Comparability of poliovirus neutralizing antibody tests. A serology panel was used to assess the comparability of results of poliovirus neutralizing antibody assays. Five laboratories from three countries provided results with seven in-house methods. A high degree of within-laboratory reproducibility was seen for all laboratories and methods, with 94% of results for repeat titrations within plus or minus one twofold dilution. Considerable differences in sensitivity between methods were, however, observed. The period of serum/virus incubation prior to inoculation of cells was shown by one laboratory to have a 10-fold effect on titres, and another laboratory showed that use of Sabin or wild-type challenge virus significantly influenced results for types 1 and 3. Expression of results as relative potencies abolished these difference due to method. The difference in sensitivity between laboratories for end-point titres (if one very sensitive method was excluded) was around fourfold for types 1 and 2, and ninefold for type 3. This range increased to 15-fold for type 2; and 20-fold for types 1 and 3 if the most sensitive method was included. Expression of results relative to a standard considerably improved agreement with a residual variation of around fourfold. Therefore, expression of results from serological studies, including vaccine trials, in International Units (i.e. relative to the new International Standard) will assure that comparisons between studies can be made with confidence.


Serum immunoassay of a small cell lung cancer associated ganglioside: development of a sensitive scintillation proximity assay. We here report an enzyme linked immunosorbent assay (ELISA) and a scintillation proximity assay (SPA) for detection of the ganglioside FucGM1 in sera from small cell lung cancer (SCLC) patients. The SPA was more sensitive and reproducible than the ELISA. In this assay, monoclonal antibodies specific for FucGM1 were bound to SPA particles and incubated with labelled FucGM1 and 100 microliters test-serum overnight, and counted in a beta-counter. The sensitivity was 0.2 ng. Seven out of twenty sera from SCLC patients were positive, whereas none of twenty sera from healthy individuals were positive for FucGM1. The SPA was more sensitive than the previously reported HPTLC as well as a direct ELISA.


[A comparative study of the action of preparations of high- and low-molecular weight heparin on hemostatic indices in vitro and in their intravenous administration to animals]. Low-molecular heparin preparations (a Soviet sample and that manufactured by the Celsus Company) in vitro, added to bovine plasma possess a lower antifactor-II activity, less time of recalcification and partial thromboplastin time as compared to high-molecular heparin of equal concentration (mg/ml) or dose (Units/ml). After intravenous injection of low-molecular heparin preparations to animals in a dose of 50 Units/200 g bw the time of hemorrhage was far less, while anticoagulant activity was lower than in animals given the same dose of high-molecular heparin. Both injection of low-molecular and high-molecular heparin results in a rise of the intensity of non-enzymatic fibrinolysis in the animals' blood plasma.


[The principles of drug classification]. The authors discuss a possibility of the design of the drug classification on the basis of their interaction with two systems of perception, conduction and realization of external signals by the cell. Review reciprocal interactions between the adenylate cyclase and polyphosphoinositide systems and the polytropic character of the action of biologically active substances within the limits of each system.


[The effect of structural analogs of ethylnorantifeine on the autophosphorylation of cAMP-independent protein kinases of neuronal chromatin]. A significant increase in autophosphorylation of cAMP-independent protein kinase No. 11 of brain neuronal chromatin occurs in the presence of ethylnorantifeine and its demethylated analog M1 rather than allyl- and propylnorantifeine. The increase is accompanied by phosphorylation of beta-regulatory and alpha-catalytic subunits of protein kinase No. 11. The nature of the direct action of antifeines on this enzyme correlates with their effects on gene activity and long-term memory storage. Whether neuronal chromatin protein kinase No. 11 is the action target of antifeines in displaying their mnemic effects is discussed in the paper.


Prenatal exposure to predictable and unpredictable novelty stress and oxytocin treatment affects offspring development and behavior in rats. Prenatal stress in rats usually results in behavioral and developmental changes in offspring. This experiment assessed body weight during the first three weeks postpartum and subsequent behavior of the offspring when tested as adults. Pregnant females allocated to the stress condition were exposed during the third week of pregnancy to either predictable (NOV1) or unpredictable (NOV2) psychological novelty stress. At this time, pregnant rats were also treated with various doses of oxytocin or vehicle solution. The exposure to unpredictable novelty stress during the third week of pregnancy resulted in pups which were significantly heavier at birth than either control animals or those which had received predictable exposure to the novelty stress. In contrast, oxytocin treatment appeared to lower body weight of offspring compared to control animals. This effect was observed right up until Day 21 postpartum for animals exposed to the larger dose (11.6 I.U.) of oxytocin. When tested as adults, NOV1 and NOV2 offspring were found to defecate more in the open field setting suggesting the they were more emotional than control animals. It was concluded that psychological stress during pregnancy has a subtle effect on development and subsequent effects on later emotionality of the offspring when tested as adults.


[Sidnofen-dependent pre- and postsynaptic activation of peripheral adrenergic transmission]. The psychostimulant sydnophen causes a spontaneous activity and increases contractile responses evoked by noradrenaline (NA) and field stimulation in rat vas deferens. The effects of the agent are independent of its ability to inhibit MAO activity. The sydnophen-induced spontaneous activity is blocked not only by alpha-adrenoceptor antagonists such as phentolamine and prazosin, but by guanethidine that blocks presynaptic neuronal NA release. Analysis of dose-response NA action has indicated that sydnophen enhances adrenoceptor sensitivity (the dissociation constant changes from 10.10(-6) M to 2.7.10(-6) M). Experimental findings suggest that sydnophen has activating presynaptic and postsynaptic action.


Epidemiology of bronchioloalveolar carcinoma. Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.


Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury. Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B1 or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. In aflatoxin B1- and M1-treated rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiation-promotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepatotoxicity in rats treated with CCl4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of alpha-fetoprotein or ferritin, nor was there a correlation with alpha-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal EH in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.


[Seroepidemiologic study of cytomegaly and rubella in pregnant women and prostitutes]. In the study antibodies for CMV were found at 74.3% pregnant women, 73% of blood donors, and 95.5% of prostitutes. These data confirm the fact that intensified sexual behavior might contribute to frequent CMV infections. In both of the samples of women examined for antibodies for the rubella virus 91% of them proved seropositive.


Effect of bulk feeds (alfalfa hay, corn silage) on the metabolism and liver parameters of growing geese. Rearing experiments were conducted with a total of 90 liver hybrid geese from Babat, divided into three groups of 30 birds each. The effect exerted by all-concentrate feeding (group 1), concentrate feeding supplemented with alfalfa hay (group 2) or with corn silage (group 3) ad libitum on the blood glucose level, blood plasma total lipid, total cholesterol and free fatty acid level, and on total lipid content of the liver was studied. In addition, aspartate aminotransferase (AST) activity of the blood plasma and carotene, vitamin A and vitamin E concentration of the blood plasma and the liver were determined. It was found that the blood and liver parameters of goose groups fed different diets changed within the physiological limits typical of the species. Excessive fibre intake resulted in reduced lipid transport within the organism at an unchanged plasma cholesterol level; at the same time, blood glucose level remained unchanged. Ad libitum feeding of alfalfa hay and corn silage enhanced carotene and vitamin A transport and carotene storage but did not affect the transport of vitamin E. The results confirm earlier data of the literature that beta-carotene and vitamin A together impair vitamin E metabolism.


Participation of a GABA-ergic system in the processes of neuroimmunomodulation. Participation of a GABA-ergic system in neuroimmunomodulation was established through the use of a large number of chemical compounds which selectively modulate the activity of the GABA-BD-receptor-ionophore complex. Activation of the GABA-receptors with muscimol or activation of the BD-receptors with diazepam or tazepam had stimulatory effects upon immunogenesis. A decrease in the GABA-BD-receptor-ionophore complex activity led to a suppression of the immune response. The effect was achieved with: a blockade of the complex with bicuculline--a competitive inhibitor of the GABA-receptors: administration of a specific antagonist of the BD-receptors flumazenil or Ro 15-3505: or with blockade of chloride channels with picrotoxin. Activation of the GABA-ergic system causes an increase in bone marrow content of T-helper cells marked by L3T4. The immunomodulatory action of the GABA-ergic system is of central origin and can occur only when the hypothalamo-pituitary system is intact. Section of the pituitary stalk prevents accumulation of the T-helper cells in the bone marrow. The result show that the influence of GABA-ergic system on immunogenesis requires participation of both dopaminergic and serotoninergic systems.


Effect of anthelmintics on phosphatases in Ascaridia galli. In vitro addition of the drugs tetramisole (TMS) and levamisole (LMS) caused an inhibition of the specific activities of acid phosphatase and Mg(++)-dependent adenosine triphosphatase. The inhibition was non-competitive in nature. No significant inhibition was caused by TMS in the activity of glucose-6-phosphatase, but LMS inhibited the enzyme in a non-competitive manner. The activity of alkaline phosphatase was, however, increased in the presence of both TMS and LMS.


[Activity of angiotensin-converting enzyme in women with hyperthyroidism accompanying Graves-Basedow disease]. Angiotensin-converting enzyme in the blood serum was assayed with Friedland's and Silverstein's Technique in 24 female patients with untreated hyperthyroidism accompanying Graves-Basedow disease. Mean ACE activity was significantly higher in patients than that in the group of healthy individuals of the same age. Increased ACE activity noted in patients with Graves-Basedow disease may, therefore, indicated a significant role of renin-angiotensin-aldosterone system in the etiopathogenesis of hypertension in this disease.


The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. V. Adherence to nylon fibres. The adherence of neutrophils from bronchopneumonic calves to nylon fibres and the influence of this adherence on O2- and H2O2 production were studied. Polymorphonuclear leukocytes from bronchopneumonic calves were found to produce much more superoxide anion and hydrogen peroxide than neutrophils from healthy animals. A higher production of these compounds was observed in granulocytes adhering to nylon fibres than in cells in suspension. It is suggested that oxygen radicals production induced by the contact of granulocytes with a solid surface plays a role in the destruction of endothelium in vivo.


