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Biomedical subjects

K Inokuchi

Publications and source records attributed to K Inokuchi.

At least 235 records · Page 13Linked to original sources

Bidirectional effects of splenectomy on the growth of syngeneic tumor in mice.

The effects of splenectomy on tumor growth following inoculation with a relatively large number of cells (1 X 10(7) ) and a smaller number of cells (5 X 10(5) ) of Meth I tumor were studied. When 1 X 10(7) tumor cells were inoculated, tumor growth in splenectomized mice was depressed, while tumor in sham-operated mice grew progressively. On the contrary, when 5 X 10(5) tumor cells were inoculated, the tumor take was lower in sham-operated than in splenectomized mice. The spleen cells from mice inoculated with either a large or small number of tumor cells, showed an equally potent cytotoxic activity, but no detectable suppressor cell activity. On the other hand, the activity of immunosuppressive factor was detected in sera from mice inoculated with 1 X 10(7) tumor cells, but not in those given 5 X 10(5) cells. The effect of splenectomy on tumor growth is, thus, bidirectional, depending on the dose of tumor cells inoculated.

Animals↗

Deficient superoxide-generating activity and its activation of blood monocytes in cancer patients.

Superoxide (O2-)-generating activity of blood monocytes, the precursors of macrophages, from patients with advanced cancer and/or infection was studied. Monocytes from normal subjects generated 0.288 +/- 0.022 nmol O2-/min/10(5) cells (mean +/- S.E.M., n = 36) after sequential stimulation with cytochalasin E and wheat germ agglutinin. Monocytes from 69 non-infected adult patients with advanced malignancy of the stomach, esophagus and liver, and 7 pediatric patients with neoplastic disease released significantly less O2- than those from normal subjects (0.176 +/- 0.015, P less than 0.005). Infection increased the activity about 4-fold in patients with malignancy compared to non-infected cancer patients. These results suggest that monocytes of cancer patients are defective in secreting O2-, though the activity may be stimulated by infection.

Adolescent↗

Limited hepatic resection effective for selected cirrhotic patients with primary liver cancer.

We evaluated in retrospect the applicability of limited hepatic resection in cases of primary liver cancer in cirrhotic patients. According to the severity of impaired liver function, 37 patients underwent limited resection, and for 13, standard major hepatic resection was done. The mortality rate in case of limited resection was 10.8%, and the rate in case of massive excision was 15.4%. One, two- and five-year survival rates of limited operation were 79.9, 60.3, and 32.6%, respectively. After standard resection, the rates were 78.7, 67.5, and 22.5%, respectively. There were no significant differences in the mortality and survival rates between the two groups. These results indicate that, for the patient with a small liver cancer, and poor liver function, the limited procedure leads to a comparatively longer survival. This limited resection can be selectively used to treat cancer associated with cirrhosis and encapsulated tumors. For the preoperative evaluation, hepatic arteriograms aid in patient selection.

Adult↗

Prophylactic portal nondecompression surgery in patients with esophageal varices. An interim report.

This is an interim report of a prospective controlled study to evaluate prophylactic surgery in 112 patients with portal hypertension and esophageal varices treated since 1980. Methods of operation were confined to those with the least influence on portal circulation, namely selective shunts and nonshunting direct interruption procedures. The bleeding rates were 19.2% in the medical group and none in the surgical group (p less than 0.01). The mortality in the medical group in case of first bleeding was 50%. Operative mortality was 3.3%. There was no difference in the survival rate between the two groups at the time of 2 years follow-up. Prophylactic surgery led to a prevention of esophageal bleeding without any increase in the mortality rates.

Adult↗

Exclusion of nonisolated splenic vein in distal splenorenal shunt for prevention of portal malcirculation.

