PubMed Health⌕ Search

Biomedical subjects

A Nagasaki

Publications and source records attributed to A Nagasaki.

At least 19 recordsLinked to original sources
PubMed1999

Analysis of 1,992 patients with anorectal malformations over the past two decades in Japan. Steering Committee of Japanese Study Group of Anorectal Anomalies.

BACKGROUND/PURPOSE: This report describes the results of a group study of the Japanese Study Group of Anorectal Anomolies (JSGA) to determine the relative incidence of specific types of anorectal anomaly in Japan, and includes discussion of rectourethral fistula regarding the relationship between the levels of the fistula and blind end of the rectum, low type deformity, rare types, and associated anomalies. METHODS: A total of 1,992 patients (1,183 boys and 809 girls) registered from 1976 to 1995 were analyzed. RESULTS: High-type deformities accounted for 26.0% of cases, intermediate 10.7%, low 57.2%, miscellaneous 4.5% and unclassified 1.8%. The most frequent deformity was male anocutaneous fistula (n = 364), followed by male rectourethral fistula (n = 333), and female anovestibular fistula (n = 241). There were 42 rectovesical fistulas in boys and 93 rectocloacal fistulas in girls. Covered anus complete occurred at the same frequency (10.1% of low deformities) as covered anal stenosis. In rectourethral fistula, the blind end of the rectum lay at or above the level of the P-C line in 40.3% of cases, at or above the M line in 39.6% and at the vicinity of the I line in 20.2%, respectively. There was no parallel relationship between the site of the fistula opening and the level of the rectal pouch. The overall incidence of patients having one or more associated anomalies was 45.2%: 70.6% in high deformity, 60.7% in intermediate, and 31.3% in low. The rate of association of Down's syndrome with deformities without fistula (40.3%) was significantly higher than with deformities with fistula (0.3%). CONCLUSIONS: Rectovesical fistula and covered anus complete were not infrequent deformities in this series. We consider that at least 20% of rectourethral fistula should be categorized as intermediate or low deformity from the viewpoint of the position of the rectal pouch. A significant preponderance of Down's syndrome in the deformities without fistula suggests that further investigation of associated anomalies in comparision with other congenital diseases may provide insights into the pathogenesis of anorectal malformation in the field of molecular genetics.

Anal Canal↗
PubMed1999

Expression of PRAD1/cyclin D1 in plasma cell malignancy: incidence and prognostic aspects.

We analysed PRAD1/cyclin D1 expression in 20 patients with plasma cell malignancy by Northern analysis. 6/17 multiple myeloma patients and 3/3 plasma cell leukaemia patients showed PRAD1/cyclin D1 expression. This incidence appeared to be higher than the expected incidence based on previous studies. Southern analysis did not show rearrangement of the bcl-1 region. Although there was no statistical difference, the PRAD1/cyclin D1 negative group showed a 1-year survival of 81.8%, 3-year survival of 45.5% and 5-year survival of 22.7%, and those for the PRAD1/cyclin D1 positive group were 63.5%, 16.9% and 16.9%, respectively. Further study is required to determine whether PRAD1/cyclin D1 expression is a prognostic factor.

Aged↗
PubMed1999

Expression of arginase II and related enzymes in the rat small intestine and kidney.

Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue.

Animals↗
PubMed1998

Dictyostelium TRFA homologous to yeast Ssn6 is required for normal growth and early development.

The TPR (tetratricopeptide repeat) family became widespread during evolution, having been found from bacteria to mammals. By means of restriction enzyme-mediated integration, we have identified a Dictyostelium gene (trfA) highly homologous to a Saccharomyces cerevisiae gene encoding a TPR protein, Ssn6 (Cyc8), which functions as a global transcriptional repressor for diverse genes. The deduced amino acid sequence of the Dictyostelium gene product, TRFA, contains 10 consecutive TPR units as well as Gln repeats, Asn repeats, and a region rich in Glu, Lys, Ser, and Thr. The sequences of some of the 10 TPR units in TRFA are more than 70% identical to the corresponding units in Ssn6. The trfA- cells produced smooth plaques on a bacterial lawn and failed to aggregate normally when starved on a plain agar plate. Individual trfA- cells also failed to correctly respond to cAMP, although the adenylyl cyclase of trfA- cells was expressed upon starvation and activated by stimulation with cAMP as in the wild-type cells. When cultured in a rich medium in suspension, they grew more slowly and stopped growing at a lower density than the wild-type cells. Furthermore, they divided into cells of various sizes and tended to be much smaller than the wild-type cells. These pleiotropic defects of the trfA- cells suggest the possibility that Dictyostelium TRFA may regulate the transcription of diverse genes required for normal growth and early development.

