Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5' end.

The 5' untranslated sequence (5' UTS) of platelet-derived growth factor B (PDGF-B/c-sis) mRNA is highly preserved through evolution, and inhibits translation of downstream coding sequences. In this study, using Northern analysis we identified two PDGF-B/c-sis mRNAs (3.5 kb and 2.6 kb) expressed in normal developing rat brain. In contrast to the constitutive expression of 3.5 kb mRNA, the expression of 2.6 kb mRNA increased markedly in accordance with those stages of brain development at which we had previously demonstrated an increased immunoreactivity for PDGF-B/c-SIS in neurons (Sasahara et al., 1992). By PCR cloning and the RNase protection assay, we determined the complete sequence of rat PDGF-B/c-sis, and found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the signal peptide. Accordingly, it is suggested that the truncation of 5' UTS contributes to the expression of PDGF-B/c-SIS protein in the CNS. Lack of translational inhibitory 5' UTS of PDGF-B/c-sis transcript and resultant efficient protein translation have been reported in only a few transformed cells and cultured umbilical vein endothelial cells. We have extended this knowledge to the developing rat brain, and suggest that a similar mechanism could operate widely in non-transformed tissue in vivo.

Increase in cardiac muscle fructose content in streptozotocin-induced diabetic rats.

To evaluate the activation of the sorbitol pathway in cardiac muscle in diabetic rats, we measured sorbitol, fructose, and myo-inositol content in cardiac tissue obtained from control and streptozotocin-diabetic rats, with or without an 8-week insulin treatment, using gas chromatography-mass spectrometry (GC-MS). Cardiac fructose and sorbitol content in 10-week diabetic rats increased by 60-fold and 3.9-fold of those of control rats, respectively (P less than .001). In contrast, cardiac myo-inositol content in 10-week diabetic rats decreased to 56% (P less than .025) of the control value. The abnormalities in cardiac fructose, sorbitol, and myo-inositol content were completely normalized by the 8-week insulin treatment, which was initiated 2 weeks after the induction of diabetes. There was no difference in cardiac aldose reductase activity between control and diabetic rats. However, cardiac sorbitol dehydrogenase activity in diabetic rats was 151% (P less than .005) higher than that of control rats, although hepatic sorbitol dehydrogenase activity was not different between the two groups. These results indicate that the sorbitol pathway is significantly activated in cardiac tissue obtained from streptozotocin-induced diabetic rats, which results in the marked cardiac accumulation of fructose.

Arrhythmogenic plasma levels of epinephrine during halothane, enflurane, and pentobarbital anesthesia in the dog.

Plasma levels of epinephrine which correspond to the arrhythmogenic doses were determined during halothane, enflurane, and pentobarbital anesthesia in the dog. The arrhythmogenic dose was established by a series of 3-min infusion of epinephrine at 10-min intervals. The mean values of the arrhythmogenic doses and the corresponding plasma levels of epinephrine were: 2.18 micrograms X kg-1 X min-1 and 38.7 ng/ml during halothane; 11.43 micrograms X kg-1 X min-1 and 206.3 ng/ml during enflurane; and 15.27 micrograms X kg-1 X min-1 and 296.5 ng/ml during pentobarbital anesthesia. The arrhythmogenic plasma levels of norepinephrine during halothane anesthesia was nearly the same as that of epinephrine.

Changes in concentrations of type IV collagen and tissue inhibitor of metalloproteinase-1 in patients with paraquat poisoning.

Respiratory failure is one of the major causes of death in patients with paraquat poisoning. In paraquat-poisoned lungs, abnormal extracellular matrix regulation occurs. The aim of the present study is to determine whether serum concentrations of type IV collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) are altered during the course of paraquat poisoning and whether haemoperfusion therapy affects these concentrations. Twenty-one patients were admitted within 3 h after ingestion of paraquat and all patients received direct haemoperfusion therapy. Five out of 21 patients survived and 16 patients died within 28 days. Plasma paraquat concentrations in non-survivors (5740 +/- 380 microg l(-1)) were not significantly different from those in survivors ( 5920 +/- 280 microg l(-1)) before treatment. Haemoperfusion reduced these concentrations in both non-survivors (120 +/- 7 microg l(-1)) as well as survivors (136 +/- 9 microg l(-1)) on day 5. Serum concentrations of type IV collagen and TIMP-1 in survivors showed little change between day 1 (type IV collagen, 90.4 +/- 3.6 ng ml(-1); TIMP-1, 172.2 +/- 7.0 ng ml(-1)) and day 5 (type IV collagen, 92.6 +/- 4.2 ng ml(-1); TIMP-1, 174.2 +/- 7.2 ng ml(-1)). In contrast, these concentrations in non-survivors on day 5 (type IV collagen, 143.6 +/- 7.8 mg ml(-1); TIMP-1, 246.8 +/- 13.6 ng ml(-1)) were significantly higher than those on day 1 (type IV collagen, 88.4 +/- 4.2 ng ml(-1), P < 0.01; TIMP-1, 170.6 +/- 9.2 ng ml(-1), P < 0.05). These data suggest that serum concentrations of type IV collagen and TIMP-1 may be useful indicators for the development of respiratory failure in patients with paraquat poisoning.

