[Endogenous digitalis-like substance in relation to glycemia and insulinemia]. The digitalis-like substance (DLS), insulin resistance, and hyperglycemia are ascribed important roles in the pathogenesis of essential hypertension. The relationship between DLS and glycemia (insulinemia) was investigated in the present study. The levels of glycemia, insulinemia and DLS were measured during oral glucose load in a group of 18 subjects with various blood pressure values. Fasting levels of glycemia and insulinemia were in each subject within the physiological range and no correlation was found to exist between the fasting levels of DLS and glycemia (insulinemia). One hour after oral glucose load the increase of glycemia and insulinemia was significantly higher in the group of subjects with SBP > 140 and/or DBP > 90 mmHg than in normotensive subjects (p < 0.001). The increase in glycemia (insulinemia) was followed by a decrease of DLS. This contrary trend could be expressed as a significant inverse correlation between the change in plasma DLS and the change in glycemia (r = -0.660 p = 0.0039), and also between the change in plasma DLS and the change insulinemia (r = -0.687 p = 0.0023). These findings are assumed to suggest certain mechanisms involved in the pathophysiology of essential hypertension. (Tab. 3, Fig. 2, Ref. 20.)


[Herpesvirus research at the Virology Institute of the Slovak Academy of Science]. Research of the herpes virus (HSV) in the Institute of Virology of the Slovak Academy of Sciences in Bratislava has achieved some interesting results. An original technique has been elaborated for the purification of HSV visions and the separation of envelopes and naked particles. Studies of the properties of the HSZP strain of HSV type 1, adapted by us, showed that this virus did not only fail to shut off host cell proteosynthesis but also interfered with this ability of the KOS strain. Interesting results were achieved in elaborating the experimental pathogenesis of HSV and pseudorabies virus, especially concerning their neural spread. Important was the discovery of latent infection established with pseudorabies virus and the detection of spontaneously nonreactivating HSV DNA sequences in the nervous system of experimental animals and in man. A new herpesvirus was isolated from rodents at large, distinct from the so far known mouse CMV. This virus proved to be of interest because of its peculiar pathogenesis (similar to that of alpha herpes viruses) and DNA structure (similar to that of gamma herpes viruses). The preparation of a subunit vaccine using primary quail embryo cells (along with the introduction of domestic acyclovir) opens up some perspectives for the suppression of recurrent herpes virus infections in man. The testing of HSV-1 deletion mutants aims at elucidating the role of individual genes and their products in the pathogenetic process. (Ref. 54.)


[Lymphocyte phenylvaleric acid hydroxylase activity (L-PVH), a new marker of peripheral neurotoxicity]. A reduction in the level of a new enzymatic assay--a phenyl valerate hydrolase (PVH)--has been found during the clinical evolution of toxic neuropathies (as almitrine-bismetilate ones) as well as alcoholic or diabetic neuropathies. The substrate and the enzymatic function are different from those used by M.K. Johnson for NTE. The method follows procedures comparable to NTE (differential determination after inhibition by paraoxon and by paraoxon plus mipafox or DFP). It may be useful to test possible neurotoxicity of drugs and chemicals.


[Chronic administration of N-methyl-D-aspartate (NMDA) receptor antagonists induced in rats, a facilitation of striatal dopaminergic type D2 transmission: behavioral and biochemical study]. Compared with control rats, rats treated with ketamine (15 mg/kg/day, p.o.) or MK-801 (0.1 to 0.4 mg/kg/day, p.o.) for 6 weeks showed significantly increased: 1) behavioural responses to D2 dopaminergic agents, either agonist or antagonist, 2) striatal D2 receptor mRNA expression, 3) striatal D2 receptor density, without any presynaptic change in dopaminergic or serotoninergic neurotransmission. These results suggest that the functional expression of striatal D2 receptor is postsynaptically regulated by glutamate-triggered events through the NMDA receptor subtype.


[Umbilical and maternal amino acid concentrations in appropriate and small for gestational age infants]. Serum amino acid concentrations were determined in 63 pregnant women and their infants at delivery. Samples were obtained from 47 appropriate for gestational age infants (AGA) and 16 small for gestational age infants (SGA). The SGA group had significantly lower concentrations of total amino acid, compared with those of AGA, in both the umbilical and maternal blood. The essential amino acids of the cord, such as isoleucine and threonine, and maternal essential amino acids like threonine and arginine in the SGA group were lower than those in the AGA group. In contrast, nonessential amino acid concentrations, such as alanine, proline and aspartic acid were significantly higher in the umbilical blood of the SGA infants, while there were no differences in the maternal blood of both AGA and SGA groups. There was a positive relationship between maternal and umbilical total amino acid concentrations in the AGA group, but no relationship exists in the SGA group.


[The incidence of low birth weight infant in north China]. From September 1989 to August 1990, the incidence of low birth weight (LBW) infant was studied collaboratively in 8 areas in north China. 29,941 infants (14,003 males and 12,938 females) were investigated, 1,348 LBW infants included those of preterm and small for gestational age (SGA) term. The incidence of LBW infant was 5.00%. The incidence of male preterm (3.15%) was higher than that of female preterm (2.39%). The incidence of female SGA term (2.46%) was higher than that of male SGA term (1.82%). 52.09% of the infants with birth weight (BW) < 2,500g was of SGA term. 35-36 weeks premature infants accounted for 61.78% and 1,500-2,499g LBW infants for 93.28%. The incidence of SGA preterm (GA < 37 weeks) was 17.8%. In this study, the incidence of LBW infant was higher in Changchun and Huhehot than in other areas.


[126 small gestational age infants. Clinical characteristics and long-term observation]. From January 1, 1987 through June 30, 1990, 126 infants of small gestational age (SGA) born in our hospital were studied prospectively. The incidence of SGA infant > or = 37 weeks was 71.4%. The incidence of very low birth weight infants was only 6.3%. The incidence of birth asphyxia in this group (14.9%) was 3 times higher than that in full term infants; this incidence showed negative correlation with gestational age and birth weight. The morbidity rates of hypoglycemia (25.7%) and polycythemia (10.1%) were much higher than those in AGA infants. Malformation was the major cause of death in SGA infants. The mortality rate of SGA infant was 5.6% and the mortality rate of SGA infant > or = 37 weeks was only 1.1%. The results of follow-up showed that the physical development was normal in about 90% of cases at 2 years of age, and only 2 cases had low motor development scale when they were one-year old.


[Fatty acid compositions of cholesteryl esters. Different species and their correlation with susceptibility to atherosclerosis]. Fatty acid compositions of serum cholesteryl esters (CE) in human and animals were analysed. Polyunsaturated fatty acids (PUFA) were the predominant fatty acids in CE. A close relation between PUFA to saturated fatty acids (P/S) ratio in CE and susceptibility to atherosclerosis (AS) was observed among different species. Animals with high P/S such as tree shrews and rats (P/S 9.0) were AS-resistant, and those with low P/S such as rabbits (P/S 2.9) were susceptible to AS. The P/S ratio in human serum CE (4.9) was between those in the above two kinds of animals, and similar to those in pigs (4.2) and monkeys (3.7). A great physiological significance of abundant PUFA in CE could be expected. As the main part of low density lipoprotein (LDL), CE might provide PUFA to cells efficiently via LDL receptor. It was assumed that PUFA in CE were closely correlated with the metabolism of cholesterol and the development of AS by regulating LDL receptor activity, platelet function and prostaglandin synthesis, all of which would be affected by PUFA in cells.


[Nosocomial infections of methicillin-resistant Staphylococcus aureus and their detection]. In 142 strains of Staphylococcus aureus randomly isolated from clinical samples in a year, methicillin-resistant Staphylococcus aureus (MRSA) accounted for 79.6% (113/142). MRSA in the samples from the respiratory, burning and hematological departments came to 92.0% (23/25), 84.6% (11/13) and 83.3% (30/36) in proportion respectively. 79.6% of MRSA strains were isolated from the patients in whom the infections were confirmed to be hospital-acquired. All the strains of Staphylococcus aureus examined were resistant to penicillin G and ampicillin, but sensitive to vancomycin. Twenty hospital-acquired strains of MRSA showed a resistance to all detected antibiotics (multi-drug resistance, MDR), but vancomycin; strains of methicillin-sensitive ones, however, showed on MDR. In 45 strains of Staphylococcus aureus isolated from swabs of fingers of 62 medical workers, 31 (68.9%) were methicillin-resistant. The resistant similarity of shares of strains between medical staff and patients indicated a potential role that medical workers play in spread of nosocomial infections.


[Dynamic changes of pulmonary glucocorticoid receptor in endotoxin-induced lung injury]. The changes of maximal binding capacity (Bmax) of glucocorticoid receptor (GCR) in the endotoxin-induced lung injury were observed by using radioligand binding assay. The content of glucocorticoid (GC) and the activity of phospholipase A2 (PLA2) were also measured. The results showed that the level of GCR in lung cytoplasma decreased continuously after endotoxin infusion, and its affinity decreased in the late phase while PLA2 activity markedly increased. There was a negative correlation between the Bmax of GCR and PLA2 activity (r = -0.87, P < 0.01). These findings indicated that there is a secondary alteration in GCR during endo toxin-induced lung injury, and that the GC hypofunction caused by reduced GCR binding capacity may be of importance in the development of ARDS.


[Restenosis after balloon angioplasty: role of platelets, thrombosis and smooth muscle cells proliferation]. Iliac atherosclerosis was produced in 50 New Zealand rabbits and followed by balloon angioplasty (BA) for the study of the mechanism of restenosis after BA. 41 rabbits undergoing successful dilatation were randomly grouped and killed at 30 min, 24 h, one and four weeks after BA, respectively. Histomorphological results showed that platelets adhered to the angioplastic areas 30 min after BA. At 24 h, a large quantity of platelets adhered to or aggregated at the areas to form a dense carpet of platelets and large or small thrombi, even a totally obstructive luman. At the 4th week, organized mural thrombi in lumen produced restenosis. There were plenty of foam cells and less smooth muscle cells (SMCs) in the vessel wall of atherosclerotic rabbits before BA. One week after BA, SMCs proliferated increasingly and migrated into the intima from the media at the second week. At the fourth week, SMCs proliferated markedly in the intima, forming new atherosclerotic plaque, which resulted in thickening of vessel wall and restenosis of originally angioplastic sites.