Amino Acid Sequence↗
PubMed1998

A novel Dictyostelium discoideum gene required for cAMP-dependent cell aggregation.

Using a method of random insertional mutagenesis called REMI (restriction enzyme-mediated integration), we isolated two mutant strains of Dictyostelium discoideum with a defect in cAMP-dependent cell aggregation. On bacterial lawns, both of the cells formed large and smooth plaques. When starved in a non-nutrient medium, they became elongated and extended pseudopods very frequently like starved wild type cells. However, they never formed streams toward an aggregation center. Genomic DNA fragments flanking the sites of insertion of the REMI tag were rescued from the mutant cells. The fragments contained one common open reading frame encoding a protein of 1148 amino acid residues. The protein's sequence is homologous to those of two hypothetical proteins of S. cerevisiae and S. pombe.

Amino Acid Sequence↗
PubMed1998

Multiple myeloma associated with serum amino acid disturbance and high output cardiac failure.

We experienced a plasma cell leukemia (PCL) patient complicated with high output cardiac failure (HOCF), proved as his elevated cardiac index and pulmonary artery wedge pressure and decreased systemic vascular resistance index in a hemodynamic study. We found no possible causes of HOCF. Interestingly, HOCF was improved as PCL responded to intensive chemotherapy. On the other hand, he showed consciousness disturbance, and had frequent attacks of generalized seizure. His electroencephalogram showed slow waves, and a spike and wave complex. Hyperammonemia and abnormal amino acid distribution were also found. This abnormal serum amino acid distribution, especially elevated glycine level, was different from that seen in chronic liver failure, and he had no hepatic disease. After intensive chemotherapy, the serum ammonia level and glycine level decreased. In this patient, PCL seemed to be responsible for HOCF, hyperammonemia, and abnormal amino acid distribution. We experienced two more cases of multiple myeloma (MM) with HOCF, hyperammonemia, abnormal serum amino acid distribution, and consciousness disturbance of unknown origin. Those two cases showed slow waves in the electroencephalogram. Improvement was seen in their HOCF, hyperammonemia, and abnormal amino acid levels after chemotherapy. The possibility of MM as a cause of HOCF is discussed.

Adult↗
PubMed1998

Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration.

Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To investigate mechanisms of drug resistance, we generated a monoclonal antibody, clone O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot analysis showed that molecular weight of O3 antigen was approximately 90 kDa. Expression of O3 antigen was approximately two times higher in KHM-11R than in parental melphalan sensitive cell line, KHM-11. O3 was preferentially expressed in plasma cell, B-cell, and monocytic cell lines, but not in T-cell lines. Analysis of bone marrow samples from myeloma patients revealed that 13 of 23 samples expressed O3 antigen at various levels, and that O3 antigen expression in patients correlate with preceding chemotherapy, advanced clinical stage and extramedullar invasion of myeloma cells. Furthermore, patients expressing O3 antigen at the time of diagnosis tended to have poor prognosis. The investigation of O3 antigen in myeloma cells will be useful to reveal the pathophysiology of extramedullar invasion and the mechanism of cell killing by melphalan.

Adult↗
PubMed1998

Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver.

Arginine is a precursor for the synthesis of urea, polyamines, creatine phosphate, nitric oxide and proteins. It is synthesized from ornithine by argininosuccinate synthetase and argininosuccinate lyase and is degraded by arginase, which consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Recently, cDNAs for human and rat arginase II have been isolated. In this study, immunocytochemical analysis showed that human arginase II expressed in COS-7 cells was localized in the mitochondria. Arginase II mRNA was abundant in the rat small intestine and kidney. In the kidney, argininosuccinate synthetase and lyase were immunostained in the cortex, intensely in proximal tubules and much less intensely in distal tubules. In contrast, arginase II was stained intensely in the outer stripes of the outer medulla, presumably in the proximal straight tubules, and in a subpopulation of the proximal tubules in the cortex. Immunostaining of serial sections of the kidney showed that argininosuccinate synthetase and arginase II were colocalized in a subpopulation of proximal tubules in the cortex, whereas only the synthetase, but not arginase II, was present in another subpopulation of proximal tubules. In the liver, all the enzymes of the urea cycle, i.e. carbamylphosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase and lyase and arginase I, showed similar zonation patterns with staining more intense in periportal hepatocytes than in pericentral hepatocytes, although zonation of ornithine transcarbamylase was much less prominent. The implications of these results are discussed.

