Search PubMedSearch

Biomedical subjects

H Maruyama

Publications and source records attributed to H Maruyama.

At least 19 recordsLinked to original sources

Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases.

A cDNA encoding a novel rat mast-cell proteinase (MCP) named rMCP-3 was successfully cloned and sequenced from the peritoneal cells of Lewis rats infected with the intestinal nematode Nippostrongylus brasiliensis by using the combination of reverse transcription-PCR and rapid-amplification-of-cDNA-ends ('RACE') methods. The cDNA was 979 bp long and included a 741 bp open reading frame. When the deduced amino acid sequence was compared with those of other known mast-cell proteinases, rMCP-3 was considered to be translated as a preproenzyme with a 19-amino-acid signal peptide, a two-amino-acid activation peptide and a 226-amino-acid mature enzyme. The amino acid identity in the mature enzyme was 52.9% and 55.1% with rMCP-1 and rMCP-2 respectively. The rMCP-3 mRNA was not detected in the peritoneal cells of mast-cell-deficient Ws/Ws rats, though it was strongly detected in those of littermate +/+ and Lewis rats, indicating the mast-cell origin of rMCP-3 In addition to being present in peritoneal mast cells, the rMCP-3 mRNA was strongly detected in the skin, tongue, and RBL2H3 rat basophilic leukaemia cells and weakly in the jejunum of N. brasiliensis-infected rats by RNA blot analysis using a rMCP-3 gene-specific probe. By reverse transcription-PCR, the rMCP-3 mRNA was also detected in the lung. While the expression of rMCP-1 and rMCP-2 are clearly restricted in connective-tissue mast cells and mucosal mast cells respectively, rMCP-3 was widely expressed in both types of mast cells with a predominance in connective-tissue mast cells.

Amino Acid Sequence

Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease.

We observed the sequential changes in serum thyroid hormones and thyroid-stimulating hormone receptor antibodies in an infant born at 30 weeks of gestation to a mother with florid Graves disease. Transient central hypothyroidism caused by pituitary suppression was observed after the resolution of peripheral thyrotoxicosis induced by thyroid-stimulating antibody. Central hypothyroidism became overt when the suppression of the pituitary gland after fetal thyrotoxicosis was combined with weak activity of thyroid-stimulating antibody after birth.

Adult

[A case of multiple sclerosis associated with lateralization of bone change].

We report a 63-year-old female, case of multiple sclerosis associated with lateralization of bone change. In 1969, at age 38 she lost sight in her right eye. After that, she had several episodes of remission and exacerbation. In 1992, left hemiparesis, sensory disturbance and vesicorectal disturbance appeared, and she was admitted to our hospital. Immediately, steroid pulse-therapy was initiated then steroids were tapered. Her muscle strength recovered to some degree. The left upper limb showed low skin temperature, edema and decreased circulation. In January and September of 1993, bone examinations were conducted using multiple scanning X-ray photodensitometry. Osteopenia was observed, especially in the left hand. The bone density in the right hand changed slightly during the 8-month course of the illness, but osteopenia in the left hand became more marked. The asymmetrical bone change suggested that osteopenia results from a disorder of the central nervous system, especially through autonomic disorder.

Bone Density

Polyclonal antiidiotypic antibodies mimicking gp120 of HIV-1.

Rabbit antiidiotypic antibodies (Ab2) were produced against anti-HIV-1 antibody 0.5 beta (Ab1), which binds to gp120 of HIV-1 and shows virus-neutralizing activity. The Ab2 bound specifically to the Ab1 and their binding to Ab2 was inhibited by a recombinant fragment of gp120 (PB1) or a peptide (residues 301-324 of gp120), both expressing the Ab1-defined epitope. The Ab2 induced in rats antiantiidiotypic antibodies (Ab3) that were Ab1-like in their binding reactivities to PB1, native gp120 or peptide and shared idiotopes with the Ab1. However, the Ab2 did not induce virus-neutralizing Ab3, probably a reflection of the low avidity of the Ab3 as compared to the Ab1.

Animals

Monoclonal anti-idiotypic antibodies that mimic the epitope on gp120 defined by anti-HIV-1 monoclonal antibody 0.5 beta.