[Expression of gene products of insulin-like-growth-factor II, insulin-like-growth-factor II receptor and colony-stimulating-factor-I receptor in human primary hepatocellular carcinoma and non-cancerous liver tissues]. Western blot technique was used to detect the expression of gene products of IGF-II and IGF-II receptor as well as CSF-1 receptor in hepatocellular carcinoma and its adjacent nontumours liver tissue. A fetal expression of IGF-II was noted in 33 KD. IGF-II receptor was expressed in 260 KD and 230 KD with mature and immature forms, and CSF-1 receptor in 180 KD, 139KD and 122KD with different forms. The close relationship between the synthesized regulation and overexpression of three gene protein products and hepatocarcinogenesis was discussed.


[Electron microscopic enzyme cytochemistry of Entamoeba histolytica trophozoite]. Electron microscopic enzyme cytochemical reactions of Entamoeba histolytica trophozoite showed that acid phosphatase (ACP) and cytidine monophosphatase (CMPase) were located in the lysosomes. The lysosome containing enzymes were distributed in the endoplasm and beneath the plasmalemma, and the releasing enzymes by lysosomes excreted outside of the plasmalemma and caused the injury to host cells. The cytochemical positive reactions of catalase and glucose-6-phosphatase (G-6-Pase) showed that E. histolytica contains microbodies and endoplasmic reticulum. The reactive products of peroxidase (POase) were seen in the lysosome-like structure. The reactions of cytochrome oxidase (COase) and succinate dehydrogenase (SDH) were both negative, indicating that E. histolytica lacked mitochondria. The reactions of thiamine pyrophosphatase (TPPase) and nicotinamide adenine dinucleotide phosphatase (NADPase) were both negative, indicating that E. histolytica lacked Golgi body. The reactions of Na(+)-K(+)-ATPase were located on plasmalemma.


[Mechanism of neuronal damage caused by cerebral ischemia]. After the middle cerebral artery of rats was occluded, changes in the content of 14 free amino acids and the activity of antioxidant enzymes in the ischemic striatum were assessed with respect to the duration of ischemia. Glu and Asp levels were significantly reduced by 60 min of ischemia, GABA was increased by 30 and 60 min and Ala was increased by 5, 15, and 30 min. During ischemia, the levels of striatal Gln, Asn, Ser, Tau, Gly and Pro were found to be normal. In comparison with the sham-operated rats, the changes in the content of Thr, His, Arg and Tyr were inconclusive, since the effect of operative stress could not be ruled out on such occasion. Concomitantly, the Zn-Cu superoxide dismutase and glutathione peroxidase activity were significantly reduced by 30 min of ischemia. It revealed that the reduced capacity to scavenge the oxygen free radicals occurred during the early stage of cerebral ischemia. The above changes of Glu, Gln, GABA and Pro level might be considered as the final outcome of the decrease of glutamate synthesis, the acceleration of its conversion to GABA, and the extracellular leakage of glutamate. According to our data, the oxygen free radicals might be involved in the evolution of primary neuronal damage at the ischemic striatum.


[Image-analysis of salivary tumors].

[Image-analysis of salivary tumors]. The image analysis of 49 cases of salivary tumors showed that the cellular DNA content of most tumors (42/49) was diploidy and near diploidy. The heteroploidy rate was only 14.29% (7/49), which may be related to such clinical behaviors of salivary tumors as slow growth, relative low invasivity and metastatic ability. Among these morphologic parameters, nuclear perim and form PE were closely correlated with the malignancy of salivary tumors, the former was positive and the latter was negative. The insignificant nuclear heteromorphous appearance of adenoid cystic carcinoma and its relatively high cellular DNA content may be related to strong invasivity and metastatic ability. In conclusion, these parameters of DNA content and nuclear morphology supplied by image analysis are of value in the diagnosis of salivary tumors.


Direct measurement of oxygen free radicals following cardiac failure of ischemic dog myocardium with the electron spin resonance technique. To determine whether the involvement of oxygen-derived free radicals in the pathogenesis of ischemic cardiac failure in dogs. Free radicals were measured in normal and ischemic myocardium from dogs with cardiac failure induced by acute coronary occlusion. The changes in free radical production in ischemic myocardium (compared with normal myocardium with or without polymorphonuclear leukocytes) were studies, with plasma superoxide dismutase and malondialdehyde analyzed concurrently. The results showed that the oxygen free radicals in the ischemic myocardium were about 42.5% higher than those in the normal myocardium, about 67.8% higher than those in the normal myocardium washed with normal saline and about 60.5% higher than those in the ischemic myocardium washed with normal saline (P < 0.05). Compared with controls, the concentration of malondialdehyde in ischemic dog myocardium was increased markedly. The activity of plasma superoxide dismutase was not significantly different between control dogs and dogs with ischemic cardiac failure. The current results indicate that there was increased production of free radicals and peroxidative damage in ischemic myocardium of dogs with cardiac failure. Polymorphonuclear leukocytes appear to be a main source of free radicals in dog with ischemic cardiac failure.


Sodium channel states control binding and unbinding behaviour of antiarrhythmic drugs in cardiac myocytes from the guinea pig. The aim was to investigate whether cardiac sodium channel states (rested, activated, inactivated) regulate the binding and unbinding behaviour of antiarrhythmic drugs on the receptor sites. Single ventricular myocytes of adult guinea pig heart were obtained by an enzymatic dissociation method in the Langendorff manner. The channel state dependent blocking effects on cardiac sodium current (INa) of quinidine and disopyramide were studied under the whole cell variation of the patch clamp technique. 10 microM quinidine and 20 microM disopyramide produced similar levels of tonic block and use dependent block. The steady state inactivation curve (h infinity curve) was shifted parallel in the negative potential direction by quinidine (10 microM) and disopyramide (20 microM) to the same extent (-10 mV). Removal of the fast inactivation process of INa by chloramine-T did not reduce tonic and use dependent block by these drugs. Onset block study using a double pulse protocol revealed that block developments by both drugs were fitted to the sum of double exponential functions. However, time constant of fast phase of block by disopyramide was faster than that by quinidine, while slow phase was not significantly different. Definition of time courses of unbinding (recovery) at -140 mV indicated that quinidine dissociated relatively slowly as compared to disopyramide. Quinidine produces more potent tonic and use dependent block of INa by binding to sodium channels at both rested and inactivated states, while disopyramide has a higher affinity for activated state. Therefore, sodium channel states regulate the binding and unbinding behaviour of antiarrhythmic drugs. Furthermore, the fast inactivation process is not essential in producing tonic and use dependent block by antiarrhythmic drugs.


Peptide leukotriene receptor antagonism in myocardial ischaemia and reperfusion. The aim was to investigate the role of peptide leukotrienes in the pathophysiology of myocardial injury during reperfusion of previously ischaemic myocardium. Adult male cats (2.9-5.4 kg) were subjected to left anterior descending coronary artery occlusion for 3 h followed by 3 h of reperfusion. The peptide leukotriene receptor antagonist, LY-171883, was given intravenously only during the reperfusion period (3 mg.kg-1 bolus; 3 mg.kg-1 x h-1 infusion). Ischaemic injury was assessed by nitroblue tetrazolium staining and tissue creatine kinase activity; neutrophil infiltration was determined by myeloperoxidase activity of myocardial homogenates. There was no significant difference at any time point in the experimental protocol between mean arterial blood pressure or pressure-rate index in cats given LY-171883 (3 mg.kg-1) and cats given vehicle. The area at risk of infarction (AAR) was 24(SEM 2)% for vehicle treated cats and 22(2)% for the drug treated cats. The necrotic area was 48(5)% of the AAR for the vehicle group but only 29(5)% of the AAR for the group given LY-171883 (p < 0.02). Left ventricular maximum +dP/dt tended to be higher with drug treatment compared to vehicle at the end of the reperfusion period. Tissue from the area at risk was assayed for creatine kinase activity and neutrophil specific myeloperoxidase activity as an index of the accumulation of neutrophils in this region. Creatine kinase activity was significantly higher (p < 0.05) in the AAR for drug nu vehicle treated cats following reperfusion, confirming the histochemical analysis. Myeloperoxidase activity increased approximately 12-fold in the AAR of cats receiving vehicle. LY-171883 did not reduce the myeloperoxidase activity significantly in the area at risk. LY-171883 has a protective effect in ischaemia-reperfusion injury to the myocardium. These findings suggest a role for peptide leukotrienes both in the extension of ischaemic damage and in post-ischaemic ventricular dysfunction during reperfusion.


[Study on radionuclide migrating along the channel]. The study of impedance line along channel had been performed with the radionuclide tracing method in 15 healthy human being and 4 guinea pigs. These images of tracer migrating routes approximately corresponded with classical courses of channel. The study proved that these line-shaped tracer migration were not by the way of lymphatic and blood vessels as well as nerves. This image of radionuclide migrating along channel may used as the guide for the observation of micro-autoradiography. In this study, satisfactory migrating image along the channel was also obtained by 131I instead of 99mTC. So a new way was opened up for both macro- and micro-autoradiographic study.


Humoral factors in chronic heart failure. A review. In chronic heart failure, dysregulation of sympathetic nerve system activity and of release of several neurohormones is present. Increased plasma levels of circulating hormones together with other factors have a negative influence on myocardial beta adrenergic receptors and induce cardiac hypertrophy with myocardial fibrosis. ACE inhibitors possess an ability to reverse these phenomena. An endogenous factor with an ACE inhibitory ability was isolated from the bovine left ventricular myocardium.


[Quantitative study on nucleolar organizer regions in salivary gland tumours]. The argyrophil staining technique for nucleolar organizer regions (NOR) had been applied to a series of benign and malignant salivary gland tumours. We have studied 38 salivary gland tumours, 16 benign and 22 malignant. In all specimens clearly defined silver-stained intranuclear AgNOR dots were visible. The differences between the numbers of AgNORs in the benign and malignant groups, notably pleomorphic adenomas, adenoid cystic carcinoma, mucoepidermoid carcinoma and adenocarcinoma, were highly significant. This result suggested that the AgNOR technique is of diagnostic help in distinguishing between these salivary gland tumours.