[Effect of aminoglutethimide on ACTH plasma levels in Cushing's disease and Nelson syndrome]. Out of all steroidogenesis inhibitors aminoglutethimide is most frequently used agent for so-called chemical adrenalectomy, especially in oncological cases. The present studies aimed at assessing an effect of the inhibition of cortisol synthesis on plasma ACTH in patients treated with aminoglutethimide. According to the rules of negative feedback, an increase in plasma ACTH should be expected. Aminoglutethimide has been administered to 24 patients with Cushing's disease for 1-6 months. Plasma ACTH did not increase but statistically significantly decreased despite a decrease in blood cortisol. It indicates that aminoglutethimide directly inhibits ACTH secretion. No return of the normal circadian rhythm of cortisol and ACTH release suggests that the drug exerts an effect on ACTH release regulating mechanisms. No definite results were achieved in patients with Nelson syndrome treated with aminoglutethimide for a short period of time. Plasma ACTH levels tend to decrease but no statistical significance was observed in comparison with placebo. It may depend on markedly increased corticotrophin secretion in Nelson tumors.


Morphological structure of the mucous membrane and submucosa of rumen in calves receiving synthetic or natural beta-carotene and vitamins AD3E. In an experiment conducted on 20 calves from 1 day to 12 weeks old, supplements of beta-carotene were fed in the form of Rovimix beta-carotene 10%, artificially dehydrated carrot or vitamins AD3E. Postmortem examination carried out at 12 weeks showed that supplementation of beta-carotene or vitamins AD3E resulted in a better structural development of the ruminal papillae as compared to the control group. In addition, beta-carotene reduced the keratinization of the stratified squamous epithelial cell layer of the rumen and increased the glycosaminoglycan level of that organ wall.


[Does the activity of angiotensin converting enzyme depend on sex, age, body weight and phase of the menstruation cycle in women?]. The study involved 274 patients, including 240 women, divided into various subgroups, according to the age, body weight, and a phase of menstruation cycle in women, and a subgroup of 34 men. According to the design of the studies, blood serum ACE activity was determined spectrophotometrically with a technique described by Friedland and Silverstein in all patients. The obtained results suggest that blood serum ACE activity does not depend on the sex, age, body weight, and phase of the menstruation cycle in women.


Comparison of different computational methods for measuring antibodies to avian infectious bronchitis virus in single serum dilution. Twenty-eight one-day-old chickens with infectious bronchitis virus (IBV) maternal antibodies were immunized with strain H120 (Bronchovac-I, Phylaxia) in spray form. The chickens were kept in an isolator. On day 42 and 56 the chickens were immunized with IBV strain M41 (10(3.0)EID50/0.1 ml). Serum antibody titres were measured by both serial dilution and single dilution ELISA on day 42, 56 and 76. "Twice negative average" (TNA), "sample to positive" (SP) and "subtraction method" (SM) titres were calculated from the serially diluted sera, and SP and SM titres were calculated from the single dilution. Titres obtained by the different methods showed a good correlation for sera of low, medium and high antibody levels. The authors recommend the use of the single dilution method.


[Hypothyroid myopathy. Physiopathological approach]. Patients with thyroid deficiency often complain of muscular weakness, exercise intolerance, cramps and excessive fatiguability. Hypothyroidism induces a metabolic myopathy, with a fall of the energetic production, and especially of the mitochondrial metabolism. This is due to a global inhibition of the main oxidative pathways (substrate incorporation, substrate oxidation) and of the respiratory chain. A diminished energetic consumption is partially related to a transition in the myosin isoforms, which express a slower ATPase, and to an impairment of the trans-sarcolemic transports. Exercise intolerance could be due to an abnormal recruitment of several metabolic pathways, such as glycolysis, related to the mitochondrial metabolism impairment, and including an abnormal accumulation of protons and monovalent phosphate ions, which are involved in the alteration of the actin-myosin interaction, and also by an abnormal Ca++ metabolism. The decreased number of NA+/K+ ATPase dependent pumps could imply an abnormal intracellular Na+ level and explain the frequent disorders of the membrane excitability.


[Role of adrenocortical scintigraphy in the exploration of incidentally discovered tumors]. To determine the utility of adrenocortical scintigraphy with I131-6 beta-iodomethyl-19-nor-cholesterol (NP59) in incidentally discovered adrenal masses, we studied 12 patients with a unilateral adrenal mass and without other primary tumors or signs of pheochromocytoma or hyperfunctioning adenoma. Ten patients had an adenoma (size: 12 to 35 mm), the diagnosis was made by surgery or by no change in size on repeated CT scans. The NP59 scintigraphy showed an increased uptake on the side of the tumor in 8 cases with a decreased uptake of contra-lateral gland in 7 cases. Hormonal investigations of glucocorticoid function suggested supranormal or fluctuant cortisol secretion in 5 cases as assessed by moderately elevated urinary free cortisol or by incomplete dexamethasone suppression test. These abnormalities disappeared after surgery. Two patients had normal bilateral uptake of NP59, the sizes of the tumors were 12 and 20 mm. Two patients had an extra-adrenal tumor. The NP59 scintigraphy showed a moderately decreased uptake on the side of the hematoma of one patient and a compression of the normal adrenal by ganglioneuroma of the other patient. Our results and those of other authors suggest that positive NP59 scintigraphy could confirm the cortical nature of an incidentally discovered adrenal mass, probably an adenoma that must be followed up morphologically and functionally. No uptake by a tumor greater than 2 cm suggests a primary malignancy or extra-adrenal origin which must be diagnosed by invasive methods.


[Serological study of the incidence of murine viruses in a population of small wild rodents (Microtus pennsylvanicus Ord, 1815)]. The results of a serological survey of a free-living population of meadow voles (Microtus pennsylvanicus) in Pinawa, Manitoba (Canada) showed that these animals possessed antibodies to six of the eleven viruses tested for, namely: reovirus type 3, murine encephalomyelitis agent, ectromelia virus, murine adenovirus, murine hepatitis virus and lymphocytic choriomeningitis virus. The significant increase in the number of individuals possessing specific antibodies suggests that these viruses, or related viruses, may be responsible for the decline in the population studied.


[Asymptomatic carriage of Pestivirus in ruminants]. Pestiviruses are enveloped single-chain ribonucleic acid viruses with a positive polarity. Pestiviruses include the viruses of classical swine fever (hog cholera), Border disease of sheep, mucosal disease of cattle, and isolates obtained from wild animals, such as red deer (Cervus elaphus). Among ruminants, pestiviruses have developed a remarkable strategy for assuring their persistence. Through epigenetic transmission, they lead to the birth of asymptomatic carrier animals harbouring non-cytopathic variants, which become immunotolerant to the strain of virus present. The presence of a small number of asymptomatic carriers enables the virus to circulate within a herd by horizontal transmission, leading to the birth of a new generation of asymptomatic carriers.


Maintenance of foot and mouth disease viruses in buffalo (Syncerus caffer Sparrman, 1779) in southern Africa. Using age-related infection rates derived from serological data in available deterministic and specially developed stochastic simulation models, it has been possible to establish that the basic reproductive rates for South African Territory (SAT) type foot and mouth disease virus in buffalo (Syncerus caffer) are high. The models predict that there is a periodicity of infection within herds and possibly the population as a whole. Thus, buffalo herds are likely to be more infectious at some times than at others. However, because most infections in buffalo are inapparent, such episodes are difficult to identify. There is wide intratypic variation within the SAT type virus populations circulating in buffalo. This was determined by sequencing part of the 1 D gene of buffalo isolates and establishing antigenic profiles with neutralising monoclonal antibodies and conventional antisera.


Diseases of the European wildcat (Felis silvestris Schreber, 1777) in Great Britain. The author describes an examination conducted in collaboration with the Nature Conservancy Council of Great Britain into the status with regard to disease, conservation and genetics of the European wildcat (Felis silvestris). Feline leukaemia virus (FeLV) infection was detected by positive enzyme-linked immunosorbent assay in blood from 2 of 23 wildcats and was tested and confirmed by FeLV isolation in one of the two cats. This is the first time the virus has been clearly demonstrated in a free-living felid, other than the domestic cat. Toxoplasmosis was detected in all cats tested, but neither feline coronavirus nor feline immunodeficiency virus was detected in any sample. The genetic analysis indicated that only 8 of 42 wildcats tested were genetically distinct. These were mainly located in the western highlands of Scotland where "relict" populations may have survived. Interbreeding with domestic cats and persecution by trapping and hunting represent major threats to the survival of the European wildcat.


Herpesvirus infections in seals: a summary of present knowledge. This review summarises the occurrence of herpesvirus infections in pinnipeds and data from investigations carried out by the authors. These data demonstrate that herpesvirus isolates collected from harbour seals (Phoca vitulina Linnaeus, 1758) during the 1988 seal epidemic were almost indistinguishable from feline herpesvirus 1 and that Antarctic Weddell's seals (Leptonychotes weddelli Lesson, 1826) carry antibodies against seal herpesvirus from the north-western Europe seal epidemic. The significance of herpesvirus infections in seals is discussed.


Incidence of hepatitis D virus infection in Japanese patients with hepatocellular carcinoma--immunohistochemical investigation of the delta antigen. In order to clarify the incidence of the delta agent among hepatocellular carcinomas (HCCs) in Kurume, where the hepatitis B infection and its related HCC are most prevalent in Japan, liver tissues from sero hepatitis B surface antigen-positive autopsy cases, with or without HCC, were immunohistochemically investigated for detection of the delta antigen. Only one patient (1.7%) among 58 patients with HCC was found to have delta-antigen in the nuclei in the hepatocytes, which were diffusely distributed throughout the non-cancerous liver. None of 26 patients with liver cirrhosis showed delta-antigen in the liver tissue. The incidence is so low that the delta agent is unlikely to have a role in the development of HCC in our areas.


