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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 955 records · Page 53Linked to original sources

Molecular cloning of rat type 2C (IA) protein phosphatase mRNA.

A full-length cDNA encoding rat type 2C (IA) protein phosphatase was isolated from a kidney cDNA library. The cDNA was identified by screening the library with oligonucleotides based on a partial amino acid sequence determined from purified rat liver phosphatase. This clone is 2.35 kilobase pairs long and has a single extended translation reading frame that predicts a 382-amino acid protein of 42,416 daltons. The deduced amino acid sequence contains segments corresponding to three peptides from rat liver type 2C protein phosphatase and two peptides from rabbit skeletal muscle type 2C phosphatase. Rat kidney type 2C protein phosphatase is distantly related to yeast adenylate cyclase but is not related to the catalytic subunits of two other protein phosphatases (types 1 and 2A).

Adenylyl Cyclases↗

Structure of the functional interleukin-2 receptor. Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line.

The structural basis of the high affinity interleukin-2 receptor which was previously reconstituted in a cultured murine T cell line, EL4 by expressing either wild-type Tac antigen complementary DNA (cDNA) or a chimeric cDNA was characterized. The chimeric cDNA encodes a membrane portion whose extracellular portion consists of that of Tac antigen whereas transmembrane and cytoplasmic portions consists of those the human insulin beta chain. The Tac antigen/anti-Tac antibody complex was treated by chemical crosslinking reagents, purified by goat anti-mouse immunoglobulin (Ig), and was analysed by SDS-PAGE. We here demonstrated the presence in mouse EL4 transfectants of a novel membrane protein which is closely associated with the products of transfected cDNAs in the absence of interleukin-2. The protein is 75 kDa in size and is detected in cells which express high affinity interleukin-2 receptor but not in cells which only express low affinity interleukin-2 receptor. The transmembrane region and the cytoplasmic region of Tac antigen is not necessary for the formation of the complex consisting of Tac antigen and 75 kDa molecule, indicating that a murine 75 kDa molecule associates with Tac antigen extra-cellularly.

Animals↗

Identification of a human T cell clone with the cytotoxic T lymphocyte and natural killer-like cytotoxic function against autologous mammary carcinoma and K562 line.

Pleural exudative lymphocytes (PLEL) from a 60-year-old female patient showed high cytotoxicity against the autologous mammary tumor line, HMC-2, and NK-susceptible K562 cells, although PLEL demonstrated only weak cytotoxic potentials against several allogeneic tumor lines. We successfully obtained seven cytotoxic T cell clones from PLEL bulk populations, and assessed the possibility that these lymphocytes are simply natural killer (NK)-like cells or have the dual cytotoxic activity of cytotoxic T lymphocytes (CTL) and NK-like cells. These clones, designated as TcHMC-2, showed strong cytotoxicity against both HMC-2 and K562 cells. In contrast, allogeneic human peripheral blood-derived NK cells could not kill HMC-2 targets. Furthermore, a blocking study of TcHMC-2 cytotoxicity using monoclonal antibodies against CD3, CD8 and human MHC class I products showed that all of these antigen molecules were involved in the cytotoxicity of TcHMC-2 clone against autologous HMC-2 cells, indicating MHC class I recognitive cytotoxicity. These data indicate that the TcHMC-2 clone may have dual cytotoxicity with CTL- and NK-like activity against autologous HMC-2 mammary tumor and K562 cells, respectively.

Antibodies, Monoclonal↗

Ectopic posterior lobe of the pituitary gland and intractable nocturnal enuresis in a case with pituitary dwarfism.

An 11 5/12-year-old girl with pituitary dwarfism had intractable nocturnal enuresis. Magnetic resonance imaging revealed pituitary stalk transection and the formation of an ectopic posterior lobe. The results of responses to dehydration, infusion of hyperosmolar NaCl solution, and 1-desamino-8-D-arginine vasopressin showed that the nocturnal enuresis in the present case was due to a partial vasopressin deficiency. We suggest that the ectopic posterior lobe is one cause of nocturnal enuresis.

Child↗

Intestinal maturation: characterization of mitochondrial calcium transport in the rat.

