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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 1,063 records · Page 59Linked to original sources

Intestinal maturation: calcium transport by basolateral membranes.

The overall characteristics of calcium transport across the intestine have been defined using in vivo perfusion techniques and in vitro everted gut sacs. However, calcium transport represents three separate processes: entry at the brush border membranes, movement across the cytoplasm, and exit at the basolateral membranes (BLM). Studies in adult animals indicated that the active step in calcium transport is located at the BLM. The present studies describe for the first time the maturational aspects of calcium transport across the BLM of the enterocyte. We utilized a percoll density gradient to prepare enriched BLMs from suckling and adolescent rats. Calcium uptake into BLMs represented mainly transport into the intravesicular space. Calcium transport in both age groups was driven by ATP; the calcium transport in the presence and absence of ATP was significantly greater in suckling rats compared to adolescent rats. Kinetics of calcium uptake calculated from uptake values in the presence of ATP minus no ATP conditions showed a Km of 0.06 +/- 0.01 and 0.03 +/- 0.01 microM for adolescent and suckling rats respectively (p less than 0.05). Vmax was 1.5 +/- 0.1 and 0.8 +/- 0.08 nmol/mg protein/min for adolescent and suckling rats respectively (p less than 0.01). Calcium/sodium exchange mechanisms was also present in both age groups. However, the magnitude of sodium-dependent calcium exchange was smaller in suckling rats compared to adolescent rats. These data suggest that calcium exit at the BLMs of enterocytes of suckling and adolescent rats occurs by an ATP-dependent and a calcium/sodium exchange mechanism. Both mechanisms exhibit maturational changes.

Adenosine Triphosphate↗

The pathophysiological role of renal dopaminergic activity in patients with essential hypertension.

To evaluate the role of the renal dopaminergic system on renal water-sodium metabolism patients with essential hypertension (EHT), urinary excretion of dopamine, urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) were all investigated before and after the administration of dopamine (3 micrograms/kg/min, intravenous infusion for 60 minutes), dopamine antagonist, metoclopramide (8 mg/m2 BSA, intravenous injection) or mild sodium loading in both normotensive subjects and benign EHT. In the basal values, no significant difference in urinary excretion of free (u-fDA), conjugated (u-cDA) or total dopamine (u-tDA) was found between normotensives and hypertensives. However, low renin EHT showed a pronounced reduction in u-fDA compared with normotensis subject and (NT) normal renin EHT. In this study, a significant reduction of u-cDA and of u-tDA was also found in those patients with low renin essential hypertension. In the normotensive and essential hypertensive groups UNaV or FENa showed a positive correlation with u-fDA (measured simultaneously), but not with u-tDA or u-cDA. The regression line between u-fDA and UNaV or FENa in EHT was shifted towards a lower u-fDA level than in NT. UNaV and FENa were increased by dopamine infusion and were decreased by metoclopramide injection in both NT and EHT. Changes of UNaV and FENa following dopamine or metoclopramide, showed a negative correlation with u-fDA measured immediately before the administration of these drugs. The enhanced natriuretic response to infused dopamine and the attenuated antinatriuretic response to injected metoclopramide were significant in low renin EHT, when compared with NT or normal renin EHT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Failure to induce puberty in a man with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism by pulsatile administration of low-dose gonadotropin-releasing hormone.

To elucidate the mechanism of hypogonadotropic hypogonadism in a patient with X-linked congenital adrenal hypoplasia, we studied the effects on serum LH and FSH of repeated iv administration of GnRH (400 micrograms, over 2 h, once a day, for 14 consecutive days), pulsatile sc administration of GnRH (5 micrograms every 90 min during days 1 approximately 56, 10 micrograms every 90 min during days 57 approximately 91) and an iv bolus injection of 10 mg of naloxone. The repeated administration of GnRH restored the hyporesponsiveness of serum FSH and increased serum testosterone level from less than 1.0 to 1.7 nmol/l, but the impaired LH response to the standard GnRH test was not improved. The pulsatile administration of GnRH for 91 consecutive days did not induce a clinical or a biochemical change of puberty. Serum testosterone remained undetectable less than 1.0 nmol/l, the hyporesponsiveness of serum LH was not improved, but basal FSH level was significantly increased and the impaired FSH response to the standard GnRH test was slightly improved. Naloxone had no effect on serum LH or FSH before or during the pulsatile administration. We conclude that hypogonadotropic hypogonadism in our patient is due to the pituitary dysfunction and that the endogenous opioid peptides may not play a role in the mechanism of inhibited gonadotropin secretions.