[Electrophoretic analysis of RNA from rotavirus strains isolated from children in the years 1986-1990]. Double stranded RNA of rotaviruses is composed of 11 segments which in standard and field strains may differ in electrophoretic mobility in polyacrylamide gel electrophoresis. This study was aimed at determination of electrophoretic differentiation of rotavirus strains found in samples of feces of children treated because of diarrhoea in two hospitals in Warsaw and in Kraków region in the years 1986-1990. Out of 85 positive samples from Warsaw and 90 from Krakow region, for investigation 44 and 36 strains, respectively were included. Totally for 71 strains well stained 11 segments of RNA were obtained which permitted for determination of their electrophoretic-types. Majority of strains, 60 (84%) were characterized by a long electrophoretic-type, whereas 11 (16%) had a short electrophoretic-type. Considering differences in migration speed of 1-4 and 7-9 segments, within long and short types, eight subtypes denominated as a-h were present. Subtypes a, c and d constituted 73% of all tested strains. These studies indicate that in Poland occur at least eight electrophoretic subtypes of rotaviruses and that this feature is partly correlated with belonging of strains to subgroups and antigenic serotypes.


[Treatment of (pre)-edentulous patients. After care and directives]. It can be expected that the percentage of edentulous people wil decrease in the coming decades as a result of an improved oral health, whereas the number of edentulous people will not decrease as a result of the strong increase of the ageing population. If the preservation of the natural dentition is no longer possible, the remaining teeth of a mutilated dentition have to be extracted according to some specific principles. But also the aftercare of the edentulous patient has to be extended according to some specific guidelines, within the framework of the so-called "preventive-prosthetic-treatment-strategy". Preservation of the alveolar process is the main goal in both cases.


Melatonin in vertebrate retina: biosynthesis, receptors and functions. The present review primarily summarizes the cellular and molecular biology of MEL synthesis by the vertebrate retina, and the nature of MEL signal generated in this tissue. Additionally, the current status of retinal MEL receptors as well as physiological roles of this indoleamine within the eye are discussed.


Influence of T-actemodulin on herpes simplex virus infection. The aim of the investigation was to study the direct influence of T-actemodulin (TAM) on the Herpes Simplex Virus (HSV) infection in vitro and in vivo. HSV-1 (strain Vic) and HSV-2 (strain Nissa) were used in the experiments in vitro. The experiments were performed using multicycle and singlecycle growth tests. Seventy-five patients suffering from HSV infections (labialis and genitalis) were locally treated by 0.04% TAM-containing hydrophilic gel or water-washable cream (applied every 3 h). The results showed that TAM: decreased the infectious virus titre; reduced the infectious virus yield at the end of the single cycle of the virus replication; prolonged the latent period; and exerted an irreversible inhibitory effect on the infectious virus titre when applied at immediate early intervals after the infection. No relapses were observed in 84% of the patients treated with TAM. Eight percent of the patients were with only reduced relapses and in 8% of the patients TAM had a mild effect. TAM exerted a preventive effect against the disease when the treatment was initiated in the period of paresthesia.


Renal salt wasting in patients treated with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small cell lung cancer. Cisplatin has many toxic effects; emesis, impairment of renal function, myelosuppression, peripheral neuropathy, ototoxicity and renal tubular wasting. We used MVP regimen (Mitomycin C, Vp-16, and Cisplatin) in advanced Non-Small Cell Lung Cancer (NSCLC). Using hydration and prophylactic supplementation of sodium and potassium before and during chemotherapy, we have observed the development of hyponatremia in 48 courses (43%), hypokalemia in 23 courses and hypomagnesemia in 11 courses. Some patients showed abnormalities of renal function in 16 courses. All the electrolyte depletion and renal problem was corrected before next courses by hydration and replacement of the wasting. Frequent measurement of serum cation and appropriate replacement are recommended when high dose Cisplatin containing regimen is used in chemotherapy of neoplasms.


[Presentation of a case of suspected herpes encephalitis with unusual clinial aspects]. The authors describe, in a patient suffering from IDDM, a case of suspected EHS the beginning of which was concealed by serious ketoacidosis. The clinical suspicion, strengthened by the tests TC and RMN, was not confirmed by CSF analysis. In spite of the severity of the documented lesion and neurological findings at the onset and the outcome has turned out favourably.


Intestinal neurofibromatosis in von Recklinghausen's disease: presenting as chronic anemia due to recurrent intestinal hemorrhage. Neurofibromatosis (von Recklinghausen's disease) is a neuroectodermal disorder characterized by pigmentary changes of the skin (café-au-lait spots), cutaneous and visceral tumors (neurofibromas) and systemic abnormalities. The involvement of gastrointestinal tract in neurofibromatosis is not common. The most common symptoms, refer able to lesions in the gut, are hematemesis, melena and abdominal pain. We experienced a case of intestinal neurofibroma in von Recklinghausen's disease. The patient was a 39 year-old female who had suffered from chronic iron deficiency anemia and recurrent gastrointestinal hemorrhage due to two neurofibromas of jejunum for 3 years, which was diagnosed by superior mesenteric and ileal arteriogram and 99mTc pertechnetate-labelled RBC scan, and treated by segmental resection of jejunum with end to end anastomosis.


[Coronaviruses].

[Coronaviruses]. Corona viruses belong to a group of not yet well known viruses isolated in patients with infections of the upper respiratory organs, especially in winter months. It is presumed that they provoke about 15% - 20% of all infections. However, in the last years more attention has been paid to the role of human corona viruses in the provocation of sickness in man and they are becoming a special field of interest in scientific studies.


[Cytomegalovirus infections and pregnancy]. Infection by Cytomegalovirus is one of the most common viral infections in obstetrics and gynaecology. Cytomegalovirus can be transmitted across placenta at any time during gestation, producing a spectrum of diseases within the newborn. The fetus is mainly involved through haematogenous spread of the virus from the mother during primary infection. Even if the mother has an antibody against cytomegalovirus it does not prevent congenital infection. First trimester infection is associated with significant congenital anomalies affecting the central nervous system and sensorial nerves. Infection of the neonate can occur through direct exposure to contaminated maternal genital tract and breast milk. Newborns affected with congenital anomalies and significant neurologic long-term sequelae. At the present time when it is almost impossible to prevent or to treat cytomegalovirus infection in pregnancy, the most important antenatal control concerns detect ion and diagnosis of acute infection in the first trimester of gestation, as one of the highest pertinal risks.


Pulmonary embolism as the initial manifestation of large cell lung cancer--a case report with review. Lung cancer is known as a risk factor of pulmonary embolism. We experienced a case of pulmonary embolism combined with pleural effusion and pleuritic chest pain as the initial manifestation of large cell lung cancer, which is a relatively rare cell type of lung cancer in Korea. We report it with a review of the literature.


Differences in histology between first and second primary lung cancer. Data from the Surveillance, Epidemiology, and End Results (SEER) Program were used to compare the histological distribution of second lung cancer following an initial cancer of the lung, head and neck, and breast to primary lung carcinoma occurring as a first cancer. Following initial head and neck cancer or initial squamous cell carcinoma of the lung, the proportion of second primary lung cancer which was of squamous cell histology rose dramatically, while the proportion of pulmonary adenocarcinomas rose following initial adenocarcinoma of the lung. The histological distribution of lung cancer following an initial breast cancer in women was similar to the distribution of de novo lung cancer in women. These results persisted as the time interval between diagnosis of the two primaries was increased from 12 to 48 months. We conclude that the histology of a second primary lung cancer following an initial cancer of the lung or head and neck tends to repeat the histology of the initial cancer (field effect), and this observation is not likely to be due to misdiagnosis of a recurrence of the initial cancer.


Effects of cereal and vegetable fiber feeding on potential risk factors for colon cancer. The effects of two doses of cereal fiber and vegetable fiber on mean transit time, stool weight, fecal pH and fecal bile acids were examined in 34 healthy volunteers. Subjects consumed five diets in random order for 23 days each, consisting of a fiber-free liquid diet and quick breads containing 0 g added dietary fiber, 10 g fiber as wheat bran (WB), 30 g fiber as WB, 10 g fiber as vegetable fiber (VF), and 30 g fiber as VF. Fecal wet and dry weights were 43% and 19% higher, respectively, on WB as compared to VF (P < 0.0001). Fecal pH was lower on WB than on VF (P < 0.0001) and decreased with increased fiber intake (P < 0.005). Transit time was 36% faster with WB than with VF (P < 0.0001). There was no VF dose effect on transit time, but transit time was 23% faster on 30 g WB than on 10 g WB (P = 0.04). Total bile acid concentrations decreased with increased fiber dose (P < 0.0001) but were not significantly different between WB and VF. Daily total bile acid excretion was 14% lower on VF compared to WB (P = 0.01). There was no VF dose effect on total bile acid excretion, but excretion was 13% lower on 30 g WB than on 10 g WB (P = 0.04). These findings are consistent with the capacity of fiber to alter potential risk factors for colon cancer but do not explain differences in epidemiological data between vegetable and cereal intake.


Regulation of human alcohol dehydrogenase genes. This review focuses upon the regulation of the three human class I alcohol dehydrogenase genes, ADH1, ADH2 and ADH3. These closely related genes are expressed at high levels in liver, and at different levels in other tissues. Multiple cis-acting sequences to which nuclear proteins bind have been mapped, and transcription factors that can bind to these sequences have been identified; these include C/EBP alpha, Sp1, USF, HNF1, CTF/NF1, the glucocorticoid receptor, and RAR alpha. There are interesting but often subtle differences in the binding to these three closely related genes, that presumably account for the differences in patterns of their expression.