The mitochondria play a major role in the regulation of intracellular calcium. Despite the fact that the enterocytes receive the majority of absorbed calcium, the role of the intestinal mitochondria in calcium transport during maturation is not known. Therefore, the current studies were designed to characterize calcium pump activity of jejunal mitochondria of rats during maturation (suckling, weanling, and adolescent rats). The functional integrity of the intestinal mitochondria of suckling and adolescent rats was determined by oxygen consumption studies demonstrating respiratory control ratios of more than 3 when succinate was used as a test substrate. Ca++ uptake was significantly stimulated by the presence of 3 mM ATP at all age groups studied. Maximal Ca++ uptake in the presence of 3 mM ATP and 2 mM succinate was 31.1 +/- 0.4, 50.2 +/- 4.2, and 94.3 +/- 1.5 nmol/mg protein (mean +/- SE) in suckling, weanling, and adolescent rats, respectively. Rates of ATP hydrolysis were 15.5 +/- 1.5 and 2.9 +/- 0.3 nmol/ATP hydrolyzed/mg protein in adolescent and suckling rats, respectively (p less than 0.001). Ca++ uptake was completely inhibited by 0.25 microM ruthenium red, oligomycin (10 micrograms/mg protein), 0.5 mM dinitrophenol and 1 mM sodium azide at all age groups. Ca++ efflux in the presence of ruthenium red occurred by a Na+-dependent pathway, indicating a Ca++/Na+ exchange mechanism. Kinetic parameters for ATP stimulated Ca++ uptake at 10 s revealed a Km of 0.84 +/- 0.11, 0.65 +/- 0.17, and 0.57 +/- 0.03 microM and Vmax of 1.83 +/- 0.07, 3.62 +/- 0.26 and 14.15 +/- 0.21 nmol/mg protein/10 s in suckling, weanling, and adolescent rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Intestinal maturation: characterization of mitochondrial phosphate transport in the rat and its regulation by 1,25-(OH)2 vitamin D3.

The mitochondria play a major role in the regulation of oxidative phosphorylation within the cell. Despite the fact that the enterocytes receive the majority of absorbed phosphate and their high metabolic turnover rate, the role of the intestinal mitochondria in phosphate transport system during maturation is not known. Therefore, the current studies were designed to characterize phosphate transport by jejunal mitochondria of rats during maturation (suckling, weanling, and adolescent rats). The functional integrity of the intestinal mitochondria of suckling and adolescent rats was determined by oxygen consumption studies demonstrating respiratory control ratios of more than 3 when succinate was used as a test substrate. Phosphate uptake was significantly stimulated by the presence of 3 mM ATP at all age groups studied. Maximal phosphate uptake in the presence of 3 mM ATP and 2 mM succinate was 16.5 +/- 1.0, 20.5 +/- 1 and 28.7 +/- 0.4 nmol/mg protein (mean +/- SE) in suckling, weanling, and adolescent rats respectively. ATP-dependent phosphate uptake was inhibited by 80% with 100 microM p-MB. Kinetic parameters for ATP stimulated phosphate uptake at 10 s revealed a Km of 4 +/- 0.9, 2.8 +/- 0.4, and 0.9 +/- 0.1 mM and Vmax of 5 +/- 0.7, 9.5 +/- 1, and 11 +/- 0.7 nmol/mg protein per 10 s in suckling, weanling, and adolescent rats, respectively. Phosphate uptake was also stimulated by an inwardly directed pH gradient (pH out less than pH inside) compared to no pH gradient condition suggesting the presence of PO4-/OH- exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

A case of primary aldosteronism with chronic renal failure undergoing hemodialysis treatment.

