Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.

OBJECTIVE: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN: Laboratory experimental study. SETTING: Research laboratory, Japan. SUBJECTS: Male Fischer rats. INTERVENTIONS: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.     

Purification of rabbit, rat and mouse protein C with the use of monoclonal antibody to human protein C, PC01

Ca(++)-dependent monoclonal antibody specific to gamma-carboxyglutamic acid (Gla) domain of protein C was produced. It did not cross-react to the other vitamin K-dependent plasma proteins but to protein C of the other species. Using this monoclonal antibody, PC01, rabbit (170 micrograms), rat (60 micrograms) and mouse (40 micrograms) protein Cs were isolated from 100 ml of their plasma by affinity chromatography. All of these protein Cs were two chain form linked by disulfide bond as well as human protein C and activated by thrombin-thrombomodulin complex. Rat and mouse protein Cs showed similar characters to human protein C. On the other hand rabbit protein C had different M(r) of heavy and light chains and showed lower anticoagulant activity compared with human protein C.     

Study on the mass-screening of after-meal serum triglyceride concentration]

The serum triglyceride concentration (TG) tested in health checks after meals cannot properly sort out hypertriglyceridemia with reference to the upper normal limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society, because TG goes up considerably after a meal. In our survey of a large number of health check examinees (free of abnormal biochemical data other than TG and diseases under medical treatment), the mean (M) of fasting TG + 2 standard deviations (SD) was close to 150 mg/dl. When the screening level was set at M + 2SD for each time span after a meal, the ratio of the screened was distributed between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on fasting. Accordingly, the nearest round number ending with zero for the first digit is suggested to be of practical use for the screening level of after-meal TG. The average TG in females was definitely lower than that of males, though proportionately increasing with age. The ratio of the screened among females aged between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively.     

Growth after bone marrow transplantation in children.

Growth of the patients with hematological malignancies, aplastic anemia, Fanconi's anemia, and Wiscott-Aldrich syndrome who had been treated with bone marrow transplantation (BMT) was studied. Fourteen out of 21 patients showed suppression of linear growth after BMT. Recovery of the growth velocity after 1-2 years tended to occur if BMT was performed at younger age. Six of eight patients with chronic graft-versus-host-disease (CGVHD) had impaired growth after BMT, whereas eight of 13 (61%) without CGVHD did. Provocative tests for growth hormone (GH) performed 5-72 months after BMT revealed three boys who showed poor response to more than two different stimuli. Two of these three boys had prolonged suppression of growth. Neither the age at BMT, difference in disease, nor presence of posttransplant growth retardation gave significant difference in the response of GH to provocative tests. It was concluded that approximately two-thirds of marrow-grafted children experienced transient decrease in growth velocity after BMT.     

A case of multiple sclerosis with paroxysmal attacks of facial paresthesia, unilateral hand tremor, epigastric pain and urinary incontinence]

A Japanese woman, aged 42, was admitted because of paroxysmal attacks consisting of paresthesia of the left face, tremor in the right hand, epigastric pain and urinary incontinence. A year prior to the admission, she noticed some difficulty in writing, dysarthria and unsteadiness of walking. These symptoms had been persistent since then. At the end of March, 1991, these symptoms rapidly worsened, and she fell down frequently. She also experienced pain behind both eyes, numbness in her left fingers and toe, urinary frequency and the above-mentioned attacks. Neurological examination disclosed bilateral internuclear ophthalmoplegia and upbeating nystagmus on upward gaze, titubation in the head, scanning speech, dysmetria in all limbs, exaggerated reflexes in jaw and both legs, bilateral extensor plantar reflexes and ankle clonus. SEP showed delayed cortical response with stimulation of the median nerves bilaterally and of the right posterior tibial nerve. P40 was absent with the left posterior tibial nerve stimulation. VEP was normal. T2-weighted image of MRI showed multiple high intensity areas located around the third ventricle, crus cerebri and the right upper part of the pons. The diagnosis of multiple sclerosis was made. Each paroxysmal attack started with numbness in the left face and burning sensation in the neck. Almost simultaneously tremor in the right hand began. The surface EMG showed the rhythmic contractions in the dorsal hand muscles and wrist extensors at a frequency of 6-7 Hz, and sometimes it revealed synchronized contractions of finger flexors and the dorsal hand muscles. A few seconds later she felt painful sensation in the epigastric region, and the tremor gradually increased in its intensity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report

Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed.     