Endogenously formed N-nitroso compounds and nitrosating agents in human cancer etiology. Humans are exposed to preformed N-nitroso compounds (NOC), but also to a wide range of precursors and nitrosating agents which can react in vivo to form potentially carcinogenic NOC and diazo compounds. Nitrite, nitrate and nitrosating agents can also be synthesized endogenously in enzymic reactions mediated by bacteria, activated macrophages and neutrophils. The latter two cell types generate, via the enzyme nitric oxide synthase, the nitric oxide radical that is involved in cytotoxicity, and is believed to be involved in formation of carcinogenic nitrosamines, DNA base deamination and oxidative damage. Thus endogenous NOC formation, DNA damage and gene mutations in humans could occur at various sites of the body such as the stomach and chronically infected or inflamed organs. Sensitive procedures to estimate the exposure of humans to NOC have been developed and applied in ecological and cross-sectional studies. These have shown that inhabitants of high-risk areas for stomach and esophageal cancer, patients with urinary tract infections (at risk for bladder cancer) and Thai subjects infected with liver fluke (at risk for cholangiocarcinoma) had significantly higher exposure to endogenous NOC. Clinical studies have examined the model of stomach carcinogenesis based on intragastric nitrosation, but the precise roles of bacterial overgrowth and of Helicobacter pylori infection in NOC synthesis and/or inducing oxidative stress in stomach mucosa remain to be clarified. Together these results support the role of NOC and other nitrite-derived mutagens in human cancer etiology, in particular when exposure starts early in life and persists over a long period.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa. Hepatocellular carcinoma is one of the major human cancers, causing at least 250,000 deaths each year. Two of the major risk factors for this disease are aflatoxin exposure and hepatitis B virus. This study was undertaken to explore the relationship between dietary exposure to aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people who were either hepatitis B virus surface antigen-positive or -negative. The diets of 20 individuals, 10 males and 10 females, with ages ranging from 15 to 56 years, were monitored for 1 week, and aflatoxin intake levels were determined for each day. Starting on the fourth day, total 24-h urines were consecutively obtained for 4 days. The subjects were generally paired for hepatitis B virus status. Preparative monoclonal antibody affinity chromatography/high-performance liquid chromatography and competitive enzyme-linked immunosorbent assays were carried out on each of the urine samples, and the relationship between aflatoxin intake values and the excretion of (a) total aflatoxin metabolites and (b) aflatoxin-N7-guanine (AFB-N7-guanine) was determined. The average intake of total aflatoxins was 12.0 micrograms for the entire study group during the 1-week collection period. However, there was considerable day-to-day variation in exposures, from a low of zero to a high of 29.6 micrograms total aflatoxins/day. Initial efforts to characterize total aflatoxin metabolites in the urine samples were made by competitive enzyme-linked immunosorbent assay. The correlation coefficient for the analysis was 0.65, with P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection and analysis of human papillomavirus type 1 infection of skin warts from a dermatology clinic in Taiwan by southern hybridization. Thirty cases of skin warts from the Dermatology Clinic at Tri-Service General Hospital were analyzed for the presence of human papillomavirus type 1 sequences by Southern blot hybridization. Thirteen of the 30 cases were HPV-1 positive. The prevalence was 43%. Episomal HPV-1 sequences were detected in 11 of 13 HPV-1 positive cases. There are two cases which probably contained integrated forms, one contained the higher molecular weight bands, and the other with 6 kb viral genome may be the result of rearrangement and deletion. Histological studies from HPV-1 positive specimens also indicated the typical features of HPV infection. Some cases with high copy number had a high frequency of inclusion bodies. Chi-square analysis showed that HPV-1 prevalence is not related to sex and different lesion locations, but the prevalence of HPV-1 in recurrent lesions is higher than that of initial lesions.


Dietary intake of aflatoxins and the level of albumin-bound aflatoxin in peripheral blood in The Gambia, West Africa. Aflatoxin is implicated as a risk factor for hepatocellular carcinoma in areas of the world with a high incidence of this tumor. The present study was designed to validate the use of aflatoxin-albumin adducts in peripheral blood as a measure of individual exposure to this carcinogen. Dietary intake of aflatoxin was measured at the individual level in 20 residents of Keneba, West Kiang, The Gambia, over a 7-day period and correlated with the level of aflatoxin bound to peripheral blood albumin at the beginning and end of the study. Complementary enzyme-linked immunosorbent assay and high-performance liquid chromatography-fluorescence techniques were used to assay the aflatoxin adducts. All subjects were exposed to aflatoxin originating from several food types, with an average daily intake of 1.4 micrograms/day. A significant correlation (r = 0.55; P = < 0.05) was observed between the dietary intake and the level of albumin-bound aflatoxin at the end of the study. In addition, a good agreement was obtained with the two analytical techniques. A comparison of matched chronic hepatitis B surface antigen carriers with noncarriers did not reveal any difference in adduct formation for a given dietary intake of aflatoxin. These studies demonstrate the validity of aflatoxin-albumin adducts as a marker of human exposure to this carcinogen.


[The coherence between 3 evaluation methods of biocompatibility]. Three successive series of tests (the primary including cytocompatibility tests and the secondary in vivo and usage tests) can be used to evaluate the biocompatibility of dental materials. The products are only submitted to secondary tests in case of satisfactory results obtained with primary tests. A coherence between the results of primary and secondary tests is necessary before performing in vivo tests. The aim of this paper is to study the coherence between two primary tests and a secondary test. The biocompatibility of Sealite and a pulp canal sealer was studied 4 and 12 weeks after mixing, according to two primary models (cell culture on agarose and a toxicity study of the extraction products) and a secondary model (intrabony implantation in the rabbit). The two primary tests gave different results for Sealite and the pulp canal sealer. Only the agarose cell culture and the intrabony implantation in the rabbit have given similar statistical results. The biological evaluation of biomaterials should begin with a study of the mechanism of action of the cytotoxic products using several in vitro tests. These latter are unable to predict the behaviour of a biomaterial in an in vivo test.


Fluoride inhibition of SCN- and Cl-peroxidase activities in whole saliva and of recombinant myeloperoxidase. Influence of pH and hydrogen peroxide concentration. Fluoride (F-) inhibition of peroxidase activity in whole saliva and of recombinant human myeloperoxidase was investigated using thiocyanate (SCN-) and chloride (Cl-) as substrates. At pH 5.5, SCN(-)-linked activity in whole saliva reduced to < 40% of its initial value at F- concentration of 20 mM, while Cl- linked activity was maintained at 90% of its initial value for the same F-concentration. Based on this Cl(-)-linked activity, the contribution of natural MP to the SCN(-)-linked activity in whole saliva can be calculated. This shows a total inhibition of SCN- dependent activity of salivary peroxidase (SP) for F-concentrations > 10 mM. At a 20 mM F-concentration, recombinant MP activity reduced to 66% of its initial value with SCN-, against 88% for Cl- as substrate. This inhibition of the SCN- linked SP activity is enhanced at acid pH for a F-concentration of 20 mM: 26% residual activity at pH 5 for whole saliva + SCN-against 93% for whole saliva + Cl-; 61% for recombinant MP + SCN- and 88% for MP + Cl-. Calculated activities for SP alone showed a total inhibition at pH 5, while the inhibition was absent at pH 6.5. F-inhibition in whole saliva could also be suppressed by the addition of hydrogen peroxide.


Itraconazole in cryptococcal meningitis in pregnancy: a case report. A 25-year-old pregnant women with cryptococcal meningitis treated with itraconazole during the first few weeks and 12th-16th week of pregnancy is reported. She delivered a normal baby. Itraconazole should be another drug for treatment of fungal infection in pregnancy.


[Carcinoma of the male breast (case contributions)]. Authors refer about their experience on 12 cases of male breast carcinoma (MBC), studied in years 1975-1985 at the Semeiotica Chirurgica e Patologia Chirurgica II dell'I.R.C.C.S. Policlinico S. Matteo of Pavia. After a thorough discussion of the etiopathologic factors, there are cited the most common histotypes of MBC, as well as the typical clinical aspects, of basic importance for the compilation of the diagnostic inquiry, which, in uncertainty, makes use of the acuaspiration and of the excisional biopsy, there is referred on the present therapeutic trends, and results of their casuistry are exposed.


[Relationship between drug resistance and oncogenes in lung cancer cell lines]. The 5-year survival of lung cancer patients is about 30% in Japan. One of the reasons for the poor prognosis seems to be drug resistance. It has been reported that certain types of oncogenes, such as ras, myc and fos, may play an important role in drug resistance. The myc protein forms a sequence-specific DNA-binding complex with Max and may act as a transcription factor; thus, it may be possible that myc family oncogenes are involved in DNA synthesis and repair processes mediating drug resistance. We report here that L-myc oncogene may be involved in the transition from drug-sensitive to drug-resistant phenotype of a certain small cell lung cancer cell line.


[Effect of eosinophil peroxidase on beta-adrenergic receptor-adenylate cyclase system]. We studied the effect of eosinophil peroxidase (EPO) on beta-adrenergic receptor (BAR)-adenylate cyclase system based on the hypothesis that eosinophils may participate in the pathogenesis of beta-blockade in acute asthma. The effect of EPO on BAR density on guinea pig lung membrane was studied first. The BAR density was decreased significantly by 10(-4) M H2O2 alone. EPO combined with 10(-4) M H2O2 and iodide caused additional decrease in BAR density, and the decrease was EPO concentration-dependent (1-10 U/ml). The effect of EPO on cyclic AMP (CAMP) accumulation in S49 cells was studied next. The CAMP accumulation with 10(-4) M isoproterenol was significantly inhibited with combination of EPO and H2O2, and the decrease was again EPO concentration-dependent (0.1-1 U/ml) without any changes in BAR density on the cells. Thus, EPO was demonstrated to have an influence on the BAR-adenylate cyclase system.