[Preliminary study on proliferative characteristics of the mixed tumor]. DNA-content was quantitatively determined in 2 monomorphic adenomas, 16 mixed tumors and 3 malignant mixed tumors by image analysis technique. While 7 cases of mixed tumor show slow proliferative activity similar to that of monomorphic adenomas, there are 6 cases of mixed tumor in which active proliferation and the appearance of polyploid and aneuploid (AN) below 10% are found. In 3 cases of mixed tumor the proportion of AN is above 10%, indicating abnormal proliferation as that of malignant mixed tumor. The results indicate that mixed tumors need to be considered as being composed of various kinds of biological behavior. Mixed tumors with long preoperation duration (> or = 6 years) are characterized by an increase in the number of proliferation diploid and AN as compared to that with short (< or = 3 years) preoperation duration (P < 0.01). Mixed tumors with the size > 2.5 cm have more AN than that with the size < or = 2.5 cm (P < 0.01). The results indicate that the risk of malignant transformation of a benign mixed tumor increases as it grows.


[Non-operative management of bleeding central hemangioma in jaw-bone]. Based on the experience of sclerosing therapy for hemangioma, the author puts forward a new method which merges the rescuing, diagnosis and treatment into an organic whole. By injecting 5% sodium morrhuate with iodized oil into the tumor body through diagnostic puncture needle, coagulation, then gradual granulation, fibrosing and mineralization could be expected. Five cases have been followed up for 5-12 years with good results.


[Bilateral primary breast cancer. An analysis of 64 cases]. 64 cases of bilateral primary breast cancer were confirmed pathologically and treated in our hospital from 1973 to 1990. There were seven synchronous cases and 57 cases of sequential type. The patients were treated by surgery, radiotherapy and chemotherapy, separately or in combination. 2-, 5-, and 10-year survival rate were 81%, 46.7% and 20%, respectively. The incidence, diagnosis, clinical features, and therapeutic indications for bilateral breast cancer were discussed.


The biology of colorectal carcinoma.

The biology of colorectal carcinoma. Rapid progress in understanding the biology of colorectal carcinoma has occurred in the last decade. During this time, the importance of tumor suppressor genes has been delineated. Mutations in proto-oncogenes, and some of the genetic and epigenetic defects that occur during neoplastic transformation, have been characterized. The very recent identification of a technology that detects some mutations in genes by analyzing fecal specimens offers the real prospect of effective, low-cost screening of large segments of the population at risk for the development of large bowel cancer. A better understanding of the mechanisms involved in metastasis is slowly leading to better methods of prognostication for patients with carcinoma of the colon or rectum. This is important because a better biologic identification of patients at high risk for subsequent metastasis will help determine which patients should receive adjuvant therapy. Further, the development of new approaches to inhibit various aspects of the cascade of events necessary to produce metastasis, notably the inhibition of neovascularization, suggests the real possibility that established metastases may be treated by relatively nontoxic medical therapies. As a result, further knowledge of the biology of colorectal cancer will translate into strategies that will continue to improve the control of this prevalent carcinoma.


Homologous islet amyloid polypeptide: effects on plasma levels of glucagon, insulin and glucose in the mouse. We examined the effects of a single intravenous injection of homologous islet amyloid polypeptide (IAPP) on the plasma levels of glucagon, insulin and glucose in the freely fed mouse. It was observed that IAPP suppressed basal glucagon levels concomitant with a decrease of the blood glucose concentrations. Basal plasma insulin levels were not affected. IAPP did not appreciably modulate the plasma concentration of glucose, insulin or glucagon after an intravenous glucose load. Further, IAPP inhibited the insulin secretory response to beta 2-adrenoceptor stimulation. IAPP also lowered the plasma glucagon levels following beta 2-adrenoceptor stimulation, whereas no apparent effect on plasma levels of glucose was observed. The data suggest that IAPP suppresses glucagon secretion and lowers blood glucose levels in the freely fed mouse. It might also exhibit a negative feedback inhibition on beta 2-adrenoceptor-induced insulin secretion, but has little influence on glucose-induced insulin release. Since IAPP is co-secreted with insulin, it is not inconceivable, that in the freely fed mouse, IAPP may act to amplify the blood glucose lowering effect of insulin through a direct suppression of glucagon secretion via the islet microcirculation.


[Changes in lymphocyte beta-receptor density in patients with heart failure before and after metoprolol or captopril administration]. Human lymphocyte beta-receptor density in heart diseases with various degrees of heart function of 41 cases was determined. beta-receptor density and ejection fraction in congestive heart failure (CHF) before and after conventional therapy with small dose of beta-blocker (metoprolol) or captopril were compared. The aim was to clarify the action and safety of beta-blocker in the treatment of CHF. The results revealed that there was no statistical difference between beta-receptor density in CHF with cardiac function of degree I and II (516.57 +/- 85.93 fmol/10(7) cells, mean +/- s) and in normal controls (576.56 +/- 97.18 fmol/10(7) cells, P > 0.05), while beta-receptor density in CHF of degree III and IV was much lower than that in normal controls (decreased by 50%). There was no statistical difference of beta-receptor density between rheumatic heart disease and cardiomyopathy. Metoprolol up-regulated beta-receptor density from 302.40 +/- 100.91 to 459.60 +/- 174.34 fmol/10(7) cells (P < 0.05), but no change was observed after treatment by captopril. Ejection fraction was increased in both groups (P < 0.01). The results revealed that beta-receptor density was decreased in certain kinds of CHF but no relationship was observed between CHF of different etiology. beta-receptor density was up-regulated by beta-blocker, thus it indicates that it is rational to use beta-blocker for the treatment of certain kinds of CHF. And the use of small dose of beta-blocker with conventional therapy of heart failure might reduce the negative inotropic action of the former.


[Effect of endothelin and endothelin-antiserum on ischemia/reperfusion injury in isolated rat hearts]. Reperfusion of isolated perfused rat hearts with 10(-9) mol/L endothelin (ET) significantly exacerbated the ischemia/reperfusion injury(I/R), in contrast, reperfusion with specific ET-antiserum dramatically alleviated myocardial I/R injury. The results suggest that ET may be an important factor, which contributes to the pathogenesis of myocardial I/R injury.


[Protective effects of high potassium administered after ischemic arrest against reperfusion injury in isolated rat hearts]. High potassium solution is one of the most commonly used cardioplegic solution, but the mechanism of action is still poorly defined. In the present study, isolated rat hearts were utilized to investigate the protective effects and mechanism of action of high potassium against ischemia/reperfusion injury. The results showed that high potassium (22 mmol/L) apparently improved the recovery of contraction amplitude (P < 0.01), inhibited the rise of resting tension (P < 0.01) and abolished ventricular fibrillation during reperfusion after global ischemia for 40 minutes. Moreover, high potassium could preserve myocardial Na+, K(+)-ATPase activity (P < 0.01) and inhibit sodium and calcium overload (P < 0.01) during reperfusion. The results indicate that small amount of high potassium solution (5 ml) administered even after ischemic arrest of rat heart has remarkable protective effects against ischemia/reperfusion injury at 37 degrees C. Its mechanism of action is at least partially by preserving Na+,K(+)-ATPase activity and inhibiting sodium and calcium overload.


Expression of alpha 1 integrin, a laminin-collagen receptor, during myogenesis and neurogenesis in the avian embryo. In this study, we have examined the spatiotemporal distribution of the alpha 1 integrin subunit, a putative laminin and collagen receptor, in avian embryos, using immunofluorescence microscopy and immunoblotting techniques. We used an antibody raised against a gizzard 175 x 10(3) M(r) membrane protein which was described previously and which we found to be immunologically identical to the chicken alpha 1 integrin subunit. In adult avian tissues, alpha 1 integrin exhibited a very restricted pattern of expression; it was detected only in smooth muscle and in capillary endothelial cells. In the developing embryo, alpha 1 integrin subunit expression was discovered in addition to smooth muscle and capillary endothelial cells, transiently, in both central and peripheral nervous systems and in striated muscles, in association with laminin and collagen IV. alpha 1 integrin was practically absent from most epithelial tissues, including the liver, pancreas and kidney tubules, and was weakly expressed by tissues that were not associated with laminin and collagen IV. In the nervous system, alpha 1 integrin subunit expression occurred predominantly at the time of early neuronal differentiation. During skeletal muscle development, alpha 1 integrin was expressed on myogenic precursors, during myoblast migration, and in differentiating myotubes. alpha 1 integrin disappeared from skeletal muscle cells as they became contractile. In visceral and vascular smooth muscles, alpha 1 integrin appeared specifically during early smooth muscle cell differentiation and, later, was permanently expressed after cell maturation. These results indicate that (i) the expression pattern of alpha 1 integrin is consistent with a function as a laminin/collagen IV receptor; (ii) during avian development, expression of the alpha 1 integrin subunit is spatially and temporally regulated; (iii) during myogenesis and neurogenesis, expression of alpha 1 integrin is transient and correlates with cell migration and differentiation.


PAX8, a human paired box gene: isolation and expression in developing thyroid, kidney and Wilms' tumors. Recent evidence indicates a crucial role for paired box genes in mouse and human embryogenesis. The murine Pax8 gene encodes a sequence-specific transcription factor and is expressed in the developing secretory system as well as in the developing and adult thyroid. This restricted expression pattern suggested involvement of the Pax8 gene in the morphogenesis of the above organs and prompted us to investigate the PAX8 gene in humans. In this report, we describe the isolation and characterization of PAX8 cDNAs from a human adult kidney cDNA library. An open reading frame of 450 amino acids contains the 128 amino acid paired domain at its amino-terminal end. The predicted human and mouse Pax8 proteins show 97.8% conservation and are identical in their paired domains. Two independent cDNA clones reveal differential splicing of the PAX8 transcripts resulting in the removal of a 63 amino acid serine-rich region from the carboxy end of the predicted Pax8 protein. The truncated Pax8 protein becomes more similar to the predicted murine Pax2 protein, that is also expressed during kidney development and lacks the serine rich region. RNAse protection analysis shows the presence of both PAX8 transcripts in human thyroid, kidney and five Wilms' tumors. No truncated Pax8 transcripts could be detected in mouse kidney. In situ hybridization to sections of human embryonic and fetal kidney showed expression of PAX8 in condensed mesenchyme, comma-shaped and S-shaped bodies. In contrast, PAX2 expression was present mainly in the very early stages of differentiation, in the induced, condensing mesenchyme. This restricted expression pattern suggests a specific role for both genes during glomeruli maturation.(ABSTRACT TRUNCATED AT 250 WORDS)