Adolescent↗

Ontogeny of atrial natriuretic polypeptide in the human heart.

To elucidate the developmental changes of atrial natriuretic polypeptide in the human heart, we studied alpha-human atrial natriuretic polypeptide (alpha-hANP)-like immunoreactivity (alpha-hANP-LI) in the extracts from the hearts of three foetuses of 10, 14 and 22 weeks' gestation, a 1-day-old premature infant of 33 weeks' gestation, and two adults, alpha-hANP-LI levels in the atria of the three foetuses of 10, 14 and 22 weeks' gestation and the premature infant (31.4, 12.2, 9.25 and 15.3 nmol/g, respectively) were comparable to those in two adult atria (16.9 and 13.6 nmol/g). The ventricles also contained alpha-hANP-LI (0.763----0.0818 nmol/g with descending values with increasing gestational age) in the three foetuses and the premature infant although it was undetectable (less than 0.0162 nmol/g) in two adult ventricles. The highest alpha-hANP-LI concentration was observed in the auricles in all the hearts except in the premature infant. The concentration in the right auricle was higher than in the left during foetal life, whereas that in the left was the higher one after birth. High performance gel permeation chromatography coupled with radioimmunoassay revealed that alpha-hANP-LI in the atria and apexes of the foetuses and the premature infant consisted of gamma-hANP, beta-hANP and alpha-hANP, with gamma-hANP being the predominant form. Essentially similar gel filtration patterns were observed in the two adult atria. These results indicate that: ANP appears in human heart tissue early in foetal life; cardiac ventricles also contain ANP in the foetus, and there is probably no difference in posttranslational processing of the precursor molecule in foetal and adult hearts.

Aged↗

A novel antigenic determinant of the T200 glycoprotein expressed exclusively by Jurkat cells.

This report describes the production and characterization of monoclonal antibody specific for an antigenic determinant, designated Y1 antigen, present on Jurkat cells. Mo-Y1 specifically reacts with Jurkat cells, but not with other cell lines. Immunoprecipitation and subsequent immunochemical analysis demonstrate that Mo-Y1 defines an antigen with a molecular weight of 200,000 and a pI value of 5.3 to 5.6. Rabbit antibody against affinity-purified Y1 antigen was prepared. A sequential immunoprecipitation study confirmed that Po-Y1 reacted with the same antigen molecule recognized by Mo-Y1. Interestingly, Mo-Y1 reacted only with Jurkat cells, whereas Po-Y1 reacted with various hematopoietic cells including T cells, B cells, macrophages, and granulocytes. Po-Y1 precipitated a 200,000-dalton component from Jurkat cells and T cells. In contrast, Po-Y1 precipitated a 230,000-dalton component from B cells. These data led us to examine the relationship between T200, leukocyte-common antigen and Y1-defined antigen. Sequential immunoprecipitation analysis clearly indicated that T200 antibody and Y1 antibody recognized the same antigen molecule. Peptide mapping of T200- and Mo-Y1-defined antigen digested with V8 protease demonstrated that there were two common major peptide chains, but one peptide chain was missing in Jurkat cells that was present in T200 glycoprotein of other cells. It is possible that minor molecular modification of T200 glycoprotein occurred in the process of oncogenesis of T cells and that the altered epitope of T200 glycoprotein was recognized by Mo-Y1. The Y1 antigen can be classified as a tumor-specific antigen.

Antibodies, Monoclonal↗

[Liver phosphotyrosine protein phosphatase and tyrosine protein kinase in chemical hepatocarcinogenesis].

