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Biomedical subjects

A Nakayama

Publications and source records attributed to A Nakayama.

At least 19 recordsLinked to original sources

Expression of HLA-DR in intrahepatic cholangiocarcinoma.

Expression of HLA-DR was investigated immunohistochemically in 20 cases of intrahepatic cholangiocarcinoma, as well as 9 normal livers that had been obtained at autopsy. Five of the nine normal livers had peribiliary glands that showed HLA-DR. Positive staining for HLA-DR on tumor cells was observed in 6 of 13 cases of cholangiocarcinoma of the hepatic hilus and in only 1 of 7 cases of peripheral cholangiocellular carcinoma. In cholangiocarcinomas of the hepatic hilus, the 5-year survival rate for tumors that had positive staining for HLA-DR was better than that for tumors that had negative staining. Based on these results, the presence or absence of HLA-DR on tumor cells could have a pathologic significance for intrahepatic cholangiocarcinoma.

Adenoma, Bile Duct

The effect of a multiple literature database search--a numerical evaluation in the domain of Japanese life science.

In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.

Biological Science Disciplines

Immunocytochemical observation of paraquat-induced alveolitis with special reference to class II MHC antigens.

The expression of class II major histocompatibility complex (MHC) antigens on alveolar epithelial cells and macrophages was investigated immunocytochemically in paraquat-induced alveolitis in the rat lung. Until 2 days after paraquat injection, class II MHC antigens were expressed on the type II alveolar epithelium without any inflammatory cellular infiltration. From the 4th to the 7th day after paraquat injection, class II MHC antigen-positive macrophages increased in the alveolar spaces, whereas the expression on the type II alveolar epithelium became obscure. Over 10 days after the injection, interstitial fibrosis progressed and the intra-alveolar inflammatory infiltrates decreased. Epithelial cells lining the thickened fibrous septa no longer expressed class II MHC antigens. These results suggest that chemical stimuli can induce class II MHC antigen expression on the type II alveolar epithelium in the early stage of cellular injury, followed by inflammatory infiltration and interstitial fibrosis.

Alveolitis, Extrinsic Allergic

Secretion of correctly processed and folded pancreatic secretory trypsin inhibitor by Bacillus subtilis.

We constructed a plasmid, designated pNPP126, containing a DNA sequence encoding a fusion protein composed of Bacillus amyloliquefaciens neutral protease prepeptide (signal peptide) and human pancreatic secretory trypsin inhibitor (hPSTI), where the mature hPSTI is accurately fused to the 3'-terminal of the prepeptide coding region. It was observed that the strain Bacillus subtilis MT600 harboring pNPP126 could secrete a trypsin inhibitory activity into the culture medium. The N-terminal amino acid sequence, the amino acid composition and the stoichiometry of the purified hPSTI produced by B. subtilis were the same as those of natural hPSTI, indicating that the transformant B. subtilis MT600 (pNPP126) could efficiently secrete the correctly processed and folded hPSTI into the culture medium.

Bacillus subtilis

Processing of the prepropeptide portions of the Bacillus amyloliquefaciens neutral protease fused to Bacillus subtilis alpha-amylase and human growth hormone during secretion in Bacillus subtilis.

A set of nested 3'-terminal deletions of the prepropeptide of the Bacillus amyloliquefaciens neutral protease gene was constructed. Alpha-amylase and human growth hormone were secreted using these truncated genes in Bacillus subtilis. The level of the secreted alpha-amylase varied with the region for the truncated prepropeptide contained in the fusion gene but was independent of its length. Even though length of the prepropeptide varied, the mobilities of secreted alpha-amylases were the same as that of the control alpha-amylase derived from the alpha-amylase clone, pTUB4 (Yamazaki et al., 1983). Analyses of the secreted N-terminal amino acid sequences confirmed that they were all identical to that of the authentic one. Precursor proteins of the alpha-amylase were found in the cell-associated fraction, suggesting that the prepropeptide portion was processed during secretion. On the other hand, the N-terminus of hGH secreted using one of these prepropeptide portions varied by 1 to 4 additional N-terminal amino acid residues derived from the junction sequence between the sequence for propeptide portion and mature hGH or from C-terminal region of the propeptide portion. These results suggest that the prepropeptide portion can be generally processed even in the heterogeneous fusion. A probable mechanism of processing and maturation of the fusion gene products is also discussed.

Amino Acid Sequence

Characterization of antibody responses of local lymph nodes to antigen given under the oral submucosa.

