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Changes in the stenotic resistance of a coronary artery following brief coronary occlusion were studied in the anesthetized open-chest dog. A critical coronary stenosis was constructed by tying a thick string around the circumflex coronary artery (LCx) near its origin. The LCx was occluded for 5, 10, 15, 20 and 30 seconds with and without coronary stenosis then the reactive hyperemia was observed. In the absence of the stenosis, resistance of the segment of the large coronary artery remained unchanged during the reactive hyperemia independent of the duration of occlusion. In the presence of the stenosis, however, stenotic resistance increased for a certain time after the release of occlusion. This increased resistance lasted longer with more severe stenosis and with longer duration of coronary occlusion. These results suggest that stenotic resistance can increase dynamically, and that the duration of increased resistance may reflect the severity of the stenosis.

This study used a Shimadzu IP-1B capillary type isotachophoretic apparatus with a potential gradient detector. An ipp-1 withdrawal cell was fitted to this and a technique for withdrawing individual components directly through this port was developed using a microsyringe. The recovery rate was up to 45% for individual target components. When 100% withdrawal of the target component was attempted by withdrawing a volume four times the calculated volume (so that the zones both before and after the target component were also included), the best recovery rate was only 78%. In all cases, the results varied less than 3%. The limit for analysis of individual components of a 0.01 M solution was around 3 microliters. If this volume was exceeded, the ion quantity was too large for the volume of the microcapillary tube and mixed zones formed such that complete separation and analysis of individual components became impossible.

Cytogenetic and dermatoglyphic studies were performed on a group of 197 institutionalized patients with severe mental and physical handicaps in order to evaluate the contribution of chromosomal aberrations on the etiology of the condition, and to determine whether any association exists between the dermatoglyphics and the severe handicaps. There were 4 patients with trisomy 21 and 2 patients with a de novo balanced reciprocal translocation. In addition, 9 patients were found to have a pericentric inversion of chromosome 9 (inv (9) (p11q13)). Other chromosome variations identified included inv (1) (p11q11) (one case), elongation of 1 qh (one case), and telocentric chromosome 13 (two cases). Dermatoglyphics from the patients excluding cases with Down syndrome were compared with those from 500 normal controls. Significant differences were observed in several dermatoglyphic characteristics, including simian crease, fingertip pattern, mean a-b ridge count, thenar/first interdigital pattern, hypothenar pattern, and hallucal pattern. The present study indicated that de novo balanced translocation as well as chromosome duplication or deficiency is causally related to the severe combined handicaps. This study also showed that the incidence of inv (9) (p11q13) in the patients was 4.2 times higher than that in the general Japanese population. If a real association exists between the inv (9) (p11q13) and severe handicaps, the increase of inv (9) (p11q13) in the patients may be explained by the concept of a risk factor. Moreover, the dermatoglyphic deviations found in patients may be evidence that pathological factors had been operating during early embryonic life in some of them.

After the experimental removal of the most part of caecum of rabbit, when it is bred over 100 days, the remained portion of the caecum is enlarged distinctly and not only the spiral plicae increases its number but it is partly formed a peculiar caecal-dilatation, projecting against the colon-side. The muscular layer of caecum-wall is generally thickened, especially the epithelium is markedly proliferated. This is a regenerative phenomenon on the caecum of which damaged portion is to be filled and partly regains the characteristic shape of caecum and at the same time shows the systematical changes on the whole caecum-tissue. Consequently it may be admitted that these changes are not merely the regeneration of tissue of caecum but it is a regenerative process as an organ. However, literature on this subject hold the same view that each tissue of intestinal canals of mammalia is independently regenerated but the regeneration of an organ is not acknowledged. Korschelt states in his book that " Die ausgebildeten Wirbeltiere zeigen keine eigentliche Regeneration der einzelnen Abschnitte des Darmkanals. Wenn von einer solchen die Rede ist, handelt es sich nur um den Ersatz von Teilen der Schleimhaut, die sowohl im Magen, wie in den darauffolgenden Darmpartien stattfindet . . . ". On the other hand, the fact shown by my experimental results on mammalia such as rabbit, proved the regenerative process of intestinal canals, and I believe that it is a new information which overthrows the old established view. On the subject of caecumregeneration, Schmalhausen and others have alreacly pointed out that the morphotgenesis of the regenerated organ or tissue is closely connected with the function or its mechanical element, and in case of the regenerative process of rabbit-caecum, its functional relation is undoubtedly the important factor. There are many theories on the caecum-function and caecum of herbivorous animal such as rabbit plays an important role on the digestion and resorption of cellulose as it has been hitherto marked by Tullberg Ustjnzezw Elllenberger and others. Any herbivorcus animal which takes food which is rich with cellulose, posseses the large caecum, and it is a well known fact that Such food taken is stored in the caecum for a long while and sufficient liquid and putrefactive action decompose the cellulose and completely digests. The remained portion of the excised caecum of rabbit partly regains its peculiar cul-de-sac which is physiologically formed as above described, and at least it may be said that the anatomical structure of caecum in which the intestinal contents isolated from the main intestinal canals is stored for a long while which signifies an importance of its function and again a part of the morphological changes in caecum-regeneration is probably a functional adaptation concerning the digestion and resorption of cellulose. Among the intestinal-tissues, the mucous membrane manifests most distinctly its regenerative activity and also the epithelium of mucous membrane on the originally remained portion of caecum is remarkably proliferated. Thus the defect of the caecum-tisseue is compensated by the hypertrophy. Such proliferation is not observed in all the intestinal canals except the caecum alone. Therefore, the epithelium of the caecum appears to monopolize this special function which the small intestines and colon are unable to compensate.

