Left ventricular contraction progresses from the apex to the base, and because the base has a large internal diameter than the apex, the workload of the left ventricular wall is greater at the base. However, many studies have revealed that the level of regional myocardial blood flow is the same in all areas of the left ventricle. This fact strongly suggests that oxygen metabolic levels differ along the long axis of the left ventricle. To clarify the differences in local oxygen metabolism of the left ventricle, regional myocardial oxygen uptake of the left ventricle was examined in the anesthetized open chest dog. Small polyethylene catheters were inserted into the veins of the lateral, the antero-basal, the mid-anterior and the apical wall of the left ventricle. Venous blood samples were collected anaerobically, and blood gases and oxygen saturation were analyzed as aortic blood. The regional myocardial oxygen uptake of the left ventricle was not homogeneous. It was higher at the base and lower at the apex indicating that the differences in the workload and oxygen demand of the left ventricular wall were met by different levels of oxygen extraction. With left atrial pacing, a small increase in myocardial oxygen demand was compensated for by increased myocardial blood flow without changes in regional oxygen extraction. In contrast, continuous intravenous infusion of isoproterenol increased both myocardial flow and regional oxygen extraction in the middle and apical wall, while the extraction of the lateral wall did not change. Differences in the extraction between each area became smaller with isoproterenol infusion, but the gradient of myocardial oxygen uptake still existed. These findings suggest that the basal area of the left ventricle has a smaller reserved capacity of oxygen extraction.
In order to elucidate the mechanism of metallothionein (MT) induction by bacterial endotoxin during acute phase alteration, I investigated direct and indirect inducers of MT by measuring the induced uptake of [35S] cysteine into cultured cells. Although zinc or dexamethasone induce MT directly when added to the culture medium of human hepatic (Chang) cells, endotoxin added to the culture medium was found to be ineffective in inducing MT synthesis. Since MT was induced during acute phase alteration, I focussed on the role of macrophages. I found that the conditional medium from endotoxin-activated macrophages (“Mφ+LPS”) induced MT synthesis in Chang cells, while the incubation medium of nonactivated macrophages did not. Primary induction by zinc, copper or cadmium in “Mφ+LPS” was denied, because the concentrations of these metals in “Mφ+LPS” were almost the same as in the control medium. To clarify the details of the process of MT induction, the kinetics of MT synthesis by “Mφ+LPS” in Chang cells were studied and compared with the kinetics of MT synthesis by zinc and dexamethasone in Chang cells. “Mφ+LPS” induces MT synthesis, proportionally to the concentration of “Mφ+LPS”, whereas zinc and dexamethasone induce MT sigmoidally and biphasically, respectively. On the other hand, the time course of MT induction by “Mφ+LPS” is similar to that by zinc, but different from that by dexamethasone. I conclude that: 1. Macrophages activated by endotoxin release a new factor which induces MT synthesis in human hepatic cells. 2. The new factor is different from dexamethasone and zinc.
A permanent cell line, MT-TY, has been successfully established in continuous culture from a metastatic lymph node of a patient with malignant thymoma (epithelial type). Most of the MT-TY cells grew in suspension with formation of cell clumps. The doubling time of the cells was 36 hours and the modal chromosome number was 68. The MT-TY line is considered to have originated from donor's thymoma cells on the basis of cytogenetic, morphological and chromosomal features.
A continuous cell line, which was designated as MT-TY, was established from an explant culture of human malignant thymoma (epithelial type) in our laboratory. In the present study, for the purpose of making an animal model of human malignant thymoma, MT-TY cells were transplanted into antilymphocyte serum-treated newborn hamsters. The MT-TY line was serially transplanted for 7 passages. When 1.2-11.0×106 cells were inoculated intraperitoneally, all of the 22 experimental animals developed invasive tumors. Of the 22 hamsters, ascites and pulmonary metastases were found in 16 and 4 hamsters, respectively. Histological characteristics of the tumors in hamsters were similar to those of epithelial type of human malignant thymoma. This animal model would be useful for various studies of human malignant thymoma.