Animals↗
PubMed1998

Regulation of the urea cycle enzyme genes in nitric oxide synthesis.

Nitric oxide (NO) is synthesized from arginine by nitric-oxide synthase (NOS), and citrulline that is generated can be recycled to arginine by argininosuccinate synthase (AS) and argininosuccinate lyase (AL). Rats were injected with bacterial lipopolysaccharide (LPS) and expression of the inducible isoform of NOS (iNOS), AS and AL was analysed. In RNA blot analysis, iNOS mRNA was induced by LPS in the lung, heart, liver and spleen, and less strongly in the skeletal muscle and testis. AS and AL mRNAs were induced in the lung and spleen. Kinetic studies showed that iNOS mRNA increased rapidly in both spleen and lung, reached a maximum 2-5 h after the treatment, and decreased thereafter. On the other hand, AS mRNA increased more slowly and reached a maximum in 6-12 h (by about 10-fold in the spleen and 2-fold in the lung). AL mRNA in the spleen and lung increased slowly and remained high up to 24 h. In immunohistochemical analysis, macrophages in the spleen that were negative for iNOS and AS before LPS treatment were strongly positive for both iNOS and AS after this treatment. As iNOS, AS and AL were co-induced in rat tissues and cells, citrulline-arginine recycling seems to be important in NO synthesis under the conditions of stimulation. Arginine is a common substrate of NOS and arginase. Rat peritoneal macrophages were cultured in the presence of LPS and expression of iNOS and livertype arginase (arginase I) was analysed. mRNAs for iNOS and arginase I were induced by LPS in a dose-dependent manner. iNOS mRNA appeared 2 h after LPS treatment and increased up to a near-maximum at 8-12 h. On the other hand, arginase I mRNA began to increase after 4 h with a lag time and reached a maximum at 12 h. Immunoblot analysis showed that iNOS and arginase I proteins were also induced. Induction of iNOS and arginase I mRNAs were also observed in LPS-injected rats in vivo. Thus, arginase I appears to have an important role in downregulating NO synthesis in murine macrophages by decreasing the availability of arginine. A cDNA for human arginase II, an arginase isozyme, was isolated. A polypeptide of 354 amino acid residues including the putative NH2-terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. mRNA for human arginase II was present in the kidney and other tissues but was not detected in the liver. Arginase II mRNA was co-induced with iNOS mRNA in murine macrophage-like RAW 264.7 cells by LPS. This induction was enhanced by dexamethasone and dibutyrul cAMP, and was prevented by interferon-gamma. These results indicate that NO synthesis is regulated by arginine-synthesizing and -degrading enzymes in a complicated manner.

Amino Acid Sequence↗
PubMed1998

Expression of Bcl-2 family of proteins in fresh myeloma cells.

Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X(L), Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X(L) were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X(L). Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X(L) tended to be expressed in samples from cases at advanced clinical stage. Bcl-X(L) was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X(L) and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X(L) although Bcl-X(L) tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X(L) and Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.

Adult↗
PubMed1998

Evaluation of hair root analysis for acute phencyclidine poisoning and behavior of phencyclidine metabolites in rat hair root.