A 56-year-old man with primary aldosteronism and chronic renal failure undergoing hemodialysis is described. He complained of numbness of the extremities and showed persistent hypopotassemia in spite of anuria. In the endocrinological examination, a very high plasma aldosterone concentration was observed, while plasma renin activity was within the normal range. From the abdominal Computed Tomography (CT), adrenal scintigraphy, and segmental venous sampling data, he was diagnosed as primary aldosteronism due to left adrenocortical adenoma. In this case, hypopotassemia could not be explained by potassium loss through the kidneys, which suggests potassium excretion in the gastrointestinal tract as the mechanism of hypopotassemia. This was clearly shown from a potassium-balance study and the results of spironolactone administration. Our report is on the first case showing hypopotassemia due to primary aldosteronism in spite of anuria. If a patient treated with maintenance dialysis should have persistent hypopotassemia, as in the present report, it is necessary to consider an association with primary aldosteronism.

Humans↗

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Adolescent↗

Interrelationship between plasma ionized calcium, plasma noradrenaline (NA) and pressor response to infused NA in patients with essential hypertension.

We evaluated the role of calcium metabolism on plasma noradrenaline concentration (pNA) and pressor response to infused noradrenaline (NA-R) in patients with mild-to-moderate essential hypertension (EHT). Mean arterial pressure (MAP), plasma ionized calcium (pCa2+), and NA-R were measured at the basal condition in 17 EHT and after the administration of calcium antagonist, nifedipine (60mg, t.i.d., for 4 weeks) in 9 EHT. Under basal condition, pCa2+ correlated positively with pNA and negatively with NA-R in EHT. Following nifedipine therapy, persistent reductions of MAP and NA-R, a transient increase in pNA and a sustained increase of urinary excretion of calcium were observed. On the other hand, no significant change in pCa2+ was found during the therapy. Percent change in MAP following 4 weeks of nifedipine administration correlated positively with pCa2+ and pNA before the therapy. In addition, change in NA-R by nifedipine therapy correlated positively with the basal values of pCa2+ and PNA and negatively with NA-R before the treatment. A significant negative correlation between NA-R and pNA was observed following nifedipine therapy as well as the basal state. However, the slope of the regression line between NA-R and pNA decreased significantly after the treatment as compared to the basal state. These results suggest that calcium metabolism relating sympathetic nerve activity and NA-R may contribute to the hypertensive mechanism in EHT. The hypotensive effects of nifedipine may be caused partly by the attenuation of sympathetic nerve activity and NA-R.

Blood Pressure↗

[Detectability and characteristics of the primary adrenal tumor by ultrasonography--comparison with CAT scan and adrenal scintigraphy].

From March 1978 to May 1987, 22 cases of primary adrenal tumors were examined by ultrasonography. The patients ranged in age from 21 to 79 years with an average of 42.6 year, including 11 cases of pheochromocytoma, 6 cases of primary aldosteronism, 4 cases of Cushing's syndrome and 1 case of ganglioneuroma. Visualization of tumors was successful in 19 of the 22 patients (86.4%). The detecting rate of right adrenal tumors was 100% (12/12), while the rate of the left was 80% (8/10). The sizes of detected adrenal tumors were larger than 10 mm on the right and larger than 20 mm on the left. Obesity and bowel gas degraded the image of left adrenal tumors, resulting in a lower detective rate of the tumors. The suprarenal area and small lesions were best demonstrated by a lateral intercostal approach using longitudinal scanning plane and by a right subcostal approach using transverse scanning plane. In pheochromocytoma, cystic lesions (echo free space) existed, and the fact that no cystic lesion in other adrenal tumors was helpful for diagnosis of pheochromocytoma. It is concluded that ultrasonography is a very useful method for diagnosis of adrenal tumors as an initial imaging procedure, because it is totally non-invasive, rapid and less expensive than all of the other techniques.

Adrenal Gland Neoplasms↗

[Anatomical studies on a supernumerary tooth considered to be a successional tooth of the lower first molar].