Kidney transplantation and liaison psychiatry, part II: A case of dissociative identity disorder.

The authors examined the case of an adolescent patient with dissociative identity disorder secondary to psychological shock of a transplant rejection response. Psychiatric symptoms consisted of three components: visual hallucinations and delusions as a psychological defense against the anxiety of a transplant rejection; appearance of three personalities including proper self, the dead child (donor), and a prophet with strong predicting power; and a twilight state. These psychiatric symptoms may have been related to two psychological factors: immature personality characteristics formed during hemodialysis, and post-traumatic stress caused by a chronic rejection reaction from the patient's first transplant.

HLA-DR2 antigen linkage in patients with apical hypertrophic cardiomyopathy in Japan.

Apical hypertrophic cardiomyopathy, a very common disorder in Japan, is characterized by giant negative T waves on the electrocardiogram and abnormal apical hypertrophy on the ventriculogram. This histocompatibility complexes (HLA-A, -B, -C, -DR) of 20 unrelated patients with apical hypertrophic cardiomyopathy (18 male, 2 female) were examined. There was no significant difference in the frequency of HLA-A, -B, -C antigens between patients and controls (n = 100). However, HLA-DR 2 was more frequent in patients with apical hypertrophic cardiomyopathy (65.0%) than controls (33.0%) (p < 0.01). We conclude that apical hypertrophic cardiomyopathy might be associated with genes in the HLA-DR region and that genetic factors linked to HLA play a role in the pathogenesis of this disease.

A case of transverse colon cancer secondarily involving the liver, duodenum, and pancreas.

A 68-year-old woman presented with transverse colon cancer invading the liver, duodenum, and pancreas. The patient underwent a curative resection including a right hemicolectomy, partial hepatectomy, and pancreaticoduodenectomy (PD). The pathological examination showed adenocarcinoma of the colon with a direct extension into the duodenum, liver, and pancreas. Several lymph nodes were also involved. The patient is still alive and disease-free 2 years and 6 months after the operation. This case illustrates that even in patients with locally advanced colon cancer, a favorable prognosis can be obtained by aggressive surgery incorporating the resection of the adjacent involved organs.

Stimulation and inhibition of interferon-beta production of human diploid fibroblasts by foodstuffs.

We screened for foodstuffs affecting interferon-beta (IFN-beta) production of human foreskin diploid fibroblasts, in the presence of poly I.poly C, cycloheximide, and actinomycin D. alpha- and beta-caseins stimulated IFN-beta production dose-dependently, but kappa-casein inhibited it. Of the two chymosin fragments of kappa-casein, glycomacropeptide was an inhibitor but p-kappa-casein was not. beta-lactoglobulin stimulated IFN-beta production weakly, but lactoferrin inhibited it strongly. It was also shown that serum contained some factors inhibiting IFN-beta induction and stimulating its production.

Simultaneous extensive resection of the liver and the pancreas in dogs.

Mortality, morbidity, liver function and regeneration were evaluated in dogs that had undergone simultaneous major resection of the liver and the pancreas. The 10-week survival rate was only 25% in the dogs that underwent 70% hepatectomy with more than 92% pancreatectomy, and many of them died of liver failure. Long-term survival was observed in more than 60% of the dogs after 70% hepatectomy with less than 92% pancreatectomy or after 40% hepatectomy with more than 92% pancreatectomy. The liver regeneration rate was reduced with the extent of the pancreatectomy, and the reduction was remarkable especially when more than 92% of the pancreas was resected. The frequency of diabetes was reduced when the pancreatectomy was combined with hepatectomy. Hyperlipemia and fatty liver were noted in all the dogs of the group that underwent more than 92% pancreatectomy alone. They were observed also in the postoperative diabetic groups but not in non-diabetic groups. The postoperative recovery of hepatic function and liver regeneration were delayed after simultaneous hepatectomy-pancreatectomy. Also, postoperative carbohydrate and lipid metabolism was better maintained in the hepatectomy-pancreatectomy groups than in the pancreatectomy-alone groups.

Effect of plasma exchange on serum tissue inhibitor of metalloproteinase 1 and cytokine concentrations in patients with fulminant hepatitis.

AIMS: The present study assessed whether the serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and cytokines are altered in patients with fulminant hepatitis and whether plasma exchange affects these concentrations. METHODS: Fifteen patients with fulminant hepatitis, 14 patients with severe acute hepatitis, and 20 healthy controls were included in this study. The serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), transforming growth factor beta (TGF-beta), and TIMP-1 were determined in all patients upon hospital admission and before and after a single course of plasma exchange in the patients with fulminant hepatitis. RESULTS: Ten out of the 15 patients with fulminant hepatitis and all patients with severe acute hepatitis survived. Serum TNF-alpha, IL-6, TGF-beta, and TIMP-1 levels in patients with fulminant hepatitis were significantly higher than the levels in patients with severe acute hepatitis (p < 0.01). IL-1beta was not detectable in either group. Plasma exchange reduced the increased serum concentrations of TNF-alpha, IL-6, TGF-beta, and TIMP-1 in patients with fulminant hepatitis (p < 0.01). CONCLUSIONS: These data suggest that increased serum levels of TIMP-1 and cytokines may reflect severe hepatic inflammation and that plasma exchange is an effective therapy to reduce these levels.