The effects of chronic treatment with verapamil(VP) on monoamine release and metabolism in rat brain in vivo were compared with the effects of methamphetamine(MAP) and reserpine(RES). These drugs were administered to rats in drinking water for two weeks. The contents of monoamines(DA and 5HT) and their major metabolites(DOPAC, HVA and 5HIAA) in eight discrete brain regions were measured by HPLC-ECD. After treatment with VP, DA levels decreased in the nucleus accumbens(N.ACC) and the suprachiasmatic nucleus(SCN), but no significant changes were demonstrated in the metabolites(DOPAC, HVA). 5HT levels decreased in the N.ACC, SCN and amygdara(AMY), and 5HIAA levels decreased in the raphe dorsalis(RD). GABA contents were increased in the N.ACC. After treatment with MAP, DA levels decreased in the N.ACC, striatum(STR) and ventro-medial hypothalamic regions(VMH). No significant change was shown in the metabolites. 5HT contents decreased in the N.ACC, STR, AMY, VMH and RD. 5HIAA contents decreased significantly in the RD. After treatment with RES, DA levels decreased in the N.ACC, STR and SCN. HVA contents decreased in the N.ACC and SCN, though they increased in the LH and SN. 5HT levels decreased in the N.ACC, SCN, AMY and RD. High 5HIAA concentrations were found in the N.ACC, STR, LH and VMH. DA, DOPAC and HVA levels were reduced more in several regions by co-administration of VP and MAP than by MAP treatment alone. DA was lowered more in the RD and HVA was lowered more in several regions by co-administration of VP and RES than by RES treatment alone. The well known locomotor hyperactivity induced by MAP was enhanced by VP. The present study suggests that there are at least two classes of voltage-gated calcium channels in the central nervous system related to the release of monioamines, one sensitive to VP and other not. In addition, chronic VP treatment may have an inhibitory effect on the release and synthesis of monoamines.
Intralobular (A) and interlobular (B) tissue fragments of the liver were separated from normal human liver tissue by tissue fractionation with a metal mesh. Connective tissue extracted from A was composed of reticulum fibers and that from B was thick and contained vascular structures, and a small amount of muscle and elastic fibers. It was revealed by histological methods that the tissue fragments and connective tissues retained the integrity of intra- and interlobular tissue as observed in vivo. These connective tissues were solubilized with either pepsin in acetic acid or 4 M guanidine-HCl, and analyzed for the amount of collagen, neutral sugar, fibronectin, laminin and hexuronic acid. Pepsin digestion resulted in solubilization of about 70% of total collagen. Collagen type analysis revealed that 29% was type I, 28% was type III and 43% was the other types in intralobular connective tissue, and that 42% was type I, 29% was type III and 29% was the other types in interlobular connective tissue. Guanidine-HCl extraction resulted in solubilization of 32.4% (A) and 22.1% (B) of total neutral sugar. The concentration of fibronectin and laminin in the guanidine extract were 16.4 μg and 53.6 ng per 1 g of A, and 3.4 μg and 157.0 ng per 1 g of B. Guanidine-HCl extraction resulted in solubilization of 41.8% (A) and 24.2% (B) of total hexuronic acid, which accounted for 3.1 mg/g and 1.3 mg/g, respectively. These results indicated that the two connective tissues histologically defined as intralobular and interlobular connective tissue were different in the amount of components.
In order to prevent farmers working in greenhouses from developing occupational low back pain, the relationship between working space and working posture was examined. Out of 61 greenhouses, the working space of 57 greenhouses was measured as a function of the height of the plant stems and the width of the pathways, The author demonstrated that the height of the stem was the best indicator of the working space. The results of a study of the relationship between working space and working posture showed that the narrower the working space is, the more frequently farmers worked in an unnatural posture. The prevalence of low back pain among 144 farmers working in eggplant greenhouses was examined. A negative correlation was observed between the prevalence of low back pain among the farmers and the width of their working spaces.
Changes in the granule cells of the rat dentate gyrus, hippocampal mossy fibers and moosy fiber boutons following administration of picrotoxin were examined at the ultrastructual level. In controls, many small round clear vesicles (20-40 nm in diameter) along with a small number of large dense-core vesicles (60-90 nm in diameter) filled the mossy fiber boutons. Following administration of picrotoxin, the large dense-core vesicles increased in number and accumulated on the presynaptic membrane. Some of the large dense-core vesicles appeared to be fused with the membrane and frequently exhibited omega-shaped exocytotic profiles. A greatly increased number of coated vesicles (60-90 nm in diameter) was observed on the maturing face of the Golgi fields in the cytoplasm of granule cells after injection of picrotoxin. In addition, the ends of the Golgi cisternae rods occasionally appeared to be coated, and coated large dense-core vesicles (60-80 nm in diameter) were seen in the mossy fibers. This study showed not only an increased incidence of large dense-core vesicle exocytosis during seizures, but also suggests that these vesicles are replaced in excess from the perikaryon.