The purpose of this study is to investigate features of the successional tooth of the lower first molar. Materials investigated in this study deal with a supernumerary tooth formed at the distolingual deep part to the lower right first molar of a male patient aged twenty-four. It was observed with binocular microscopy and under X-ray. The occlusal surface of it was observed with scanning electron microscopy. Horizontal ground sections of it were prepared and observed with polarizing microscopy, fluorescent microscopy, and scanning electron microscopy. It is thought that this supernumerary tooth is a true successional tooth of the lower first molar because it was formed at the distolingual deep part to the lower first molar and the fissure of it is Y-shaped and it has five cusps. It is considered that two impressions at buccal and distal surfaces of it isn't original hereditary features but was accidentally formed by pressures of mesial and distal roots of the lower first molar. The rough form of it has most resemblance to the lower second premolar and distal and lingual parts of it are smaller than that of the lower first molar. But fundamental features of the lower first molar are preserved in it. It is thought that the center of the molarization field of human lower successional teeth lies at the successional tooth of the lower first molar because the form of the occlusal surface of it is more complex and functional than those of the lower first and second premolars.

Adult↗

[Effects of mastication on the growth and development of salivary glands in male mice].

Mastication has attracted considerable attention in recent years for its effects on the postnatal growth and development of the mandible, brain, salivary glands and other organs in children. In this study, the relationship between mastication and growth and development of the salivary glands was examined, because the salivary glands are rich in growth factors and many kinds of biological polypeptides, and have endocrine and exocrine actions and effects, on the growth and metabolic rates in developing animals. The experiment utilized two groups of male mice, a control group fed a solid diet, and an experimental group receiving the paste diet ad lib. In the experimental group fed the paste diet, the increase of the tissue weights and the contents of DNA and RNA in the parotid and submandibular glands were lower than those of the control group. Also the rise of amylase activity in the parotid glands was depressed. Next, the polyamine metabolism in the parotid and submandibular glands was examined. The activities of the late limiting enzymes in polyamine syntheses, ornithine decarboxylase and S-adenosylmethionine decarboxylase and the lev- putrescine and spermidine in both parotid and submandibular glands were in the experimental group. These results suggest that mastication plays an important roles in the growth development of the parotid and submandibular glands in mice.

Animals↗

[Effects of mastication and submandibular gland ectomy on the growth ability of isoproterenol-stimulated parotid gland and other tissues in male mice].

In a previous article we reported that mastication played an important role in the development of submandibular glands in male mice. Submandibular glands contain epidermal growth factor (EGF) which stimulates the proliferation of various cells in developing animals. In this study, the effects of the hypotrophy of submandibular glands caused by reduction of mastication and the removal of the glands on the growth ability of isoproterenol (IPR)-stimulated parotid glands and other tissues were investigated. The animals in the experiment were male mice and they divided into three groups, a control group fed a solid diet, a group fed a paste diet and a group with removed submandibular glands fed a solid diet. In comparison with the group fed a solid diet, in the group fed a paste diet a small decrease was found, and in the group with the ectomized submandibular gland a significant decrease in the rise of ornithine decarboxylase (ODC) activity, S-adenosylmethionine decarboxylase (SAMDC) activity and DNA synthesis of parotid glands caused by IPR stimulation were found. The DNA synthesis of the heart tissue of mice with ectomized submandibular glands was lower than that of the control group, but in liver, lung, stomach and testis tissue no decrease of DNA synthesis was found. These results suggest that mastication and the submandibular glands have an effect of the growth of the tissues in male mice.

Animals↗

[Adjuvant chemotherapy for gastric cancer--the third study. First report: central randomization by telephone method and analysis of patients' background factors].

JFMTC conducted the third adjuvant chemotherapy study for gastric cancer patients after curative surgery from 1982 to 1983. Patients were randomly allocated to one of the three arms by telephone method controlled at the headquarters of the foundation. This method resulted in the marked reduction of ineligible cases (253 cases, 6.0% of 4,236 cases), compared with those in the first study (18.3%). Main reasons of ineligibility were the violation of entry criteria due to the misjudgment of noncancer, duplicate cancers and operative curability. Telephone method for random allocation seems to contribute to the improvement in the data quality of a clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗

[Multi-institutional cooperative study of adjuvant immunochemotherapy in gastric cancer--five-year survival rate].

