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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 217 records · Page 12Linked to original sources

Glucocorticoids potentiate effect of ACTH on cortisol secretion in isolated perfused guinea pig adrenal glands.

To clearly understand the autoregulation of glucocorticoid secretion by the glucocorticoid level, we studied the effects of cortisol and dexamethasone on the cortisol secretion in the perfused guinea pig adrenal glands. The basal cortisol secretion was suppressed by cortisol infusion at 0.1 microgram/ml, but not affected by dexamethasone infusion at 1 microgram/ml. The cortisol response to ACTH after pre-perfusion for 35 min was much quicker and larger in the presence of 0.1 microgram/ml cortisol, and was quicker in the presence of 1 microgram/ml dexamethasone than in the absence of glucocorticoid. It is considered that glucocorticoids play a permissive role in the action of ACTH on the adrenal gland.

Adrenal Glands↗

Surgical management of late esophageal perforation.

Over sixteen years we have gained experience in the delayed surgical management of esophageal rupture in nine patients who received treatments more than 24 hours after perforation. The causes of perforation were Boerhaave's syndrome or barotrauma in four patients, foreign bodies in two, and other causes in three. Three patients presented in septic shock and four in respiratory failure. Three surgical options were used for treatment: simple thoracic drainage in two patients, T-tube placement in four, and esophagectomy with secondary reconstruction in three. Eight patients (89%) survived. T-tube placement was effective in that it was a one-stage operation which could be used on severe esophageal injuries in patients in poor general condition. Three patients who underwent esophagectomy and secondary alimentary restoration required long hospital stays (119,201, and 648 days). Although the number of cases is small, T-tube insertion for the late management of esophageal rupture appears to be a simple and effective method which avoids the postoperative complications associated with primary closure or two-stage operations.

Drainage↗

Inhibition of tumor promoter activity toward mouse fibroblasts and their in vitro transformation by tissue inhibitor of metalloproteinases-1 (TIMP-1).

Tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural inhibitor of matrix metalloproteinases (MMPs), is known to inhibit invasion and metastasis of tumor cells. In the present study we examined anti-tumor promoter activity of TIMP-1 and its effect on in vitro cell transformation using BALB/3T3 cells in low serum culture medium. In the dye transfer assay the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) continuously blocked gap-junctional intercellular communication (GJIC) of BALB/3T3 cells in confluent phase. TIMP-1 did not prevent transient inhibition of GJIC induced by TPA, but it quickly restored the reduced GJIC level to the control level. The recovery of GJIC was dependent on the concentration of TIMP-1 from 1 to 1000 ng/ml. In an in vitro two-stage transformation assay in which BALB/3T3 cells were treated with 0.5 microg/ml N-metyl-N'-nitro-N-nitrosoguanidine as initiator and 100 ng/ml TPA as promoter, TIMP-1 at concentrations > 10 ng/ml inhibited the focus formation of transformed cells by approximately 60%. TIMP-2 and a synthetic MMP inhibitor showed a similar inhibitory activity on in vitro cell transformation. Furthermore, zymographyic analysis showed that TPA treatment of BALB/3T3 cells induced secretion of gelatinase B and stromelysin-1 into the culture medium. These results indicate that TIMP-1 and TIMP-2 have inhibitory activity on in vitro transformation of cells. It seems likely that TPA-inducible MMPs are involved in carcinogenesis and TIMPs have a protective role against carcinogenesis in vivo.

3T3 Cells↗

A simple stenting method for management of hepatic ductal injury secondary to blunt abdominal trauma: two case reports.

We report two cases of liver injury with hepatic ductal disruption after blunt abdominal trauma. The first case involves a 23-year-old male. Because the bifurcation of the hepatic duct was longitudinally torn, two stenting catheters were inserted toward the right and left hepatic ducts without suture closure of the tear. The patient is well 10 years after the injury. The second case involves a 22-year-old male who suffered an infarction of the inferior portion of the medial segment of the left hepatic lobe as well as a laceration of the left hepatic duct, a 50% circumferential tear. A stenting catheter was introduced into the left hepatic duct, but the defect was not sutured. The patient is well 1.5 years after the injury. The catheter stenting method without suture repair or defect plasty is a simple and effective way to manage hepatic ductal injury.

Abdominal Injuries↗

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects.

To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.

Adult↗

Immunohistochemical study of tumor-infiltrating lymphocytes before and after intravesical bacillus Calmette-Guérin treatment for superficial bladder cancer.

BACKGROUND: This study investigated changes in the phenotypic characteristics of tumor-infiltrating lymphocytes during intravesical bacillus Calmette-Guérin (BCG) treatment using an immunohistochemical technique. METHODS: A total of 16 patients with superficial bladder cancer underwent intravesical BCG treatment for therapeutic purposes. Tissue specimens were obtained from these patients before and after BCG treatment by cold cup biopsies. RESULTS: The numbers of CD3+ cells, CD4+ cells, CD8+ cells, and CD19+ cells significantly increased after treatment compared with numbers before treatment (P < 0.01). Although gamma/delta T cells were not observed before treatment, they appeared after treatment in 6 patients. In all these patients, the tumors disappeared or their size was reduced by more than 50%, and none of the tumors recurred. The induction of CD25+ cells after treatment was seen in 11 of the 16 patients. CONCLUSION: gamma/delta T cells may play an important role in the immune response of the host to the tumor in intravesical BCG treatment (although this correlation was statistically insignificant.

Adjuvants, Immunologic↗

GRO-alpha in human serum: differences related to age and sex.

