Interventional left vertriculograms (LVGs) using postextrasystolic potentiation (PESP), nitroglycerin (TNG) and a combination of both were analyzed in order to decide the degree of efficacy of each intervention as a predictor of reversibility in impaired left ventricular segments. Segmental wall motion (SWM) in less severely impaired segments increased to the normal range and SWM in severely impaired segments increased but remained in the abnormal range after CABG. The effects of both PESP and TNG on SWM in impaired segments correlated (r = 0.78 and 0.78) with that of CABG. The increase in SWM due to TNG + PESP was significantly (p < 0.01) greater than that due to either PESP or TNG alone or that of CABG. Either PESP or TNG was clinically reliable for prediction of contractile reversibility in the segments with impaired wall motion prior to CABG. Including the global left ventricular function, PESP reflected the efficacy of CABG more sufficiently than TNG. TNG + PESP provoked more contractile reserve and exaggerated the results of CABG, but may predict reversibility in severely reduced wall motion.
To assess how polymorphonuclear leukocytes act on coronary vasomotion, we measured the changes in isometric tension of isolated canine coronary arterial rings by adding autologous polymorphonuclear leukocytes to the organ chamber. Ring preparations of the left circumflex coronary artery developed isometric tension with a maximum of 80 +/- 21% of PGF2 alpha (5 muM)-induced contraction at the addition of polymorphonuclear leukocytes (5 x 10(5) cells/ml) isolated by the Percoll gradient method. This increase in tension was dependent on the amount of added polymorphonuclear leukocytes (10(4)-5 x 10(6) cells/ml). The integrity of endothelial cells was not disrupted after the addition of polymorphonuclear leukocytes, because the developed tension was reversed by the addition of acetylcholine in an endothelium-dependent manner. The mechanical rubbing of endothelium completely abolished this polymorphonuclear leukocyte-induced vasoconstriction, which was regained by placing an endothelium-unrubbed ring inside the rubbed ring ("sandwich preparation"). The supernatant of either polymorphonuclear leukocyte suspension or polymorphonuclear leukocyte incubation medium with A23187 could not induce the development of vascular tension. Lipoxygenase inhibitors partially suppressed polymorphonuclear leukocyte-induced vasoconstriction. These findings indicate that polymorphonuclear leukocytes and endothelial cells. This polymorphonuclear leukocyte-induced vasoconstriction is not an increase in resting tension due to endothelial injury caused by added polymorphonuclear leukocytes, but the development of active tension. Lipoxygenase product(s) of arachidonate may partially mediate this contraction.
We previously reported that zonisamide inhibits both [3H]flunitrazepam and [3H]muscimol binding in rat brain. In the present study, [3H]zonisamide was found to bind in a saturable fashion to the crude synaptosomal fraction of whole rat brain. Linear regression analysis of the binding data in the Scatchard plot indicated a Kd of 90 nM, and a maximal binding capacity of 1.40 x 10(3) fmol/mg protein. Displacement studies revealed an inhibitory effect of clonazepam and an enhancement effect of GABA on specific [3H]zonisamide binding. These results suggest that specific [3H]zonisamide binding sites may have a tight correlationship with benzodiazepine receptors in rat brain.
Two lines of the transplantable colon carcinoma were established. They were from the spontaneous colon carcinoma of WF-Osaka rat strain which had been set up in our laboratory. Transplant procedure was carried out mainly by the intraperitoneal implantation, and, in particular, the treating with a specified way of HIBITANE for disinfection against colonic flora at the primary transplant was quite effective. The growth speed of the transplanted colon carcinoma was slow at first and gradually increased its speed. Histology of the transplanted tumor altered gradually from the glandular pattern at first to the medullary pattern in the late stage of the transplant generation. Each tumor node in the late stage of transplant generation was composed of numerous small nodules separated by thin stromal tissue. Squamous metaplasia and central necrosis were seen in the center of the small nodules. Two lines of the transplantable colon carcinoma were named C1 and C2 and the former is at now the 101th generation and the latter is at the 107th generation.
