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Biomedical subjects

J Scotto

Publications and source records attributed to J Scotto.

At least 37 records · Page 2Linked to original sources

[Serum DNA of hepatitis B virus in children with chronic infection].

Viral replication has been studied in 44 children with chronic infection induced by hepatitis B virus (HBV) investigating HBV-DNA by molecular hydridization technique, correlating its presence with immunological markers and activity of liver disease. HBV-DNA presence is correlated to HBe Ag detection, but this antigen was also found in absence of viral DNA (7 cases of 31). That can mean viral replication diminishes or disappears before the seroconversion. No differences were found in viral replication phases as for clinical manifestations in children. In presence of viral DNA, serum aminotransferases were higher (p less than 0,005) and active hepatic lesions more frequent. Therefore, more cytolysis an inflammation are found in presence of circulating virus. On the other, more developed lesions (inactive cirrhosis and hepatocellular carcinoma) have been found in viral replication absence.

Adolescent

Presence of HBV DNA in spermatozoa: a possible vertical transmission of HBV via the germ line.

Using molecular hybridization we studied the presence and state of HBV DNA in sperm samples obtained from 17 patients with HBV infection (eight HBsAg chronic carrier, nine acute hepatitis B). Presence of HBV DNA was detected in three samples of seminal fluid from three patients with acute hepatitis. Restriction enzyme patterns of cellular DNA were consistent with presence of integrated HBV DNA sequences in spermatozoa from two of these three patients. The results indicate that HBV DNA may be present in the semen, at least during the acute phase of HBV infection. The presence of HBV DNA in seminal fluid confirms the possibility of venereal transmission. The presence of integrated sequences in spermatozoa suggests the possibility of true vertical transmission of HBV via the germ line.

DNA, Viral

Psoriasis and susceptibility to nonmelanoma skin cancer.

Using data from a national skin cancer survey, we assessed the risk of basal cell and squamous cell carcinoma among patients with psoriasis compared with the general population. For both male and female psoriatic patients, the risk of basal cell carcinoma was significantly elevated (relative risk = 2.2 and 1.7; p less than 0.05, both comparisons). The risk of squamous cell carcinoma was not significantly or substantially different for persons with a history of psoriasis compared with other persons (relative risk = 1.3; p greater than 0.05). The relative risk of basal cell skin cancer among patients with psoriasis was significantly higher even after stratification for factors associated with both psoriasis and cutaneous malignancy, which include fair complexion, exposure to coal tar or pitch, and exposure to radiation. Contrary to long-standing beliefs, our findings support the hypothesis that even after allowing for possible greater exposures to cutaneous carcinogens, the risk of nonmelanoma skin cancer in patients with psoriasis is at least as great as in the general population. Thus persons with psoriasis who are treated with potential carcinogens such as ultraviolet radiation, tar, and oral methoxsalen photochemotherapy merit careful, long-term monitoring.

Adult

Hepatitis B virus DNA in Dane particles: evidence for the presence of replicative intermediates.

Half the Dane particle concentrates isolated from 84 serum samples of patients infected with hepatitis B virus (HBV) contained more than one HBV DNA species. At most, six HBV DNA molecules migrated on hybridization blots. The fastest migrating species was single minus-strand DNA, and the five slower species all were double-stranded relaxed circular DNA. One of the latter forms corresponded to the full-length HBV genome; the four others contained shorter plus strands of different lengths and might represent replicative intermediates. These results indicate that the replicative forms of HBV previously found in infected liver cells might be coated and exported as early as the step of single minus-strand synthesis.

Centrifugation, Density Gradient

Methionine metabolism and ultrastructural changes with D-galactosamine in isolated rat hepatocytes.

The biochemical and morphological effects of 2, 10 and 100 mM of D-galactosamine (GalN) were studied in isolated rat hepatocytes during 2 h of incubation. Lactate dehydrogenase (LDH), alanine aminotransferase (ALAT) and cell viability did not change, whatever the concentration used. The variations observed, which were dose dependent, included a large drop in ATP levels and inhibition of RNA and protein synthesis. A very high concentration of GalN was necessary, however, to induce a significant decline in methionine adenosyltransferase activity compared to control cells. The use of L-[methyl-14C]methionine during cell incubation with GalN demonstrated a decrease of S-adenosyl-L-methionine (SAMe) and an accumulation of L-methionine content related to the GalN concentration. These results suggested that an hepatotoxic agent such as GalN was able to induce disturbances of methionine metabolism. Some of the ultrastructural changes observed were different from those previously found in vivo, in rats given GalN intraperitoneally, underlining the marked difference between in vivo and in vitro intoxication.