A possible involvement of DNA topoisomerase I in "caffeine effect" after ultraviolet irradiation. Caffeine has been known to enhance lethal and chromosome damaging effects of chemical and physical mutagens. In spite of numerous investigations, the mechanism is not fully elucidated. In this paper, we describe that 1) post-treatment with camptothecin (CPT), a specific inhibitor of DNA topoisomerase (topo) I, enhances SCE-induction by ultraviolet light (UV), as post-UV caffeine treatment does, 2) the lethal effect of UV is also enhanced but to a lesser degree than by post-UV caffeine treatment, and 3) caffeine, like CPT, inhibits calf thymus topo I activity, as determined by relaxation of pBR322 supercoiled DNA. These results suggest that the mechanism(s) of lethal and SCE enhancement involves the ability of caffeine to inhibit topo I.


Inhibitory effects of antipromoters and radical scavengers on the promotion process in two-stage cell transformation. To find the mechanism of promotion process, we have investigated the antipromoting effects of radical scavengers and specific inhibitors for phospholipid metabolism and for protein kinase C using a two-stage transformation assay system in BALB/3T3 cells. All radical scavengers and inhibitors tested showed the antipromoting effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted transformation. Diacylglycerols, activators of protein kinase C, showed promoting effects in vitro and the promoted-transformation by them was suppressed by radical scavengers employed. By an electron spin resonance (ESR) spin-trapping method, inhibitors, which suppressed promoted-transformation by TPA markedly, had .OH scavenging action. It was found using a ESR spin-trapping method that treatment of TPA on BALB/3T3 cells generates .OH in a dose-dependent manner. These results suggest that generation of oxygen radicals, especially .OH, which occurs in the processes of phospholipid metabolism as well as activation of protein kinase C, is essential to the promotion process.


Involvement of the membrane-bound Na,K ATPase in the evolution of experimental injuries of the spinal cord. Rat spinal cords have been compressed at the region corresponding to D4-D5 by a 50 mg/cm force. After 5, 30 and 60 min this section has been dissected together with the surrounding cord. The ATPase activity of the homogenates was decreased, suggesting an involvement of this enzyme in the generation of edema.


Brain calcifications and dementia in children treated with radiotherapy and intrathecal methotrexate. In the last five years we observed 8 young patients aged under 15 years, in whom the basal ganglia were calcified after application of methotrexate and/or radiotherapy for treatment of a brain or cerebellar tumor. In both patients leukoencephalopathy was evident besides calcification of the basal ganglia and, in one, the ventricles were enlarged and he had also signs of cerebral and cerebellar atrophy. In the production of leukoencephalopathies and calcifications by chemo- and radiotherapy, the age is a very important factor. In adult patients it is exceptional to see them. Brain immaturity is probably associated with the presence of leukoencephalopathy and intracranial calcifications.


Mutations of the APC (adenomatous polyposis coli) gene in FAP (familial polyposis coli) patients and in sporadic colorectal tumors. We have isolated several genes on chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One (APC) of them was also found mutations in the germ line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer.


Multiple tumor suppressor genes in multistep carcinogenesis. One of the most exciting areas of molecular oncology is the convergence of two independent lines of evidence suggesting involvement of multiple tumor suppressor genes in a given type of cancer. First, epidemiology and somatic cell genetics indicate the presence of multiple tumor suppressor genes in each of several malignancies. Second, cancers often lose multiple chromosomal regions during tumor progression. We will use two tumors, colorectal cancer and Wilms tumor, to illustrate the questions that multiple tumor suppressor genes raise.


Possible involvement of nuclear oncoproteins in regulation of DNA replication. Polyomavirus DNA replication requires its enhancer which contains an AP-1 site. We have shown that protooncogenes, c-jun and c-fos, whose products form heterodimeric transcription activator, AP-1, strongly stimulate polyomavirus DNA replication through the AP-1 site. The mechanisms by which this enhancer stimulates replication and transcription are different. By replacing the enhancer with the oligonucleotides representing the binding site of a transcription factor of interest, any transcription factor with the known binding sequence can be characterized in this replication assay. When Rel protein was examined, we were able to reveal a new domain in v-Rel protein which can stimulate replication strongly. Whether this domain also coincides with transforming potential of v-Rel protein is currently under investigation.


Detection of DNA aberrations in human cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. We have developed a simple, sensitive method, single-strand conformation polymorphism (SSCP) analysis, to detect a single nucleotide substitution in a DNA fragment amplified and labeled by the polymerase chain reaction (PCR). Mobility shift of single-stranded DNAs due to their specific conformations on non-denaturing polyacrylamide gel electrophoresis can reveal DNA aberrations. By the PCR-SSCP analysis of DNAs from surgical specimens of human cancers, mutated ras genes (17%) and aberrations of tumor suppressor p53 gene (53%) including loss of one of the two alleles and a mutation in the remaining allele were detected in lung carcinomas and aberrations of both of the p53 and retinoblastoma (RB) genes were detected exclusively in advanced hepatocellular carcinomas.


Immunohistochemical identification of transforming growth factor-beta and its binding protein in human gastrointestinal carcinoma. We attempted to clarify the tissue localization of TGF-beta and latent TGF-beta binding protein (LTBP) in human gastrointestinal carcinomas by immunohistochemistry. The immunoreactivity for TGF-beta was observed in both carcinoma cells and stromal cells, particularly in diffuse-type gastric carcinoma. The immunoreactivity for LTBP was observed only in stromal cells. These results suggest that both carcinoma cells and stromal cells may produce TGF-beta, and that only stromal cells may produce LTBP in gastrointestinal carcinoma.


Alteration of the level of protein phosphatase 2C (IA) mRNA during the course of differentiation of skeletal muscle cells. On Northern hybridization using the cDNA of type 2C protein phosphatase as a probe, substantial amount of the mRNA of type 2C protein phosphatase was detected in various organs of rats, suggesting that the type 2C protein phosphatase gene is a housekeeping gene. A relatively high level of the mRNA, however, was found in skeletal muscle compared with other organs. Similar results were obtained with the organs of mice. In addition, the mRNA level in C3H10T1/2 cells (embryonal mesenchymal cells of mice) was much lower than in mature skeletal muscle of mice. The mRNA level of type 2C protein phosphatase was enhanced in accordance with the differentiation of the C3H10T1/2 cells into myoblasts induced by the transfection of MyoD cDNA. These results suggest that type 2C protein phosphatase is related to the mechanism of differentiation of skeletal muscle cells.


Thymidine kinase activity in familial adenomatous polyposis. Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of normal colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of normal; this increase seems attributable mainly to increased activity of cytosolic TK isozyme activity; the colorectal TK isozymes were separated into two types, i.e., fetal type and adult type isozymes predominantly in, respectively, cytosolic and mitochondrial fractions, by DEAE-cellulose column chromatography. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over normal. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity being elevated in some cases (8 of 15) and remaining low in others. Thus FAP polyps seem to be a heterogenous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.


Characterization of experimental rat nephroblastoma and its cell line. Rat nephroblastoma (Wilms' tumor) was induced by transplacental administration of N-ethyl-nitrosourea (ENU). The induced renal tumors were histologically compatible with human nephroblastoma. A cultured cell line (ENU-T-1) established from a xenotransplant, showed similar morphological and biological features to cultured embryonal kidney cells. Introduction of normal human chromosome #11 (#11) bearing Wilms' tumor suppressor gene(s) (WT) suppressed colony-forming ability on soft agar plates (CFA) but tumorigenicity of ENU-T-1 was not affected. Whereas tumorigenicity of human nephroblastoma cell line, SK-NEP-1 was completely suppressed, CFA was unchanged. These facts indicated that pathogenetic mechanism is different between human and experimental rat nephroblastomas.


Chemotherapy in small cell lung cancer--from view point of dose intensity. Results of chemotherapy trials for small cell lung cancer carried out for the past 5 years were analyzed from view point of dose intensity. Early study of CDDP+EP+ADM (1985 to 1987) showed moderate response rate (RR) of 72% with MST of 369 days. Succeeding alternative protocol of CDDP+EP+VCR/CPM+ADM+MTX (1989-1990) showed improved RR of 88% and MST of 13 months. Actual dose and interval for the alternating regimen was superior to the single arm regimen. Projected relative dose intensity against MAOP protocol including 6 drugs common to our regimen was 0.86 and delivered RDI was 0.61 with comparable RR and MST. The results may indicate that change of dose intensity within the conventional range does not result in major advantage or disadvantage for substantial prolongation of the survival in SCLC patients.


A brief review of the Ah locus.

A brief review of the Ah locus. The Ah locus, first described as a functional polymorphism among inbred strains of mice, encodes the Ah receptor--a ligand dependent transcriptional activator. This paper reviews the work on the Ah receptor and its importance in the expression of cytochrome P-450IA1 and the pleiotropic effects of halogenated aromatic hydrocarbons.


Chemotherapy of advanced epithelial cancer--a critical review. This article is a short version of a report which presents a comprehensive analysis of clinical trials and publications examining the value of cytotoxic chemotherapy in the treatment of advanced epithelial cancer. As a result of the analysis and the comments received from hundreds of oncologists in reply to a request for information, the following facts can be noted. Apart from lung cancer, in particular small-cell lung cancer, there is no direct evidence that chemotherapy prolongs survival in patients with advanced carcinoma. Except for ovarian cancer, available indirect evidence rather supports the absence of a positive effect. In treatment of lung cancer and ovarian cancer, the therapeutical benefit is at best rather small, and a less aggressive treatment seems to be at least as effective as the usual one. It is possible that certain sub-groups of patients benefit from the treatment, yet so far the available results do not allow a sufficiently precise definition of these groups. Many oncologists take it for granted that response to therapy prolongs survival, an opinion which is based on a fallacy and which is not supported by clinical studies. To date, it is unclear whether the treated patients, as a whole, benefit from chemotherapy as to their quality of life. For most cancer sites, urgently required types of studies such as randomized de-escalations of dose or comparisons of immediate versus deferred chemotherapy are still lacking. With few exceptions, there is no good scientific basis for the application of chemotherapy in symptom-free patients with advanced epithelial malignancy.