We evaluated the usefulness of hair root analysis to diagnose acute phencyclidine (PCP) poisoning. Male rats were i.p. administered acute poisonous doses (80, 100 and 120 mg/kg) of PCP hydrochloride and the hair roots were plucked out with hair nippers at certain times after administration. The hair root samples were extracted with methanol/HCl. After evaporation of the solvent, the residue was derivatized with N,O-bis(trimethylsilyl) acetamide and analyzed with GC/MS. PCP was detected at high concentrations (up to 181.7 ng/mg) from all samples. The peak concentrations at every dose were observed at 6 h. The concentrations of PCP in the rat hair roots increased dose-dependently in the range of the doses. 1-(1-Phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-phenyl-1(4'-hydroxypiperidino)-4-cyclohexanol (t-PCPdiol) were also detected from 5 and 15 min to 48 h after administration, respectively. It is concluded that hair root is a useful specimen for the diagnosis of acute PCP poisoning because PCP, PCHP and t-PCPdiol are detected very soon after administration and a large amount of them is retained in hair root for a long time. PCHP was found from the early stage in hair roots and its concentration was higher than that of t-PCPdiol for 6 h. However, the concentration of t-PCPdiol became higher than that of PCHP after 6 h. These phenomena could be explained by the time lag of production of the primary (PCHP) and the secondary metabolite (PCPdiol).

Acute Disease↗
PubMed1997

Coinduction of nitric-oxide synthase and arginase I in cultured rat peritoneal macrophages and rat tissues in vivo by lipopolysaccharide.

Nitric oxide is synthesized by nitric-oxide synthase from arginine, a common substrate of arginase. Rat peritoneal macrophages were cultured in the presence of bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of nitric-oxide synthase (iNOS) and liver-type arginase (arginase I) was analyzed. mRNAs for iNOS and arginase I were induced by LPS in a dose-dependent manner. iNOS mRNA appeared 2 h after LPS treatment and increased to a near maximum at 8-12 h. On the other hand, arginase I mRNA that was undetectable prior to the treatment began to increase after 4 h with a lag time and reached a maximum at 12 h. Immunoblot analysis showed that iNOS and arginase I proteins were also induced. mRNA for arginase II, an arginase isozyme, was not detected in the LPS-activated peritoneal cells. mRNA for CCAAT/enhancer-binding protein beta (C/EBPbeta), a transactivator of the arginase I gene, was also induced, and the induction was more rapid than that of arginase I mRNA. Changes in iNOS and arginase I mRNAs were also examined in LPS-injected rats in vivo. iNOS mRNA increased rapidly in the lung and spleen, reached a maximum 2-6 h after the LPS treatment, and decreased thereafter. Arginase I mRNA was induced markedly and more slowly in both tissues, reaching a maximum in 12 h. Thus, arginase I appears to have an important role in down-regulating nitric oxide synthesis in murine macrophages by decreasing the availability of arginine, and the induction of arginase I is mediated by C/EBPbeta.

Animals↗
PubMed1997

Hyperdiploid myeloma cell as an indicator of poor prognosis and drug refractoriness.

Although almost 40% of patients with multiple myeloma respond to initial chemotherapy, myeloma with no response to initial chemotherapy remains a serious problem. To understand the characteristics of drug-refractoriness of myeloma, fresh tumor cells from 13 untreated myeloma patients were fixed and stained with anti-human immunoglobulins and propidium iodide for subsequent flow cytometric analysis of DNA content. More than 10% of myeloma cells were hyperdiploid in eight cases (hyperdiploid + cases) while less than 10% of myeloma cells were hyperdiploid in five cases (hyperdiploid - cases). The proportion of hyperdiploid cells among all myeloma cells was highly correlated with incidence of myeloma cells with morphologically abnormal nuclei such as those with multiple-nuclei or convoluted nuclei (P = 0.001). Among the eight hyperdiploid + cases, two (2/8) showed good response to subsequent chemotherapy while four of five hyperdiploid - cases (4/5) responded well. Cases with poor response had more hyperdiploid myeloma cells (average 25.7% of all myeloma cells) than sensitive cases (average 6.8%), suggesting a contribution of hyperdiploid myeloma cells to primary drug resistance (P = 0.065). The 3 year survival rate of hyperdiploid+cases was 0% while that of the control group was 41.9%. These results suggest that myeloma cells with abnormal nuclear morphology may show hyperdiploidy and poor response to chemotherapy.

Adult↗
PubMed1997

Acetylcholinesterase (ACE) staining shows the abnormal innervation of a pulled-through rectum in a case of repaired anorectal malformation.