Monoclonal antibodies (MAbs) against the major gag protein (p34) of a retrovirus produced in a human lymphoblastoid cell line (HLB) were prepared for the characterization of this virus. Immunoelectron microscopy showed that one of these MAbs, MAb 14H10, immunoreacted specifically with the core protein of this virus. p34 and its partially degraded products were recovered in a one-step manipulation from the crude extract of HLB cells by immunoaffinity chromatography using MAb 14H10. p34 was highly purified by polyacrylamide gel electrophoresis, and the amino acid sequence of 27 amino acid residues in the N terminal region of the purified p34 was determined by a gas-phase microsequenator. The fact that the sequence begins with Pro-Val-confirmed that p34 was the major gag protein of this virus. Comparing the N-terminal sequence (27 amino acid residues) of p34 with the known counterpart sequences of major gag proteins of other retroviruses, no retroviruses highly homologous in the N-terminal region were found. The N-terminal sequence (Pro-Val-) of p34 and Mg2+ preference of the reverse transcriptase of this virus suggested that this virus belonged to a retrovirus other than mammalian type C retroviruses whose prototype is Moloney murine leukemia virus having the N-terminal sequence (Pro-Leu-Arg-) of the major gag protein and Mn2+ preference of the reverse transcriptase.
The superoxide production of peripheral blood monocytes stimulated by concanavalin A and cytochalasin E was examined in sarcoidosis patients. The superoxide production of monocytes was significantly enhanced in sarcoidosis patients (9.8±6.4 nmol/min/106 cells) compared with healthy controls (6.6±3.5) (p<0.02). The levels of superoxide production were 12.4±8.7 in 14 patients with stage 1 sarcoidosis (bilateral hilar lymphadenopathy), 9.4±3.9 in 15 patients with stage 2 sarcoidosis (bilateral hilar lymphadenopathy and parenchymal involvement) and 6.1±2.6 in 4 patients with stage 3 sarcoidosis (parenchymal involvement). These levels were significantly higher in patients with stage 1 and 2 sarcoidosis than in healthy controls. The superoxide production was significantly enhanced in patients with elevated serum lysozyme activity and slightly enhanced in patients with high percentages of T-lymphocytes (over 28%) in bronchoalveolar lavage fluid. These data suggest that peripheral blood monocytes in sarcoidosis patients have been activated by unknown factors.
In order to clarify the role of monocytes and macrophages in the formation of sarcoid granulomas, primary cultures of sarcoid tissues were initiated with biopsied specimens from patients with sarcoidosis (6 lymph nodes and one subcutaneous nodule), and compared with primary cultures of 5 lymph nodes obtained from patients with other disorders. The number of monocytes and macrophages migrating from tissue explants was larger in sarcoid tissues than in non-sarcoid tissues. In the cultures of sarcoid tissues, the monocytes and macrophages aggregated at the second week of cultures and multinucleated giant cells were observed at the third week. However, these findings were not observed in the culture of non-sarcoid tissues. At the fourth week, the aggregated macrophages and multinucleated giant cells disappeared and fibroblasts developed. The lysozyme activity of the culture medium of sarcoid tissues was higher than that of non-sarcoid tissues, but no difference was observed in angiotensin-converting enzyme activity. These results suggest that the monocytes and macrophages in sarcoid granulomas have been activated by unknown factors and may transform to epithelioid cells constituting sarcoid granulomas.
The effects of heat used either alone or in conjunction with 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on cultured rat (C-6) and human (KY) glioma cell lines were quantitatively studied by colony formation assay. Flow-cytometric analysis of the cell cycle progression of C-6 glioma cells after exposure to 43°C was also carried out. The results obtained were as follows. 1) These cell lines had differences in heat sensitivity and in their response to the cytocidal effect of ACNU. 2) Synergistic effects of combined heat and ACNU were observed on both cell lines. 3) After exposure to 43°C asynchronous C-6 cells accumulated initially in late S phase and later in the G2+M phase. These results suggest that the combined use of heat and ACNU is effective in the management of malignant tumors.