We found and characterized three forms of phosphotyrosine protein phosphatase, subsequently designated PTPP-1, -2 and -3, respectively, in rat liver. Chemical hepatocarcinogenesis according to Solt and Farber was accompanied by a slight increase in liver phosphotyrosine protein phosphatase activity and a remarkable increase in liver tyrosine protein kinase activity. A maximum 8-fold increase in tyrosine kinase activity was observed in hepatomas induced with 3'-methyl-4-dimethylaminoazobenzene (MeDAB). Tyrosine protein kinase that increased with the progress of chemical hepatocarcinogenesis was solubilized from the particulate fraction of MeDAB-induced hepatoma. The enzyme was shown to require Mg2+ for its activity, to immunoprecipitate with anti-pp-60src-IgG and to phosphorylate the IgG. Rat liver also contains another tyrosine protein kinase which requires Mn2+ and does not immunoprecipitate with anti-pp60src; the level of this enzyme appears to diminish with the progress of chemical hepatocarcinogenesis.

Animals↗

[A case of perineal (extramammary) Paget's disease].

A case of perineal Paget's disease in a 67-year-old male patient is reported. The perineal polyp, having shown no increase in size for 3 years, wks resected. The microscopic features of the polyp was comprised of clusters of a pale, large tumor cell (Paget cell) only in the epidermis. The skin that was resected around the polyp showed almost the same histological appearance as the polyp, except for an infiltration of tumor cells forming a small gland structure on the minimal region of the dermis. Both the Paget's cells and these tumor cells showed positive for mucin staining. Ultrastructurally, we confirmed two types of Paget's cells, one containing much granules and the other lacking in these granules but rich in other organelles. Further, the Paget's cells formed lumen and intercellular canaliculus, suggesting a differentiation to the eccrine sweat gland. From our findings and a review of the literature, we favor presuming that extramammary Paget's disease without a cancer of the neighbouring organs originates from the epidermis and extends to the dermis.

Aged↗

[Cooperative study of surgical adjuvant chemotherapy of colorectal cancer (first report): Investigation of background factors and adverse effects. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

In order to evaluate the efficacy of surgical adjuvant chemotherapy in patients undergoing gross curative resection for colorectal cancer (excluding m and sm cancer), a randomized controlled study was conducted from January, 1982 to October, 1983. Four hundred and ninety-one institutions participated in this study. The schedules for drug administration differed according to each district. In the Hokkaido and Shikoku districts, the patients were divided into the following two groups, one was a combination of ACNU and Futraful (FT) and the other was FT only. In the Chubu and Kinki districts, three groups were studied, namely those receiving a combination of ACNU and FT, those receiving FT only and those given no adjuvant chemotherapy. In the Tohoku and Kanto districts, a combination of MMC and FT and administration of FT only were studied. In the Chugoku and Kyushu districts, the patients were divided into a combination of ADM and FT, and FT only group. Among the 3,926 registered cases, 3,421 cases were valid for the study. As to the background factors, there were no significant differences among the groups in each district. There were no significant differences in one-year survival rates and one-year disease-free rates. No serious adverse effects were observed in any of the groups.

Alopecia↗

[A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II)].

A multi-institutional cooperative study of postoperative immunochemotherapy for gastric cancer was studied using PSK and/or OK-432 combined with Tegafur (FT) and/or MMC. A total of 3,630 gastrectomized patients from 412 institutions were entered into the study using 6 randomly assigned protocols. Unbiased background cases were analyzed by 4-year or 5-year survival rates (SVR) for each protocol. The efficacy of combined PSK with FT was noticed in all cases of curative operation macroscopically and in n(-) X ps(+) cases (4-y SVR). The combination of MMC, FT and PSK produced better survival than MMC with FT or PSK administration in all cases of macroscopic curative operation (5-y SVR) and in non-curative operation (4-y SVR). The combination of MMC, FT, PSK and OK-432 was effective for poorly differentiated cancer (4-y SVR). Immunochemotherapy with MMC, FT, PSK and OK-432 was more effective in patients with preoperative positive PPD skin test than in those with negative PPD skin test. These results suggested that adjuvant immunochemotherapy using PSK and/or OK-432 combined with MMC and FT is effective for the improved survival of gastrectomized patients with gastric cancer.