[Long-term results of small cell lung cancer treated by surgical resection and multimodality therapy]. 241 patients with small cell lung cancer (SCLC) were operated in our hospital from 1957 to 1985. The early postoperative mortality was 1.7%. The 5-yr survival rate was 23.2% (56/241). The 10-yr survival rate was 16.5% (15/91) (only 4 patients died during 5-yr to 10-yr after surgery but none of them died of SCLC). We analysed the 5-yr survival group. The 5-yr survival rate for stage I patients was 52.3% (23/44), stage II 34.1% (14/41), stage III 12.8% (19/149) [IIIa12.3% (17/138),IIIb 18.2% (2/11)]. Stage IV 0 (0/3). The P value: I vs IIIaP < 0.001, II vs IIIaP < 0.01. 125 patients received chemotherapy (CT) and/or radiotherapy (RT) postoperatively (group A) and the other 112 cases received surgical resection only (group B). 4 patients (3 IIIa, 1 IIIb) who died in early postoperative period were not counted. The 5-yr survival rate for group A and B was 40.8% (51/125) and 4.5% (5/112) respectively, P < 0.001; for group A and B stage I was 71.4% (20/28) and 18.8% (3/16), P < 0.01;for group A and B stage II was 54.5% (12/22) and 10.5% (2/19), P < 0.01; for group A and B stage IIIa was 25.4% (17/67) and 0 (0/71), P < 0.001. There were no differences in 5-yr survival rate on types of surgical resection and locations of the disease. The present results revealed that the total 5-yr survival rate for SCLC was 23.2%, among them for resection only was 4.5% and for resection plus multimodality therapy was 40.8%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Flow cytometric analysis of DNA content in lung cancer]. DNA index (DI) was studied with flow cytometry in surgical samples from 35 patients with lung cancer, 10 patients with benign lesions, 10 normal persons. The results showed that DI of lung cancer is significantly higher than that of benign pathological lesion and normal lung (P < 0.001). Aneuploid lung cancer was 88.57%, diploid was 11.43%. The DNA content of benign and normal lung was diploid. In the meantime, A significant positive correlation between the lung cancer DI and histopathological grade and cancer cell type was also observed, but there is not correlation between the TNM staging and lung cancer DI. Our results suggest that the flow cytometric analysis of DNA is useful for clinical pathologic diagnosis of lung cancer.


Lysosomal enzymes and superoxide production in polymorphonuclear leukocytes of patients with primary varicose veins. In order to clarify the role of reactive oxygen species and lysosomal enzymes in the etiopathogenesis of varicose veins, the investigation of their activities in serum and peripheral neutrophils of 17 patients with primary varicose veins was done. The mean activities of acid phosphatase, beta-D-glucuronidase (BDG) and N-acetyl-beta-D-glucosaminidase were higher in serum of patients with varicose veins than in serum of normal subjects. However, the mean BDG activity was lower in the patients' neutrophils and the activities of elastase and myeloperoxidase were higher than in clinically healthy persons. No changes have been observed in the lysozyme activity. The neutrophils of patients with varicose veins had a greater ability to increase superoxide production after their stimulation with opsonized zymosan or phorbol myristate acetate than the neutrophils of normal subjects, while no differences were found in the total reduction of iodonitrotetrazolium (INT) incubated with these leukocytes. The results may represent another piece of evidence suggesting the activation and involvement of neutrophils in pathogenesis of chronic venous insufficiency of lower limbs.


The mechanisms of free-radical lipids and antioxidant heart protection in experimental ischaemia and infarction. Free-radical lipid peroxidation (FRLP) during experimental myocardial ischaemia and infarction was studied on the first author's model using coronary occlusion in more than 1500 albino rats. FRLP was tested at various intervals after coronary occlusion (from the 20th minute to 14--30 days) in myocardial lipid extracts using various methods: 1) chemiluminescent method determining the intensity of free radical reactions, 2) diene conjugate production, 3) malone dialdehyde reaction, 4) Schiff bases fluorometric determination. The severity of ischaemia and infarction was assessed according to electrocardiographic, light and electron microscopic findings and morphometry of the damaged area. Intensified FRLP was registered in all four indicators at most tests performed within the first 14 days after production of ischaemia and infarction. The severity of ischaemic lesion could be reduced by FRLP inhibition using antioxidative agents of sharply differing chemical nature (sodium selenite, alpha-tocopherol a.o.). The authors conclude that FRLP intensification plays a role in the pathogenesis of myocardial ischaemia and infarction, and recommend to include antioxidative drugs in comprehensive heart protection.


[Effect of vitamin D over-dosage on the tooth and bone development of rabbits]. The paper investigated the changes of rabbit's tooth and jaw tissues by vitamin-D poisoning experiment. The results showed the dentin, periodontium, jaw bone and long bone of rabbit were all changed. X-ray showed subperiosteum absorbation and periosteum reaction. The mineral content of the rabbit's epiphysis and long bone diaphysis in experiment group were lower than that of control group. The histopathological findings were irregular hyperplasia of dentin, arrange disturbance of periodontal fibers, absorbation of the alveolar bone and mal-ossification of long bones. The above changes were more significant during 30-45 days of rabbit poisoning, after 60 days of poisoning the above signs were gradually released.


Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients. Eperimental toxicity and pharmacokinetics, and clinical trial. Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2-20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 +/- 0.39 microgram/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2-4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatment of CMV retinitis.


Density and distribution of excitatory amino acid receptors in the developing human fetal brain: a quantitative autoradiographic study. The binding of [alpha-3H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to quisqualate receptors, [3H]kainate (KA) to KA receptors, and L-[3H]glutamate to N-methyl-D-aspartate (NMDA) receptors was determined by quantitative autoradiography in brains obtained from twelve aborted human fetuses ranging from 16.5 to 26 weeks of gestational age. Among the three receptor subtypes, specific binding to AMPA was the highest, followed by NMDA and KA, respectively, in all age groups. Receptor binding was already apparent by 16.5 weeks in the hippocampus, thalamus, and subthalamic nucleus, rose sharply by 20-21.5 weeks, and subsequently declined to their lowest levels by 24-26 weeks. Anatomically distinct binding patterns for each of the three major excitatory amino acid (EAA) receptor subtypes were well established by 20-21.5 weeks. Within the hippocampus, AMPA was localized primarily in the stratum pyramidale, NMDA in the stratum radiatum, and KA in the molecular layer of the dentate gyrus and in the stratum lucidum of the CA3 region. The cerebral cortex showed dense labeling of AMPA in the outer layers, whereas KA binding was more prominent within the inner layers. The putamen and globus pallidus also showed relatively dense receptor binding in all age groups. The sharp rise in receptor density at 20-21.5 weeks of age suggests involvement of EAA pathways in developmental plasticity, including reorganization of neuronal processes or synapses, during this period of development. Developmental changes in the density and distribution of EAA receptors, as shown in this study, may also provide insight into shifts in the localization of age-dependent selective vulnerability within the developing human fetal brain.


Insulin-induced and constitutive internalization of the insulin receptor. The characterization of the cellular and molecular mechanisms governing insulin receptor internalization is of crucial importance to better define the functional role of this process in insulin receptor regulation and insulin action both in normal and pathological conditions. In the present work we have characterized the factors intrinsic to the receptor which are responsible for the triggering and regulation of insulin receptor internalization. We found that: (a) insulin induces the internalization of its receptor via activation of the tyrosine kinase intrinsic to the cytoplasmic domain of the molecule; (b) this ligand-specific step consists in the redistribution of the receptor from microvilli where binding occurs to the nonvillous region of the cell surface where internalization occurs; (c) the second step of the internalization process, i.e. association with clathrin-coated pits, requires a consensus sequence of the juxtamembrane domain of the receptor, and (d) this step is ligand-independent and is responsible for the constitutive internalization of the receptor.


Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. This study was performed to characterize the matrix metalloproteinases (MMPs) produced during the degradation of cotton-wrapped cartilage, implanted into the murine air pouch. One, two or three weeks following cartilage implantation, proteins were extracted from the granulation tissue and MMP activities were measured. Although collagenase-, gelatinase- and stromelysin-like activities were detected at each time point, gelatinase activity was by far the most prominent. These enzymes were inhibited by EDTA, but not by NEM or PMSF, indicating that these proteinases were metalloproteinases. Gelatin zymography revealed several lysis zones amongst which a major 92-kDa band shifted to 83- and 68-kDa species during the course of implantation. The emergence of these species coincided with enhanced gelatinolytic activity and collagen loss from the implanted cartilage.


Osteoclastic superoxide generation: taking control of bone resorption using modulators of superoxide concentrations. We have examined the role of superoxide in bone resorption by stimulating defective superoxide production and bone resorption in patients with osteopetrosis and inhibiting superoxide production and bone resorption in murine calvarial explants. Interferon gamma treatment did stimulate superoxide generation and bone resorption in patients with osteopetrosis as evidenced by a reduction in bone volume and an increase in biochemical markers of bone resorption. Further, lowering the superoxide concentrations within calvarial osteoclasts using a scavenger, desferal manganese, decreased bone resorption. We conclude that superoxide generation by osteoclasts is necessary for normal osteoclastic function.