We studied the function of submandibular lymph nodes (MLN) in the oral mucosa immune system as compared with that of inguinal lymph nodes (ILN) in the cutaneous one. Primary IgM, IgG and IgA antibody responses in MLN to sheep red blood cells (SRBC) as a model antigen given submucosally occurred more extensively than those in ILN to the antigen injected subcutaneously. Particularly, definite IgA synthesis was seen in MLN but not in ILN. This IgA synthesis was shown to be originated locally in oral submucosal lymphoid tissue or MLN but not in gut-associated lymphoid tissue (GALT). This suggested that the oral mucosal tissue including MLN acts like Peyer's patches in GALT for IgA synthesis. When mice were administered with SRBC and bacterial lipopolysaccharide (LPS) submucosally, the adjuvant effect of LPS was only observed on the capacity of MLN cells for secondary antibody response in vitro. This contrasted to the marked augmentation by LPS of both the primary antibody response in ILN and capacity for in vitro secondary antibody response of ILN cells of mice given SRBC and LPS subcutaneously. The radioactivities detected in the local lymph nodes and other tissues of mice given 51Cr labeled SRBC submucosally or subcutaneously were comparable with each other. MLN, however, contained more Ig+/B220+ B cells and less Thy1+/Ly-1+ T cells than ILN did, and the L3T4/Ly-2 ratio of T cell subpopulations in MLN was lower than that in ILN. Partially corresponding to this observation, the B cell-dependent area was developed more extensively in MLN than in ILN. This difference in cellular composition and organization might in part explain the reason why MLN and ILN display distinct modes of response and sensitivity to the action of LPS.

Animals

Induction of irreversible glomerulosclerosis in the rat by repeated injections of a monoclonal anti-Thy-1.1 antibody.

The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity-purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis.

Animals

[Mammalian toxicity of empenthrin (Vaporthrin, S-2852F)].

1. Acute toxicity: Empenthrin ((RS)-(EZ)-1-ethynyl-2-methyl-2-pentenyl (1R)-cis/trans-chrysanthemate) caused some toxic signs such as muscular fibrillation, tremor, hypersensitivity, decrease of spontaneous activity, ataxic gait, lymb paralysis, irregular respiration, excretion of oily substance, loose stool and urinary incontinence in oral acute toxicity studies at 1000 mg/kg and above in rats, and at 2000 mg/kg and above in mice. The oral LD50 value was estimated greater than 5000 mg/kg (male) and greater than 3500 mg/kg (female) in rats and greater than 3500 mg/kg (both sexes) in mice. In both rats and mice, the toxic signs were not found at 2000 mg/kg by dermal administration. The dermal LD50 value was estimated greater than 2000 mg/kg (both sexes) in both rats and mice. The LC50 value in rats for the acute inhalation toxicity of empenthrin was estimated to be greater than 4610 mg/m3 for both sexes. The LC50 value in mice was determined to be 2700 mg/m3 for male and 2300 mg/m3 for female. Mice showed higher sensitivity to empenthrin than rats. 2. Reproductive and developmental toxicity: Empenthrin was orally administered to fetal organogenesis periods of rats at the dose levels of 50, 150 and 500 mg/kg, and of rabbits at 100, 300 and 1000mg/kg. Maternal toxicity was found at 500 mg/kg in rats and at 300 mg/kg or more in rabbits. There were no teratogenicity, no embryotoxicity and no fetal retardation in rats or rabbits. In addition, there were no adverse effects on F1 pups growth, development or reproductive performance. 3. Subchronic toxicity: Empenthrin was orally administered to male and female SD rats at dose levels of 0 (corn oil), 10, 100 and 300 mg/kg for 26 weeks. Clinical signs, body weight, food and water consumption were monitered, and hematological, blood biochemical, ophthalmological and histopathological examination were carried out. As a result, changes related to administration of empenthrin were observed mainly in the liver and kidneys in rats receiving 100 mg/kg or more. Therefore, the no-effect-level of empenthrin is determined to be 10 mg/kg in both sexes of rats in this study.

Administration, Oral

Establishment and characterization of a malignant melanocytic tumor cell line expressing the ret oncogene.

We established a cell line (designated Mel-ret) from a melanocytic tumor developed in a metallothionein/ret transgenic mouse. Unlike primary melanocytic tumors, which did not show malignant features, when the Mel-ret cells were transplanted into nude mice they invaded into surrounding tissues and had metastatic ability. Although the Ret proteins were expressed at similar levels in the cell line and the primary tumors, the level of tyrosine phosphorylation in the Mel-ret cells was much higher than that in the primary tumors. In particular, an 85-kDa tyrosine-phosphorylated band was specifically detected in the Mel-ret cells. These results suggest that the increase in tyrosine phosphorylation may be responsible for malignant transformation of the Mel-ret cells. Immunofluorescence and cell fractionation studies showed that the Ret proteins and most of tyrosine-phosphorylated proteins in the Mel-ret cells localized in the membrane fraction. No activation of phosphatidyl-inositol-3 kinase (PI-3 kinase), a target protein for several tyrosine kinases, was detected in the Mel-ret cells.