Biological Products↗

[The problems of postoperative adjuvant chemotherapy in gastric cancer].

We studied the survival rate and state of recurrence of histologically curatively resected cases in the 1st (Method II) and the 2nd studies of the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer. The administration of MMC combined with Futraful was most effective, but there was no difference of survival rate between the patients in the 1st study given Futraful for 3 months and those in the 2nd study given the drug for 12 months. Irrespective of the kind of drug and term of administration, cases with stage I showing recurrence within 2 years after surgery accounted for ca. 50% of all stage I cases recurring within 5 years. In spite of histological malignancy, cases with stage II showing recurrence within 2 years after surgery accounted for ca. 65% of all stage II cases recurring within 5 years. As to the recurrent hazard rate for each recurrent type of case with stage III, all types showed a high peak between 0.5 and 1.5 years after surgery. The peritoneal metastatic hazard rate was the highest. The hazard rates for Groups B (MMC + Futraful) and C (Futraful) were lower than those for Group A (MMC). The above findings suggest the importance of postoperative adjuvant chemotherapy, which is performed repeatedly and intensively for 2 years in order to prevent recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

[Functional and biochemical characterization of interleukin 2 receptor-associated molecules].

The interaction of interleukin 2 and the interleukin 2 receptor plays a crucial role in T cell proliferation. Unlike other growth factor receptors, the interleukin 2 receptor has a rudimentary intracytoplasmic portion that is too short to mediate any kinase activity. There are two classes of interleukin 2 receptor, with either high or low affinity. Only the high-affinity receptor mediates interleukin 2-driven transmembrane signal transduction. However, the mechanisms that control the affinity of the receptor and mediate transmembrane signal transduction are unknown. We report here that the rat interleukin 2 receptor has an associated molecule. The association of the rat interleukin 2 receptor with rat lymphocyte activation antigen, 5C6-F4 was demonstrated using the chemical cross-linking reagent, DTSSP. It is likely that the formation of a complex between the receptor and 5C6-F4 is important for the generation of the functional interleukin 2 receptor.

Animals↗

[A case of a primary localized amyloidosis (amyloid tumor) of the renal pelvis and ureter].

A 62-year-old woman complaining of asymptomatic hematuria was hospitalized. Although a cytologic examination of the urine was negative, abnormal findings in the right renal pelvis by DIP, RP and CT led us to suspect a pelvic tumor, and a right nephroureterotomy was performed. Light microscopy revealed deposits of amorphous, eosinophilic material in the pelvis and proximal portion of upper ureter, however tumor cells were not found. Electron microscopy revealed that these materials were aggregates of linear, non-branching fibrils, measuring about 8 nm in diameter. Histochemically, these were seen to be consistent with amyloid, producing an apple-orange birefringence with Congo red staining under a polarized light. Alkali Congo red staining after pretreatment of KMnO4 demonstrate that this amyloid protein was composed largely of AA protein in addition to lesser amounts of non-AA protein, and a primary localized amyloidosis (amyloid tumor) was diagnosed. A clinicopathologic study that was performed on 12 cases of primary localized amyloidosis of the pelvis, including our case, also is reported.

Amyloidosis↗

Endoscopic manometry of the sphincter of Oddi in dogs. Pharmacological effects of anticholinergic and selective antimuscarinic agents.

A dog model was used for direct measurement of the sphincter of Oddi using endoscopy. The effects of anticholinergic agents and a selective antimuscarinic agent on the canine sphincter of Oddi motility were studied. Manometric tracing at the canine sphincter showed rhythmical phasic contractions which were not affected by respiration. The mean values of the basal motility were as follows: the peak pressure was 61.5 +/- 2.2 (m +/- SE) cmH2O, trough pressure was 2.18 +/- 1.2 cmH2O, and the frequency was 17.4 +/- 0.2 waves/min. Intravenous administration of atropine sulfate, butropium bromide, butylscopolamine bromide and also pirenzepine significantly reduced the amplitude and frequency of canine sphincter contractions. From these results, it appeared that the cholinergic autonomic nervous system might be the one of the regulators of the canine sphincter of Oddi activity.

Ampulla of Vater↗