Species and sex differences of aflatoxin B1-induced glutathione S-transferase placental form in single hepatocytes.

Species and sex differences of aflatoxin B1 (AFB1)-induced glutathione S-transferase placental form (GST-P) positive single hepatocytes have been investigated 48 h after an intraperitoneal injection of AFB1 to young male and female Fischer rats (2 mg AFB1/kg body wt) and male Syrian golden hamsters (6 mg AFB1/kg body wt). The presence of GST-P positive hepatocytes was examined by the immunohistochemical method. Male rats formed three times as many AFB1-induced GST-P positive hepatocytes as females. Pretreatment of both male and female rats with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO) (4 mmol/kg body wt), 2 h and 4 h before AFB1 injection increased AFB1-induced GST-P positive hepatocytes by about 120% above the controls. Male hamsters formed several-fold less AFB1-induced GST-P positive hepatocytes than male rats. Pretreatment with BSO did not increase AFB1-induced GST-P positive hepatocytes in hamsters even though it produced an increase in hepatic necrosis. It appears that GSH and GSH S-transferases play an important role in modulating hepatic AFB1-DNA binding and AFB1-induced GST-P positive hepatocytes in rats and hamsters.     

Effect of caffeine on expression of cardiac myosin heavy chain gene in adult hypothyroid and fetal rats.

Changes in cardiac myosin heavy chain (MHC) gene expression and isozyme transitions have been shown to be caused by developmental changes, hemodynamic overload, or the activity of various hormones. In this study, to examine whether caffeine, which has teratogenic effects on the fetal cardiovascular system, causes the distribution of cardiac MHC phenotype and, if so, to evaluate the mechanisms of the distribution of cardiac MHC phenotype by caffeine, we examined the effects of caffeine, theophylline, and cAMP on the cardiac MHC isoform transitions at the gene and protein levels using hypothyroid adult rats. Furthermore, we examined the expression of alpha- and beta-MHC gene in cardiac muscles of fetuses whose dams had received caffeine. The results showed that caffeine, theophylline, and cAMP caused accumulations of alpha-MHC mRNA and MHC isozyme V1. Furthermore, in the fetal hearts, it was recognized that caffeine induced an accumulation of alpha-MHC gene expression, as was also seen in the dams. However, this effect of caffeine on the heart was stronger in the fetus than in the dam. Intracellular cAMP concentration was increased by the administration of caffeine, theophylline, or cAMP, and the levels showed a positive correlation with those of alpha-MHC mRNA. These results suggest that the induction of alpha-MHC mRNA expression by the administration of caffeine may be induced by an increase in intracellular cAMP concentration.     

Binding of Clostridium botulinum type C neurotoxin to different neuroblastoma cell lines.

Binding of type C neurotoxin (C1 toxin) from Clostridium botulinum (strain Stockholm) to neuroblastoma cell lines was studied by using biotinylated anti-toxin antibody and avidin-biotinylated peroxidase complex. The neurotoxin bound with high efficiency to mouse neuroblastoma (NS-20Y and NIE-115) cells and to hybridomas of rat glioblastoma and mouse neuroblastoma (NG108-C15) cells. The toxin bound little to human neuroblastoma, rat astrocytoma, and nonneural cell lines. Binding of the neurotoxin to NG108-C15 cells was inhibited by gangliosides (GT1b and GM1) and by monoclonal antibodies (CA-12 and C-9), although inhibition was not complete. Sequential preincubation of C1 toxin with GT1b and CA-12 caused complete inhibition. A Scatchard plot of binding of 125I-labeled C1 toxin to NG108-C15 cells showed a hyperbolic curve. Monoclonal antibody CA-12 but not C-9 neutralized the lethal activity of the toxin toward mice. Only C-9 clearly inhibited toxin binding to GT1b. These results suggest that NG108-C15 cells have at least two kinds of receptors for C1 toxin. From the results of binding tests with neuraminidase-, pronase-, and trypsin-treated NG108-C15 cells, the chemical nature of the high-affinity site was presumed to be a glycoprotein containing sialic acid. GT1b may have an important role in low-affinity sites.