Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.     

Simultaneous repair of pectus excavatum and tetralogy of fallot: report of a case.

We report an 18-month-old boy with the association of pectus excavatum and tetralogy of Fallot (TOF). We successfully performed simultaneous pectus repair using sternal elevation without any prosthetic support and total correction of TOF after a prior modified Blalock-Taussig shunt. Retracting a divided costo-sternal complex with a rectus abdominal flap away from the operative field before the cardiac operation provided excellent surgical exposure. The modified Blalock-Taussig shunt prior to the combined repair prevented life-threatening hypoxic spells during dissection of the deformed sternum and costochondral cartilages before institution of cardiopulmonary bypass.     

Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.     

Malignant Rhabdoid Tumor of the Breast: A Case Report

A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments.     

Effects of bifemelane on the free fatty acid levels during ischemia

Using the four-vessel extracranial one staged occlusion model of adult Wistar rats, we analyzed quantitatively released free fatty acids during ischemia. Also have we analyzed the effect of bifemelane to reduce free fatty acid accumulation after the onset of ischemia. Bifemelane (15 mg/kg, 30 mg/kg) and saline as control were intraperitoneally administered to adult Wistar rat prior to 30 minutes of experimentally induced ischemia. The results obtained were analyzed by one or two way analysis of variance (ANOVA). Physiological variables (systemic arterial pressure, PaO2, PaCO2, pH) did not change significantly in all four experimental groups. Total free fatty acid levels (sum of 5 fatty acid) increased significantly after ischemia (30 minutes). Higher dose (30 mg/kg) of bifemelane administration significantly reduced total free fatty acid accumulation, though lower dose (15 mg/kg) did have no effect. Bifemelane (30 mg/kg) reduced significant accumulation in the amount of saturated and monounsaturated fatty acid (palmitic acid [16:0], stearic acid [18:0] and oleic acid [18:1]). Arachidonic (20:4) and docosahexaenoic (22:6) acid failed to show any effective reduction by bifemelane pre-treatment of lower nor higher dose. Bifemelane is supposed to have many pharmacological effects such as increase in cerebral blood flow, augmentation of glucose uptake, monoamine metabolism, cerebral vasodilatation and platelet antiaggregation. Free fatty acid accumulation is effectively suppressed by the higher dose of bifemelane administration. Although the exact mechanism are not clearly identified by the result obtained in this experiment, selective inhibition of accumulation in saturated and monounsaturated fatty acids by bifemelane pretreatment may be obtained by the improvement of energy metabolism, which may help to reacylation of fatty acid into phospholipid.     

Histiocytic necrotizing lymphadenitis

Eleven cases of histiocytic necrotizing lymphadenitis were studied. Originally four were misdiagnosed as cervical tuberculous lymphadenitis. The characteristic symptoms and signs were local tenderness, fever, leucocytopenia and good prognosis. Antibody to Epstein-Barr virus was elevated in 2 of 3 cases. Biopsy of the affected lymph node was necessary when the differential diagnosis from lymph node tuberculosis or malignant lymphoma could not be made. The characteristic histological feature was focal necrosis without neutrophil infiltration in cortical or subcortical areas. Ultrastructurally, we found characteristic inclusions ('tubulo-reticular structures') in histiocytes and lymphocytes.     

Continuous lumbar subarachnoid pressure monitoring as an indicator of shunt operation for so-called normal pressure hydrocephalus

Lumbar subarachnoid pressure (LSP) was continuously monitored via intrathecally introduced polyethylene catheter to select the patients for shunt operation. A total of seventy cases included so-called normal pressure hydrocephalus (NPH) secondary to subarachnoid hemorrhage (SAH; 34 cases), idiopathic NPH (17 cases), secondary NPH whose symptoms developed after operations for brain tumors, head injuries or meningitis (12 cases) and other intracranial diseases including pseudotumor cerebri or meningeal carcinomatosis, etc. (7 cases). Shunt operation was effective in 36 cases and not effective in 9 cases, while 25 cases were not shunted since LSP was not elevated or clinical manifestations were slight. Mean values of baseline pressure and maximum pressure in shunt effective group, shunt non-effective group and non-shunted group were 14.5, 12.7, 9.0 and 29.9, 25.0, 17.9 mmHg, respectively. Statistical difference was observed between shunt effective group and non-shunted group. Frequency of pressure waves was also significantly higher in shunt effective group than in non-shunted group. Above all, measurement of LSP was regarded as useful in idiopathic NPH. However, preoperative clinical symptoms had a closer relationship to shunt response than results of LSP in post SAH patients. Complication related to this monitoring was negligible except in one case of meningitis which was easily treated by administration of antibiotics. Follow-up study also justified our selection since no further deterioration was noted in non-shunted group. The present study indicates that measurement of LSP would be useful in selecting the patients who will benefit from shunting and in eliminating unnecessary shunt operations because this simple method is easily performed at bed side without perforating the skull.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel responses of peripheral lymphocytes of cancer patients to chemical induction of sister chromatid exchanges

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.