A transmembrane protein specifically expressed in zona glomerulosa.
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Animals↗
Biomedical subjects
H Takemori
Publications and source records attributed to H Takemori.
Cytochrome P450(11 beta): ectopic expression in oocyte and its physiological implication.
Cytochrome P450(11 beta) (steroid 11 beta-hydroxylase) catalyzes an essential step for biosynthesis of glucocorticoid as well as mineralocorticoid, and therefore is believed to exist specifically in the adrenocortical mitochondria. We previously isolated a complementary DNA clone encoding this enzyme from bullfrog (Rana catesbeiana) adrenal tissues and characterized the enzyme expressed in COS cells. To explore the tissue distribution of the enzyme we performed Northern blot analysis. Unexpectedly we found that a large amount of the mRNA exists in the ovary as well as the adrenal gland. It was present in oocytes, but not in follicular cells. The P450 protein was not found during early stages of oocyte development, and at the final stage of maturation the message appeared to be translated. Evidence was obtained that the stage-dependent translation of the mRNA was due to the regulated polyadenylation at its 3'-end. In oocytes of various organisms several maternal mRNAs are known to add poly(A) tails in the cytoplasm during the progesterone-induced maturation.
Adrenal Glands↗
Compensatory enlargement of angiographically normal coronary segments in patients with coronary artery disease. In vivo documentation using intravascular ultrasound.
Intravascular ultrasound (IVUS) frequently reveals plaque formation at sites with a normal angiographic appearance. However, whether angiographically normal coronary arteries undergo adaptive expansion in vivo remains uncertain. The authors studied 12 patients (11 men, 1 woman; mean age fifty-three +/- ten years [mean +/- SD]) with focal coronary stenosis. Sixty IVUS images from angiographically normal coronary segments were analyzed (14 left main, 44 left anterior descending, and 2 left circumflex coronary arteries). The mean percent area stenosis was 36 +/- 5% and the circular shape factor of the lumen cross section averaged 0.97 +/- 0.02. Both total arterial area and internal elastic lamina area increased as the plaque area expanded (y = 2.13x + 8.07, r = 0.87, P = 0.0001; y = 2.06x + 4.57, r = 0.87, P = 0.0001, respectively), suggesting that for every 1 mm2 increase in plaque area, the total arterial area increased by approximately 2.13 mm2 and the internal elastic lamina area increased by approximately 2.06 mm2. The lumen area also increased as the plaque area expanded (y = 1.06x + 4.57, r = 0.68, P = 0.0001), suggesting that for every 1 mm2 increase in plaque area, the lumen area increased by approximately 1.06 mm2. The medial area did not correlate with the plaque area (r = 0.15, P = 0.26). Thus, compensatory enlargement precedes development of angiographically, detectable coronary atherosclerosis. Furthermore, in early stages of atherosclerosis, arterial enlargement may overcompensate for plaque area. The reduction of the total medial mass does not appear to contribute to the mechanism of compensatory enlargement.
Adaptation, Physiological↗
[A case of advanced esophageal cancer showing good partial response by combination therapy of low dose 5-FU and low dose CDDP].
A 66-year-old man with a complaint of dysphagia was diagnosed as advanced esophageal cancer. Barium swallow examination of the esophagus showed a narrowing 10 cm in length at Ei (type 3), and biopsy specimen from the lesion on endoscopic examination revealed adenosquamous carcinoma. Multiple lymph node metastasis were detected by CT scan. He was treated with a combination of low dose 5-fluorouracil (5-FU) and low dose cisplatin (CDDP). The regimen consisted of 5-FU (300 mg/body/day continuous infusion) and CDDP (10 mg/body/day continuous infusion) for 3 weeks. After 2 courses of this regimen, his symptoms disappeared, and only mild irregularity of the esophageal wall remained on Barium swallow examination. The effect of the therapy was evaluated as a partial response. No side effect was observed. From this case, the possibility that CDDP is able to function as a biochemical modulator for 5-FU was suggested.
Aged↗
[Chemotherapy for pancreatic cancer].