In order to assess the effectiveness of chest irradiation in addition to intensive chemotherapy in the treatment of limited stage small cell lung cancer, 56 patients were randomized to receive either chemotherapy alone or chemotherapy plus chest irradiation, between April 1981 and September 1986. The chemotherapy regimen consisted of a four-drug combination of cyclophosphamide, vincristine, methotrexate and procarbazine, and a three-drug combination of VP-16, adriamycin and nimustine, given alternately every 8 weeks. One group of 28 patients received chemotherapy alone, and another group of 28 patients received chest irradiation of 40Gy, in 20 fractions over 4 weeks, between cycles 1 and 2 of the chemotherapy. Complete response rate were similar in the two groups; 46% for those receiving chemotherapy alone, and 62% for those receiving chemotherapy plus chest irradiation. There was no significant difference in the median survival time (14.5 months for chemotherapy alone versus 12.0 months for chemotherapy plus chest irradiation). The combined modality treatment was more toxic than chemotherapy alone; two patients receiving such treatment died of radiation pneumonitis. However, as far as the 3-year survival rate, there was a trend favoring patients receiving the combined modality treatment (11% versus 19%). Although additional studies are required to determine the optimal dose and schedule, timing, and selection of patients as for chest irradiation, the major need for the treatment of small cell lung cancer is better systemic chemotherapy. It seems likely that the role of chest irradiation will become more important as improved chemotherapy is developed.
In order to assess the usefulness of prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer, 43 complete responders to chemotherapy were randomized either to receive PCI or to have observation only between April 1981 and September 1986. Twenty-one patients were given 40 Gy of PCI in 20 fractions over 4 weeks after they had achieved complete response. Of those, 5 patients (24%) developed brain metastases within a median follow-up period 47.5 months (range, 15.5 to 67 months), while 11 of 22 patients (50%) not receiving PCI developed brain metastases within a median follow-up period of 40.5 months (range, 13 to 70 months). Cumulative actual probability of a brain metastasis was 5% at 12 months and 25% at 24 months for those receiving PCI, while it was 38% at 12 months and 53% at 24 months for those not receiving PCI. Thus, the probability of a brain metastasis was significantly lower in the PCI group than in the control group. The median survival time was 21 months for the PCI group and 14.7 months for the control group. The 2-year survival rate was also higher in the PCI group (35% versus 14%). However, the differences were not statistically significant due to the small number of patients. These interim results suggest the possibility of reducing brain metastases and prolonging survival by PCI in complete responders to chemotherapy.
The cultured smooth muscle cell offers several advantages to investigation of cell character. It can be utilized to make studies on aging and atherosclerosis. This work was carried out to investigate the effects of intracellular lipid peroxides and aging on the growth rate of cultured aortic medial smooth muscle cells obtained from normal rats and rats with streptozotosin-induced rats. Cells from young and old rats showed similar growth and contained the same amount of intracellular lipid peroxides. However the rate of growth of cells from diabetic rats was inversely proportional to the period of illness and also to the quantity of lipid peroxides contained in the cells. When normal cells were cultured in an adriamycin-containing medium, their growth rate was inversely proportional to the adriamycin concentration of the medium and also the amount of intracellular lipid peroxides.
We found in the segment of this study that lipid peroxides inhibit the proliferation of aortic medial smooth muscle cells derived from rats with streptozotocin-induced diabetes (STZ-rats) and normal cells cultured in an adriamycin-containing medium. It was then supposed that vitamin E, an antioxidant, may restore cell proliferation by its inhibitory effect on lipid peroxides. This led us to study the effect of vitamin E on the proliferation of cells derived from STZ-rats and normal cells cultured in an adriamycin-containing medium. The growth rate of normal cells was increased by the addition of vitamin E. However, its effect was reduced with aging. on the other hand, the growth rate of cells derived from STZ-rats was hardly affected and intracellular synthesis of lipid peroxides was not attenuated by the addition of vitamin E. The effect of vitamin E on cell proliferation and the synthesis of intracellular lipid peroxides was not found in cells obtained 12 months after STZ injection. Adriamycin inhibited normal cell proliferation concentration-dependently with an increase in intracellular lipid peroxides. However, when normal cells were planted in a medium containing adriamycin and vitamin E, the effect of adriamycin on cell proliferation was reduced. Namely, when lipid peroxides coexisted with adriamycin for a short period of time, vitamin E prevented the effect of lipid peroxides on cell proliferation. However, when they remained in the cells for a long period of time, vitamin E did not show any inhibitory effect on the lipid peroxides. The results suggest that the effect of vitamin E on cell proliferation is dependent on the period of intracellular existence of lipid peroxides.