Function of pituitary-thyroid axis was studied in rats with experimentally induced thyroiditisWistar strain female rats were immunized with homologous thyroid extract in Freund's complete adjuvant and with simultaneous intradermal injection of pertussis vaccine concentrate. They received booster shots at the first and third week after the initial immunization. Serum thyroid hormones and TSH were measured just before, and at weekly intervals after, the initial immunization. Histological examination of the thyroid gland at the second week after immunization showed slight infiltration of macrophages in the thyroid follicles. From the third to the fourth week, massive lymphoid cell infiltration and destruction of follicular architecture developed in all immunized rats. Serum R3 levels slightly decreased during the second week, increased transiently during the third week, then decreased again thereafter. Serum T4 levels decreased slightly durinf the fourth week. Serum TSH levels were not elevated significantly during the third week, but the response to TRH was significantly increased at this time. Basal TSH levels were increased during the fourth week. The TRH test was a sensitive method capable of detecting minimal failure of thyroid function undetected by other routine measuremens of thyroid hormones and TSH.

A permeable cell system has been developed by treatment with digitonin for studying in vitro DNA replication of chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in digitonin-treated permeable cells was analyzed by electrophoresis in agarose-gel. Autoradiography of the agarose-gel revealed that [32P]dCTP was incorporated in SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated the complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The digitonin-treated permeable cell system will serve as a useful system for studying in vitro DNA replication of chromatin.

In 156 cases of gastric cancer, levamisole (LMS) was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started 3 days before operation. This medication was repeated for more than one month. The survival rate up to two years after surgery was studied. The survival rate was not affected in patients with Stage I and II gastric cancer, but in patients with Stage III, the difference in the survival rate between the LMS group and the control group was significantly higher than that in the control group (p less than 0.05). In patients with Stage IV, the survival rate in the LMS group was higher than that in the control group although the difference was not significant. In patients of Stage III and IV, the effect of LMS on the survival rate was highest in cases with curative resection (p less than 0.01). In cases with noncurative resection, the difference between the LMS group and the control group was greatest (24.4%) 12 months after surgery but not significant (p less than 0.5), and also in cases without resection the difference between the two groups was greatest (20.3%) 12 months after surgery but not significant (p less than 0.2).

A shortage of donor organs in clinical transplantation prompted us to study whether resuscitated dead hearts could be utilized for successful orthotopic heart transplantation. After 60 min of hypoxic cardiac arrest, one group of canine hearts was resuscitated (Res group, n = 6). The other group was harvested directly (Non-Res group, n = 6). In the Res group, cardiopulmonary bypass was utilized for resuscitation at 37 degrees C and the animals were then core-cooled to 15 degrees C. The hearts then were preserved in University of Wisconsin solution and orthotopically transplanted. Stable prostacyclin analogue (OP2507) and verapamil, a calcium antagonist, were added to the cardioplegia, and substrate-enriched warm blood cardioplegia and a hydroxy radical scavenger (EPC) were administered at the time of reperfusion of the transplanted heart. All animals in each group were successfully weaned from cardiopulmonary bypass with dopamine (5 micrograms/kg/min). Cardiac function without dopamine was better preserved in the Res group than the Non-Res group (Emax: 130.6 +/- 41.5% vs. 47.1 +/- 24.7%; mean +/- SD, as percent of postbrain death values, P < 0.01 by unpaired t-test). Cadaver hearts 60 min after anoxic arrest can be successfully re-animated and orthotopically engrafted. In addition, the core-cooling technique is useful. We believe this study serves as the key step in the clinical application of dead hearts to successful cardiac transplantation.