An audit of drug usage for in-hospital cardiopulmonary resuscitation. The objective of this study was to assess the changes in outcome of cardiac arrest due to ventricular fibrillation, asystole and electromechanical dissociation in relation to the changing guidelines for drug therapy set by the U.K. Resuscitation Council. It was a retrospective study of 667 resuscitation records for the years 1982, 1986, 1988, 1989, 1990 and 1991. It took place in a large district general hospital with a regional cardio-thoracic centre. We have audited the asystolic cardiac arrests (N = 271) which occurred outside the cardiac care unit (CCU). Adrenaline (intravenous 1 mg) is now the first line drug followed by atropine at an increased dose (2 mg intravenously); calcium is no longer recommended and sodium bicarbonate should be reserved for cases in which an acidosis has been documented. Atropine use has increased over the 9-year period. Bicarbonate use did not change from 1982 to 1986 but fell progressively to no use at all in 1991. Calcium use has declined since 1982. Adrenaline use has remained unchanged. Survival from asystolic arrests (hospital discharge) has remained unchanged at 0-5.5%. Asystole as a primary event in the CCU was uncommon (N = 17) and no patient was discharged. Over the same period, 60% of patients (N = 92) with a cardiac arrest on CCU due to ventricular fibrillation (VF) were discharged and 55% were alive after 6 months. For VF on the wards (N = 192), only 20% of patients were discharged from hospital. A similar proportion was successful for each year.(ABSTRACT TRUNCATED AT 250 WORDS)


Effectiveness of nedocromil sodium 2% eyedrops on clinical symptoms and tear fluid cytology of patients with vernal conjunctivitis. A double-masked, randomised, placebo-controlled study was conducted to evaluate the effectiveness of nedocromil 2% eyedrops, a mast cell stabilizer, in 20 symptomatic patients with vernal conjunctivitis. A 1-week baseline period was followed by 6 weeks of treatment. Clinical examination and cytological evaluation of tear fluid were performed weekly, and the patients recorded their subjective assessment on a daily diary card. The nedocromil group showed significantly less hyperaemia in the course of treatment than did the placebo group, and significantly less itching at all visits compared with baseline itching. In the nedocromil-treated group, but not in the placebo group, the number of neutrophils, eosinophils and lymphocytes in tears decreased significantly during some treatment weeks when compared with baseline. The overall assessment of treatment efficacy by both clinician and patient was significantly in favour of nedocromil treatment over placebo.


Modification of the redox state of cytochrome c oxidase of rice due to certain stress treatments. The redox state of cytochrome alpha 3 during in situ respiration of leaves of 20-day-old rice seedlings was assessed by in vivo aerobic assay of nitrate reductase, after 1 min exposure to carbon monoxide. Different stress treatments like water and salt stresses, disintegration of leaf tissues and darkness modified the redox state of cytochrome c oxidase. The dark treatment altered the redox state of cytochrome oxidase from reduced to the oxidized state, as judged by its reaction with CO in CO-sensitive rice cultivar. The water and salt stresses as well as the disintegration of leaf tissue on the contrary altered cytochrome oxidase from the oxidized to its reduced state in CO-insensitive cultivars; probably by changing the cellular integrity, turgidity and structure of mitochondrial membrane, and also due to decreased mitochondrial energization.


Detection of human papilloma virus types 16 & 18 DNA in cervical lesions of Indian women using in situ hybridization. Fifty one biopsies from women with malignant lesions of the uterine cervix and 9 biopsies fron non-malignant lesions were examined for the presence of HPV 16 and 18 DNA sequences by in situ hybridization method using 35S-labelled DNA probes. HPV 16 DNA sequences were detected in 82.4 per cent biopsies from women with malignant lesions, whereas HPV 18 DNA was detected in only 3 biopsies which were also positive for HPV 16 DNA. Two biopsies from non-malignant lesions were positive for HPV 16 DNA only. Data were also analysed according to the histologic type of cancer. It was observed that no significant correlation existed between HPV types and different histologic types of cervical cancer.


CMV infections following allogeneic BMT: risk factors, early treatment and correlation with transplant related mortality. The impact of early detection of CMV infections in allogeneic bone marrow transplantation (BMT) and of early treatment with ganciclovir is still uncertain. 98 patients undergoing allogeneic BMT for hematologic malignancies (n = 91) or aplastic anemia (n = 7) were monitored weekly for the expression of the lower matrix protein pp65 of cytomegalovirus (CMV) on peripheral blood cells (PB) and urine sediments (U) as detected by C10 and C11 monoclonal antibodies (Clonab, Biotest) and immunoperoxidase. Bronchoalveolar lavage (BAL) cytospin preparations were also studied in patients with clinically documented interstitial pneumonia. Patients were considered to be infected with CMV if pp65 was detected in PB (n = 15) or BAL cells (n = 6), or in the presence of serum CMV-IgM with (n = 7) or without (n = 3) pp65-positive cells in urine sediments. The overall actuarial risk at 300 days of developing a CMV infection was 35%. CMV serum/status (IgG) pre-BMT of donor and/or recipient predicted the occurrence of CMV infections post-BMT: in neg/neg donor/recipient pairs (n = 17) the actuarial risk at 300 days was 0%, compared to 41% in pairs in which donor and/or recipient were CMV seropositive (n = 81) (p = 0.001). 24/31 patients were treated with ganciclovir (DHPG), and 17 survive. Mortality of patients treated early with DHPG on the basis of CMV antigenemia was 18% compared to 42% for untreated patients (p = 0.9). Pretransplant donor/recipient seropositivity accurately predicted transplant related mortality (TBM): 6% in neg/neg pairs vs 41% in all other combinations (p = 0.008). The risk of developing CMV infections post-BMT can be predicted by pre-transplant serostatus, diagnosed by monitoring the expression of pp65-protein and correlates with transplant related mortality. The latter appears to be reduced by early treatment with DHPG.


Promotional role for glucocorticoids in the development of intracellular signalling: enhanced cardiac and renal adenylate cyclase reactivity to beta-adrenergic and non-adrenergic stimuli after low-dose fetal dexamethasone exposure. Fetal exposure to high doses of glucocorticoids, as used to aid lung maturation in the therapy of Respiratory Distress Syndrome, causes growth retardation and interference with development of beta-adrenergic receptor-mediated cell signalling. The current study examined whether lower levels of steroids might instead play a positive trophic role in receptor transduction. Pregnant rats were given dexamethasone at or below the threshold for growth impairment (0.05-0.2 mg/kg) on gestational days 17, 18 and 19, and the beta-receptor-mediated stimulation of adenylate cyclase was evaluated in membrane preparations from heart and kidney. The enzymatic response to isoproterenol was compared with effects on: (1) basal (unstimulated) adenylate cyclase, (2) adenylate cyclase stimulation mediated by forskolin, which bypasses the beta-receptor, and (3) development of beta-receptor binding capabilities, assessed with [125I]pindolol. In the heart, prenatal exposure to dexamethasone produced a dose-dependent enhancement of beta-receptor-mediated stimulation of adenylate cyclase activity; however, both basal and forskolin-stimulated activity were also increased and beta-receptor binding was relatively unaffected. These results suggest that enhanced responsiveness was occurring at the level of the cyclase itself, rather than by effects on receptors on their G-protein coupling to enzyme activity. Promotional effects on adenylate cyclase were detectable at the low dose of dexamethasone, without any evidence of growth impairment.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular epidemiology of endemic ciprofloxacin-susceptible and -resistant Enterobacteriaceae. To elucidate the epidemiology of widespread ciprofloxacin resistance in our Veterans Affairs medical center using whole cell DNA analysis. In vitro study of ciprofloxacin resistant and susceptible Enterobacteriaceae isolated during the course of a clinical epidemiologic study of quinolone resistance. Veterans Affairs Medical Center with acute care and long-term care divisions. We examined 40 ciprofloxacin-resistant strains of Serratia marcescens, Proteus mirabilis, and Providencia stuartii using restriction endonuclease analysis of whole cell DNA and compared them with concomitantly isolated ciprofloxacin sensitive strains. We sought to determine whether resistant strains were identical to susceptible strains, indicating in vivo emergence of resistant strains from susceptible strains, and whether resistant strains were shared among patients. All 26 ciprofloxacin-resistant S marcescens isolates shared a single ecoRI restriction pattern. Multiple patterns were seen in the ciprofloxacin-susceptible S marcescens isolates; however, several isolates had a pattern matching that of the resistant isolates. Similar results were seen among the P mirabilis isolates. Three different ecoRI patterns were found among the ciprofloxacin-resistant P stuartii isolates; none matched those found among the susceptible isolates. The frequency of spontaneous emergence of ciprofloxacin resistance in susceptible S marcescens strains with restriction pattern matching that of the resistant strains was significantly higher than that of nonmatching strains. Ciprofloxacin-resistant strains of Enterobacteriaceae became widespread within a short period of time. Resistant strains of S marcescens and P mirabilis arose from endemic susceptible strains. The resistant strain of S marcescens appeared to arise from a susceptible strain with a relatively high frequency of spontaneous ciprofloxacin resistance.


BK virus.

BK virus. BK virus is a human polyoma virus that infects the renal epithelium and remains latent until immunosuppression triggers reactivation. After reactivation, BK virus can be detected in the urine by methods currently available in the clinical laboratory. Correlations can be made between BK viruria and the occurrence of both renal and hepatic pathologies. BK virus is emerging as a significant pathogen in transplant patients. Additionally, the presence of BK virus DNA in primary brain and pancreatic tumors suggests that it may have oncogenic potential. Thus far, attempts to treat BK virus infection have been ineffective, though research has opened new avenues for treatment possibilities. Prevention of BK virus and other latent viral reactivation remains a challenge to viral research.


Virus-specific effects of recombinant porcine interferon-gamma and the induction of Mx proteins in pig cells. Interferon-alpha (IFN-alpha) and -gamma differed in their action against influenza virus and vesicular stomatitis virus (VSV) on pig cells. Recombinant IFN-alpha severely impaired the cytopathic effect of VSV on PK-15 cells, whereas recombinant porcine IFN-gamma did not. IFN-alpha impaired also the replication of VSV and of influenza virus in primary pig kidney cells in contrast to IFN-gamma, which failed to induce an efficient antiviral state against both viruses. Otherwise, the IFN system seemed to work properly in pig cells since both IFN-alpha and IFN-gamma induced an efficient antiviral state to mengovirus. The establishment of the antiviral state to VSV and influenza virus correlated with the induction of two cytoplasmic proteins related to the murine Mx protein involved in the selective resistance of mice to influenza virus infection. The results are discussed in the context of the susceptibility of pigs to influenza virus strains that are in circulation in birds and in humans.