In an attempt to prevent portoprival malcirculation after distal splenorenal shunt (DSRS), a splenic hilar renal shunt (HRS) with proximal flush ligation of splenic vein was designed. To accomplish this procedure, two methods were compared: HRS alone (Group A) and HRS plus proximal flush ligation of the splenic vein (Group B). In Group A, which included 20 cirrhotic patients with esophageal varices, angiographic as well as pulsed Doppler flowmetric follow-up study revealed a portal thrombosis in two patients and severe narrowing of a portal vein in another two. Considerable stealing flow was observed in these four patients. In the Group B series, which included 33 cirrhotic patients, there were no gross changes in the portal hemodynamics. Normal prograde portal flow was confirmed by Doppler flowmeter in this series including 14 patients of more than 8 months after surgery. When the amount of nonisolated splenic vein embedded in the pancreas is minimized, portal malcirculation after distal splenorenal shunt can, to a great extent, be prevented.

Collateral Circulation↗

Simultaneous occurrence of primary carcinoma and chondrosarcoma in the liver. A case report and a review of the literature.

We treated a 67-year-old man with primary carcinoma and sarcoma arising from the different areas of the cirrhotic liver. Histologically the carcinoma was of hepatocellular origin and the sarcoma consisted mainly of poorly differentiated mesenchymal cells partly with a chondrosarcomatous component. Among nine similar cases reported in the literature, only one was a rhabdomyosarcoma and the others were described simply as of spindle cell variety without evidence of mesenchymal differentiation. In the present case, the sarcoma consisted of mesenchymal cells with distinctive areas of unequivocal chondrosarcoma.

Aged↗

Promoter exchange between ompF and ompC, genes for osmoregulated major outer membrane proteins of Escherichia coli K-12.

Expression of the ompF and ompC genes coding for major outer membrane proteins OmpF and OmpC is regulated in opposite directions by medium osmolarity. Chimera genes were constructed by a reciprocal exchange of the promoter-signal sequence region between the two genes. The chimera gene construction was designed so that the proteins synthesized by these genes were essentially the same as the OmpC and OmpF proteins. Studies with the chimera genes demonstrated that the osmoregulation of the OmpF-OmpC synthesis was promoter dependent. They also showed that cells grew normally even when the osmoregulation took place in opposite directions. The effects of the ompR2 and envZ mutations, which suppress ompC and ompF expression, respectively, also became reversed. The reduced expression was still subject to the promoter-controlled osmoregulation. Based on these observations, the mechanism of regulation of the ompF-ompC gene expression and its physiological importance are discussed.

Bacterial Outer Membrane Proteins↗

Mutation causing reverse osmoregulation of synthesis of OmpF, a major outer membrane protein of Escherichia coli.

Supplementation of growth media with high concentrations of substances like sucrose results in the induction of OmpC synthesis and the suppression of OmpF synthesis. We isolated a novel mutant in which OmpF synthesis is in the opposite direction from normal osmoregulation. By transductional mapping, the mutation was localized at 75 min between malA and aroB on the Escherichia coli chromosome map where the ompR-envZ region is. The mutation was suppressed by a plasmid carrying the ompR gene but not by a plasmid carrying the envZ gene alone. The mutation also resulted in the almost complete suppression of OmpC synthesis. However, the remaining OmpC synthesis was osmoregulated normally. Based on these observations, the mechanism of osmoregulation of OmpF-OmpC synthesis is discussed.

Bacterial Outer Membrane Proteins↗

Attenuation by prostaglandins of adrenergically induced renal vasoconstriction in anesthetized rats.