The Gastric Cancer Immunochemotherapy Study Group, constituted of 412 institutions, carried out six independent trials simultaneously from 1978 to 1981. A total of 4,456 cases were subjected to the study, from which 826 cases (18.5%) were excluded due to the violence of entry criteria. Curative gastrectomy, followed by a combination of mitomycin C (MMC), Ftorafur (FT)and Krestin (PSK) produced better postoperative survivals than either combination of MMC and FT, or MMC and PSK (5-year survival rate: 71.7% in MMC + FT + PSK, 64.1% in MMC + PSK, and 58.5% in MMC + FT). In the subset of patients with negative nodes (n(-)), and with involved serosa by histological examination (ps(+)), a combination of FT and PSK after gastrectomy seemed to be more favorable for the post-operative survivals than the single use of either drug. Four drug combinations of MMC, FT, PSK and Picibanil (OK-432) also had a clinical benefit in the group of patients with poorly differentiated adenocarcinoma, compared with chemotherapy alone. These results, though there are biases due to excluding 18.5% of cases, suggest some clinical benefits in the control of cancer relapse after surgery. The conclusion should be confirmed by a further elaborate trial.

Adjuvants, Immunologic↗

[Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): a preliminary report. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

In a prospectively randomized study, the effect of adjuvant chemotherapy with mitomycin C (MMC) and tegafur (FT) on survival and recurrence was analyzed in 2,477 evaluable patients with colon or rectal cancer who underwent macroscopically curative resection. Patients (1,256 with colon cancer, 1,221 with rectal cancer) were divided into the treatment group (group A) and the control group (surgical resection only, group B). In group A, chemotherapy consisted of intravenous administration of MMC (12 mg/m2 on operative day, followed by 6 mg/m2/2 months, 6 times) and oral administration of FT (800 mg/day for one year). No serious adverse effects were observed in the treatment group. There was no significant difference between group A and group B in three-year survival rate. The disease-free interval curve in group A of rectal cancer revealed significantly better results than group B (p = 0.044). There was no difference in the incidence of local recurrence at three years after operation between group A and group B. The incidence of metachronous liver metastases in group A of rectal cancer was significantly lower than in group B (p = 0.036).

Antineoplastic Combined Chemotherapy Protocols↗

[Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): 3-year survival after surgery of non-curatively resected patients. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

A prospective randomized study was carried out to evaluate the efficacy of surgical adjuvant chemotherapy for non-curatively resected colorectal carcinoma patients as a collaborative study at 428 institutes in Japan from Jan., 1984 to Dec., 1985. A total of 1,138 patients were entered in this study. All patients were divided according to disease location (colon or rectum) and received one of two chemotherapeutic regimens after surgery (Regimen C: MMC 12 mg/m2 i.v. at operation day and 6 mg/m2 in every 2 months +UFT 600 mg/day p.o., D: the same dose of MMC + UFT 400 mg/day p.o.) randomly. 556 cases (colon carcinoma regimen C: 148, D: 185 cases, rectal carcinoma regimen C: 94, D: 129 cases) were evaluable at this presentation. Three-year-survival rate of histologically confirmed non-curatively resected colon carcinoma patients was higher in the group receiving regimen C than in regimen D. But no significant difference was found among the other groups.

Antineoplastic Combined Chemotherapy Protocols↗

[Breast carcinoma with features of osteosarcoma--a light and electron microscopic and immunohistochemical study].

Reported is the case history of a 58-year-old woman with a lump in the left breast. The tumor was composed of two nodules, sharing a common portion. Grossly, one was an irregular hard tumor that was grayish in color, and the other was a well circumscribed cystic tumor that showed necrosis and a hemorrhage that had filled it with a reddish soft mass. Light microscopically, combined features of a scirrhous carcinoma and of an osteosarcoma were observed in each nodule, but the common portion was consistent with a metaplastic carcinoma, with cancer cells and sarcoma-like cells closely mingled. An ultrastructural study showed that the sarcoma-like cells were composed of polymorphic cells that resembled osteoblasts, myofibroblasts, osteoclasts, histiocytes, and undifferentiated tumor cells. Immunohistochemically, vimentin and alpha 1-antitrypsin in the sarcoma-like cells were positive, suggesting these cells were of a mesenchymal rather than of an epithelial origin.

Adenocarcinoma, Scirrhous↗