Few antitumor agents are effective for advanced pancreatic cancer. 5-fluorouracil, doxorubicin, epirubicin, and mitomycin C were tested as single agents for their respective efficacy against pancreatic cancer. Their response rates were 15, 12, 24 and 24%, respectively. Several trials of combination chemotherapy using mitomycin C, doxorubicin and 5-FU (FAM) were performed, but their response rates did not go exceed those of single agents. Recently, the goal of chemotherapy for pancreatic cancer is thought to be quality of life. Combination of 5-FU and cisplatin or 5-FU, leucovorin and alpha interferon were effective for the prolongation of life with less toxicities. Their median survival times were 7.6 months, and 22 months in PR cases, respectively. CPT-11, gemcitabine, taxotere and BOF-A2 are promising new drugs for their effectiveness and benefits for patients with pancreatic cancer. Combination of mitomycin C, carboquone and 5-FU with angiotensin II was effective in terms of antitumor effect and prolongation of life. Generally, a large number of patients with advanced pancreatic cancer cannot receive chemotherapy because of deterioration in performance status. For them, combination of continuous venous infusion of low-dose 5-FU and low-dose cisplatin could be effective. The majority of patients with pancreatic cancer must await new agents and methodology in the future.
Antineoplastic Combined Chemotherapy Protocols↗
Frog cytochrome P-450 (11 beta,aldo), a single enzyme involved in the final steps of glucocorticoid and mineralocorticoid biosynthesis.
A cDNA for cytochrome P-450(11 beta,aldo) was cloned from a library of bullfrog interrenal tissue (tissue corresponding to the mammalian adrenal gland). The 1919-bp cDNA encoded a protein of 517 amino acids. Its amino acid sequence was highly similar to the sequences of bovine P-450(11 beta) and rat P-450(11 beta,aldo) when P-450(11 beta) family enzymes reported to date were examined. The enzyme expressed in COS7 cells had the 11 beta-hydroxylation, 18-hydroxylation activities and aldosterone synthetic activity. Northern-blot and immunoblot analyses suggested that a single P-450(11 beta) enzyme was expressed in bullfrog interrenal tissue. These results suggest that a single enzyme catalyzes the final steps of glucocorticoid and mineralocorticoid biosynthesis in bullfrog interrenal tissue as in bovine adrenal gland. A phylogenetic tree of CYP11B genes suggests that the frog enzyme diverged at an earlier evolutionary time from other vertebrate enzymes. Immunohistochemical and in situ hybridization studies indicated that steroidogenic cells existed in the outer region of interrenal tissue more densely than in the inner region, whereas some medullary cells made clusters like islets. Most of the cells were diffusely distributed in the tissue.
Amino Acid Sequence↗
Cytochrome P450(11 beta): structure-function relationship of the enzyme and its involvement in blood pressure regulation.
Cytochrome P450(11 beta) is deeply involved in the final steps of biosynthesis of mineralocorticoids. This paper deals with following issues about this enzyme. (1) The structure and function of the enzymes of various animal species are discussed. By making alignment of amino acid sequences of the enzymes, we identified peptide domains essential for the enzyme actions such as a putative steroid binding domain and a heme binding region. Estimates of molecular similarity among the P450(11 beta) family enzymes suggested that the enzymes having both 11 beta-hydroxylation activity and aldosterone (ALDO) synthetic activity of certain animals such as frog, cattle and pig are more similar to the ALDO synthases of the other animals, such as rat, mouse and human, than the 11 beta-hydroxylases of these animals. (2) The molecular nature of the P450(11 beta) family enzymes of genetically hypertensive rats as well as adrenal regeneration hypertension (ARH) rats is examined. (i) Mutation was found in the P450(11 beta) gene of Dahl's salt-resistant normotensive rat. Steroidogenic activity expressed by the mutated gene accounted well for abnormal plasma levels of steroid hormones in this rat. (ii) 11 beta-, 18- and 19-Hydroxylation activities of adrenal mitochondrial prepared from spontaneously hypertensive rat (SHR), Wistar-Kyoto rat (WKY), and stroke-prone (SP)-SHR were not significantly different from each other. Levels of mRNA of ALDO synthase in adrenal glands of 50-week-old SHR was significantly lower than those of 10-week-old SHR, WKY and SHR-SP. (iii) No significant difference in 19-hydroxylation activity was found between adrenal mitochondria prepared from ARH rat and those from control rat. The level of message of ALDO synthase was lower in adrenal glands of ARH rat.
Aldosterone↗
Vasomotor response to ergonovine of epicardial and resistance coronary arteries in the nonspastic vascular bed in patients with vasospastic angina.