Animals

Increment of alpha B-crystallin mRNA in the brain of patient with infantile type Alexander's disease.

To estimate the expression level of alpha B-crystallin in the brain of infantile type Alexander's disease, the amounts of protein and mRNA of alpha B-crystallin were measured by enzyme immunoassay (EIA) and Northern blot analysis, respectively, in the brain of patient and controls, and in the tissues from glioblastoma and astrocytoma. The alpha B-crystallin protein in the brain of patient was remarkably increased as compared with those of controls. The amount of alpha B-crystallin mRNA of patient was increased about 7-fold compared to the mean value of the control group and higher than that of glioblastoma tissue. These data suggest that increment of alpha B-crystallin mRNA in astrocytes leads to the overexpression of this protein and may be one of the main causes of infantile type Alexander's disease.

Adolescent

Lack of a requirement for strict rotational alignment among transcription factor binding sites in yeast.

The MF alpha 1 gene of Saccharomyces cerevisiae is an alpha specific gene whose expression is regulated by two upstream activation sites (UASMF alpha 1S), which are the binding sites for activator proteins, MAT alpha 1 and MCM1. UASMF alpha 1 elements act in a synergistic fashion; lack of either element causes reduced expression levels that are 6- to 45-fold less than that of intact promoter in alpha cells. We investigated the effect of manipulating rotational alignments among transcription factor binding sites of MF alpha 1 on the expression of the gene. The expression level of MF alpha 1 decreased with the spacing between the two UASMF alpha 1S and no synergism was observed when the distance of the two elements was longer than 90 base pairs. No strict rotational alignment was required for their synergistic action. We also show that the spacing between UASMF alpha 1 elements and TFIID binding site, the TATA box, had little, if any, effect on MF alpha 1 expression. We chose a sufficient number of positions for UASMF alpha 1S to ensure that, in several of these positions, MAT alpha 1 and MCM1 were on the opposite side of the DNA helix with respect to the TATA box.

Base Sequence

Necrotizing tubulointerstitial nephritis associated with adenovirus infection.

We report 10 autopsy cases of necrotizing tubulointerstitial nephritis induced by adenovirus (ADV). Hemorrhagic, necrotizing tubulitis with intranuclear inclusion bodies was observed in the kidneys of five bone marrow transplant recipients and five patients treated with intensive chemotherapy for malignancies (four cases of leukemia and one case of lung cancer). It was histopathologically demonstrated that necrobiotic tubular cells had inclusion-bearing cells of three types: "smudge cells," Cowdry A intranuclear inclusion cells, and full-type intranuclear-containing cells. Immunofluorescent examination with anti-ADV antibody demonstrated specific fluorescence on the affected tubular cells of all 10 kidneys. Specific antigens for ADV type 11 were also revealed in all but one case by an immunofluorescent test using type-specific antiserum and convalescent serum containing high titer antibody to this serotype. Electron microscopy revealed intranuclear crystalline arrays of viral particles, 75 to 80 nm in diameter, in each of the seven cases examined. Extrarenal involvement, indicated by ADV-induced cytopathologic change, was confined to bladder or prostate. Hemorrhagic cystitis was recorded in all the bone marrow transplant cases as well as in one leukemia case. Adenovirus type 11 was isolated from urine in all five cases tested during these episodes. Renal failure was ascribed to ADV infection in two of five patients who died from renal dysfunction. The presence of hemorrhagic cystitis and localization of invasive infection in urogenital organs suggested that renal infection might occur by ascending route from the bladder. We propose that ADV should be added as a viral agent to the pathogenetic list of tubulointerstitial nephritis.

Adenoviridae Infections

Pure apocrine nevus. A study of light-microscopic and immunohistochemical features of a rare tumor.

The pure apocrine nevus is a rare tumor. A new case of pure apocrine nevi of the bilateral axillary regions in a 48-year-old man is herein reported. The patient had two soft masses of both axillae. The time of onset of the masses was unknown. They were not accompanied by problems of sweating. Histologically, these lesions comprised numerous apocrine glands extending from the reticular layer of the dermis to the subcutaneous tissue. In addition, sections from both of the lesions were stained by immunoperoxidase techniques for the presence of epithelial membrane antigen, carcinoembryonic antigen, and the alpha and beta subunits of S100 protein. Immunohistochemical features of the tumor stained by these antibodies are consistent with a pure proliferation of mature, well-differentiated apocrine glands. The tumor of the present case seems to have developed spontaneously. It is believed, therefore, that the tumor seen in this patient is best categorized as a pure apocrine nevus.