Serum angiotensin converting enzyme in diabetic retinopathy. Serum levels of angiotensin converting enzyme (SACE) were measured in 118 diabetic patients divided into the following four groups: 44 insulin-treated diabetic patients with severe retinopathy, 38 non insulin-treated diabetic patients with severe retinopathy, 18 diabetic patients, including both insulin-treated and non insulin-treated subjects with background retinopathy, 18 diabetic patients, insulin-treated and non insulin-treated without signs of retinopathy. Nineteen retinopathic patients non diabetic were also studied in order to verify whether SACE levels are altered when retinopathy is present independently from diabetes. The control group was composed of 44 normal subjects. When the data from the above six groups of subjects were submitted to statistical tests (one-way ANOVA, T-test of Bonferroni and test of Student-Newman-Keuls), the study yielded the following results: i) a remarkable difference between the SACE levels in healthy subjects and those in the three groups of diabetic retinopathic patients considered; ii) a non statistically significant difference of SACE levels between normal subjects and diabetic patients without retinopathy; iii) a non statistically significant comparison of SACE levels of normal subjects versus non diabetic retinopathic patients. Therefore, we concluded that while primitive diseases of the retina are not associated with an increase of SACE levels, yet when diabetes and retinopathy coexist, the SACE levels increase remarkably (in rather an independent way from the type of diabetes, the age of subjects, the stage of retinal disease and the daily average insulin dose), suggesting that most of the enzyme's increase originates from the endothelium of peripheral vasa, widely involved in most of the retinopathic diabetic patients.


[Changes of the retinal pigmented layer in familial polyposis of the colon]. Ophthalmoscopic examinations were performed in 96 patients with polyps or another disturbances of the colon, among them 3 cases suffered a histopathologically confirmed familial polyposis of the colon. All 3 cases of the familial polyposis exhibited in the ophthalmological examination pathological changes of the retinal pigment epithelium of both eyes.


[Does arthritis due to varicella zoster virus exist?]. Occurrence of monoarthritis or oligoarthritis during the course of zoster is exceedingly rare (three previously reported cases). In the additional case reported herein, an immunocompetent female exhibited oligoarthritis (right shoulder followed by two metacarpophalangeal joints in her right hand) a few days before developing a typical zoster eruption in the ipsilateral upper limb. Pathogenesis of zoster-related arthritis is discussed. The most likely hypothesis is infection of the joint via the nerve supply rather than via the bloodstream. Evidence in support of this mechanism includes recovery of the virus from synovial fluid specimens in a previously published case.


Three monoclonal antibodies against human LFA-1 alpha and beta chains with different biological activities. Three murine monoclonal antibodies (MAbs) directed against human lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18), designated as MAY.017, MAY.035, and MAY. 044, were newly generated. The hybridomas were screened for their ability to inhibit a phorbol ester-stimulated aggregation of Epstein-Barr virus-transformed B-lymphoblastoid cell line (B-LCL). The MAbs bound to peripheral blood leukocytes, T cell lines, B cell lines, and some of myeloid/monocytic lines, but not to B-LCL derived from a patient with leukocyte adhesion deficiency. MAY.035 immunoprecipitated a complex of proteins with molecular masses of 155 kDa and 95 kDa, while MAY.017 and MAY.044 did a complex of 130 kDa, 155 kDa and 95 kDa proteins. MAY.035 was shown as to recognize the alpha chain of LFA-1 (CD11a), and both MAY.017 and MAY.044 the beta chain of the beta 2 integrin family (CD18). All the three MAbs inhibited lymphocyte proliferative responses to mitogens or alloantigens. MAY.017 blocked cytolytic activity mediated by natural killer cells.


The laboratory and clinical safety evaluation of a dentifrice containing hydrogen peroxide and baking soda. This study reports the laboratory, clinical, and microbiological finding of the safety testing and daily use of a dentifrice delivering 0.75% hydrogen peroxide and 5% baking soda. Laboratory studies using Ca45 labeled teeth and biologically stained teeth confirmed that the dentifrice did not decalcify enamel or bleach teeth. Over the course of a six-month period, 62 subjects using a hydrogen peroxide-baking soda dentifrice and 21 subjects using a control dentifrice were examined for oral soft tissue change and hard tissue alterations. No soft tissue changes attributable to the use of either dentifrice were noted. Experienced clinicians using Trubyte shade guide teeth observed no significant changes to the subjects' anterior teeth following 6 months use of the test dentifrice. Paired discrimination tests revealed that the examiners could distinguish color differences in the shade guide teeth at 0.7%. Microbiological monitoring of the subjects for six months use of their assigned dentifrice and for the following months on the control dentifrice, revealed neither an increased incidence of candida nor increased candida counts.


Reduction in the levels of oral malodor precursors by hydrogen peroxide: in-vitro and in-vivo assessments. The potential of hydrogen peroxide to reduce the levels of salivary thiol precursors of oral malodor was investigated in-vitro and in-vivo. In both cases the concentration of thiol groups was determined colorimetrically by quantitative reaction with 4,4'-bis (dimethylamino) diphenyl carbinol. Addition of volumes of hydrogen peroxide solution (containing between 0.18 and 0.90 mmol) to premeasured aliquots of saliva in-vitro, resulted in reductions in salivary thiol levels of between 53% and 75% compared to controls. This positive indication prompted an in-vivo investigation. The efficacy of a fluoride-containing test toothpaste also containing 0.67% hydrogen peroxide and 5.48% sodium bicarbonate was evaluated in a crossover study using ten male and female subjects (non-smokers). All subjects used the test product and a control fluoride dentifrice, in a random order. For the duration of the study subjects used a standard silica based toothpaste containing 1500 ppm F (as sodium monofluorophosphate) exclusively for their normal oral hygiene. On each sampling morning they refrained from oral hygiene and eating and drinking on rising. At the test facility they generated a background saliva sample stimulated by chewing unflavored, unsweetened gum. Subjects brushed for 1 minute with 1.50 (+/- 0.05) g test or control paste and generated another saliva sample as before, 30 minutes after product application. Using the same analytical procedures the mean (+/- SEM) percent reduction in salivary thiol levels post treatment compared to baseline was found to be 59.0 (+/- 7.0)% for the test product compared with 12.5 (+/- 5.2)% for the fluoride control paste.(ABSTRACT TRUNCATED AT 250 WORDS)


The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years. In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


Low p53 level in immortal, non-tumorigenic oral keratinocytes harboring HPV-16 DNA. The p53 protein level was determined in normal oral keratinocytes and two non-tumorigenic, immortal oral keratinocyte lines harboring human papillomavirus-16 (HPV-16)DNA. The p53 mRNA level in the immortal cells was higher than the normal counterpart, but the p53 protein level was notably lower in the immortalised cells. The half-life of p53 protein in the normal and immortal cells was < 1 h, and the p53 cDNA sequence of these cells showed no mutation. The immortal cells transcribed a high amount of E6/E7 mRNA encoded by HPV-16, but normal cells did not. These observations suggest that the immortal keratinocytes may translate normal level of wild-type p53 protein, and the low p53 level in these cells may be due to the enhanced degradation of the protein by HPV-16 E6 protein.


In vitro and animal studies of the role of viruses in oral carcinogenesis. The linkage of herpes simplex virus (HSV) and human papillomavirus (HPV) to the development of oral cancer has been studied. In spite of the presence of viral nucleic acids in some human oral cancer specimens, HSV alone is not carcinogenic in animals: repeated viral inoculation to mouse or hamster oral mucosa fails to produce tumours or histopathological evidence of malignancy. However, HSV demonstrates co-carcinogenicity in vivo: viral inoculation significantly enhances the oncogenic capacity of chemical carcinogens in the oral cavity of mice and hamsters. Though the detailed mechanisms of HSV cocarcinogenicity are unknown, HSV promotes the chemical carcinogen-induced activation of certain cellular proto-oncogenes and inactivation of p53 tumour suppressor gene. Human papillomaviruses type 16 (HPV-16) and 18 (HPV-18) demonstrate oncogenicity by transforming normal human oral keratinocytes in vitro. While normal cells exhibit a limited life-span, cells transformed by these viruses show immortality and altered morphology in comparison with their normal counterparts. The HPV-immortalised cells contain multiple copies of intact viral genome integrated into cellular chromosomes. These cells also express several viral-specific mRNAs including viral E6/E7 mRNAs. Notably, these cells contain low levels of p53 protein and overexpressed cellular myc proto-oncogene compared to their normal counterpart; however, the immortilised cell lines are non-tumorigenic in nude mice.


[The importance of the adrenals in altering the properties of the hypothalamo-hypophyseal-adrenocortical system after stress]. The effect of stress on adrenal response to ACTH was studied in vivo and in vitro in rats. There were a decrease of capacity and an increase of responsiveness to ACTH of adrenals from rats which were exposed to electrical stimulation of foot. The date explain the mechanisms of hypothalamo-pituitary-adrenocortical system changes in total after stress which was obtained in our previous work.


[A clinical analysis of 13 cases of adult osteomalacia]. 13 cases of renal tubular osteomalacia, consisting of 5 cases of Vitamin D resistant rickets (VDRR), 6 cases of renal tubular acidosis(RTA) and 2 cases of Fanconis syndrome were reported. The biochemical findings of the serum and urine from the 13 cases were compared with those from normal controls. The clinical findings, diagnosis and treatment of renal tubular osteomalacia were reviewed. The differential diagnosis of osteomalacia with laboratory methods and the mechanism of its pathogenesis were discussed.


[Microwave technique in hepatic surgery: report of 70 cases]. 70 hepatic resections were performed using 2450 MHz microwave scalpel. Primary diseased included hepatocellular carcinoma (46 cases), hemangioma (18), hepatobiliary tract stone (2), biliary cystadenoma (1), inflammatory pseudotumor of the live (1), metastatic liver cancer (2). Hemostasis was excellent despite liver cirrhosis in all cases. The average amount of blood loss and blood transfusion was 249 ml and 294 ml respectively. Blood transfusion was not necessary in 30 patients. All cases were free from postoperative bleeding from the liver stump and abdominal infection. No complications attributable to microwave coagulation were noted. We conclude that this new operative technique can be used safely and easily in the field of hepatic surgery.