Immunoglobulins and histamine were estimated in bronchoalveolar lavage fluid (BALF) of 25 patients with bronchial asthma, 7 patients with hypersensitivity pneumonitis, 8 patients with sarcoidosis and 3 patients with bronchiolitis. In 8 healthy subjects, relation levels of immunoglobulins and histamine in BALF were: IgG/alb ratio, 0.28±0.17 (mg/mg); IgA/alb ratio, 0.19±0.15; IgM/alb ratio, 0.01±0.01; IgE/alb ratio, 0.36±0.29×102 (IU/mg), and His/alb ratio, 0.67±0.29 (ng/mg). In asthmatic patients, the relation levels of immunoglobulins and histamine in BALF were: IgG/alb ratio, 0.26±0.21; IgA/alb ratio, 0.11±0.06; IgM/alb ratio, 0.01±0.01; IgE/alb ratio, 0.89±0.99×102, and His/alb ratio, 1.38±0.84. These patients showed a moderately higher His/alb ratio than healthy subjects. The increased His/alb ratio was closely related to immediate skin tests and serum IgE levels, especially in atopic patients. An inverse relationship was noted between an elevated IgE/alb ratio and/or His/alb ratio and the degree of peripheral airway obstruction. There was a relationship between an elevated IgG/alb ratio and peripheral airway obstruction, although there was no significant relationship between immunoglobulins/alb and/or His/alb ratios and the results of pulmonary function tests. Somewhat higher IgG/alb and IgM/alb ratios were found in the patients with hypersensitivity pneumonitis than in the healthy subjects, although significantly higher ratios were not observed in patients with sarcoidosis or bronchiolitis. In conclusion, the estimation of immunoglobulins and histamine in BALF is considered to be useful for the explication of the pathogenic mechanism of bronchial asthma.
The function of granulocytes was evaluated in bronchoalveolar lavage fluid (BALF) in 25 patients with bronchial asthma. In 8 healthy subjects, BALF contained 87.0% macrophages, 12.1% lymphocytes, 0.6% neutrophils, 0.3% eosinophils and 0% basophils. The arylsulfatase (AS)/alb ratio was 6.2 (μg/mg). In asthmatic patients, BALF contained 57.1% macrophages, 13.2% lymphocytes, 8.6% neutrophils, 21.0% eosinophils and 0.1% basophils. The AS/alb ratio was 9.8 (μg/mg). These patients had a much higher number of eosinophils and neutrophils than healthy subjects. An increased number of eosinophils was found in BALF of atopic type asthma patients, and an increased number of neutrophils was found in BALF of intractable asthma patients. An increased AS/alb ratio was closely related to serum IgE levels and peripheral eosinophilia. A moderately higher AS/alb ratio was found in atopic patients than in healthy subjects or non-atopic patients. There was a relationship between the AS/alb ratio and the percentage of eosinophils and/or number of eosinophils in BALF. An inverse, but insignificant, relationship of a high AS/alb ratio to the degree of peripheral airway obstruction was found. In conclusion, analysis of cells and enzymes in BALF is considered to be useful for the explication of the pathogenic and regulatory mechanisms of bronchial asthma.
This study was carried out to investigate the effects of lidocaine (Ld) on brain edema, local cerebral blood flow (lCBF), and neural function. Vasogenic brain edema was induced by exposing a cat's brain surface to air for 12 hours. The animals were divided into three groups as follows: the brains were not exposed to the air with Ld administration (unexposed group), the brains were exposed to the air without Ld (untreated group), and with Ld (Ld-treated group). In the unexposed group, Ld had no influence on either cerebral water content or the latency of N1 component of somatosensory evoked response (SER). In the untreated group, the cerebral water content in the cortex, white matter and thalamus increased 12 hours after exposure. Local CBF decreased in these areas. The latency of N1 component of SER was prolonged significantly 6 hours after air exposure. The amplitude of the direct cortical response (DCR) decreased significantly. In the Ld treated group, water content decreased and lCBF increased significantly in the cortex compared with untreated group. There was no significant prolongation of SER N1 component latency even after 12 hours of air exposure. These beneficial effects of Ld on cerebral water content and lCBF of the cortex, and neuronal electrical activity were presumably due to the stabilizing effect on the cellular membrane and the improvement of microcirculation.
Purification of mast cells from the peritoneal cavity of rats and reactivity of the cells to antigen were studies. After peritoneal lavage, the peritoneal cells were washed, the mast cells were isolated by a density gradient centrifugation method. The recovery rate of mast cells was highest when mast cells were separated by BSA density gradient centrifugation after washing the cells on time by low speed centrifugation (50xg). The purity of mast cells obtained by this method was 94.1±1.0%, and the number of mast cells obtained was approximately 1.46×106 cells/rat. Mast cells of actively sensitized rats showed a significant increase in 45Ca uptake and histamine release after stimulation by antigen. 45Ca uptake by mast cells of passively sensitized rats was affected by BSA medium, and the most suitable results were obtained using mast cells passively sensitized before separation of the cells by BSA. Mast cells showed a significant increase in 45Ca uptake after stimulation by various stimulatory agents, such as Con. A, Comp. 48/80 and Ca ionophore A 23187. These results indicate that rat peritoneal mast cells isolated by the present method can be used in studies on Ca2+ influx into the cells.
Inhibitory effects of DSCG, tranilast, ketotifen, azelastine, antiallergic agents, and nicardipine, a calcium ion antagonist, on 45Ca uptake and histamine release by rat peritoneal mast cells were examined when the cells were stimulated with antigen and com. 48/80. All of these agents inhibited both 45Ca uptake and histamine release by mast cells stimulated with antigen in a dose-dependent manner. When the cells were stimulated with both antigen and phosphatidylserine (PS), inhibitory effects of DSCG and tranilast on 45Ca uptake decreased, although effets of ketotifen and nicardipine were not affected by the addition of PS. Only the effect of DSCG on the release of histamine decreased in the experiments in which PS was added. When the cells were stimulated with com. 48/80, inhibitory effects of DSCG and tranilast on 45Ca uptake and histamine release decreased, although the inhibitory effects of ketotifen and nicardipine did not decrease. The effects of the preincubation time with the agents on 45Ca uptake and histamine release of mast cells were examined. The inhibitory effects of DSCG and tranilast were reduced by prolonged preincubation of mast cells with the agents. Tachyphylaxis to tranilast and to DSCG was observed, and cross tachyphylaxis between DSCG and tranilast was also observed.
Serum levels of calcium and phosphorus and total urinary hydroxyproline excretion were determined in 30 elderly persons over 65 years of age who had primary hyperalkalinephos-phatasemia and clear osteoporotic changes in their lumbar spinal column. The clinical and biochemical status of individual patients was compared. The total urinary hydorxyproline excretion was 7.75mg/day to 32.29mg/day (mean: 15.11±7.19mg/day by patient with gait activity and 16.95mg/day to 35.00mg/day (mean: 24.08±6.86mg/day) by patient without gait activity. The lower total urinary hydroxyproline excretion by patients with gait activity than by patients without gait ativity suggested lower bone turnover in the former. In 20 out of these 30 elderly patients, 80 I.U. of porcine calcitonin was injected intramuscularly, and changes in serum calcium and phosphorus levels and total urinary hydroxyproline excretion were observed. This test revealed no correlation between the observed changes and the grade of gait activity of severity of osteoporotic bone changes. The serum calcium level decreased significantly from 4.2mEq/L to 5.3mEq/L (mean: 4.67±0.37mEq/L) before the load test to 4.0mEq/L to 5.0mEq/L (mean: 4.35±0.27mEq/L) after the test in 10 patients. It is postulated that in these 10 patients osteoclastic activity was higher with greater resorption of bone as compared to patients in whom no decrease in the serum calcium level was induced by the carcitonin load test.
Embryological and electron microscopic studies were conducted on pyramidal cells in the CA4 area of the hippocampus of rats. In rats 1-3 days after birth, a few mitochondria and poorly developed Golgi apparatus were noted in the cytoplasm of pyramidal cells. In rats 5 days after birth, a few mitochondria, moderately developed Golgi apparatus and a small amount of rER were noted in the cytoplasm of pyramidal cells. At 7 days after birth, mitochondria, Golgi apparatus and rER were slightly better developed than those 5 days after birth. From this stage on, it became possible to observe a structure similar to the apical dendritic process of pyramidal cells. On the ninth day after birth, mitochondria and Golgi apparatus were not very well-developed, but rER was considerably well-developed within the cytoplasm near the two poles of the nucleus. At this srage, apical dendritic processes, with synapses on the surface was noted. On the 12th day after birth, mitochondria were distributed throoghout the cells. Golgi apparatus were also well-developed. The number of apical dendritic processes had increased, and 2-3 large synapses were noted on the surface of these cell membranes. On the 14th day after birth, the distribution of mitochondria, degree of development of Golgi apparatus and distribution of rER became similar to those in pyramidal cells of mature rats.
Althogh the pulmonary funutional disorder of patients with pneumoconiosis thought to be a restrictive change selective alveolo-bronchography and postmortem pathological studies have shown that such patients also have an obstructive change. Ventilation examinations, including single breath, equilibrium and wash-out, using Xe-133 gas and perfusion examiations using Tc-99m MAA were done in 24 patients with pneumoconiosis. The patients were divided into four types according to the classification of chest Xray findings of the Japanese labour Ministry: type I, 7pts type II, 6pts: 6pts: type III, 7pts, and type IV, 4pts. There were many abnomal findings in the upper ung field in the single breath phase (133Xe gas) and also in the perfusion study. 133Xe retention was found in the upper lung field in of type I patients, and also in the middle and lower lung fields according to the seriousness of the patient's condition fromctype II to type IV. The mean transit time in the region of interest of the lung field increased with increasing seriousness of disease. These studies show that patients with pneumoconiosis have not only restrictive changes, but also obstructive changes even in the early stage.
Phenytoin (PHT) metabolism and brain monoamine levels were examined daily after chronic administration of 40mg/kg/day of PHT-Na into ddY mice. The blood PHT level increased remarkably the first day and then tended to decrease, attaining a transitory minimum on the third day of a 7-day experiment. The half-life of PHT after a single injection was about 12 hours, and the administration of PHT for 3 days shortened the half-life to about 6 hours. The urinary excretion of 5-(p-hydroxyphenyl)-5-phenylhydantoin tended to increase from the first day and attained a maximum on the fourth day of a 7-day experiment. Levels of 5-hydroxytryptamine (5-HT) and catecholamine in the mouse brain increased transitorily from the third to sixth day of a 14-day experiment. On the 14th day, these levels remained at the control level. Effects of PHT on convulsions and on regional levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the El mouse brain were examined. PHT completely inhibited convulsions in El mice after intraperitoneal injections of 40mg/kg of PHT-Na twice a day for three days. After the injection of PHT twice a day for three days, the 5-HT level was increased in the striatum, hypothalamus, midbrain and pons-medulla oblongata, and the 5-HIAA level was increased in the cortex, hippocampus, midbrain, pons-medulla oblongata and cerebellum. These results suggest that the inhibitory effect of PHT on the convulsions may be based on the activation of the 5-HTergic neurone system in El mice.
The CNS action of 2-guanidinoethanol (GEt), that has been identified in human urine, was investigated in male S.D. rats. Effects of GABA (1 μmol, on the pia mater), diazepam (DZP) (10mg/kg, i.p.), muscimol (50 nmol, on the pia mater), (3R)-(-)-4-amino-3-hydroxybutanoic acid (L-GABOB) (1 μmol, on the pia mater), phenobarbital (PB) (20mg/kg, i.m.), dephenylhydantoin (PHT) (25mg/kg, i.p.) or valproate (VPA) (200mg/kg, i.p.) on convulsive seizures or on spike discharges (Sp-D) induced by GEt were examined. Several min after the intraventricular injection of 25 μl of GEt solution (300mM), rats started to show myoclonic twitching, running fit and tonic and clonic convulsions. When GEt was injected intraventricularly about 3040 min after the administration of DZP or PB, rats started to show myoclonic twitching several min after the application of GEt, but rats did not show running fits, tonic convulsions or clonic convulsions for over 4h. EEG (epidural electrodes) revealed initiation of Sp-D several min after an intraventricular injection of GEt (25 μl). Thereafter, polyspikes, 3 cps spike & wave complex and finally ictal seizures developed about 30 to 60 min after the injection. EEG revealed Sp-D within 210 min on the side of the GEt application on the pia mater (3 μmol), and then a burst of multiple Sp-D developed. During the burst, Sp-D propagated to the opposite cerebral hemisphere. Two hours after the topical application, propagation of Sp-D was completed. In rats given muscimol topically together with GEt, Sp-D were not induced, and Sp-D induced by GEt were suppressed withiin 10 min by the supplimentation of muscimol. While L-GABOB and GABA showed a suppressive effet on Sp-D induced by GEt, after pre-application of these two substances, GEt induced Sp-D with longer latency. About 20 min after injection of PB, DZP or PHT, GEt was applied on the pia mater, but Sp-D were not induced. PB, DZP, PHT or VPA, applied 20 min after the application of GEt, suppressed Sp-D induced by GEt. While VPA showed a suppressive effect on Sp-D, GEt induced Sp-D after preapplication of VPA. These findings suggest that GEt acts on the GABAergic system to induce convulsive activity.
In 81 cases of resected rectal cancer, quantitative analysis of B-mode ultrasonographic texture was studied in order to establish an ultrasonic tissue characterization of rectal cancer. A microcomputer-based system, interfaced with conventional diagnostic systems, was used for digital signal processing. The memory of the digital scan converter has 6-bit elements. The echo level of texture, which is the average amplitude of echo scattered back from the tissue, was compared between cancer and normal tissues. The echo level of rectal cancer tissue was significantly lower than that of the normal mucosal layer (p<0.01). The echo level ratio was 0.7790±0.0838 (mean±S.D.). A high correlation of echo level was found between cancer tissue and the normal mucosal layer (r=0.7367, p<0.01). However, there was no significant difference between the echo level ratios of tissue of each histological type. Fixation with formaldehyde resulted in an equal increase in the echo levels of these tissues. It was demonstrated objectively and quantitatively that the echo level as an ultrasonic tissue characterization of rectal cancer was the lowest at the muscular layer and increased in the order of cancer, mucosal layer and subserosal layer. From these results, the author recommends that the obtained data should be applied to the clinical objective diagnosis of the spread of rectal cancer. This new method of ultrasonic tissue characterization is very useful.
Accurate preoperative staging is very important to the planning of the appropriate treatment for patients with rectal cancer. The author studied the utility and accuracy of ultrasonography in the detection and staging of rectal cancer. Intrarectal linear scanning with a 5.0 MHz probe by the water enema method was conducted to determine the depth of invasion and degree of lymph node metastasis in 23 cases of lower rectal cancer. Real-time longitudinal tomograms of the rectal wall and adjacent pelvic organs were clearly observed. The normal rectal wall was delineated as a 3- or 5-layer structure. The most hypoechoic layer was the proper muscular layer. The ultrasonograms of cancer and lymph node tissue were hypoechoic and heterogeneous. The depth of invasion was evaluated from the destruction of the layer structure. The overall accuracy rate was 82.6%. Misdiagnoses were mostly overestimatious. The metastatic lymph node was shown as a round shaped lesion. In the diagnosis of lymph node metastasis, 82.6% of the cases were diagnosed correctly, with 100% sensitivity and 71.4% specificity. The ultrasonogram also provided information about the extent of lateral and distal cancer spread. The cases diagnosed as Dukes A by this method may be indicated for function preserving operations. It was concluded that this new imaging method is very useful for precise preoperative staging and choice of operative procedure.
The systemic and hepatic circulation dynamics of 30 mongrel dogs were investigated during and after isoflurane anesthesia at concentration of 1.5, 2.2, and 3.0%. Alveolar and arterial isoflurane concentrations increased rapidly after starting inhalation, and decreased rapidly after stopping of inhalation. At the 3 concentrations, MAC was about 1, 1.5, and 2, respectively. Mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI) all decreased dose-dependently after starting inhalation. After stopping inhalation, MAP recovered rapidly, but the recovery of HR was slow and the recovery of CI was poor. Hepatic arterial blood flow (HABF), portal venous blood flow (PVBF), and hepatic tissue blood flow (HTBF) decreased dose-dependently after starting inhalation. After stopping inhalation, HABF and HTBF recovered rapidly, but the recovery of PVBF was poor. Arterial isoflurane concentrations correlated wiht MAP, CI, HABF, PVBF, THBF, and HTBF. HABF was correlated with MAP, and PVBF was correlated with CI. Systemic vascular rasistance (SVR) and mesenteric vascular resistance (MVR) changed similarly during and after inhalation of isoflurane.