Antigens, Neoplasm

Undifferentiated carcinoma of the parotid gland in a 10-month-old child.

Malignant salivary gland tumors in children are very rare. This report describes the autopsy of a child with parotid gland cancer. The patient, a 10-month-old girl, was admitted to the Nagoya First Red Cross Hospital with facial nerve palsy. Incisional biopsy of a post-auricular tumor was performed, and undifferentiated carcinoma was diagnosed. The patient died 6 months later of respiratory failure due to pulmonary lymphangitis carcinomatosis. Light and electron microscopic and immunohistochemical examinations of the tumor tissue were performed. The tumor cells were arranged in a medullary, sheet-like manner. Keratinization or mucus lakes were not observed. PAS-alcian blue staining demonstrated intracytoplasmic mucus as granules, and also small intercellular droplets of mucus that might otherwise have been unnoticed. Ultrastructurally, some of the tumor cells had tonofilament-like keratin filaments, and also small hollow spaces bounded by microvilli and containing secretory particles. These were stained by antisera against CEA and keratin. These findings are suggestive of differentiation to mucoepidermoid carcinoma. We also review and discuss malignant salivary tumors of epithelial origin in children.

Carcinoma

A novel Bacillus subtilis gene involved in negative control of sporulation and degradative-enzyme production.

We have cloned a 2.5-kilobase fragment of the Bacillus subtilis genomic DNA which caused the reduction of extracellular and cell-associated protease levels when present in high copy number. This fragment, in multicopy, was also responsible for reduced levels of alpha-amylase, levansucrase, alkaline phosphatase, and sporulation inhibition. The gene relevant to this pleiotropic phenotype is referred to as pai. By DNA sequencing, two open reading frames--ORF1 and ORF2, encoding polypeptides of 172 and 207 amino acid residues, respectively--were found. These open reading frames seemed to form an operon. Deletion analysis revealed that an entire region for ORF1 and ORF2 was necessary for the pai phenotype. In addition, it was observed that the presence of the pai gene, in multicopy, caused overproduction of two proteins (molecular masses, 21 and 24 kilodaltons [kDa]). Analyses of the N-terminal amino acid sequences of these two proteins suggested that they were products of ORF1 and ORF2. Disruption of the pai gene at ORF1 in the genomic DNA resulted in the release of repression on protease synthesis and sporulation in glucose-enriched (2%) medium. The mutant carrying insertional disruption at ORF2 could not be constructed, suggesting that the ORF2 product, the 24-kDa protein, is essential for growth. The 21-kDa protein contains a helix-turn-helix domain observed in other DNA-binding proteins. Chromosomal mapping of pai indicated that this gene is located close to thr-5. These results suggest that the pai gene is a novel transcriptional-regulation gene involved in glucose repression.

Alkaline Phosphatase

[A progressive gastric cancer in which preoperative oral chemotherapy resulted in a histopathological "Grade 2" rating].

This paper describes a case of a Borrmann type 3 gastric cancer, in which the preoperative intermittent oral administration of 5'-DFUR over a short term resulted in a histopathological rating of Grade 2. A 56-year-old man preoperatively received an intermittent, oral administration of 5'-DFUR, 2, 100 mg/day. An upper gastrointestinal series and endoscopy revealed macroscopically an extremely slight remission. Histopathologically, however, a widespread, remarkable degeneration of cancer cells and fibrinogenesis of the framework were observed, these results leading to a change of rating to Grade 2.

Adenocarcinoma

[Treatment of paroxysmal nocturnal hemoglobinuria with danazol].

Glucocorticoid and androgen therapy have been used with moderate success in paroxysmal nocturnal hemoglobinuria (PNH). However, both are poorly tolerated, especially in women, although the side effects of glucocorticoid can be diminished by alternate day therapy. We have treated two patients with PNH with danazol. One of patient is man, 64 years old age with stomach cancer, and the other patient is 34-year-old man. Their disease has existed for 6-14 years. They required many blood transfusions, their hemoglobins ranging between 7.1 and 9.9 grams per deciliter. When treated with danazol by mouth, the hemoglobin level increased approximately 2 to 5 grams in each patient within 3 week, and clinical hemoglobinuria improved. None of the patients has had any side effects.

Adult