OBJECTIVE: To develop effective, specific and safe anti-idiotypic antibody (Ab2) vaccines against HIV-1. DESIGN: Murine monoclonal Ab2 were generated against anti-HIV-1 antibody 0.5 beta (Ab1), which binds to gp120, neutralizes HIV-1 and inhibits virus-induced syncytia formation. METHODS: Mice were immunized with Ab1, and Ab2 were produced from immunized mice by the hybridoma technique. The Ab2 were characterized in vitro, injected into rabbits, and the anti-anti-idiotypes (Ab3) induced in the rabbits were analyzed for binding and antiviral reactivities by enzyme-linked immunosorbent assay, p24gag release and syncytia formation assays. RESULTS: Seven Ab2 bound to the antigen-combining site of Ab1, one of which (UD7) induced Ab3 in rabbits that were Ab1-like in their binding reactivities to PB1 (recombinant gp120 fragment) or peptides of gp120, and shared idiotypes with the Ab1. Crude Ab3-containing sera specifically and effectively neutralized the virus. CONCLUSION: Monoclonal Ab2 UD7 has potential as a vaccine against HIV-1.

AIDS Vaccines

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

Amino Acids

Molecular cloning of murine monoclonal anti-idiotypic Fab.

Anti-idiotypic antibodies (Ab2) binding to idiotopes on antibodies with various antigen binding specificities (Ab1) are potential regulators of immunity in a variety of diseases, such as autoimmunity, cancer, and viral, bacterial, or parasitic infections. Furthermore, Ab2 are useful probes for the characterization of receptor/ligand interactions. Thus far, Ab2 production has been limited to the isolation of polyclonal Ab2 from immune sera or monoclonal Ab2 from hybridoma supernatants. However, both approaches have produced a limited number of Ab2. As an alternative approach, we demonstrate here the production of Ab2-Fab by using repertoire cloning. Using HIV-1 as a model system, the Ab2-Fab were generated from the spleens of mice immunized with the virus-neutralizing and syncytia-inhibiting anti-HIV-1 monoclonal antibody 0.5 beta. A bacteriophage lambda vector system was used to express a combinatorial library in Escherichia coli. Iodinated 0.5 beta was used to identify 17 Ab2-Fab clones. DNA sequence analysis of five clones revealed three similar kappa and Fd combinations. The Ab2-Fab bound with high affinity (3.5-6.5 x 10(9) liters/mol) specifically to the Ab1 and not to isotype-matched antibodies with unrelated specificities. The three Ab2-Fab probably bind to the same idiotope on the Ab1 as demonstrated in cross-competition binding studies. The Ab2-Fab inhibited binding of the Ab1 to antigen, and therefore, may functionally mimic the epitope defined by the Ab1. Repertoire cloning of Ab2-Fab may facilitate the generation of Ab2 that have potential as modulators of immune responses against various antigens.

Amino Acid Sequence

Lack of modifying effects of 6-mercaptopurine in a medium term bioassay system for liver carcinogenesis using male F344 rats.

Carcinogenic and modification potential of 6-mercaptopurine (6-MP) was studied in a medium-term bioassay system for rat liver carcinogenesis. F344 male rats were initiated with a single dose (200 mg/kg body wt.) of diethylnitrosamine (DEN) i.p. and fed diets containing either 0.005% or 0.02% 6-MP with or without 0.05% phenobarbital (PB) for 6 weeks. Quantitative data revealed that 6-MP did not enhance the appearance of enzyme-altered preneoplastic foci and nodules even when administered at the highest dose (0.02%) despite showing an immunosuppressive effect and slight liver cell damage. Neither of the doses of 6-MP exerted any significant influence on the enhancing effect of PB when administered simultaneously in the medium-term-bioassay.

Animals

Multiple colorectal carcinomas and colorectal carcinoma associated with extracolonic malignancies.

In this study, we analyzed 149 surgical cases of colorectal cancer between January 1983 and August 1989. Thirteen cases (8.7 percent) of colorectal primary cancer associated with extracolonic primary malignancy of 14 lesions and 10 cases (6.7 percent) of multiple primary colorectal cancers were included. Among the 14 lesions of extracolonic primary malignancy, there were 6 gastric carcinomas, 2 endometrial carcinomas, 2 urinary bladder carcinomas, and one each in the esophagus, liver, bile duct and jejunum. The second tumor was not detected preoperatively in 3 of 4 cases of synchronous multiple primary colorectal carcinoma. A curative resection was done in 10 (77 percent) out of 13 cases of colorectal cancer associated with extracolonic malignancy, while 7 (88 percent) out of 8 cases of multiple colorectal cancers had a curative resection. Nine patients (69 percent) with colorectal cancer associated with extracolonic malignancy were disease-free for 2 months to 14 years. Seven patients (88 percent) with multiple colorectal cancers were disease-free for one to 22 years. We recommend, therefore, that in any patient with colorectal cancer, the entire large bowel should be thoroughly searched for any other primary tumors, by taking the existence of extracolonic tumors into account. A curative resection should be performed, and the follow-up period should be life-long.