Expression of active human interferon-beta in transgenic plants. Tobacco plants were transformed with the human gene for interferon-beta (IFN-beta). Transformation was determined by the polymerase chain reaction (PCR), and expression was determined by Western blot analysis, by purifying the IFN from the transgenic plants, and by bioassays indicating its activity in human cells. Plants expressing IFN-beta were self-pollinated. IFN-beta-expressing progeny plants were selected and produced active IFN-beta, indicating stable transformation.


Argyrophilic nucleolar organizer region counts in exocrine pancreatic tumors. We enumerated the number of Ag-NORs in normal pancreatic ducts and exocrine pancreatic tumors to assess their cellular activity. Our results indicate that the mean number of Ag-NOR counts increased stepwise in the following order: normal pancreatic duct (1.26), serous cystadenoma (1.27), mucinous cystadenoma (1.65), mucinous cystadenocarcinoma (2.29), noninvasive intraductal variant of mucin-producing papillary adenocarcinoma (3.16), and a common type of invasive duct cell adenocarcinoma (3.78). These results suggest that cellular proliferative activity is low in normal pancreatic ducts and serous cystadenoma, intermediate in mucinous cystadenoma, and high in mucinous cystadenocarcinoma and duct cell adenocarcinoma. In addition, mucinous cystadenocarcinoma has significantly lower Ag-NOR counts than duct cell adenocarcinoma. We conclude that a clear quantitative difference between the Ag-NOR content of tumor cells of serous cystadenoma, mucinous cystadenoma, mucinous cystadenocarcinoma, and duct cell adenocarcinoma reflects the underlying different biologic behavior (chiefly, grade of malignancy) of these lesions.


Actions of parathyroid hormone on cultured human dental pulp cells. The responsiveness of human dental pulp (HDP) cells to parathyroid hormone (PTH) was investigated by measuring their cyclic AMP (cAMP) content, DNA synthesis, alkaline phosphatase activity, collagen synthesis, and glycosaminoglycan (GAG) synthesis. PTH dose-dependently increased the intracellular cAMP 1 min after the addition of PTH. Confluent HDP cells on day 14 expressed a high level of cAMP production after addition of 3 units/ml PTH. The hormone did not affect DNA synthesis by HDP cells. Alkaline phosphatase activity was suppressed by PTH to 81% of control (p < 0.01), and addition of dibutyryl cAMP to the medium mimicked the effect of PTH (79% of control, p < 0.01). The hormone inhibited collagen synthesis (15% decrease of [3H] proline incorporation, p < 0.01), and stimulated non-collagen protein synthesis (10% increase, p < 0.05). The increase of non-collagen protein by PTH was in accordance with the enhancement of GAG synthesis (17% increase of [35S]sulfate incorporation, p < 0.01). Dibutyryl cAMP caused further increase of GAG synthesis, to 155% of control (p < 0.01). Observations of the radiolabeled proteins on 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis after metabolic labeling with [14C]proline and [35S]sulfate revealed a similar tendency to the quantitative determinations in which PTH inhibited collagen synthesis and stimulated GAG synthesis. These findings suggest that HDP cells have some osteoblastic characteristics in terms of PTH responsiveness, and that this culture system is a useful model for studies of human dental pulp.


Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against leukemia and myeloma: V. The effects of monoclonal antibodies and interferon on the levels of cyclic nucleotides in leukemic cell lines. After the leukemic cell lines were treated with monoclonal antibodies (McAbs) and interferon (IFN-alpha), the changes of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in the corresponding leukemic cell lines were measured by radioimmunoassay. The results showed that when the ratio of antigen to antibody was 80 to 1, the cAMP levels in the leukemic cell lines were obviously higher than those in the controls while the cGMP levels were obviously lower after being treated with the corresponding McAbs for 16-24 h (P < 0.001). The average level of intracellular cAMP was remarkably increased and that of cGMP underwent no significant changes in the leukemic cell lines after treatment with IFN-alpha.


Alterations of calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats. We examined the possible alterations in calcium handling through the calcium channels of spontaneously hypertensive rats (SHR) using 45Ca2+ uptake measurements in cultured aortic cells. Primary cultures of vascular smooth muscle cells (VSMC) were obtained by enzymatic dissociation of the thoracic aortas from 8-week-old SHR and age-matched Wistar-Kyoto rats (WKY). The functions of voltage sensitive calcium channels (VSCC) and receptor operated calcium channels (ROCC) were estimated from the activated 45Ca2+ uptake in VSMC with high K+ depolarization and arginine vasopressin (AVP), respectively. Compared to basal conditions, depolarization with 55 mM KCl increased 45Ca2+ uptake at 20 min by 94 +/- 17 (SE) % in SHR and 38 +/- 6% in WKY. The activated 45Ca2+ uptake was significantly greater in SHR than in WKY (p < 0.01). There was no significant difference in 45Ca2+ uptake at 20 min in the presence of 5 x 10(-8)M AVP between SHR and WKY. These results suggest that calcium uptake, at least through VSCC, is increased in VSMC of SHR. This enhanced activity may be implicated in the hypertensive mechanisms in this model of hypertension.


Long-term observation of neutralization antibody after enterovirus 70 infection. There is the need for more information on the persistence of the immune response to enterovirus 70 (EV70) infection. In August 1984, an outbreak of acute hemorrhagic conjunctivitis occurred at a nursing home in Sapporo, Japan. During the subsequent 7 years, we have monitored the neutralization antibody of EV70 in 13 patients with acute hemorrhagic conjunctivitis and 15 persons with subclinical EV70 infection among the 108 persons in the nursing home. During the first one to two years, the neutralization antibody in 6 of the 28 subjects (21.4%) decreased to less than 1:8. Seven years later, the neutralization antibody had decreased to less than 1:8 in 92% of the subjects. There was an individual difference in the level of neutralization antibody titer against EV70. However, overall the antibody levels markedly decreased every year. It is important to remember that the neutralization antibody titer of EV70 decreases with the passage of time. Consequently, most of the patients who had acute hemorrhagic conjunctivitis will not have resistance against reinfection 7 years after the initial infection.


[Adult T-cell leukemia with various pulmonary complications]. A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.


The inhibition of the paracrine progression of prostate cancer as an approach to early therapy of prostatic carcinoma. The prevalence of neural elements in prostatic carcinoma and their effects on the behavior of the lesion have recently been recognized. Recent reports suggest that chromogranin-A- and neuron-specific enolase-expressing tumors have an earlier progression and a lower response rate to hormonal therapy. The extreme presentation of this tumor is presumed to be small cell carcinoma of the prostate. This bombesin-secreting tumor, which has a characteristic clinical picture of early visceral involvement, wide-ranging metastases, and a relatively low rate of expression of PSA and PAP, is highly responsive to chemotherapy. The relatively high rate of expression of neural elements in primary prostatic carcinoma is discordant with the low frequency of clinical small cell carcinoma of the prostate. In order to account for these differences, one can assume that neural elements may play a role in the progression of this disease by either developing their own neoplastic process (small cell carcinoma of the prostate) or, in the majority of cases, causing paracrine progression of the tumor. Bombesin is typically secreted by small cell carcinoma of the lung and possibly by the prostate. It has been shown to be a growth factor mediating the progression of this disease in a number of experiments. Preclinical data demonstrate increased invasiveness and increased proliferation associated with bombesin in the treatment of prostatic carcinoma. Based on the hypothesis that neural peptides may be important mediators of androgen-independent growth of prostatic carcinoma as well as predicting poor prognosis, inhibition of these factors may represent a therapeutic strategy of relevance for the treatment of patients with prostatic carcinoma.


Chemoprevention of prostate cancer: guidelines for possible intervention strategies. The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.


[The role of serotonin in the pathophysiology of migraine]. Of the many factors that have been implicated in the pathophysiology of migraine, none seems to have a better claim than serotonin (5-hydroxytryptamine, 5-HT). The evidence for this is: 5-HT concentrations in blood increase during the prodromal (aura) phase and subsequently, decrease to subnormal levels in the headache phase; migraine attacks may be triggered, in susceptible, subjects, by reserpine which depletes body serotonin; migraine attacks may be triggered, in susceptible subjects, by reserpine which depletes body serotonin; migraine attacks may be relieved by intravenous injection of 5-HT; medications known to affect 5-HT concentrations have been shown to be efficacious in both aborting (agonists of 5-HT1 receptors) and preventing (antagonists of 5-HT2 receptors) migraine attacks. Since most of 5-HT in blood is stored in the platelets, attention of many investigators focused on the platelet function abnormalities. The positive findings provoked some of them to hypothesise that migraine is a primarily platelet disorder. Advances in the understanding of the role of 5-HT in migraine and the pharmacology of this amine have now resulted in the development of a highly selective 5-HT1 -like receptor agonist which selectively constricts cranial blood vessels and inhibits neurogenically-mediated plasma protein extravasation in the dura mater.


[Sumatriptan and its use in treatment of migraine and cluster headaches]. The methods used presently for abortion of the attacks of migraine and cluster headache are not fully satisfactory which causes that the search for new therapies is continuing. Although the mechanism of migraine attacks remains unexplained, it is thought that an important role in it is played by serotonin receptors, vasodilation in certain regions and opening of arteriovenous communications in the head. Sumatriptan is an agonist of 5-HT1 -like receptors and exerts a selective vasoconstricting effect on the arteries of the head, particularly in the rami of the carotid artery. In 1988 the first reports appeared on the effectiveness of the drug in migraine attacks. In the following years extensive, multicentre and international studies of the drug were carried out on over 600 healthy volunteers and nearly 6000 patients with migraine. The studies demonstrated that Sumatriptan was effective in abortion of migraine attacks. After oral administration of 100 mg or subcutaneous injection of 6 mg in nearly 70% of cases the attack regressed or was greatly alleviated, similarly as other symptoms accompanying the headache such as photophobia, nausea, vomiting. Studies were undertaken also on the effectiveness of Sumatriptan in emergency treatment of cluster headache, and good results were again achieved. The tolerance of the drug is good, although in some cases side effects develop, usually transient and mild, among them tingling, feeling of pressure, heat or heaviness of the head or chest, taste change and burning sensation at the site of injection. Sumatriptan, similarly as all novel drugs, requires caution in its use, particularly in patients with coronary heart disease and hypertension, and also in old patients. As yet, the use of the drug in paediatric migraine or in pregnancy is not recommended.