The hypothesis that a coronary vasomotion disorder may exist in the entire coronary artery tree in patients with vasospastic angina was investigated by examining the coronary responses to atrial pacing (130 beats/min) before and after the administration of ergonovine (16 micrograms) into nonspastic coronary arteries. Seven patients with angiographically normal coronary arteries and focal spasm in the right coronary artery and 7 control patients with atypical chest pain and angiographically normal coronary arteries without spasm were studied. Great cardiac vein flow (GCVF) and left anterior descending coronary artery diameters (CDs) were measured by the thermodilution method and quantitative arteriography, respectively. Although the CDs before ergonovine were similar in the 2 groups, the pacing-induced increased in GCVF before ergonovine administration was smaller in patients with vasospastic angina than in control patients (22 +/- 4% vs 49 +/- 11%, respectively; p < 0.05). After ergonovine administration, pacing both increased GCVF and decreased anterior regional coronary resistance (ACR) to a lesser extent in patients with vasospastic angina than in control patients (GCVF, 16 +/- 4% vs 47 +/- 8%, respectively [p < 0.01]; ACR, -12 +/- 3% vs -29 +/- 3%, respectively [p < 0.01]). The decreases in CDs in patients with vasospastic angina observed after ergonovine administration were greater than those in control patients (-18 +/- 2% vs -9 +/- 2%, respectively; p < 0.05). Thus, not only epicardial, but also resistance coronary arteries are affected by the coronary vasomotion disorder in the nonspastic vascular bed in patients with vasospastic angina.
Adult↗
A neuropathological study of a case of lupus erythematosus with chorea.
Neuropathological examination in a 48-year-women of SLE with chorea was performed. Histological examination of the putamen showed a widespread neuronal loss associated with reactive astrocyte proliferation and neuropil rarefaction at both sides. Disappearance of large neurons was more prominent than that of small ones. Although a few old and fresh microinfarcts were scattered in the same area, there was no significant pathological abnormality in small vessels. The caudate nuclei also showed a few irregular microinfarcts and spotty loss of neurons associated with reactive astrocytosis. These neuropathological changes might be related to the appearance of choreatic movement in patients with SLE.
Astrocytes↗
High-level expression of the photorepair gene in Drosophila ovary and its evolutionary implications.
DNA photolyase catalyzes light-dependent repair of cis, syn-cyclobutane dipyrimidines (pyrimidine dimers); its apoenzyme is encoded by the photorepair (phr) gene. The phr cDNA was cloned from D. melanogaster; it has an open reading frame to encode a 61,483-Da protein. The phr cDNA hybridized to band 44C-D of Drosophila polytene chromosome, equivalent to the locus of the phr- gene. Drosophila photolyase is made of an apoenzyme with a molecular weight of 62 kDa. Drosophila photolyase is extraordinarily abundant in the embryo and adult ovary, whereas mRNA of the phr gene is abundant only in the ovary. The action spectrum of Drosophila photolyase for photoreactivation has a maximum at 440 nm. The phr gene of Drosophila has about 60% identical amino acid sites with that of goldfish but only 13-18% with those of microorganisms. Implications of the unique characteristics of the Drosophila phr gene are discussed overviewing the diversified characteristics of phr genes in various organisms that have presumably evolved from a common ancestral gene.
Amino Acid Sequence↗
A new photoreactivating enzyme that specifically repairs ultraviolet light-induced (6-4)photoproducts.
Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts ((6-4)photoproducts) are the two major classes of cytotoxic, mutagenic and carcinogenic DNA photoproducts produced by ultraviolet light irradiation of cells. The phenomenon of photoreactivation, the reduction of the lethal and mutagenic effects of ultraviolet radiation by simultaneous or subsequent irradiation with near ultraviolet or visible light, has been identified in several organisms and in some cases the enzymes that catalyse this process have been characterized in sufficient detail. CPDs are the only known substrate for the photoreactivating enzymes so far analysed and enzymatic photoreactivation of (6-4)photoproducts has not yet been reported. We report here that an enzyme that catalyses the light-dependent repair of (6-4)photoproduct exists in Drosophila melanogaster. This is, to our knowledge, the first report of such photoreactivating activity specific for (6-4)photoproducts in any organism.
Animals↗
The growth of mouse hybridoma cells between Peyer's patch lymphocyte and myeloma cell in the gastrointestinal tract. A model for human multiple lymphomatous polyposis of the gastrointestinal tract.