Adenocarcinoma

Focal nodular hyperplasia of the liver.

We present herein two successfully treated cases of focal nodular hyperplasia (FNH) of the liver, a relatively rare disease. Case 1 was a 3 year old child in whom typical FNH developed in the left lateral segment of the liver, whereas Case 2 was a 22 year old man in whom characteristic findings were lacking on preoperative diagnostic imaging. Scintigraphy was not performed in either case, however, postoperative histological examination confirmed FNH. Thus, in patients with a hypervascular tumor and normal liver function, FNH should be strongly suspected and a series of scintigraphy proposed. Both cases showed a negative association with oral contraceptive intake but no other obvious etiology was suggested.

Adult

Efficacy of combination treatment--(TAE with adriamycin and ethanol)--for hepatocellular carcinoma.

Among 44 patients with hepatocellular carcinoma (HCC), combination treatment with both transhepatic arterial embolization (TAE) and ethanol injection therapy (EIT) was performed in 10 patients. Only two had tumors measuring less than 3 cm in diameter. In all, eight patients had solitary tumors and two had multiple tumors. The tumor was classified as stage I in one patient, stage II in six subjects, stage III in two patients, and stage IV in one subject prior to TAE, but one stage II case was changed to stage III after laparotomy. The clinical stage was I in two patients, II in six subjects and III in two patients. Five patients with tumors of stages I and II achieved either a complete response (CR) or partial response (PR). However, three patients with tumors of stages III and IV showed progressive disease (PD). Thus, the response rate (CR+PR) was 50%. For tumor stages I and II, the 1-, 2-, and 3-year survival values were 100%, 100%, and 83%, respectively. For tumor stages III and IV, the 1- and 2-year survival values were 75% and 25%, respectively. Combination treatment of HCC appears to be efficacious for tumor stages I and II.

Adult

Split notochord syndrome in an adult presenting with colonic duplication. Report of a case.

A case of tubular colonic duplication, sigmoid colon diverticulum, and lumbar anterior spina bifida in a 28-year-old man was diagnosed as split notochord syndrome. After subtotal colectomy, including the duplicated colon, the patient recovered. Histologic study of the duplicated colon revealed multifocal, ectopic gastric fundic mucosa in a mosaic pattern. Since bleeding and perforation occur most frequently in conjunction with ectopic gastric mucosa within the duplication, we believe that complete resection of the duplicated bowel is the best procedure. Split notochord syndrome is a rare congenital anomaly. It is usually discovered in the first year of life, and the majority of reported cases have involved the cervical or thoracic region. Our patient is exceptional in having reached the age of 28 years without complaints and in that his case involved lumbar anterior spina bifida and tubular colonic duplication.

Adult

Arachidonic acid metabolites and alpha 2-adrenoceptor-mediated glucagon secretion in rats.

Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the alpha 2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50 mumol/l significantly inhibited glucagon secretion induced by 0.1 mumol/l clonidine (P less than 0.01, respectively), whereas 5 mumol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 mumol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100 mumol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P less than 0.01, respectively), whereas neither 10 mumol/l acetylsalicylic acid nor 10 mumol/l caffeic acid affected clonidine-induced glucagon secretion. None of the drugs at the tested concentrations affected insulin secretion at a glucose concentration of 5.5 mmol/l. These results suggest that not only cyclooxygenase metabolites but also lipoxygenase metabolites are involved in the stimulation of glucagon secretion mediated through the alpha 2-adrenergic receptors in perfused rat pancreas.

Animals

Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP) on focal lesion development in cirrhotic liver induced by carbon tetrachloride but not furfural in F344 rats.

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.

Alkaline Phosphatase

T-cell-dependent production of IgG by human cord blood B cells in reconstituted SCID mice.

Reconstitution of severe combined immunodeficient (SCID) mice with human lymphocytes has recently allowed the elucidation of abnormalities of immune responses in various immunological disorders. In the present study, mononuclear cells (MNC) from neonatal cord blood and adult peripheral blood were intraperitoneally injected into SCID mice to examine induction of human Ig in respective mice recipients. Human IgG was consistently detected in the serum of SCID transferred with adult MNC, but only a few SCID recipients of cord blood MNC showed detectable but low levels of IgG in the serum. The combination experiments of isolated B and T cells disclosed that some interactions between B and T cells might be necessary for IgG production in transferred SCID mice. Notably, transfer of cord blood B cells with adult but not cord blood T cells resulted in efficient induction of IgG, associated with a change in subclass distribution. The results suggest that inability of neonatal B cells to produce IgG can be overcome by transfer with adult mature T cells into SCID mice.

Animals