This study was undertaken to assess postoperative gastric motility and gastric acid secretion, and pre- and postoperative carbohydrate metabolism in patients with esophageal cancer. The gastric motility was compared among 3 different reconstruction routes in 26 patients who were divided into 2 groups according to the duration of postoperative follow-up; group A, 3 months or less; and group B, 18 months or more. The routes used for subtotal resection of the stomach were the posterior mediastinal, retrosternal, and subcutaneous routes. All patients showed positive resting pressure in the esophagus, but peristaltic waves did not reach the gastric tube at dry swallowing in any patients and peristaltic waves appeared after eating pudding only in 1 patient in group B. The resting pressure and gastric emptying time were similar among reconstruction routes, but the incidence and amplitude of metoclopramide (MCP)-induced peristaltic waves were significantly higher in group B than in group A. Furthermore, 24-h intragastric pH monitoring of gastric secretion in a group of 9 patients revealed individual variation in gastric secretion. Some patients showed high acidity soon after operation, suggesting the need for prophylactic treatment for preventing gastric ulcer. Postoperatively, postprandial serum gastrin levels were significantly higher than preoperative levels. In the other group of 11 patients tested, preoperative and postoperative carbohydrate metabolism were not significantly different. Postoperatively, carbohydrate metabolism recovered to preoperative levels after a transient decrease. These results demonstrated that postoperative motility improved over time although no difference was found among the 3 reconstruction routes used.

Since platelets accumulate taurine, they provide a model for studying the taurine transport in anisosmotic disorders. Thus, in this work we studied the taurine concentration and uptake in the platelets of Brattleboro rats, homozygous (DI) and heterozygous (HZ) for hereditary hypothalamic diabetes insipidus, and Long Evans (LE) normal rats after free water intake and after dehydration induced by water deprivation for 24 h. The decreased ability of the DI rats to concentrate urine led to plasma hypernatremia and hyperosmolality despite excessive drinking. Water deprivation in the DI rats induced drastic dehydration with exacerbated hypernatremia and hyperosmolality. Plasma hypernatremia and hyperosmolality resulted in a significant elevation of the taurine concentration and uptake by platelets of the DI rats. Kinetic assays showed that plasma hypernatremia and hyperosmolality did not alter the affinity of taurine to platelet membrane carrier, as expressed by Km, but caused a profound increase in the maximal transport capacity, Vmax. After free water intake the Vmax of the DI rats was about two times higher than that in the HZ and LE rats and after water deprivation it was about three times higher. Water deprivation doubled the Vmax of the DI rats without changing the Km.

The use of ligand-binding methods to study neurotransmitter-receptor sites has made its impact on almost all aspects of biological pursuits including research on aging and neurodegenerative diseases. In the past, most of the research in biochemical gerontology has largely centered around changes in various neurotransmitters and enzymatic activities. The molecular basis of aging and neurodegeneration at the level of neurotransmitter-receptor interactions has been highly appreciated in the last two decades as a result of receptor binding studies. It is now possible to obtain information about the regional distribution of neurotransmitter receptors in the brain, the pharmacological and biochemical characteristics of these sites, and the functional interrelationships between different neuronal systems in normal and pathological conditions. The passage of time after maturity is accompanied by measurable physiologic decline in virtually all systems. It is the aim of this work to discuss the practical aspects of neurotransmitter and/or drug (ligand)-receptor binding studies, highlighting some examples of their applications to geriatric neuropharmacology research, with special consideration to learning impairment and memory loss in normal and in pathological aging processes.