Abnormal innervation of the anorectum was noted in relation to anal incontinence in a case of repaired high-type anorectal malformation (ARM). A ten-year-old boy presented with anal incontinence after reconstructive surgery of ARM with a recto-urethral fistula. An anorectal manometrical examination revealed both an adequate tonus of the anal sphincter muscles and the absence of rectoanal reflex relaxation. And a barium enema showed a narrow region in the rectosigmoid colon, which was similar to that of Hirschsprung's disease (HD). Furthermore, an acetylcholinesterase (ACE) histochemical study of the rectal suction biopsies revealed an increased number of ACE-positive nerve fibers in the lamina propria mucosae and muscularis mucosae of the pulled-through colon. At the same time, however, some ganglia cells were also observed in the submucosa of the affected rectosigmoid colon and these cells could not be found in HD. Although the mechanism by which the abnormally innervated parasympathetic nerve fibers arose in the pulled-through colon remains unclear, this neuronal abnormality is considered to be the cause of anal incontinence in this case.

Acetylcholinesterase↗
PubMed1996

Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line.

Arginase exists in two isoforms. Liver-type arginase (arginase I) is expressed almost exclusively in the liver and catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase II) is expressed in extrahepatic tissues. Arginase II has been proposed to play a role in down-regulation of nitric oxide synthesis. A cDNA for human arginase II was isolated. A polypeptide of 354 amino acid residues including the putative NH2-terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. The arginase II precursor synthesized in vitro was imported into isolated mitochondria and proteolytically processed. mRNA for human arginase II was present in the kidney and other tissues, but was not detected in the liver. Arginase II mRNA was coinduced with nitric oxide synthase mRNA in murine macrophage-like RAW 264.7 cells by lipopolysaccharide. This induction was enhanced by dexamethasone and dibutyryl cAMP, and was prevented by interferon-gamma. Possible roles of arginase II in NO synthesis are discussed.

Amino Acid Sequence↗
PubMed1996

Coinduction of nitric oxide synthase, argininosuccinate synthetase, and argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot, and immunohistochemical analyses.

Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS), and citrulline which is generated can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). Rats were injected with bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of NOS (iNOS), AS, and AL was analyzed. In RNA blot analysis, iNOS mRNA was undetectable before the LPS treatment but was induced by LPS in the lung, heart, liver, and spleen, and less strongly in the skeletal muscle and testis. AS mRNA was induced in the lung and spleen, and AL mRNA was weakly induced in these tissues. AS and AL mRNAs were abundant in the control liver and remained unchanged after the treatment. Kinetic studies showed that iNOS mRNA increased rapidly in both spleen and lung, reached a maximum 2-5 h after the treatment, and decreased thereafter. On the other hand, AS mRNA increased more slowly and reached a maximum in 6-12 h (by about 10-fold in the spleen and 2-fold in the lung). AL mRNA in the spleen and lung increased slowly and remained high up to 24 h. In immunoblot analysis, increase of iNOS protein was evident in the lung, liver, and spleen, and there was an increase of AS protein in the lung and spleen. In immunohistochemical analysis, macrophages in the spleen that were negative for iNOS and AS before LPS treatment were strongly positive for both iNOS and AS after this treatment. As iNOS, AS, and AL were coinduced in rat tissues and cells, citrulline-arginine recycling seems to be important in NO synthesis under the conditions of stimulation.

Animals↗
PubMed1996

Aggressive CD5-positive diffuse large B cell lymphoma showing c-myc rearrangements developed in a patient with autoimmune hemolytic anemia.

A case of CD5-positive diffuse large cell lymphoma in a patient with autoimmune hemolytic anemia (AIHA) is reported. The patient was diagnosed with AIHA in December 1988. Three and a half years later, the patient complained of fever and left sided flank pain. Abnormal lymphocytes appeared in the peripheral blood and were positive for HLA-DR, CD5, CD19, CD20, and surface immunoglobulin (mu, lambda). The pathological diagnosis of the cervical lymphnode was non-Hodgkin lymphoma; diffuse large cell type with a starry sky-like appearance. Although the 8q24 translocation was not detected by karyotypic analysis of the peripheral blood mononuclear cells (PBMNC), Southern blot analysis revealed that the c-myc rearrangements had occurred. This case showed two rearranged bands with Eco RI, Bam HI, or Bgl II digestion, and a germline band with Hin dIII digestion using a second exon fragment of the c-myc gene as a probe. Despite intensive chemotherapy, this patient died 6 months after being diagnosed with malignant lymphoma. We discuss the c-myc rearrangements in this aggressive CD5-positive diffuse large B cell lymphoma.

Anemia, Hemolytic, Autoimmune↗