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Biomedical subjects

K Seyama

Publications and source records attributed to K Seyama.

At least 37 records · Page 2Linked to original sources
PubMed1997

Progressive interstitial pneumonia associated with myelodysplastic syndrome: implication of superoxide hyperproduction by neutrophils.

Interstitial pneumonia and aseptic neutrophilic infiltration in the lung are rare pulmonary manifestations of myelodysplastic syndrome (MDS). We report a patient with progressive interstitial pneumonia associated with MDS. Histological examination of the lung revealed infiltration of atypical haematopoietic cells associated with MDS and diffuse alveolitis with honeycombing. Neutrophils obtained from the patient showed superoxide hyperproduction after stimulation with phagocytosis and phorbol myristate acetate, which might be attributed to the pathogenesis of interstitial pneumonia.

Bronchoalveolar Lavage↗
PubMed1996

Classification of mutations in the human CD40 ligand, gp39, that are associated with X-linked hyper IgM syndrome.

The interaction between the T cell activation antigen gp39 and CD40, its receptor CD40 on B cells, plays a critical role in the regulation of humoral immune responses. Using a detailed three-dimensional model of the gp39 extracellular region, we have analyzed 20 mutations in gp39 that were, with one exception, isolated from patients with X-linked hyper IgM (XHIM) syndrome. On the basis of this analysis, the mutations were classified according to their predicted locations and effects. Twelve mutations are thought to compromise the gp39 structure by affecting interactions in hydrophobic core regions or at monomer interfaces, whereas seven others map closely to gp39 residues important for interaction with CD40. The latter mutations may thus, directly or indirectly, interfere with CD40 binding. One naturally occurring mutant whose carrier displays normal immune responses maps to a solvent-exposed position in a loop region of the molecule.

CD40 Antigens↗
PubMed1996

Genomic structure and PCR-SSCP analysis of the human CD40 ligand gene: its application to prenatal screening for X-linked hyper-IgM syndrome.

To develop a general method for analysis of the mutation and prenatal diagnosis of X-linked hyper-IgM syndrome (XHM), the human CD40 ligand (hCD40L) gene was cloned and sequenced with special reference to the 5' and 3' flanking regions and exon/intron boundaries. The hCD40L gene consists of five exons and four introns, as already reported by others. Two major transcription initiation sites were identified at 67 bp and 64 bp upstream from the ATG initiation codon. The hCD40L mRNA transcripts terminated at 321 bp, 327 bp and 987 bp downstream from the TGA stop codon. Based on the intronic sequences, oligonucleotide primers were designed for amplifying the coding region of each exon separately. Polymerase chain reaction--single-strand conformational polymorphism (PCR-SSCP) analysis was successfully applied to screening for the defective hCD40L gene in a family with XHM. The nonsense mutation, Trp140 (TGG)-->stop (TAG) in exon 5, was found in the mother and an affected child. We also performed prenatal diagnosis by PCR-SSCP during the first trimester of pregnancy in this family.

Amino Acid Sequence↗
PubMed1996

[Alpha 1-antitrypsin deficiency in Japan].

Alpha 1-antitrypsin (alpha 1-AT) deficiency is very rare in Japan although it is one of the most common hereditary disorders in Caucasians. Only 12 cases of alpha 1-AT deficiency have been reported in Japan. Their genetic abnormalities have already elucidated in 10 cases: Mnichinan, a heterozyge of Mmalton, 7 unrelated cases of Siiyama, and a case of 14q-syndrome. The Siiyama is the first prevalent deficient variant in the race other than the Caucasian race. The Siiyama mutation occurred on the normal alpha 1-AT variant M1 (Val213) which seems to be evolutionally newer than M1 (Ala213) on which the Z type mutation occurred. The result that alanine residue was not detected at 213 amino acid position in alpha 1-AT genes of 193 Japanese volunteers may be the reason why genetically proved Z deficient variant have not been reported yet in Japan.

Amino Acid Sequence↗
PubMed1995

Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung.