We have investigated the role of prostaglandins (PG) in the modulation of adrenergic neuroeffector events by examining the effect of PGI2 and PGE2 and their precursor, arachidonic acid, on the decrease in renal blood flow elicited by renal nerve stimulation or by injected norepinephrine in pentobarbital-anesthetized rats, with or without pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate. Administration of PGI2 or PGE2 (0.4 micrograms X kg-1 X min-1) or arachidonic acid (5 micrograms X kg-1 X min-1) into the renal artery reduced vascular resistance and inhibited the vasoconstrictor response elicited by renal nerve stimulation or by injected norepinephrine. In contrast, administration of sodium meclofenamate (10 mg/kg iv + 30 micrograms X kg-1 X min-1) into the renal artery increased renal vascular resistance and enhanced the renal vasoconstrictor response to both adrenergic stimuli. In animals pretreated with the cyclooxygenase inhibitor, the ability of arachidonic acid, but not that of either PGE2 or PGI2, to reduce renal vascular resistance and the vasoconstrictor response to either nerve stimulation or injected norepinephrine was abolished. These data indicate that one or more prostaglandins, probably PGE2 or PGI2, formed in the kidney reduce renal vascular tone by their direct action on the vascular smooth muscle and by attenuating the influence of adrenergic stimuli on renal vasculature.

Anesthesia, General↗

Inhibition by bradykinin of renal adrenergic effects in anesthetized rats.

We studied the contribution of prostaglandins to the actions of bradykinin at the renal vascular adrenergic neuroeffector junction by examining the effect of the peptide on the decrease in renal blood flow elicited by renal nerve stimulation and injected norepinephrine in pentobarbital-anesthetized rats with or without pretreatment with the cyclooxygenase inhibitors sodium meclofenamate or indomethacin. Infusion of bradykinin, 10 ng X kg-1 X min-1, into the renal artery reduced both the basal and the rise in renal vascular resistance produced by nerve stimulation or norepinephrine. The prostaglandin precursor arachidonic acid, 5 micrograms X kg-1 X min-1, infused into the renal artery, also reduced renal vascular resistance and the vasoconstrictor response elicited by either adrenergic stimulus. In animals pretreated with either sodium meclofenamate or indomethacin, the effect of arachidonic acid, but not that of bradykinin, to produce renal vasodilation and to attenuate adrenergically induced renal vasoconstriction was abolished. These data suggest that bradykinin produces renal vasodilation and inhibits the renal vasoconstrictor effect of adrenergic stimuli in the rat kidney in vivo by a mechanism unrelated to prostaglandin synthesis.

Acetylcholine↗

Effect of hemorrhagic shock on pulmonary transvascular fluid and protein exchange in anesthetized dogs.

We demonstrated the effect of hemorrhagic shock with resuscitation on pulmonary fluid and protein exchange in anesthetized dogs. Lung lymph flow decreased during early shock and then increased gradually to baseline during late shock as the pulmonary vascular pressures reverted toward baseline levels, while the lymph-to-plasma protein ratio remained relatively constant throughout the shock period. During resuscitation, lung lymph flow increased significantly with the decreasing lymph:plasma protein ratio, suggesting no change in permeability to proteins. Lymph protein flow, which is characteristic of increased endothelial permeability, was also not altered during resuscitation, compared to that following increased vascular pressure induced by inflation of a left atrial balloon catheter. These findings suggest that no change in pulmonary vascular permeability occurs in anesthetized dogs after hemorrhagic shock with resuscitation.

Animals↗

Pulmonary interstitial edema in experimental cirrhosis of the liver in rats.

To determine whether interstitial pulmonary edema occurs or not in experimental cirrhotic rats, male Sprague-Dawley rats were given carbon tetrachloride subcutaneously in order to induce liver cirrhosis. The percent lung water content of the cirrhotic rats increased to 79.1 +/- 0.7% compared to 77.4 +/- 0.9% in control rats (p less than 0.001). Microscopically, 8 of 10 cirrhotic rats show the pulmonary interstitial thickening with lymphocytic infiltration. Moreover, perivascular edema with dilatation of lymphatics was frequently recognized. This suggested that fluid retention of pulmonary interstitial tissue would occur in the cirrhotic rats, and then perivascular edema would compress the small airways of the lung in cirrhotic rats.

Animals↗

Promoting effect of partial gastrectomy on carcinogenesis in the remnant stomach of rats after oral administration of N-methyl-N'-nitro-N-nitrosoguanidine.

