled trial comparing 5-fluorouracil (5-FU) with or without biological response modifiers (BRMs) as a maintenance therapy for hepatocellular carcinoma (HCC) after treatment with percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or arterial infusion of antitumor agents (AI). A total of 58 cases of HCC were classified into 4 groups as follows: group I, PSK with 5-FU (n = 15); group II, lentinan with 5-FU (n = 15); group III, OK-432 with 5-FU (n = 12); and group IV, 5-FU alone as the control (n = 16). The mean survival time, mortality rate, time to progression, and T4/T8 ratio of lymphocytes in the peripheral blood were compared among the four groups. There was no significant difference in the background factors among the groups. In group I, the T4/T8 ratio of lymphocytes was reduced after the therapy. No significant difference was found among the groups in terms of the mean survival time, mortality rate, or time to progression. PEI for initial therapy was superior to the other therapies in terms of the mean survival time and mortality rate. These results suggest that the addition of BRM to maintenance therapy with 5-FU exerts no prognostic benefit on HCC patients treated with PEI, TAE, or AI.

Aged↗
PubMed1994

A case of metastatic chondrosarcoma of the stomach.

A case of metastatic chondrosarcoma of the stomach in a 34-year-old female is reported. This patient had been diagnosed as having chondrosarcoma of the right knee and was operated on in 1984. Thereafter, there was repeated local recurrence and operations were performed on multiple metastases, including those of the lung, brain, ovary and spleen. In September, 1990, the patient was readmitted because of advanced anemia. Gastroendoscopy disclosed a firm elevated lesion with central irregular erosion. Histologically, there was cellular atypical cartilage with pleomorphic chondrocytes, which showed the same staining reactions as those in the primary lesion. Therefore this case was diagnosed as metastatic chondrosarcoma. This may be the first documentation of a case of gastric metastasis of chondrosarcoma.

Adult↗
PubMed1994

Gastroepiploic artery graft for anterior descending coronary artery bypass.

In 308 right gastroepiploic artery (GEA) grafting procedures performed for myocardial revascularization, 38 GEA, 34 in situ, and four free grafts were used to bypass the left anterior descending coronary artery (LAD). Indications for using the GEA for the purpose of LAD bypass were: unavailability of the internal thoracic artery (ITA) at reoperation, surgical damage to the ITA at the time of the operation, or an apparently better free flow versus that in the left ITA, particularly in patients with diabetes mellitus in whom it was considered inadvisable to use bilateral ITAs. There were 21 male and 17 female patients with a mean age of 62 years (range, 31 to 77 years). Ten patients had undergone a previous myocardial revascularization. The mean number of distal anastomoses was 2.8 (range, 1 to 5). Concomitantly used conduits were the ITA in 27 patients, saphenous veins in 21 patients, the inferior epigastric artery in 4 patients, and the bovine internal thoracic artery in 1 patient. All but 1 patient survived. Follow-up ranged from 3 to 84 months (mean, 27 months). Postoperative angiography was performed in 33 patients. At the short-term evaluation (mean, 1 month), 32 of 33 (97%) GEA grafts were found to be patent; all 4 GEA grafts studied at the long-term evaluation (mean, 25 months) were also found to be patent. In no patients did angina recur postoperatively. In 25 patients who underwent an exercise study postoperatively, the stress test results were negative in 23.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1994

Mixed germ cell tumor of the basal ganglia: a case report.

A case of mixed germ cell tumor (germinoma and immature teratoma) of right cranial basal ganglia is presented. We followed the natural course for 8 months, and the change in his clinical, radiologic, and endocrinologic features was remarkable.

Adolescent↗
PubMed1994

Erb's point stimulation produces slow positive potentials in the human lumbar spinal cord.

Evoked spinal cord potentials (SCPs) were recorded from the posterior epidural space (PES) at the cervical and lumbrosacral enlargements in response to electrical stimulation of the brachial plexus at Erb's point in 17 chronic pain patients. Erb's point stimulation produced slow positive potentials (heterosegmental slow positive potentials, HSPs) in the PES at the lumbrosacral enlargement in all 13 subjects without spinal cord lesions but not in 4 subjects with spinal cord lesions. The HSP1 with a central peak latency of 21 +/- 2 ms (mean +/- SE) was recorded at the stimulus intensity up to two to three times the threshold strength (T) of the initially positive spike (P1) of the segmental SCP, which was simultaneously recorded from the PES at the cervical enlargement. At the stimulus intensity of more than 3T, another slow positive potential (HSP2) with central peak latency of 71 +/- 6 ms was recorded. These slow positive potentials (HSP1 and HSP2) might be produced by a feedback loop via supraspinal structures, presumably primary afferent depolarizations, in comparison to the HSPs of our previous studies in the rat. Slow negative potentials were sometimes noted before (5 of 13) and/or after (2 of 13) the HSP1. These slow negative potentials probably reflect the activities of dorsal horn neurons producing the HSP1 and HSP2, respectively, also elicited by a feedback loop via supraspinal structures.

Adolescent↗