To better understand the mechanisms responsible for the increase in numbers of fibroblasts and increased collagen synthesis in fibrotic intestitial lung diseases, platelet-derived growth factor (PDGF)-A and PDGF-B, PDGF receptor-alpha and -beta, insulin-like growth factor I (IGF-I), and IGF-I receptor were evaluated immunohistochemically. Additionally, the messenger ribonucleic acids (mRNAs) for PDGF-A and PDGF-B, PDGF receptor-alpha and -beta, and IGF-I were investigated by in situ hybridization in alveolar macrophages and lung tissues from patients with interstitial lung disease. In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, and IGF-I were local in alveolar macrophages in patients with idiopathic pulmonary fibrosis (IPF), patients with sarcoidosis (Sar), and normal individuals. Although there were no differences between IPF and Sar in terms of the staining intensity or number of positive cells, the number of such cells was smaller in the normal controls. In lung tissues with early-stage IPF, PDGF and IGF-I proteins were localized exclusively in alveolar macrophages, mononuclear phagocytes, fibroblasts, alveolar Type II cells, vascular endothelial cells, and vascular smooth-muscle cells. In lung tissues with late-stage IPF and those from normal controls, only alveolar macrophages contained PDGF and IGF-I proteins. Interestingly, the cellular localizations of PDGF receptor-alpha and -beta, and of IGF-I receptor were the same as those of the PDGF and IGF-I proteins in early-stage IPF, whereas these cells were not positive for any of these substances in late-stage IPF or normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.

In contrast to the fact that alpha 1-antitrypsin (alpha 1-AT) deficiency is one of the most common hereditary disorders of Caucasians, deficient variants among Orientals have been recognized to be extremely rare. Only 12 cases of alpha 1-AT deficiency have been reported in Japan, including five cases in which the genetic defects have already been elucidated: Mnichinan (delta Phe52[TTC] and Gly148[GGG]-->Arg148[AGG]), two unrelated cases of Siiyama (Ser53[TCC]-->Phe53[TTC]), a heterozygote of Mmalton (delta Phe52[TTC]), and one additional case of 14q- syndrome (sporadic deletion of the neighboring region of the alpha 1-AT gene locus). alpha 1-AT Siiyama is a deficient variant originally identified in a 38-yr-old patient with pulmonary emphysema in Japan. The amino acid substitution in this variant occurs in a highly conserved residue of the serpin (serine protease inhibitor) backbone (Seyama K, et al. 1991. J. Biol. Chem. 266:12627-12632). We attempted to determine whether alpha 1-AT deficiency in Japan was caused by independent genetic defects or whether it shared some common mutations in the alpha 1-AT gene. We examined five of seven available families for which the genetic defects causing alpha 1-AT deficiency have not yet been explored. When the allele-specific polymerase chain reaction (PCR) was performed with a pair of oligonucleotide primers having the mutated base sequence of the alpha 1-AT Siiyama allele at the 3' end, all eight cases of alpha 1-AT deficiency among five unrelated families turned out to be homozygous carriers of the alpha 1-AT Siiyama mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Cardiac sarcoidosis with myopathy and advanced A-V nodal block in a woman with a previous diagnosis of sarcoidosis].

In 1992, a 49-year-old woman was admitted to the hospital because of exertional dyspnea. Three years earlier sarcoidosis had been diagnosed, and the patient was found to have bilateral hilar lymphadenopathy. The eye, skin, and knee joint were also involved. During the second hospital stay, atrial flutter with advanced A-V nodal block, scattered defects on a 201T1 scintigram, and marked cardiomegaly on chest roentgenogram led to the diagnosis of cardiac sarcoidosis. Signs and symptoms of cardiac failure subsided after placement of an artificial cardiac pacemaker, but the patient still complained of mild muscle weakness in the lower extremities on exertion. 67Ga scintigraphy revealed marked accumulation in the lower extremities, and muscle biopsy of the left gastrocnemius revealed numerous epithelioid cell granulomas with muscle fiber degeneration. Oral corticosteroid therapy was effective. A review of the 24 cases of sarcoid myopathy reported in Japan indicated that the male-to-female ratio is 1:3.8. As compared to patients in whom myopathy led to the diagnosis of sarcoidosis, those in whom myopathy developed after sarcoidosis was diagnosed were (1) relatively older, (2) more likely to have multiple organ involvement, and (3) more likely to have cardiac sarcoidosis. Corticosteroids were beneficial in about three quarters of these 16 cases, who received corticosteroid therapy.