Nervous and immune systems as targets for developmental effects of benzodiazepines. A review of recent studies. Prenatal exposure to benzodiazepines (BDZ) can cause behavioral dysfunctions both in humans and in experimental animals. In addition, prolonged impairment of cellular immune functions is found in rats after low dose BDZ exposure (e.g., diazepam 1.25 mg/kg/day) during part of fetal life [gestational days (GD) 14-20]. Analysis of diazepam and its metabolites in maternal and fetal tissues revealed that in this rat model the drug is no longer present at birth, which excludes direct effects of diazepam during the postnatal period. The main target of BDZ in brain, the GABAA receptor complex, is structurally and functionally heterogeneous. Besides alpha- and beta-subunits, gamma 2- or gamma 3-subunit should be coexpressed for a fully functional BDZ response. Signals of mRNAs encoding for alpha 1, beta 2 and gamma 2 are detected in fetal rat spinal cord and lower brainstem by GD 14 and reach telencephalic regions in later fetal life, reminiscent of BDZ receptor ontogeny. Regional subunit distribution differs from the adult brain, one interesting feature being a preponderance of gamma 2 mRNA throughout fetal life. Since subunit composition influences the sensitivity to BDZ, these data suggest that prenatal effects of BDZ depend upon regional subunit compositions present at different developmental stages. The delayed depression of cellular immune responses in prenatally BDZ-exposed rat offspring during the first 2 postnatal months is accompanied by various changes in immune cell biology. Binding characteristics of the peripheral (omega 3) type BDZ receptor are altered until adulthood (8 weeks). Membranes of spleen cell preparations containing mainly lymphocytes exhibit a decrease of affinity for the peripheral ligand [3H]PK11195, splenic macrophage preparations a decrease of maximal binding capacity. Various defects in cytokine production by macrophages and T lymphocytes were observed: Mitogen-stimulated release of macrophage-derived tumor necrosis factor-alpha (TNF-alpha) and of the T cell-derived interleukin-2 (IL-2) was drastically reduced at 2 and 4 weeks of life and recovered in young adulthood, exhibiting the same time course of depression as lymphocyte proliferation in response to immune stimuli. Interleukin-6 (IL-6) release remained diminished until adulthood. In female offspring, additional alterations were found in splenic noradrenaline turnover after immune stimulation. The mechanisms underlying the breakdown of the cytokine network in prenatally diazepam-exposed offspring, and the long-term consequences are as yet unknown.


Further evaluation of IGF-I responsiveness to ACTH in children affected with IGHD. In our previous studies we had demonstrated that, in children affected with isolated GH deficiency (IGHD), a short-term recombinant growth hormone (rGH) therapy increases the 11-deoxycortisol (S) secretion and induces an IGF-I responsiveness to the ACTH challenge. The aim of the present study was to further investigate the mechanisms by which IGF-I is secreted after ACTH challenge in children affected with IGHD by correlating IGF-I versus cortisol (F) time courses after ACTH administration. Ten children affected with IGHD were subjected to rGH therapy (4 IU/day subcutaneously) for 10 days. The responsiveness of IGF-I, F and S to the ACTH 1-17 test were evaluated before and at the end of the therapy. No IGF-I response to the ACTH test was recorded in the patients before the rGH treatment, whereas after rGH administration ACTH induced a significant IGF-I release (p < 0.001) which started at the 1st hour, reached a peak value between the 5th and 6th hours and disappeared at the 10th hour. In conclusion, our study confirms that a short-term rGH therapy induces an IGF-I responsiveness to ACTH and helps to better define the kinetics and the mechanism of this IGF-I response to ACTH.


Effect of naloxone administration upon the diurnal concentrations of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys. A diurnal pattern in oxytocin concentrations is present in cerebrospinal fluid (CSF) removed from the spinal subarachnoid space of monkeys, with elevated levels occurring in the early light hours. In order to investigate the possible role of endogenous opioid peptides in the generation of this oxytocin rhythm, we administered naloxone (0.4 mg/kg/h x 48 h) to rhesus and cynomolgus monkeys and examined the effects on the diurnal pattern of oxytocin in CSF collected from the lumbar subarachnoid spinal space. Monkeys maintained on jacket/tether/swivel systems and in a 12 h light: 12 h dark cycle (lights on 07.00-19.00 h) were implanted with temporary spinal subarachnoid catheters. CSF was continuously collected from the lumbar subarachnoid space and assayed for oxytocin. Oxytocin concentrations in CSF showed a diurnal variation with peak and nadir concentrations during light and dark hours, respectively. The lumbar CSF concentrations of oxytocin were not significantly different during naloxone vs. saline infusion. Plasma oxytocin concentrations, measured in the same animals, displayed no diurnal variation and were not significantly different during naloxone vs. saline infusion. We conclude that naloxone administration for 48 h does not perturb the diurnal variation in oxytocin concentrations in the CSF of monkeys. Mu opioid receptors are unlikely to be involved in modulating the diurnal rhythm of oxytocin in the CSF of monkeys.


[Uptake of 86Rb by human erythrocytes: modification of the method and applications]. In this study we applied a method generally used for the study of Na+,K(+)-ATPase, as well as other systems of potassium transport, which makes use of a rubidium isotope (86Rb) as analogue of the potassium and is known as uptake of the 86Rb. This method proved to be particularly sensitive and versatile for kinetic studies of this pump system, allowing to assess possible alterations. Its application in the study of sodium and potassium transport in erythrocytes of uremic subjects in extracorporeal dialysis made it possible to reveal certain alterations due both to pump-dependent and pump-independent uptake. In fact, the results show the hypothesis of restoration of Na+,K(+)-pump activity for elimination during dialysis of one or more inhibitor present in the uremic plasma. Furthermore, a reduction in aspecific flows was noted which could be the result of more generalized damage of the membrane.


Effects of fetal growth retardation on the development of central and peripheral catecholaminergic pathways in the sheep. Regional norepinephrine and dopamine content and cerebral alpha 1- and beta-adrenergic receptor mechanisms were studied in the brain of sham operated control and single umbilical artery ligation (SUAL) induced growth retarded newborn sheep. Brain sparing was evidenced by relative preservation of brain weight compared to other organ systems. Norepinephrine and dopamine content of the brain were not affected by SUAL. This is in contrast to decreased norepinephrine levels in the brown fat, a normally densely innervated peripheral tissue. Alpha 1- and beta-adrenergic receptor numbers and affinity states were similar between the two groups. Coupling between beta-receptor and guanine nucleotide stimulatory protein and agonist stimulated adenylyl cyclase activity were unaffected by SUAL. Brain regional DNA content and protein/DNA ratios were not different between the two groups. These data suggest that single umbilical artery ligation induced fetal growth retardation modifies peripheral but not central catecholaminergic pathways in the sheep. Both growth and expression of specific catecholaminergic signal transduction system are protected in the brain.


Disinfection of irreversible hydrocolloid impressions: a comparative study. This paper demonstrates the potential for cross contamination with bacteria and viruses from impression materials and evaluates the efficacy of four disinfection systems on irreversible hydrocolloid impressions contaminated with Streptococcus sanguis or poliovirus. An irreversible hydrocolloid impression was made of a contaminated acrylic resin template. The impression was disinfected and residual microorganisms were harvested by sonication, cultured, and counted. The results showed that the impression material could act as a vehicle for the transfer of both bacteria and viruses. Further, the virus was shown to be present in the body of the impression and under certain conditions may evade decontamination.


The genomic structure of the human skeletal muscle sodium channel gene. Electrical excitability of neurons and muscle cells reflects the actions of a family of structurally related sodium channels. Mutations in the adult skeletal muscle sodium channel have been associated with the inherited neuromuscular disorders paramyotonia congenita (PMC) and hyperkalemic periodic paralysis (HPP). We have deciphered the entire genomic structure of the human skeletal muscle sodium channel gene and developed a restriction map of the locus. SCN4A consists of 24 exons spanning 35 kb of distance on chromosome 17q. We describe the sequence of all intron/exon boundaries, the presence of several polymorphisms in the coding sequence, and the locations within introns of two dinucleotide repeat polymorphisms. This is the first sodium channel for which the entire genomic structure has been resolved. The organization of the SCN4A exons relative to the proposed protein structure is presented and represents a foundation for functional and evolutionary comparisons of sodium channels. Knowledge of the exon structure and flanking intron sequences for SCN4A will permit a systematic search for mutations in PMC and HPP.


Genomic organization of a cDNA (QM) demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells and its localization to Xq28. Using a cosmid clone derived from human Xq28 as a probe which shows cross-species homology, we isolated cDNA clones and the nucleotide sequence analysis of the cDNA revealed that the cDNA is identical to QM cDNA. The QM cDNA has recently been reported as a cDNA with down-regulation in tumorigenic Wilms' tumor microcell hybrid. Comparison of the nucleotide sequences of the cDNA with those of the genomic DNA allowed us to determine the genomic organization of the QM gene. The QM gene consists of at least 7 exons and is located at Xq28. Southern blot analysis of a somatic cell hybrid panel indicates that the QM genes are scattered at least to chromosome 2, 3, 6, 14, 16, and possibly to other chromosomes. Northern blot analysis demonstrated the QM gene is expressed in all the examined adult human tissues as well as cell lines including HeLa cells, fibroblasts, and somatic cell hybrids with increased expression in liver, spleen, testis, and adrenal gland. The results suggest that the QM gene belongs to a new multi-gene family with yet undetermined function.