PROBLEM: Human GRO-alpha (GRO-alpha) is a new member of the chemokine family that is supposed to play an important role in inflammatory and immune reactions. We established a sandwich enzyme-linked immunoassay (ELISA) system with polyclonal antibodies against human GRO-alpha and investigated the serum level of healthy donors to establish normal ranges for this chemokine in adults. METHODS: GRO-alpha concentrations were measured cross-sectionally in the sera of 240 healthy adults. The variability of serum GRO-alpha levels was also measured in normal volunteers, samples from whom were obtained by sequential venipunctures or by a small plastic cannula with a heparin-saline lock, to determine short-term variability. RESULTS: Whereas there was no difference between the concentration of human GRO-alpha from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73). However, we could not detect any significant difference between healthy donors' serum levels and those of donors with acute inflammation. Fewer variations were recognized in the case of the sequential venipunctures method than in that of the heparin-saline lock method. CONCLUSION: We found that the GRO-alpha concentration of postmenopausal women was significantly lower than that of women with normal menstrual cycles. These results suggest the GRO-alpha serum levels of normal healthy women may have some correlation with sex hormones.

Acute Disease↗

Cyanide suppression of inwardly rectifying K+ channels in guinea pig chromaffin cells involves dephosphorylation.

Treatment of chromaffin cells with cyanide induced a gradual decrease in an inwardly rectifying K+ current (IIR), and washout of the mitochondrial inhibitor resulted in a rapid recovery of IIR. This diminution of IIR was reversed in a time-dependent manner by infusion of ATP or UTP, but not by that of GTP, ITP, or CTP. The restoration by ATP was not altered by addition to the pipette solution of 50 microM fluorescein 5-isothiocyanate, an inhibitor of various ATPases. A similar recovery of IIR occurred with injection of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), but not of 5'-adenylylimidodiphosphate or alpha,beta-methyleneadenosine 5'-triphosphate. The ATP gamma S effect was biphasic, resulting in first a run-up of the current in ATP-depleted cells followed by a rundown of the current. This rundown was almost abolished by addition of guanosine 5'-O-(2-thiodiphosphate) to the ATP gamma S solution, suggesting the involvement of a G protein. Bath application of the protein kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine at 100 microM, but not N-(2-[methylamino]-ethyl)-5-isoquinolinesulfonamide, induced a reversible inhibition of IIR in the presence of pipette ATP, and the inhibition was diminished by 1 microM calyculin A, a phosphatase inhibitor. Bath application of 1 microM phorbol 12,13-dibutyrate did not affect IIR. It is concluded that cyanide suppresses inward rectifier K+ channel activity via dephosphorylation and that protein kinase C, adenosine 3',5'-cyclic monophosphate-dependent kinase, or guanosine 3',5'-cyclic monophosphate-dependent kinase is not involved in modulation of the channel.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Renal scarring by mannose-sensitive adhesin of Escherichia coli type 1 pili.

Most Escherichia coli isolates from patients with pyelonephritis possess both pap (mannose-resistant) pili and type 1 (mannose-sensitive) pili. In the experimental pyelonephritis model of rats, the mannose-sensitive-piliated strain caused severe renal scarring, whereas the mannose-resistant or nonpiliated strain did not. Type 1 pili consist of several subunits; one major subunit and other minor subunits. One of the minor subunits, adhesin, is responsible for mannose-sensitive adhesion to eukaryotic cells. The role of adhesin was examined in scar formation after infection with a newly constructed adhesin-deficient mutant which has pilus structure but cannot agglutinate guinea pig erythrocytes. A mutant plasmid, pYMZ84, containing a deletion in the adhesin gene of type 1 pili, failed to agglutinate guinea pig erythrocytes even though the bacteria expressed pili morphologically indistinguishable from those produced by plasmid pSH2, carrying the intact genes for the type 1 pili. E. coli harboring pYMZ84 caused negligible or minimal renal scarring, whereas E. coli harboring pSH2 caused severe renal scarring in rats. These data suggest that the mannose-sensitive adhesin of type 1 pili stimulates renal scarring.

Adhesins, Escherichia coli↗

Efficient and beta-stereoselective synthesis of 4(5)-methyl-5(4)-(5-amino-5-deoxy-beta-D-ribofuranosyl)imidazole and related compounds exhibiting antiulcer activity.

The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of an imidazole derivative gave an adduct 17RS. Treatment of 17RS with 1.5N HCl in refluxing tetrahydrofuran gave the beta-4(5)-ribofuranosylimidazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was converted into beta-19 in 86% yield by the Mitsunobu cyclization. This synthetic method produced only the desired beta-anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group followed by debenzylation gave 21, which was successively derived to the 5'-amino derivative 1 via the 5'-substituted phthalimide 23, followed by hydrazine degradation in excellent yield. Compound 1 was then converted into the 5'-cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacking a methyl group were efficiently synthesized. Among them, the cyanoguanidine 5 and phenylthiourea 8 exhibited antiulcer activities with half the efficacy of cimetidine. The molecular conformation of 5 was determined by X-ray structure analysis.

Animals↗

Hepatic damage influences the decay of nitroxide radicals in mice--an in vivo ESR study.

To determine the role of the liver in the elimination of free radicals from the body, the clearance rate (K) of nitroxide radicals (Tempol) at the hepatic domain was compared with that at the pelvic domain of live mice, using L-band ESR spectroscopy. The reduction of Tempol in biopsy specimens (liver tissue and femoral muscle) and blood obtained from Tempol-treated mice was also monitored using X-band ESR spectroscopy. Results indicated that the reduction of nitroxide radicals was delayed in both the liver and peripheral tissues when the liver was damaged. The decrease in both blood supply and reductants in the damaged liver might be involved in delaying the reduction in the whole body, because the liver can reduce the radicals supplied via the blood from the peripheral tissues, and the reductants such as reduced, glutathione in the peripheral tissues are supplied from the liver.

Animals↗