The promoting effect of partial gastrectomy in the development of cancer in the remnant stomach was examined in rats after oral administration of N-methyl-N'-nitro-N-nitrosoguanidine, using various surgical approaches. The incidence with which cancer developed in the remnant stomach following gastrectomy was lower than the incidence of gastric cancer in the entire glandular stomach. The incidence of cancer in the remnant stomach following Billroth II procedure according to Mayo's method, was higher than the incidence of cancer with other reconstructive methods as well as the corresponding area in the nonresected groups. There was a correlation between the incidence of cancer and the total bile acid concentration in the remnant stomach.

Administration, Oral↗

Decreased superoxide (O2-)-generating activity of blood monocytes from patients with hepatic cirrhosis.

The superoxide-generating activity of blood monocytes from patients with hepatic cirrhosis was studied by the rapid and sensitive method using cytochalasin E and wheat germ agglutinin as triggering agents. The initial rates of superoxide generation by the patients' monocytes were 0.110 +/- 0.072 n mol/min/10(5) cells (mean +/- SD, n = 22) after sequential treatment with cytochalasin E and wheat germ agglutinin, while those of controls were 0.305 +/- 0.123 n mol/min/10(5) cells (mean +/- SD, n = 33) (P less than 0.001). The activity correlated inversely with indocyanine green retention rates; the regression line was Y = 0.220-0.0028 X (Y; superoxide-generating activity, n mol/min/10(5) cells, X; indocyanine green retention rate, per cent), whose test of significance of the regression coefficient was 0.010 less than P less than 0.025. The presence of ascites, a decreased in the number of white blood cells, and increased serum total bilirubin, also inversely correlated with the superoxide-generating activity. These show that in cirrhotic patient, the superoxide-generating activity of blood monocyte, which may reflect NAD(P)H oxidase activity, is impaired in proportion as the grade of hepatic cirrhosis increases.

Adult↗

The natural history of non-alcoholic cirrhosis.

To assess the natural history of non-alcoholic liver cirrhosis, one hundred and eighty medically treated Japanese cases, including 110 accompanied by esophageal varices were investigated retrospectively. Among those patients with varices fifty-one (46.4%) bled from the upper gastrointestinal (GI) tract and thirty-two (29.1%) from esophageal varices, while GI bleeding was found in only six out of 70 patients without varices. The GI bleeding rate was the highest in patients with varices and concomitant hepatoma (76.5%). The mortality rate of the GI bleeders was 68.6% in patients with varices and 33.3% in patients without varices. The mortality on the first variceal bleeding episode was 65.6%, and another 25.0% had rebleeding from varices, resulting in a one-year survival of 9.4%. The ten-year cumulative percentage of variceal bleeding was 61.2% in patients with varices, and that of occurrence of hepatoma was 50.7% in total of 180 patients. This study revealed that the non-alcoholic cirrhotic patients have a highly rate of complication by hepatoma and that the development of hepatoma doubles the risk of varix rupture.

Adult↗

A desktop computer to visualize the intraluminal velocity profile and its clinical application.

Based on our previous study that the outcome of reconstructive surgery for lower limbs could well be predicted by flow waveforms and that this state was defined by variation of wall shear stress (tau) in a cardiac cycle, we set up a desktop computer that could calculate wall shear stress in a given patient. This work is based on a principle of a computational method for simulating pulsating blood flow. The flow data from the patient are sent to the waveform analyzer, where the intraluminal velocity profile as well as the shear stress variation is demonstrated. Our study revealed no late occlusion in patients with flow waveforms over 70 dynes/cm2 in tau-variation, early graft failure in those below 20 dynes/cm2, and late occlusion in considerable numbers of patients whose waveforms were between 70 and 20 dynes/cm2. Intraoperative use of the waveform analyzer disclosed the occult cause of obstruction, which would otherwise be overlooked, leading to a remarkable decrease in the rate of immediate graft failure. Follow-up of outpatients with this approach facilitated early detection of late failure, making it possible to repair the graft with minor surgery. Use of the waveform analyzer proved superior to ankle pressure index in predicting graft failure.

Aged↗