Formation of sulfate in rat liver mitochondria was studied. About 0.1 mumol of sulfate was formed in mitochondria from 1 g of liver in 60 min when 10 mM L-cysteine was used as the substrate. Addition of either 10 mM 2-oxoglutarate or 10 mM glutathione to this system increased sulfate formation 3 to 4 times. The addition of both 2-oxoglutarate and glutathione resulted in a 20-fold increase in sulfate formation. Sulfate formation in the presence of 5 mM L-cysteine was 58% of that with 10 mM L-cysteine. L-Cysteine-glutathione mixed disulfide was not a good substrate, indicating that this mixed disulfide was not an intermediate of sulfate formation in the present system. Incubation of 3-mercaptopyruvate with rat liver mitochondria also resulted in sulfate formation, and the addition of glutathione accelerated it. Formation of sulfite and thiosulfate was also detected. These results indicate that sulfate is produced in mitochondria, at least in part, from L-cysteine through the transamination pathway (3-mercaptopyruvate pathway).

The concentration of lipoperoxides in maternal blood increases as gestation progresses. The concentration in pregnant women at 40 weeks gestation is 1.6 times higher than in nonpregnant women. The concentration in the cord blood, however, is 70% lower than that in maternal blood. To study the role of placental tissue in the difference in the lipoperoxide concentration between the cord blood and maternal blood, we investigated the lipoperoxide concentration, antioxidant activities and in vitro lipoperoxide formation in placental tissue during pregnancy. The lipoperoxide concentration was 50% lower in placental tissue of 40 weeks gestation than in tissue of 5-11 weeks gestation. Catalase and superoxide dismutase activities in placental tissues increased as gestation progressed, while glutathione peroxidase activity and alpha-tocopherol concentration did not change significantly during the gestational period. The in vitro formation of lipoperoxides in placental tissue decreased as gestation progressed. These results show that placental tissue suppresses lipoperoxide formation in the late gestational age, lowers the concentration of lipoperoxides in the blood and protects the fetus against oxygen toxicity.

We demonstrated the ultrastructure of rat glomerular basement membrane (GBM) by ultra-high resolution scanning electron microscopy. GBM prepared by sonication methods and conductive-staining could be observed without metal coating at magnifications as high as 400,000 times. The GBM showed an irregular meshwork structure composed of various strands and pores. The width of the strands ranged from 6 to 15 nm, and the diameter of pores ranged from 6 to 50 nm. The present study confirmed our molecular sieve theory of the basement membrane.

The effect of coenzyme Q10 (Co Q10) was examined on the survival time and lipid peroxidation of adriamycin (ADM)-treated ICR mice. Co Q10 showed a protective effect against a subacute toxicity in mice induced by two intraperitoneal administrations of ADM (15 mg/kg). The group treated orally with 10 mg/kg of Co Q10 showed the longest survival time of all the groups studied (16.81 +/- 10.29 days, mean +/- S.D.) and a significantly longer survival time (p less than 0.001) than the ADM-alone group (7.48 +/- 1.99 days). The inhibitory effect of Co Q10 on the plasma and tissue lipid peroxidation levels did not correlate with the effect of prolonging the survival time of mice. Co Q10 tended to inhibit rises in plasma and liver lipid peroxidation levels induced by ADM administration, but there was no statistically significant difference between treatments. There was a statistically significant different inhibitory effect in the kidney lipid peroxidation levels, but was not in those of the heart.

A comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC) accompanied with hepatocellular carcinoma (HCC) (of which 35 had ascites and 24 did not at the time of admission) and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not). HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96%) died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.

Six quantitative psychometric tests were performed on 51 healthy subjects, 19 cirrhotic patients with subclinical hepatic encephalopathy (SHE), 32 cirrhotic patients without SHE, and 26 patients with other diseases. Strong correlations between age and the results of all the psychometric tests were observed in the healthy subjects (p less than 0.005). Sex and etiology of liver cirrhosis did not affect the test results. SHE patients, compared with non-SHE and health subjects, presented impairment in the ability to perform the tests, even in the absence of obvious clinical and electroencephalogram findings. In SHE patients, trailmaking test A (TMT A) yielded the highest frequency of abnormal values, 63%. TMT A results were abnormal in 80% of SHE patients with abnormal scores in other tests, and thus it seemed to be the most sensitive test. Liver function tests did not correlate with psychometric testing in any of the groups. Blood ammonia levels in SHE patients with abnormal TMT A scores correlated with TMT A scores (r = 0.752, p less than 0.01); this was not the case in SHE nor non-SHE patients with normal TMT A results. These data demonstrate the usefulness of psychometric tests in detecting SHE.