[Sumatriptan--future development, alternative features and potential new indications]. Sumatriptan is a highly selective 5 HT1 receptor subtype agonist. The efficacy and safety profiles of sumatriptan given by tablet or subcutaneous injection have been extensively investigated in the acute treatment of migraine attacks, where it has proved effective and well tolerated. A substantial proportion of patients with an acute attack of migraine suffer from once or more gastrointestinal symptom, including nausea, vomiting and occasionally diarrhoea. The presence of these symptoms may make the oral administration of acute treatments unsatisfactory. Subcutaneous administration is an alternative, but fear or dislike of injections or an inability to self inject makes subcutaneous treatment unacceptable to some patients. Alternative routes of administration are being investigated to overcome these difficulties including intranasal sprays and rectal suppositories. For those patients who experience difficulties swallowing whole tablets, an effervescent tablet is under development. Recent data have demonstrated that sumatriptan offers effective relief of cluster headache attacks, a condition where suffers experience repeated severe headache attacks, of short duration, during a cluster period. Further new indications are being investigated including the treatment of menstrual migraine, paediatric migraine and other headaches.


Practical choices of fast spin echo pulse sequence parameters: clinically useful proton density and T2-weighted contrasts. With the development of fast spin echo (FSE) MRI techniques, T2-weighted images of the brain may be obtained much more quickly than when using conventional spin echo techniques (CSE), because made the individual echoes on the FSE pulse sequence are phase encoded, allowing acquisition of the same spatial information as in CSE with less excitations. The pulse sequence parameters (echo train length, bandwidth, echo spacing) are discussed. Images were obtained on four volunteers using both CSE and FSE while varying repetition time, echo time and matrix. Comparison for signal intensity gray-white differentiation, fat and CSE signal, arifacts and vascular resolution showed that FSE images comparable in quality to those of CSE can be obtained in less than half the time. A practical choice of FSE parameters is recommended for clinical use. However, artifacts, possibly related to CSF and vascular pulsation, of which the radiologist should be aware, were identified on the FSE images.


CT and MRI: prognostic tools in patients with AIDS and neurological deficits. To determine the prognostic value of CT and MRI in AIDS we studied the survival of patients with neurological involvement, in relation to the initial imaging results. Twenty-six initial CT and 15 MRI examinations of 41 patients were reviewed for the presence of cerebral atrophy and/or focal lesions. The mean survival time of patients with initially normal imaging was longer (700 +/- 89 days) than that of patients with isolated cerebral atrophy (326 +/- 65) or isolated focal lesions (202 +/- 97). The shortest survival (78 +/- 44 days) was found in patients with both cerebral atrophy and focal lesions. The risk of death in patients with atrophy alone was 3.6 times higher, that in patients with focal lesions alone 6.4 times higher, and in patients with both changes 19.3 times higher than in patients with initially normal imaging. Cerebral imaging with CT and/or MRI thus allows identification of AIDS-related cerebral changes and may contribute to assessment of prognosis.


The diagnosis of recent herpes simplex virus type 2 genital infections by the simplex-2 test. The prevalence of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) was determined in patients with culture confirmed HSV-2 genital herpes and control groups using a commercial HSV-2 early antigen (Simplex-2; Gene Link Australia Ltd). Eighty seven per cent of 39 sera collected between 14 and 28 days after confirmed primary and recurrent HSV-2 infection were positive. In acute sera collected between 2-10 days after onset the Simplex-2 test was negative in all 90 patients with presumed primary infection but positive in 53% of 230 sera from recurrent infection. A specificity of 90-94.5% was obtained by testing 36 patients with recent proven HSV-1 infection and 331 control group patients. The Simplex-2 test may be useful in some cases of culture-negative, clinically suspected genital HSV-2 lesions only when sera are collected between 14-28 days after primary and recurrent infection. Its lack of specificity makes it unsuitable for the routine diagnosis of recent HSV-2 infection in the general population.


Tumors presenting as aural polyps: a report of four cases. All biopsy material from the ear, received over an 8 yr period by a private practice, was reviewed. Four unusual neoplasms presenting as aural polyps are described (meningioma, embryonal rhabdomyosarcoma, eosinophilic granuloma and adenoid cystic carcinoma). The relevant literature is briefly reviewed and the importance of histopathological examination of aural polyps is discussed.


[The place of new therapies in the treatment of congestive heart failure. The combination of digitalis and diuretics is always in good place]. In recent years, thanks to a better understanding of the pathophysiology of congestive heart failure and progress made in the pharmacology of cardiovascular drugs, new therapeutics have been advocated in the treatment of congestive heart failure. Among them, converting enzyme inhibitors are the most useful. However, the classical association of digoxin-furosemide and general measures remains a very effective first-choice treatment in most cases. Only in particular situations, such as cardiomyopathy and decompensated atrio-ventricular insufficiency, should priority be given to converting enzyme inhibitors. Phosphodiesterase inhibitors are essentially used within the context of post-cardiac surgery intensive care. Beta-blockers which have been recently proposed for treatment of adult patients must not be used, as there is still no data available on their effectiveness and tolerance in pediatric patients.


[Thrombosis of superior longitudinal sinus and pulmonary embolism in nephrotic syndrome]. The authors report on the case of a child with the nephrotic syndrome complicated by thrombosis of superior longitudinal sinus, bilateral massive pulmonary embolism resulting in a sudden death. A dramatic deficiency in factor XII was demonstrated; the pathophysiology and management of such an abnormality are discussed.


[Iron salt poisoning complicated by gastric stenosis]. Iron salt poisoning has been reported in a 7-year-old child. Desferioxamine was used for 6 days; systemic toxicity remained moderate. The clinical course was marked by gastro-intestinal symptoms and gastric stricture. The treatment principles for iron salt poisoning are reviewed.


[Congenital diverticulum of the tracheal carina in neonates. A case report]. A 17 day-old neonate with no history of broncho-pulmonary disease presented with a severe respiratory distress which was found to be related to a congenital tracheal diverticulum. An excision of the diverticulum was performed. Histologically it was characterized by a lining wall of stratified columnar ciliated epithelium and the presence of smooth muscle and cartilage in the wall. This rare entity was reported only once in the pediatric literature. It gives a history of chronic respiratory tract infections or acute respiratory distress. Bronchoscopy or bronchography and CT scan are necessary for the diagnosis. The treatment is surgical.


[Sharp syndrome in an infant: a case report]. We report on a case of Sharp syndrome which was diagnosed late in on 11-year old boy. After 5 years of corticosteroid treatment, he presented with myopericardic aggravation, glomerular disease, and seizures with delirium, which responded to high-dose steroid therapy with early switch using synthetic antimalarial drugs. Six years later the results are still satisfactory.


[Results and complications of induction treatment of acute leukemia in children. A personal series of 79 cases (1988-1989)]. In 1988 and 1989, 79 children have been treated for induction of acute leukemia. 68 presented an acute lymphoblastic leukemia (ALL) and 11 an acute non-lymphoblastic leukemia (ANLL). The complete remission rate was 92% (96% in ALL, 73% in ANLL). Fever occurred in 50% of the children, with positive blood cultures in 11 of them. One child died from streptococcal sepsis. No metabolic disorder was noted. Four patients were transferred into the intensive care unit. After 8 days, the treatment of ALL was continued in the outpatient clinic in more than 50% of the cases. The treatment of ANLL is frequently complicated by hemorrhages and sepsis and needs adapted supportive care in a specialized unit.


[An outbreak of allergy to horses in children. A review of 56 recent cases]. Over the past 11 years, signs of allergy were observed in 56 children and adolescents in contact with horses. The cases consisted of 35 boys and 21 girls, 35 of them were under 10 years of age. The main clinical signs were ocular symptoms (36), asthma (30) and rhinopharyngitis (24). All the children had very positive cutaneous prick tests and specific IgE (class 3 and 4: 62%) and were polysensitized. In several children, the first manifestation occurred at the time of the first known contact with a horse or pony. No further contact was usually the only therapeutic solution. In disabled children, allergy to horses must be considered when clinical signs of allergy occur during therapeutic riding sessions.


[Home cardio-respiratory monitoring with alarm record system in infants at risk of life-threatening events]. In few infants, home monitoring is useful to prevent recurrent apparently life-threatening events. Some devices have an alarm record system. We report our experience of home monitoring with such a device in 22 infants. 43.3% of the recorded events were considered as false alarms and 56.7% as true alarms. Among the alarms relative to abnormal respiratory events (38%), more than half occurred after two min of very low impedance thoracic signal. Among the true alarms relative to cardiac abnormalities (18.7%) more than half occurred during high amplitude fluctuations of the thoracic impedance signal and were relative to obstructive apnea or hypertonic vagal reactivity. Three infants presented an apparent life threatening event during an alarm, and two of them were hospitalized. These results indicate that it is important to define precisely the significance of the alarms during the survey of home monitoring of infants at risk for sudden infant death.


[Congenital umbilical fistulas. A report of 12 cases]. A brief report of 12 cases of congenital anatomical fistula (CUF) has been presented (4 cases of persistent omphalo-mesenteric, 3 persistent urachus, 4 urachal sinus, 1 persistent omphalo-mesenteric duct with urachus) with some general comments. CUF are discovered at birth or later in case of umbilical granuloma, redness, local swelling or umbilical discharge. Diagnosis and anatomical type are determined by instrumental exploration and fistulogram. Lower urinary obstruction should be eliminated in the case of persistent urachus. Complete excision is the correct treatment.


Streptomyces ATP nucleotide 3'-pyrophosphokinase and its gene. Streptomyces ATP nucleotide 3'-pyrophosphokinase is an extracellular, ribosome-independent, and stringent factor-mimic ppGpp synthetase with an unusually broad acceptor spectrum. The gene-containing DNA fragments cloned from chromosomal DNA of a producer S. morookaensis into pIJ699 and pUC plasmids were found to express the active enzyme in the transformed S. lividans TK24 and enteric E. coli JM109 and nitrogen-fixing Klebsiella pneumoniae M5a1 and 5022, respectively. Base sequence of the structural gene and the deduced amino acid sequence exhibited little homology to those of E. coli stringent factor and related proteins. Growth retardation was seen in some transformants.


Enzymatic synthesis of PAPS with an ATP-regeneration system. Sulfate activating enzymes, ATP sulfurylase and APS kinase, were newly isolated from a thermophile, Bacillus stearothermophilus. Adenosine 3'-phosphate 5'-phosphosulfate (PAPS) was synthesized by these enzymes. The reaction proceeded more efficiently when an ATP-regeneration system, using acetate kinase, was coupled to the reaction system.