To elucidate the mechanism of multiple lesions in human primary lymphoma or multiple lymphomatous polyposis of the gastrointestinal tract, we developed a experimental model utilizing mouse hybridoma cells. Syngeneic mice were immunized with human hemoglobin via gastric intubation and a hybridoma clone (13c) between the Peyer's patch cell and mouse myeloma cell was obtained. The 13c cells were infused into normal syngeneic mice through a lateral tail vein. About 2 months after injection mice were sacrificed and their viscera were scrutinized histologically. All 11 mice receiving 13c showed multiple tumors at the colon, microscopic massive invasions at the small intestine, and scattered invasions at Peyer's patch, mesenteric lymph nodes and the spleen, exhibiting the similar distribution patterns as in human multiple lymphomatous polyposis of the gastrointestinal tract. ME-1 or MU-1 cells (hybridomas between P3 and mouse spleen cell) were distributed at the liver, spleen and paraaortic lymph nodes. Such migration patterns of 13c cells and their adherence to vessel walls suggest that multiple invasions may be lymphocyte homing receptor-mediated phenomena.
Animals↗
Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice.
We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.
Animals↗
A case of malignant histiocytosis successfully treated with combination interferon and etoposide therapy.
A 66-year-old woman with malignant histiocytosis was treated with a combination of recombinant gamma interferon (GI-3) and etoposide. Following partial response to intravenous gamma interferon (9 x 10(6) units (U)/day) alone, the patient received an eight-months course of subcutaneous gamma interferon (0.5 x 10(6) U/day) and intravenous etoposide (100 mg/week). After two years, the patient remains in complete remission. The present case report discusses the successful use of combination gamma interferon and etoposide for the treatment of malignant histiocytosis.
Aged↗
[Clinical evaluation of imipenem/cilastatin sodium against severe infections complicated with hematological disorders and solid tumors].
Imipenem/cilastatin sodium (IMP/CS) was administered to patients with severe infections complicated by hematological disorders and solid tumors to assess its efficacy and safety. Primary diseases in this series of 76 cases included 37 cases of hematological disorders (acute leukemia in 25 cases, malignant lymphoma in 7 cases, aplastic anemia in 3 cases and 2 other diseases) and 38 cases of solid tumors (lung cancer in 7 cases, gastric cancer in 11 cases, esophageal cancer in 6 cases, pancreatic cancer in 3 cases, bile duct cancer in 4 cases, hepatocellular cancer in 3 cases, and 4 other diseases). Following results were obtained. 1. Types of infection in hematological diseases were sepsis in 5 cases, suspected sepsis in 24 cases, pneumonia in 5 cases and 3 others. The efficacy rates were 100% in sepsis, 62.5% in suspected sepsis, 80% in pneumonia and 73% in all cases. 2. Types of infection in solid tumors were sepsis in 2 cases, suspected sepsis in 13 cases, pneumonia in 10 cases, cholecystitis in 2 cases, cholangitis in 5 cases, liver abscess in 2 cases, and 4 others. The efficacy rates were 50% in sepsis, 69.2% in suspected sepsis, 80% in pneumonia, and 71.1% in all cases. 3. IPM/CS was administered in single use in 66 cases and in combination with other antibiotics in 9 cases. The efficacy rate in the single use was 72.7% and that in the combination use was 66.7%. 4. The efficacy rate in 35 cases of first use was 71.4% and that in 40 cases of second use was 72.5%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[A case of congenital hemolytic anemia with red cell membrane lipid abnormalities (increased phosphatidyl choline and free cholesterol) associated with enhanced sodium transport].
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Adult↗
[Immune mechanisms and lesions of the gastrointestinal system].
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B-Lymphocytes↗
Implication of ZOG protein (zona glomerulosa-specific protein) in zone development of the adrenal cortex.
The three zones of adrenal cortex are thought to arise from a single multipotential stem cell. Immunohistochemical studies of fetal and adult adrenals using an antibody against a previously-cloned ZOG protein, a rat homolog of Pref-1, were conducted to explore its roles in the differentiation of cortical tissues. At the early embryonic stage, ZOG was already expressed in adrenogonadal primordial cells. The ZOG-positive cells gradually formed the adrenal primordium by E14.5. By E17.5 the expression was repressed in the inner part of the aggregate and these cells began to express CYP11B1. The ZOG-positive cells at this stage existed at the periphery of the aggregate but they did not express CYP11B2 yet. Not until E20.5 did the aldosteronogenic cells appear among the ZOG-positive cells at the outermost part of the gland. Based on these and the other findings the zonal development of the adrenal cortex is discussed.
Adrenal Cortex↗