Alanine Transaminase

DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum.

Xeroderma pigmentosum (XP), is a rare, autosomal recessive disease with sun sensitivity and multiple neoplasms in association with reduced DNA repair. As a reflection of the clinical consequences of deficient DNA repair, XP serves as a model for determining the effects of proficient DNA repair. To estimate the risk of developing neoplasms in XP, we abstracted reports of 726 XP patients (from 41 countries) published from 1874 to 1982. Despite limitations of a literature survey, the XP patients under age 20 years had an estimated 2000-fold increase in frequency of basal cell and squamous cell carcinoma of the skin, of cutaneous melanoma, of cancer of the anterior eye, and of cancer of the anterior tongue, in comparison to the general population. These sites are all potentially exposed to u.v. radiation, a strong carcinogen which produces DNA damage that is poorly repaired by XP cells. XP patients under age 20 years also had an estimated 12-fold increase in occurrence of neoplasms in sites not exposed to u.v. radiation. Among the XP patients under age 40 years with internal cancer, there was a disproportionate representation of malignant neoplasms of the brain (especially sarcomas), and oral cavity (excluding tongue) compared to US whites under age 40 years. These internal neoplasms may be related to exposure to chemical environmental carcinogens that cause DNA damage which, like u.v.-induced damage, is poorly repaired by XP cells. These reports provide no evidence of an increase in XP of common lethal neoplasms such as lymphomas, or female genital tract or endocrine system cancers. These findings suggest that DNA repair plays a role in protection against u.v.-induced neoplasia and in protection against some internal neoplasms in the general population.

Adolescent

Hepatitis B virus DNA in children's liver diseases: detection by blot hybridisation in liver and serum.

Molecular hybridisation using cloned hepatitis B virus DNA (HBV DNA) was applied to liver and serum samples from 46 children (39 with liver diseases and seven controls) for detection of HBV DNA sequences, free and integrated into the liver cell genome. HBV DNA integration was observed in 10 children. The young age of some of these cases indicates that such integration can occur early in liver disease and is not related to the duration of viral infection. Thirteen children exhibited serological evidence of active viral multiplication. All but one had free HBV DNA in liver tissue and integrated HBV DNA sequences were found in four cases. Integrated HBV DNA sequences alone were also detected in three children with neither HBV-antigens nor HBV DNA in serum. One had inactive cirrhosis, and the two others, chronic active hepatitis. Consequently DNA hybridisation may be useful for diagnosis, in the absence of serological signs of HBV infection; its specificity was enhanced in the present investigation by negative results in six children with autoimmune chronic active hepatitis. Taken together, the above results imply that HBV-DNA integration can occur in both active and inactive liver disease. Integrated HBV DNA was also observed in the liver of three children with fatal hepatic failure who presented with antibodies to HBsAg and/or to hepatitis B core antigen in the serum. This finding raises the question of the relationship between the host immune factors and the state of HBV DNA.

Adolescent

Estimating increases in skin cancer morbidity due to increases in ultraviolet radiation exposure.

It is generally accepted that if ozone levels in the stratosphere are depleted, greater amounts of shortwave ultraviolet radiation (UVB) will reach the earth's surface, resulting in increased morbidity of nonmelanoma skin cancer. The incidence and UVB data are now available from a new epidemiologic study of skin cancer conducted at eight locations of the United States. We found that either a simple power function or a simple exponential function could be used to describe these new data. According to estimates based on the power model, should the amount of exposure to UVB increase by 30%, then the incidence of skin cancer will increase by 60% in males and 45% in females. Estimates based on the exponential model vary by location, (53-96)% in males and (39-68)% in females. These estimates are somewhat lower than those based only on earlier data. We emphasize that skin cancer rates also depend on variables other than UVB which may be location specific.

Adult

Changes in skin cancer morbidity between 1971-72 and 1977-78.

Skin cancer incidence rates for two geographic areas of the United States were analyzed for detection of significant changes in risk over a 6-year period (1971-72 to 1977-78). Changes in rates were examined by cell type, anatomic site, sex, and age. In general risk has increased, but the size of the increase varied by cell type, sex, and anatomic site. Statistically significant increases were limited to tumors of the basal type. The risk of basal cell skin cancer appears to have increased about 18% or almost 3% per year. Increases did not depend on age group. Among males the increases were most notable for sites other than face, head, and neck, whereas among females the increases were not associated with site.

Adult

Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state.

The detection of hepatitis B virus (HBV) DNA in the liver and the serum permits direct study of the interaction between the virus and the liver cell. 40 HBV chronic carriers were studied by the blot technique of Southern to detect HBV DNA, and the results were compared with the serological status and histological status of the patients. It was possible to define two different chronic carrier states. The first is characterised by free viral DNA in the liver, with viral DNA and hepatitis B e antigen (HBeAG) in the serum; integrated HBV DNA is also present, at least in some patients. The second carrier state is characterised by the presence of only integrated HBV DNA sequences in the liver: viral DNA and HBeAg are not present in the serum. In one HBeAg-negative patient, however, free HBV DNA was detected in the liver and HBV DNA was present in the serum. The hybridisation technique appears to be a very sensitive test which could reflect viral multiplication better than HBeAg radioimmunoassay. Since a needle biopsy sample provides sufficient tissue for the Southern blot technique, it should be useful in understanding chronic hepatitis, the selection of patients for antiviral therapy, and the estimation of its efficiency.

Autoradiography

Effects of Pexid on liver cell cultures. Ultrastructural and histoenzymological studies.

The effects of different doses of Pexid on cultured liver cells have been studied by ultrastructural and histoenzymological techniques. Two types of abnormal lysosomal inclusions were seen: clear matrix inclusions with either homogeneous or tiny lamellar structures, and dark matrix inclusions with clear vacuoles and either random or myelin-like lamellar structures. These patterns correspond to storage of triglycerides, phospholipids and gangliosides, either singly or together.

Cells, Cultured

Severe giant cell hepatitis with autoimmune hemolytic anemia in early childhood.

Four children, aged 6 1/2 months to 2 years, presented with liver disease and autoimmune hemolytic anemia. Clinical signs included fever, jaundice, firm or hard hepatomegaly, and splenomegaly. Direct Coombs test results were of the mixed (IgG + C) type. Liver function tests showed high direct bilirubin transaminase, and serum gamma globulin values, and a prolonged prothrombin time. The liver histology was characterized by marked lobular fibrosis and giant cell transformation. The course of the disease was severe, resulting in the death of three patients from liver failure. However, the liver disease seemed responsive to corticosteroid treatment, which in one patient was clearly beneficial.

Anemia, Hemolytic, Autoimmune

State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases.

Using the Southern blot technique and cloned hepatitis B virus (HBV) DNA as a probe, we studied the state of HBV DNA in the liver of 13 patients with hepatocellular carcinoma, 17 patients with chronic hepatitis, and 2 patients with acute hepatitis. The hybridization results were compared with the serological and immunohistological data. Integration of HBV DNA in cellular DNA of the liver from patients with hepatocellular carcinoma was demonstrated. In two patients from which tumorous and nontumorous liver tissue samples were available the integration patterns were different. In one patient with hepatitis B e antigen (HBeAg)-positive early hepatocellular carcinoma, free viral DNA was present in the liver. In some patients with HBeAg-negative chronic hepatitis, without tumor, integration of HBV DNA in cellular DNA was also demonstrated. This suggests that HBV is not the only factor involved in the development of a tumor. In patients with HBeAg-positive chronic hepatitis, free viral DNA was detected in the liver. In the two acute hepatitis patients analyzed, the restriction endonuclease patterns strongly suggested HBV DNA integration. Therefore, viral DNA integration seems to occur early in infection. Whatever the form of the disease, discrete bands were observed, suggesting the existence of limited and specific integration sites in host cellular DNA. The presence of integrated or free DNA sequences has implications for antiviral therapy. In addition, detection of HBV DNA in the liver is another sensitive viral marker that could be useful for diagnostic purposes.

Carcinoma, Hepatocellular

[Clinical, biological, histological, ultrastructural and therapeutic studies in one case (author's transl)].

The diagnosis of glucagonoma was made in a 51 year-old woman who suffered from a polymorphous dermatitis and an insulin-dependent diabetes mellitus. Denutrition was present and there was a previous history of thrombo-embolism. Immunoreactive plasma glucagon was constantly higher than 1 000 pg/ml (N less than 175). Plasma aminoacids were low. After angiographic confirmation, the tumour and part of its hepatic metastases were resected. The dermatitis disappeared soon after. Its recurrence required chemotherapy (successively mithramycin, streptozotocin, DTIC) and good clinical results were obtained. On histological examination, the cutaneous lesions consisted of an epidermal edema, and a bullous intra-epidermic detachment. The pancreatic tumour was of the trabecular type with a very important sclerosis. On electron microscopy, the tumoral cells, some with a syncitial aspect, contained granules of the D1 type. These granules are different from the typical glucagon granules. The clinical and biological features in this case are compared with those of the 41 cases of glucagonoma previously published.

Adenoma, Islet Cell