Sequence-specific DNA recognition by basic peptides. A chiral template with C2 symmetry has been used for modeling a dimeric interface of DNA binding protein. An oligopeptide derived from the basic region of MyoD, a recently described "helix-loop-helix" class of DNA binding protein, has been tethered to the template. Among the four models which differ in chirality and polarity with respect to the arrangement of two subunits, only one dimer model with right-handed and C-terminus to C-terminus arrangement of the peptide subunits binds DNA containing native MyoD binding sequence.


dNTP pool imbalance induced endonuclease: 5-fluorodeoxyuridine induced DNA double strand break in mouse FM3A cells and the mechanism of cell death. The mechanism of intracellular deoxyribonucleotide triphosphates (dNTP) pool imbalance-induced cell death in mouse FM3A cells was studied. When the cells were treated with 1 microM 5-fluorodeoxyuridine (FdUrd), the imbalance of the cellular dNTP pool was induced. The imbalance was followed by DNA double stranded breaks and subsequent cell death. The endonuclease toward double stranded DNA has been found in a fraction of FdUrd treated cell lysate, and isolated using column chromatography. SDS-polyacrylamide gel electrophoresis showed a major protein species of approximate 45 kDa. The endonuclease was revealed, using electrophoretic separation in SDS-polyacrylamide gels containing DNA, by incubating the gels in buffer to remove SDS and to allow renaturation and enzyme activity.


Inhibitory effect of oligoribonucleotide phosphorodithioates against the 3'-exonuclease activity. Oligoribonucleotides consisted of modified nucleotides at 3'-turmini were chemically synthesized on the solid phase method. Moreover, these analogues were investigated the stability in a prokaryotic cell-free translation system and the resistance against a few kind of nucleases containing 3'-exonuclease activity.


High performance liquid chromatography of nucleic acids and the related compounds on a fluorinated silica gel column. Separations of nucleic acids and the related compounds were investigated by HPLC on a new fluorinated bonded silica gel column. Polyadenylate (Poly (A)) enzymatic partial hydrolysate sample and the mixture of various polynucleotide samples were sufficiently separated by the reversed-phase mode using a gradient elution with aqueous ammonium acetate/acetonitrile system. Mixed-mode separation on the fluorinated bonded phase coated with a tert-alkylammonium salt was also examined for the separation of the various polynucleotides including tRNAs.


Immobilization of nucleoside on silica gel and specific separation of oligonucleotides. Deoxyadenosine was immobilized on silica gel, in order to use as HPLC resins for selective separation of oligonucleotides. The longest retention time was observed for the complementary pd(T)4, and increased with decrease of temperature. This fact suggested that the main separation factor was the base pairing between complementary nucleic acid bases. These resins may be useful for separation of components of nucleic acids and polynucleotides as a specific separation system.


Oxygen-independent photocleavage of DNA by xanthene dyes. Plasmid DNA has been efficiently photocleaved by a series of xanthene dyes in the absence of molecular oxygen. The cleavage by fluorescein proceeds mostly via its singlet excited state.


Enormous catalyses of lanthanide metal ions for unprecedentedly fast hydrolysis of 3',5'-cyclic adenosine monophosphate. 3',5'-cyclic adenosine monophosphate (cAMP) is efficiently hydrolyzed by use of lanthanide metal(III) ions as catalysts. The acceleration by 10(-2) M of Ce(III) is remarkable (more than 10(11) fold) at pH 8.0, 30 degrees C, decreasing the half-life from a half million years to 35 seconds. The catalytic activity is in the following order: Ce >> Pr > Nd, La > Y, Sm, Dy > others. The catalysis is ascribed to cooperation of three or four lanthanide metal ions.


The structure of the human retinoic acid receptor-beta DNA-binding domain determined by NMR. The solution structure of the DNA-binding domain (DBD) of the human retinoic acid receptor-beta (hRAR-beta) has been determined by nuclear magnetic resonance (NMR) spectroscopy and distance geometry (DG). The assignments of 1H and 15N resonances were carried out by the use of 1H homonuclear and 15N-1H heteronuclear two- and three-dimensional NMR experiments. The structure of RAR DBD has been obtained on the basis of distance constrains derived from NMR experiments. The structure shows that two "zinc-finger" domains of the protein are followed by two perpendicular alpha-helices and a short beta-sheet near the N-terminus. Apolar residues in both helices form a hydrophobic core. Binding models of RAR DBD to its inverted and direct repeat response elements have been constructed based on this three-dimensional structure.


Isolation, characterization and biological activity of a CRF-related diuretic peptide from Periplaneta americana L. A diuretic peptide (Periplaneta-DP) has been isolated from extracts of whole heads of the cockroach, Periplaneta americana. The purified peptide increases cyclic AMP production and the rate of fluid secretion by isolated Malpighian tubules in vitro. In the fluid secretion assay, the response to native Periplaneta-DP is comparable to that obtained with crude extracts of cockroach corpora cardiaca, and the EC50 lies between 10(-8) and 10(-9) M. The primary structure of Periplaneta-DP was established as a 46-residue amidated peptide: T G S G P S L S I V N P L D V L R Q R L L L E I A R R R M R Q S Q D Q I Q A N R E I L Q T I-NH2. Periplaneta-DP is a further member of the recently established family of CRF-related insect diuretic peptides.


Neuropeptide Y inhibits sympathetic neurotransmission in ipsilaterally innervated but not contralaterally reinnervated superior tarsal smooth muscle of the rat. The superior tarsal smooth muscle (STM), which elevates the upper eyelid, normally is innervated by sympathetic neurons from the ipsilateral superior cervical ganglion that are not neuropeptide Y-immunoreactive (NPY-ir). Following neonatal ganglionectomy, this target is reinnervated by sympathetic nerves from the contralateral superior cervical ganglion that are strongly NPY-ir. We examined the effects of exogenously administered NPY on STM tone, response to norepinephrine, and sympathetic neurotransmission in ipsilaterally innervated and contralaterally reinnervated STMs. NPY (2-10 micrograms/kg iv) increased blood pressure but did not alter STM tone. Similarly, contractile responses to co-administered norepinephrine were not affected. These findings imply an absence of direct and indirect postjunctional actions of NPY on STM. Contractions elicited by stimulation of the cervical sympathetic nerve (1.5 Hz) were not affected by NPY on the contralaterally reinnervated side; however, ipsilateral contractions were decreased in a dose-dependent fashion, with an inhibition of about 40% at 10 micrograms/kg. We conclude that while the STM is unresponsive to exogenously administered NPY, this peptide exerts selective inhibitory effects on the ipsilateral NPY-ir-negative but not the contralateral NPY-ir-positive innervation. This suggests that the neonatally denervated STM is reinnervated by contralateral fibers that are functionally different from the normal ipsilateral innervation in being devoid of functional prejunctional NPY receptors.


Immunohistochemical study of transforming growth factor-alpha in human lung cancers. The expression of transforming growth factor-alpha (TGF alpha) was assessed by immunohistochemical staining in 52 human lung tumor samples. All of the 8 small cell lung cancers were negative whereas all of the 18 adenocarcinomas and 23 of the 26 squamous cell carcinomas showed positive immunoreaction to TGF alpha. Distribution of TGF alpha stainings in the squamous cell carcinomas was weaker and more heterogeneous as compared to the adenocarcinomas. Ultrastructural localization of TGF alpha in the squamous cell lung carcinomas by indirect immunogold staining revealed that TGF alpha is present in the cytoplasm as well as the cell membrane but not in the nucleus. This suggests that the lung cancer cells are not only the producer of TGF alpha, but also the target cells of the TGF alpha action. The expression of TGF alpha in lung tumors may be useful diagnostically in differentiating small cell lung cancer from non-small cell lung cancer and may also be important in the study of the biological properties of primary lung cancers.


Coexpression of ganglioside antigen Fuc-GM1, neural-cell adhesion molecule, carcinoembryonic antigen, and carbohydrate tumor-associated antigen CA 50 in lung cancer. With the aid of specific monoclonal antibodies, tumor tissues from 68 patients with lung cancer were examined for their expression of two small cell lung carcinoma (SCLC) antigens, Fuc-GM1 (fucosyl GM1; IV2FucII3NeuAc GgOse4) and neural-cell adhesion molecule (NCAM), and two broader tumor antigens, carcinoembryonic antigen (CEA) and carbohydrate cancer-associated antigen CA 50. Expression of Fuc-GM1 was seen in 75% and NCAM in 78% of the SCLC specimens, but also in 12 and 20% of non-SCLC. Either or both of these antigens were expressed in more than 90% of SCLC and in 25% of non-SCLC. CEA was found in more than 80% of SCLC and non-SCLC. Expression of CA 50 was seen in 65-68% of non-SCLC and SCLC, showing preference for SCLC and lung adenocarcinoma. In SCLC, cellular expression of Fuc-GM1 was generally seen together with NCAM and CA 50, but rarely with CEA. There was considerable inter- and intratumor heterogeneity in the expression of all four antigens. The results suggest that CEA is the antigen of choice for the detection of lung cancer regardless of histotype. In combined analysis of CEA, CA 50, Fuc-GM1 and NCAM, two patterns of antigen expression were recognized that appear to discriminate between SCLC and non-SCLC tumors, respectively. A considerable fraction of SCLC and non-SCLC tumors, however, exhibited similar patterns of antigen expression. The biological and clinical significance of these observations remains to be investigated.


[Endosonographically directed transesophageal fine needle aspiration in diagnosis of mediastinal para-esophageal space-occupying processes]. Endoscopic ultrasonography with high-frequency ultrasonic beams allows detailed study of the gastrointestinal wall structures and the surrounding Tissues. Moreover most echoendoscopes carry a biopsy channel for biopsy or cytologic puncture guided by endoscopic ultrasonography. We present a patient with a tumor in the posterior mediastinum in whom conventional diagnostic techniques failed to obtain speciments for cytologic evaluation. Transesophageal fine needle aspiration guided by endoscopic ultrasonography confirmed the diagnosis of lung cancer consisting of adeno and small cells in this patient. Transesophageal fine needle puncture guided by endoscopic ultrasonography might become a valuable aid for the diagnosis of tumor masses in the posterior mediastinum.