Anti-Inflammatory Agents↗
PubMed1994

Amylase mRNA transcripts in normal tissues and neoplasms: the implication of different expressions of amylase isogenes.

To understand the cellular origin and mechanism of gene expression in amylase-producing cancers, the phenotyping of amylase isogenes by the polymerase chain reaction and restriction-fragment-length polymorphism using restriction endonucleases TaqI, DdeI, HinfI, and AfaI were performed for 3 amylase-producing lung adenocarcinomas, 16 lung cancers without hyperamylasemia, other human malignant neoplasms, cultured cell lines, and normal tissues. In addition, amylase mRNA transcripts were semi-quantified by the limited polymerase chain reaction. Amylase mRNA transcripts were detected in all of the tissues examined. The AMY1 gene (salivary type) was exclusively and highly expressed in the salivary glands and the amylase-producing lung adenocarcinomas. Coexpression of the AMY1 gene and AMY2 gene (pancreatic type) was observed in most of the lung cancers without hyperamylasemia, lung tissue, and cells scraped from the tracheal epithelium, thyroid, and female genital tract (ovary, fallopian tube, and uterus cervix), while minimal levels of mRNA transcripts of the AMY2 gene were detected in other malignant neoplasms, various normal tissues, and the cultured cell lines. All mRNA transcripts identified as being those of the AMY2 gene were further identified as being from the AMY2B gene except for the transcripts from the pancreas, in which the AMY2A gene and AMY2B gene were coexpressed. On the basis of these results, the clinical occurrence of amylase-producing cancer likely relates to the tissues expressing the AMY1 gene, while the AMY2B gene, which evolutionarily is the oldest gene among human amylase isogenes, is constitutively expressed in various tissues.

Amylases↗
PubMed1993

Alpha 1-antitrypsin Siiyama (Ser53-->Phe). Further evidence for intracellular loop-sheet polymerization.

Antitrypsin Siiyama is a rare example of the deficiency variants of antitrypsin that accumulate in the endoplasmic reticulum of the hepatocyte. The common example is Z antitrypsin, which has a mutation (Glu342-->Lys) at the junction of the head of the fifth strand of the A sheet and the base of the reactive center loop. It was previously shown that Z antitrypsin spontaneously polymerizes due to the insertion of the reactive center loop of one molecule into the A sheet of a second. The mutation in antitrypsin Siiyama (Ser53-->Phe) affects a residue that provides a ridge for the sliding movement that opens the A sheet, and it had been predicted that this would result in the same type of loop-sheet polymerization observed with the Z variant. We confirm this here and show that virtually all the plasma antitrypsin in a homozygote for the Siiyama variant was polymerized due to non-covalent bonding with a loss of accessibility of the reactive center loop. The common basis of the polymerization of Z and Siiyama antitrypsin is supported by identical findings on electron microscopy. Taken together these results confirm that loop-sheet polymerization is a general mechanism and as such is likely to be responsible for the intracellular inclusions associated with liver pathology.

Adult↗
PubMed1992

A new variant of alpha-1-antitrypsin deficiency (Siiyama) associated with pulmonary emphysema.

A 38-year-old male with pulmonary emphysema due to severely reduced serum alpha-1-antitrypsin (AAT) level (14.5 mg/dl) was found to have an inherited new AAT deficient variant Siiyama. Chest roentgenogram and CT scanning revealed advanced emphysema, and severe obstructive ventilatory impairment was observed. During the 4-year follow-up period, the annual rate of decline of FEV 1.0 showed approximately 10-fold greater than the normal decline in FEV 1.0 (-380 ml/yr). Treatment with tamoxifen in order to raise the serum AAT level only resulted in an insufficient increase. Augmentation therapy of human AAT should be considered in the future.

Adult↗
PubMed1992

[Graphic evaluation of the significance band for hypercapnia in pulmonary disorders].

Alveolar hypoventilation due to the chronic obstruction of the airway such as pulmonary emphysema, or severe restrictive dysfunction due to sequela of pulmonary tuberculosis causes chronic hypercapnia (chronic respiratory acidosis). Ninety-five percentile of significance band of chronic and acute hypercapnia of both experimental and clinical setting is introduced in the graphic display of the acid-base balance. On acute exacerbation of these disorders, examination of arterial blood gas in series are usually plotted along the significance band of hypercapnia. With clinical improvement, the plot will gradually drop down to the chronic stable area of the band. Although cases with metabolic disorders complicate the interpretation, evaluation of the acid-base status using the graphic display will be of help at bedside assessment.

Bicarbonates↗
PubMed1992

[Alpha 1-antitrypsin genes in patients with alpha 1AT deficiency in Japan: mutational analysis and allelic background].

Deficiency of alpha 1-antitrypsin (alpha 1AT), a plasma serine protease inhibitor, increases the risk of precocious pulmonary emphysema. Patients with alpha 1AT deficiency in Japan are extremely rare and no Z type alpha 1AT deficiency, which is one of the most frequent genetic disorders among Caucasians, are reported in Japan at the level of gene analysis. It is not yet clear why Z type alpha 1AT is rare among Japanese. When Ala213(GCG)-Val213(GTG) mutation in the alpha 1AT gene was examined by restriction endonuclease BstPI, all of 156 Japanese samples were Val213(GTG) in contrast to the finding that 30% of U.S. Caucasians are Ala213(GCG), indicating that alpha 1AT genes among Japanese were diverted from M1(Val213) variant and are different from M1(Ala213) variant, from which Z variant was likely diverted. This may explain why Z type alpha 1AT deficiency is not found among Japanese. A new alpha 1AT deficient variant, Siiyama (Ser53(TCC)-Phe53(TTC)), was found in a 39-year-old male with pulmonary emphysema (Seyama K, et al, J Biol Chem, 266, 12627, 1991). Interestingly, 6 out of 10 families with alpha 1AT deficiency in Japan shared the identical substitution as Siiyama. This indicates that although Caucasian type Z alpha 1AT deficiency is not found, Siiyama variant may be relatively common in Japan and even in other oriental countries because of the historical migration of people.

Alleles↗
PubMed1992

[The fate of patients with intermittent claudication-comparison of surgical and non-surgical treatment].

The purpose of this study was to determine the operative indication for patients with intermittent claudication because of arteriosclerosis obliterans, and to compare the late result of the surgical treatment group (182 cases, 250 limbs) with that of the non-surgical treatment group (35 cases, 43 limbs). There were 3 operative deaths and 34 late deaths in the surgical group, and 14 late deaths in the non-surgical group. The number one cause of death was heart failure, including ischemic heart disease, in both groups. The 4-year cumulative patency rates were 91% in the aorto-iliac, 71% in the femoro-distal and 79% in the aorto-femoro-distal arterial reconstructions. Long term symptom free rates of the surgical group and the non-surgical group, except fatal case, were 83% and 44% in the aorto-iliac, 79% and 27% in the femoro-distal, 87% and 33% in the aorto-femoro-distal arterial regions, respectively. Late result of intermittent claudication in the surgical group was better than that in the non-surgical group. We concluded that intermittent claudication should be considered to be the indication for surgery, except for the cases with high risk diseases or malignant diseases.

Aged↗
PubMed1991

Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone.

alpha 1-antitrypsin (alpha 1AT), a plasma serine protease inhibitor, increases the risk of precocious pulmonary emphysema in individuals when deficient. Although more than 25 years have passed since a deficiency in the serum level of alpha 1AT was reported, it is only recently that the consequence of the amino acid replacement which leads to the deficient state has been discussed in terms of the crystallographic structure of alpha 1AT and the amino acid residues conserved in the superfamily to which it belongs. Our case involved a 38-year-old Japanese male with alpha 1AT deficiency which was analyzed and identified as a new deficient variant. The serum alpha 1AT of the proband migrated to the S position of the reference serum which is more cathodal than M1, the predominant normal variant, when isoelectric focusing (pH 4.2-4.9) is performed by a combination of Western blotting and crossed immunoelectrophoresis. The new deficient variant is designated as Siiyama after his birthplace. Although liver biopsy specimen showed no apparent pathological findings, PAS-positive with diastase-resistant inclusion bodies and immunoreactive aggregates were detected in several hepatocytes. In addition, similar alpha 1AT mRNA transcript levels were observed in peripheral blood leukocytes from the proband and healthy subjects by Northern analysis. All the coding exons (exon Ic, II, III, IV, and V) of the alpha 1AT gene of the proband and his family were amplified by polymerase chain reaction and followed by direct sequencing. A single missense mutation, Ser53 (TCC) to Phe53 (TTC was identified in exon II of the proband's alpha 1AT gene. All his family examined were heterozygous at this base. Ser53 is one of the most conserved residues as predicted by Huber and Carrell (Huber, R., and Carrell, R. W. (1989) Biochemistry 28, 8951-8966) and is thought to contribute to the organization of the internal core element of the alpha 1AT molecule. The mutational matrix number of Ser to Phe substitution is -3, indicating that this change is evolutionally rare. In this regard, a possible explanation for the deficient state in alpha 1AT Siiyama is that the change from an uncharged polar to a nonpolar amino acid imposed on the conserved serpin backbone exerts severe effects on the integrity of the molecule, and hence alters the intracellular processing of alpha 1AT.

Adult↗
PubMed1989

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with special reference to the mechanism of cerebral manifestations.

A 29-year-old man with mitochondrial encephalomyopathy caused by partial deficiency of mitochondrial NADH-ubiquinone oxidoreductase (Complex I) is described. Clinical manifestations were characterized by generalized convulsion, dementia and stroke-like episodes consisting of hemianopsia, Gerstmann's syndrome and visual hallucination. Blood and cerebrospinal fluid lactate and pyruvate levels were elevated. Biochemical studies on a muscle biopsy specimen revealed partial deficiency of Complex I activity, and decreases in the 75-kDa and the 20-kDa subunits of Complex I by immunoblotting analysis. Serial brain CT scans revealed multiple low-density areas with fluctuating densities. Single photon emission tomographic study revealed preservation of blood circulation where CT scans showed diminished density in acute stage, suggesting the presence of abnormal cellular metabolism rather than vascular occlusion as the basic mechanism of his stroke-like episodes. Pathogenesis of neurological manifestations in MELAS is discussed with reference to the possible involvement of free radicals in inducing brain damage.

Acidosis, Lactic↗
PubMed1987

Biochemical characterization of acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase in rat spleen microsomes.

Acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) ultrasonic disruption in the presence of 25% glycerol from rat spleen microsomes. About 26% of the enzymatic activity was recovered in the 225,000 X g supernatant by this treatment, although the specific activity was slightly decreased compared with the original microsomes. The solubilized enzyme was remarkably susceptible to various kinds of metal ions. Sulfhydryl reagents such as p-chloromercuribenzoate and N-ethyl-maleimide significantly inhibited the enzyme reaction, suggesting that the enzyme is an SH enzyme. Based on the sedimentation pattern in sucrose density centrifugation, the isoelectric point, the kinetic characteristics and the sensitivity to tryptic digestion of microsomes, it appears that acetyl-CoA:lyso-PAF acetyltransferase does not differ from the acetyltransferase responsible for the transfer of acetate from acetyl-CoA to 1-acyl-2-lyso-sn-glycero-3-phosphocholine.

Acetyltransferases↗
PubMed1986

Metabolism of platelet-activating factor in primary cultured adult rat hepatocytes by a new pathway involving phospholipase C and alkyl monooxygenase.

The metabolic fate of 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether) upon interaction with primary cultured adult rat hepatocytes was investigated. [3H]PAF-acether was transformed time-dependently into [3H]lyso-PAF-acether, 1-O-[3H]alkylglycerol and finally converted to 3H-labeled fatty aldehyde. 1-O-[3H]Alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) was formed after a long incubation time and with a smaller amount compared with that formed in platelets and neutrophils. When lipids from cells, cell surfaces and incubation medium were analyzed separately, most of the transformed products of [3H]PAF-acether remained in the cells. When 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine was incubated with hepatocytes, it was mainly converted into 1-O-[3H]alkylglycerol. 3H-labeled fatty aldehyde and [3H]alkylacyl-GPC were also found. Hepatocytes metabolized slowly from 1-O-[1-14C]hexadecylglycerol to 3H-labeled fatty aldehyde and 3H-labeled phospholipid. These findings suggest that cultured hepatocytes mainly catabolize exogeneous PAF-acether by removing the acetyl residue and the polar head group and, finally, by cleaving an ether bond. The deacetylation-reacylation step, which is important in platelets and neutrophils, was not shown to be a main metabolic pathway of PAF-acether in cultured hepatocytes.

Animals↗