The effects of zonisamide on [3H]flunitrazepam binding and [3H]muscimol binding were studied in Sprague-Dawley rat brain. Specific [3H]flunitrazepam bound was decreased to 64.6 +/- 5.6% (mean +/- SD, n = 5, p < 0.002) and 91.9 +/- 4.0% (p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Scatchard plot analysis of [3H]flunitrazepam binding with 10(-3) M of zonisamide revealed an increased Kd value with no change in Bmax. No inhibitory effect of zonisamide was seen on the enhancement of specific [3H]flunitrazepam binding by GABA. As for the effects on GABA receptors, specific [3H]muscimol bound was decreased to 27.7 +/- 10.4% (mean +/- SD, n = 4, p < 0.005) and 68.3 +/- 3.7% (mean +/- SD, n = 4, p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Since therapeutic serum level of zonisamide are around 10(-4) M, these results suggest that zonisamide neuropharmacologically interacts with the GABA/benzodiazepine receptor ionophore complex in a manner similar to phenytoin.
Sizes of spleen and liver were studied by measuring spleen index calculated by multiplying the maximal length by the maximal width of the spleen and liver length at right mid-clavicular line below the costal margin using ultrasonography in 26 Papua New Guineans and in 25 Japaneses living in Papua New Guinea. In Papua New Guinean, spleen index and liver length were 77.4 +/- 9.9 cm2 and 5.4 +/- 0.7 cm, respectively. Their spleen index correlated inversely (p < 0.05) with hemoglobin level. In Japanese, spleen index and liver length were 24.5 +/- 2.1 cm2 and 0.8 +/- 0.3 cm, respectively and spleen index correlated positively with the duration of stay in Papua New Guinea (p < 0.05). These results indicate that the clinical and subclinical infections acquired in P.N.G. may play some role on the development of splenomegaly. Malaria is the prime suspect for the high prevalence of observed splenomegaly in both studied groups.
Renal tubular function was investigated in 98 non-insulin-dependent and 18 insulin-dependent diabetics under conditions of standard glycemic control. Mean urinary excretion of lysozyme, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) in both Albustix-negative and positive patients were significantly elevated above the control range. The increased excretion of lysozyme, beta 2-microglobulin and NAG was found in 21, 55 and 62% of the normoalbuminuric patients, and in 40, 57 and 74% of the microalbuminuric patients, respectively. Besides the parameters cited above, urinary acid-soluble glycoprotein (ASP) was measured to assess its potential as an indicator of early renal dysfunction. Mean urinary ASP excretion was also elevated in both Albustix-negative and positive patients. The albumin/ASP ratio increased as nephropathy advanced. Such a mode of excretion was similar to those of low-molecular-weight proteins (lysozyme and beta 2-microglobulin). The results of multiple regression analysis showed that serum creatinine most highly correlated with the excretion of the urinary proteins except for NAG.
We have established a colon cancer-prone substrain in WF strain rats strictly bred by sister x brother mating for more than 20 years. Colon carcinomas were located only in the ascending colon with no remote metastases. Each incidence of colon carcinoma varied from 30 to 40% in the respective investigation. There was no apparent sex difference. Approximately 9% of colon carcinomas were associated with gastric carcinoma in the prepyloric region and they died within four months of age due to malnutrition and intestinal bleeding. There were a few cases of carcinomas of the terminal ileum and the rectum. All of these carcinomas from three different portions showed histologically well differentiated tubular adenocarcinoma. It was found that about 40% of colon carcinomas showed spontaneous regression in the period from four to twelve months old. We have also succeeded in establishing two lines of the transplantable colon carcinoma (C1 and C2) and the transplantable gastric carcinoma (S1 and S3) from those of spontaneous colon carcinomas and gastric carcinomas. Then recipient female rats inoculated intraperitoneally with these transplantable carcinomas newly developed adenocarcinomas of the corpus uteri, which had never been found in the rats of this strain. In addition, the transplantable tumor line of adenocarcinoma of the corpus uteri was also established (U2). When transplanted these tumors intraperitoneally (S1, S3, C1, C2 and U2), male and female recipient rats extremely increased in the incidence of carcinomas of the stomach and the colon. As far as female recipient rats were concerned, a large number of carcinomas of the corpus uteri were also found regardless of the derivation of tumors. We believe that the established colon cancer-prone rat strain (WF-Osaka) as well as those of transplantable tumor lines will open a further research fields and will be available as an animal model of colon cancer for human beings.