Preaortic iliac venous confluence ("marsupial cava"): a rare anomaly of the inferior vena cava. A patient was shown by computed tomography (CT) to have a rare developmental anomaly of the inferior vena cava (IVC), in which the iliac venous confluence is located anterior (rather than posterior) to the right common iliac artery. Recognition of the anomaly is important prior to surgical intervention in that area, as well as to prevent misinterpretation of the anomaly as representing adenopathy.


Primary retroperitoneal neoplasms: how close can we come in making the correct diagnosis. The primary retroperitoneal tumors form a rare and diverse group of neoplasms, the origin of which is independent of the various retroperitoneal organs and unrelated to systemic diseases, such as lymphomas, lymphadenopathy, or metastases. Radiologic investigation, mainly cross-sectional imaging and, to a lesser extent, angiography is essential in the diagnosis and management of these tumors. The radiologist often is challenged to identify the origin and specific tissue composition of the imaged neoplasms. When the radiologic findings are combined with patient information and clinical data, the correct diagnosis may be made in many cases. Imaging-guided percutaneous needle biopsy further enhances the diagnostic yield of the various imaging modalities by establishing the diagnosis without the need for exploration.


In vitro interactions between murine neutrophils and Eimeria falciformis sporozoites. The in vitro interactions between elicited mouse peritoneal neutrophils, antibodies and newly excysted sporozoites of Eimeria falciformis resulted in lysis of the parasite. This lysis required the presence of a heat-labile component of normal mouse serum, and was antibody- and cell-concentration-dependent. Under optimal conditions (serum dilution = 1/192, effector cell/sporozoite = 10/1) this lysis, which began after incubation at 37 degrees C for 4 h, was nearly complete after 18 h. It began by opsonization of the sporozoites by antibodies and complement. Inhibition studies performed with inhibitors of neutrophil function did not enable us to determine the mechanism of this extracellular lysis (oxidative respiratory burst or enzyme release), since only metal chelators, lysosomotropic reagents and compounds known to interfere with adenylate cyclase activity were truly inhibitory.


Seroprevalence of cytomegalovirus infection in a selected population in Jamaica. The prevalence of antibodies to cytomegalovirus (CMV) was determined by the indirect enzyme-linked immunosorbent assay in a selected population of 2655 in Jamaica. The overall prevalence rate was 95%, increasing from 56.2% in children 1-4 years of age to 90% in the 15-19 years age group and by 25 years of age 97% of subjects had been exposed to CMV. The prevalence rate in children (58.4%) was significantly lower than that in blood donors (84%), sexually transmitted disease clinic attendants (95%) and antenatal women (97%) (p < 0.001). The prevalence rate in STD clinic attendants and pregnant women was also significantly higher than in blood donors (p < 0.05). The prevalence of CMV infection in the selected population, the clinical implications, routes of transmission and socioenvironmental factors are discussed.


[Adrenergic beta receptors and guanine nucleotide binding proteins (G-proteins) of the failing human heart]. In heart failure, the sympathetic nervous system is activated. The increased release of norepinephrine from the heart and the elevated levels of circulating catecholamines produce a downregulation of myocardial beta 1-adrenoceptors. In ischemic cardiomyopathy and mitral valve disease, a downregulation of beta 2-adrenoceptors has been observed also. The beta-adrenoceptor downregulation closely correlates to the reduced positive inotropic effects of beta-adrenoceptor agonists. In addition, an increase of the inhibitory guanine-nucleotide binding protein (Gi alpha) has been observed, while the levels of the stimulatory guanine-nucleotide binding protein (Gs alpha), the activity of the catalyst and the anti-adrenergic effects of A1-adenosine receptor- or m-cholinoceptor stimulation remain unchanged in the failing human heart. The increase of Gi alpha correlated closely to the reduced positive inotropic responses to the cAMP-phosphodiesterase inhibitor milrinone. In the failing human heart, the beta-adrenoceptor downregulation and the increased expression of Gi alpha represent pathobiochemical alterations which are involved in the reduced effects of cAMP-dependent positive inotropic agents. The therapeutic reversal of these pathobiochemical alterations is a future promise in the treatment of heart failure.


[Changes in the gene expression of the hepatitis B virus in PLC-PRF-5 cells of human hepatocarcinoma during their acquisition of drug resistance]. Mutant clones of hepatocarcinoma cell line PLC-PRF-5 containing integrated hepatitis B virus genome were derived by multistep selection for resistance to some toxic agents. These clones were found to display various stages of cell differentiation according to growth rate, ability to synthesize alpha-fetoprotein, to grow in semisolid medium and to cloning in agar. In the majority of the clones with higher stages of differentiation the expression of HBsAg gene was demonstrated to be increased as compared to the original line, and in some of these clones the expression of silent HBcAg was activated.


[Human hybridoma neutralizing antibodies to the herpes simplex virus]. Human hybridoma cells producing monoclonal antibodies to human herpes simplex virus were generated. The antibody produced by the hybrid cells interacted with herpes virus types I and II in enzyme immunoassay and complement fixation test, had neutralizing activity both in vivo and in vitro. These human monoclonal antibodies may be used for immunotherapy of herpes virus infection.


[Variants of the interaction of the human T-cell leukemia virus (HTLV-I) with the B-cells of lymphoblastoid lines]. B-cell lymphoblastoid lines which are known to be derived by in vitro inoculation of B-lymphocytes with Epstein-Barr herpes virus (EBV) were shown to be infected with HTLV-1. Three possible variants of HTLV-1 interaction with cells were demonstrated by immunoblot, polymerase chain reaction, and virus isolation: (1) prolonged productive infection; (2) infection of the cells manifested only by the presence of "silent" virus sequences; (3) temporary production of HTLV-1 (3.5 months) after the end of which genetic material persisted in the cells. The long-term productive HTLV-1 infection in EBV-infected B-cells was found to influence the functioning of EBV genome which was manifested by expression of two additional proteins of EBNA-5 group and by changes in the intensity and pattern of LMP and EBNA-2 proteins the functioning of which is associated with immortalizing and transforming properties of EBV.


Oral cephalosporins.

Oral cephalosporins. The arrival of new cephalosporins faces the clinician with an evergrowing confusion as to the drug of choice. The older agents (cephalexin, cephradine, cefadroxil and cefaclor) and the newer formulations cefatrizine and cefuroxime axetil are intensively used for treatment of mild and moderate infections. The oldest agents have a better pharmacokinetic profile but are less active against Gram-positives and Gram-negatives. Cefaclor, cefatrizine and cefuroxime axetil have improved in vitro activity against H. influenzae and/or against S. aureus and M. catarrhalis. However the mean free serum concentrations after proposed standard daily doses of cefaclor (3 x 250 mg/d), cefatrizine (2 x 500 mg/d) and cefuroxime-axetil (2 x 250 mg/d) are lower than those of the older cephalosporins. In comparison amoxicillin-clavulanate is equally efficacious, has a more reliable pharmacokinetic profile and is less expensive than cefaclor and cefuroxime axetil in a comparable dose (e.g. 3 x 500 mg/d).


Infections with verotoxin-producing Escherichia coli. The production of verotoxins is one of the mechanisms by which Escherichia coli can produce diarrhea. First associated with hemorrhagic colitis and hemolytic uremic syndromes, the so-called verotoxin-producing Escherichia coli strains (VTEC) have been shown to cause also uncomplicated watery or bloody diarrhea. They have been found both in outbreaks and sporadic cases and were isolated in all countries where they were searched for. Inadequately cooked meat of bovine origin is thought to be the first source of contamination but person-to-person transmission has also been demonstrated. Until now most studies focused on serotype O157:H7, easy to detect thanks to its rare biotype. However a screening by PCR confirmed by VTEC strain isolation and cytotoxicity testing showed that in Belgium only 18% of VTEC strains belong to this serotype.


Hepatic resection for hepatocellular carcinoma. One hundred and eighteen patients underwent hepatic resection for hepatocellular carcinoma from 1979 to 1987. Ninety-eight of these patients had co-existing cirrhosis of the liver; 18 patients underwent lobectomy, 28 patients had segmentectomy, and 52 patients had subsegmentectomy. In the 21 non-cirrhotic patients, 11 patients underwent lobectomy, 5 patients had segmentectomy, and 5 patients had subsegmentectomy. The operative mortality rate of patients with cirrhosis was 11% and of patients without cirrhosis was 5%. There was no significant difference in hepatic function tests between survivors and nonsurvivors. Lobectomy of < 55% of the parenchymal hepatic resection rate was well tolerated in the patients with cirrhosis. One-year, 3-year, and 5-year survival rates of patients with hepatocellular carcinoma and co-existing cirrhosis were 57.9%, 36.8% and 20.0% following lobectomy, 82.8%, 82.8% and 57.6% following segmentectomy, and 72.0%, 46.2% and 24.0% following subsegmentectomy. The tumor recurrence rate appeared to be lower after segmentectomy than subsegmentectomy. Multiple gross lesions, tumors > 5 cm, and presence of gross vascular invasion were poor prognostic signs in terms of survival rates as well as recurrence rates. Of the 51 patients with tumor recurrence limited to the residual liver, 13 patients underwent repeat resection, and 23 patients were treated by transcatheter arterial chemoembolization. The survival rates of the patients undergoing repeat resection were significantly better than those of other groups.


Hypothyroidism associated with myeloid neoplasia. About 2 cases. We report 2 cases of hypothyroidism in whom the associated haematological disturbances (macrocytic anaemia in both cases, mild leukopenia and thrombopenia in one patient) failed to be corrected by thyroid hormone replacement therapy. Further investigations led to the diagnosis of acute myeloid leukaemia (AML) in the first patient and myelodysplastic syndrome (MDS) in the other. The reasons of the delayed diagnosis and the possible mechanisms explaining this rare combination are discussed. The hypothesis of a purely coincidental association seems most likely.


Paroxysmal hypertension and spontaneous periodic hypothermia. We report the case of a 42-year-old Zairian male who presented with paroxysmal attacks of hypertension accompanied by spontaneous recurrent hypothermia and profuse sweating of unknown origin. Routine and extensive examination failed to indicate a usual cause of arterial hypertension or for periodic hypothermia. Based on the hypothesis of an epileptic center influencing both the thermoregulatory and the vasomotor mechanisms, an anticonvulsant treatment was successfully installed. The present study makes a correlation between the present condition and certain neurologic abnormalities described in the literature.


Immunizations for foreign travel.

Immunizations for foreign travel. One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers.