Tricuspid annuloplasty and right ventricular function in mitral valve disease

From 1985 to 1987, we examined relationship between the lesion of tricuspid valve and right ventricular function in 31 patients (male: 9, female: 22) with mitral valve disease. The median age at operation was 52 years (range 37-69 years). Group I consisted of 17 patients (MS: 10, MSR: 5, MR: 2) accompanied with tricuspid regurgitation (TR) and Group II 14 patients (MS: 12, MSR: 2) without TR. In all cases of Group I tricuspid annuloplasty (TAP) were performed correctly. De Vega methods were done in 12 cases and Carpentier rings were used in 5 cases. Cardiac catheterization was done before and after operation. And right ventricular volume was measured by right ventricular angiography. In both groups pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac index were improved postoperatively. Pulmonary artery resistance (PAR) and total pulmonary resistance (TPR) in Group I were significantly higher before operation but there were no difference between two groups postoperatively. Right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) in Group I were significantly improved postoperatively, but in Group II these were within normal range both pre- and postoperatively. Preoperative PAR was correlated inversely with postoperative right ventricular ejection fraction (RVEF). It means that patients with severe pulmonary vascular lesion had postoperative lower right ventricular function. In both groups, RVESVI was in inverse correlation with RVEF pre- and postoperatively. In both groups, there was an inverse correlation between the per cent change of RVESVI and that of RVEF. This means that RVESVI influenced right ventricular pump function.     

Characterization of certain hepatocyte-proliferating and/or protective factors induced by the sensitization of freezing-thawing hepatic tissue

Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [³H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI₄)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide (MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI₄ with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment of liver failure.     

Effect of XKJ-001, a crude drug preparation, on body water distribution and water excretion in mice

The effect of XKJ-001, a crude drug preparation based on Seisho-ekki-to, was investigated on the hematocrit, plasma volume, extracellular and interstitial fluid volumes as well as water excretion in mice. Mice were housed in an animal room maintained at 34 degrees C for 3 d with water and food freely available. While the hematocrit, extracellular and interstitial fluid volumes increased, the plasma volume decreased. These results suggest that the distribution of body water in mice housed at high environmental temperature exhibit the state of water metabolism disorders (Suitai) described in Kampo medicine. After the administration of XKJ-001 (3 g/kg, once a day) for 5 d, mice were housed in an animal room maintained at 34 degrees C for 3 d. The administration of XKJ-001 was allowed to continue on the day 0, day 1 and day 2. XKJ-001 inhibited the increase in hematocrit and the changes in body water distribution of mice induced by high environmental temperature. An effect of XKJ-001 on water excretion in mice was investigated in comparison with hydrochlorothiazide (HTZ). Distilled water (D.W., 100 ml/kg) or bicarbonate saline (B.S., 100 ml/kg) was intraperitoneally injected immediately after the oral administration of XKJ-001 (1.5 g/kg) or HTZ (15 mg/kg). The water excretion was enhanced after 3 h for XKJ-001 and after 6 h for HTZ after the intraperitoneal injection of D.W. As for the intraperitoneal injection of BS, HTZ enhanced the water excretion, however, XKJ-001 exhibited no effect. These results suggest that XKJ-001 has activities on water maldistribution and facilitates the water excretion.     

Effect of portal infusion of hypertonic saline on neurons in the dorsal motor nucleus of the vagus in the rat

Effects of hepatoportal osmo-receptive (or sodium-receptive) afferents on neurons within the dorsal motor nucleus of the vagus (DMV) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Responses of 56 spontaneously active neurons to antidromic stimulation of the ventral trunk of the subdiaphragmatic vagus were recorded in the left DMV. Among them, 35 neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve (inhibitory neurons), except two neurons that were slightly excited. Effects of portal infusion of 3.6% NaCl were examined on 26 inhibitory neurons. Sixteen neurons increased their discharge rates and one neuron decreased its discharge rate in response to portal infusion of hypertonic saline. Thirty-five DMV neurons responded to electrical stimulation of the dorsal trunk of the subdiaphragmatic vagus were inhibited by electrical stimulation of the hepatic branch of the vagus. Four neurons were excited by this stimulation. Relatively smaller number of neurons (5 out of 22 inhibitory neurons) increased their discharge rates in response to portal infusion of hypertonic saline. In conclusion, the response of DMV neuron observed in this experiment was characterized by increasing the frequency of spike discharges in response to portal infusion of hypertonic saline. However, these neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve. These results suggest that the hepatoportal osmoreceptive afferents may be conveyed to the DMV via inhibitory synapses.     

Flat adenoma and flat mucosal carcinoma (IIb type)— A new precursor of colorectal carcinoma?

Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."     

Effects of dietary iodine on chemical induction of thyroid carcinoma

Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2-hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/or promoting effects of TSH.     

Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development

The nature of signals that govern the development of immunoglobulin heavy chain-dependent B cells is largely unknown. Using mice deficient for the B cell-expressed Src-family protein tyrosine kinases (SFKs) Blk, Fyn and Lyn, we show an essential role of these kinases in pre-B cell receptor (pre-BCR)- mediated NF-kappaB activation and B cell development. This signaling defect is SFK specific, as a deficiency in Syk, which controls pre-B cell development, does not affect NF-kappaB induction. Impaired NF-kappaB induction was overcome by the activation of protein kinase C (PKC)-lambda, thus suggesting the involvement of PKC-lambda in pre-BCR-mediated SFK-dependent activation of NF-kappaB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development.     

Osteosarcoma. Ultrastructural and immunohistochemical studies on alkaline phosphatase-positive tumor cells constituting a variety of histologic types

The osteosarcomas were subclassified into osteoblastic, fibroblastic, chondroblastic and telangiectatic types and examined by electron microscopy. Their immunohistochemical reactions were also studied. In an overall survey of the above types, fibroblast-like cells revealed poorly developed cytoplasmic organelles with rather short, branching rough endoplasmic reticulum, mixed with osteoblast-like cells that were hardly distinguishable from the former. They appeared to be an early stage of an osteoblastic cell lineage from the distribution and development of their cell organelles and highly positive vimentin activity. The tumor cells in malignant cartilage varied in appearance from chondroblast-like to osteoblast-like cells. All types of tumor cells expressed alkaline phosphatase activity to a significant degree. Immunohistochemical staining showed a mixture of procollagen type I-positive cells among the cells positive for both procollagen type II and S-100 protein in the malignant cartilage. Irrespective of any ultrastructural differences between these various tumor cell types, they all revealed a significant degree of ALPase activity unlike other types of bone tumors, suggesting that the tumor cells which constitute the various types of osteosarcoma are derived from a common precursor cell.     

Use of 125I-secretin to identify and characterize high-affinity secretin receptors on pancreatic acini

We prepared 125I-secretin and studied the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini prepared from guinea pig pancreas. Iodinated secretin retained intrinsic biological activity in that it was as effective but 2.5-times less potent than native secretin in its ability to bind to pancreatic acini and to increase cellular cAMP. Scatchard analysis of binding of 125I-secretin indicated that each pancreatic acinar cell has approximately 93,000 binding sites, half of which are occupied by 11 nM iodinated secretin. Binding of 125I-secretin was rapid, reversible, saturable, specific, and temperature dependent. Binding of 125I-secretin was inhibited by secretin, vasoactive intestinal peptide, PHI, and Gila monster venom but not by glucagon, gastric inhibitory polypeptide, cholecystokinin, caerulein, gastrin, bovine pancreatic polypeptide, somatostatin, neurotensin, leucine-enkephalin, methionine-enkephalin, carbachol, bombesin, litorin, eledoisin, physalaemin, or substance P. With agonists (secretin, vasoactive intestinal peptide, PHI, or Gila monster venom), as well as antagonists (C-terminal fragments of secretin), there was a close correlation between their relative potencies for inhibiting binding of 125I-secretin and their relative potencies for increasing cAMP (agonists) or inhibiting the secretin-induced increase in cAMP (antagonists). For a given agonist, however, a 40-fold higher concentration was required for half-maximal inhibition of binding of 125I-secretin than was required to produce a half-maximal increase in cellular cAMP. Thus, maximal stimulation of cellular cAMP occurs when approximately one-third of the secretin receptors are occupied by an agonist.