An outbreak of intrafamiliar hepatitis A associated with clam consumption: epidemic transmission to a school community

When human parathyroid hormone (hPTH) is expressed as a secretory product in yeast, the main problem is the aberrant proteolytic cleavage that reduces the yield of intact protein. To overcome this problem, we developed an hPTH expression system using a host strain in which the YAP3 gene encoding yeast aspartic protease 3 (YAP3) was disrupted. After 48 h of culture, most of the hPTH secreted by the yap3 disruptant remained intact, whereas more than 90% of the hPTH secreted by the wild-type strain was cleaved. When the authentic hPTH was incubated in each of the culture supernatants of untransformed yap3 disruptant and wild-type strain, the proteolysis proceeded much more slowly in the culture supernatant of yap3 disruptant than in that of the wild type. The extent of hPTH proteolysis was also significantly reduced by the addition of pepstatin A, a specific aspartic protease inhibitor. The results suggest that YAP3 is involved in the internal cleavage of hPTH expressed in yeast. The correct processing of the intact hPTH secreted in the yap3 disruptant demonstrates that the yeast mutant lacking the YAP3 activity is a suitable host for the high-level expression of intact hPTH.     

Genetic evidence for mother-to-infant transmission of hepatitis G virus

Administration of a single high dose of methamphetamine (METH) causes a rapid and reversible decrease in the activity of the tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine. This effect can be reversed completely by exposing the METH-impaired enzyme to a reducing environment, which suggests that the decrease in TPH activity is a reversible oxidative consequence of free radical formation. Consistent with this hypothesis, a single METH administration to male rats increased oxygen radical formation, as demonstrated by increased striatal dihydroxybenzoic acid formation after coadministration of salicylate with METH. Prevention of METH-induced hyperthermia attenuated both the increase in dihydroxybenzoic acid formation and the decrease in TPH activity observed 1 h after METH administration. These data suggest that both reactive oxygen species and hyperthermia contribute to the acute decrease in TPH activity which results from a single METH administration.     

Immunohistochemical evidence of immunopathogenetic mechanisms in chronic hepatitis C recurrence after liver transplantation

Viremia and genotype are implicated in a rapid course of posttransplant hepatitis C virus (HCV) infection recurrence, but the role played by host immune reactions has not yet been evaluated. We correlated the degree of liver injury with the intrahepatic expression of molecules involved in immune response. The study included 32 biopsies of 30 liver transplant recipients. Recurrence of viremia was detected by Amplicor assay. Genotype was tested by Inno-Lipa. Cryostat sections were assessed by immunohistochemistry, using a wide panel of monoclonal antibodies. Correlations between histological-immunohistochemical semiquantitative evaluation and levels of viremia were performed. In severe hepatic inflammation, high numbers of activated cytotoxic T cells were found, along with marked hepatocellular expression of beta 2-microglobulin (beta 2-MG) and intercellular adhesion molecules. Likewise, a strong vascular adhesion molecule expression was observed mainly in those areas that were more inflamed. A striking endoglin reactivity was detected in enlarged portal tracts, and the presence of neoformed microvessels was also noteworthy. By contrast, in mild hepatic inflammation only a few activated T cells were detected, together with a weaker reactivity for all molecules studied. The level of viremia did not correlate with the degree of liver damage. The severe forms of post-transplant HCV infection recurrence are associated with a marked and aberrant intrahepatic expression of molecules involved in antigen recognition, and intercellular and vascular adhesion, decisive in regulating the recruitment and activation of cytotoxic T lymphocytes.     

First evidence of natural vertical transmission of yellow fever virus in Aedes aegypti, its epidemic vector

Entomological investigations were conducted in 1995 in Senegal, following a yellow fever (YF) outbreak. A total of 1125 mosquitoes collected in the field, including males, females and 12-48 h old newly emerged adults reared from wild-caught larvae, were tested for YF virus. Among the 22 species captured, Aedes aegypti was the most common. 'Wild' vectors of YF were also captured, including A. furcifer, A. metallicus and A. luteocephalus. In all, 28 YF virus isolations were made: 19 from A. aegypti females, including 2 from newly emerged specimens; 5 were obtained from A. aegypti males, including one from a pool of newly emerged specimens, 2 from A. furcifer females, and one each from a female A. metallicus and a female A. luteocephalus. The true infection rates (TIRs) were much higher in adult A. aegypti than in specimens reared from larvae--8.2% and 31.4% for female and male A. aegypti captured on human volunteers, respectively (P < 0.0001). The TIRs for A. aegypti reared from larvae were 1.4% and 0.5% for females and males, respectively (P > 0.05). This outbreak was an intermediate YF epidemic, involving 4 vector species. Our data provide the first evidence of vertical transmission of YF virus in nature by A. aegypti, its main vector to humans, and strongly suggest that vertical transmission played a major role in the spread of the epidemic.     

Risk factors associated with chronic hepatitis C virus infection: limited frequency of an unidentified source of transmission

Acute hypoxaemia is a life-threatening emergency. Diagnosis of the exact aetiology maybe complicated by the presence of pre-existing lung conditions. A case report is presented of a non-intubated patient with a pre-existing lung tumour who developed sudden profound hypoxaemia 3 days after emergency abdominal surgery. Definitive aetiological diagnosis was delayed due to chest X-ray features suggestive of compression and erosion of tumour tissue into the airway. Emergency computerised tomography (CT) imaging however revealed mucous plugging leading to massive atelectasis as the main aetiology.     

Incidence of and risk factors for hepatitis B virus and hepatitis C virus infection among haemodialysis and CAPD patients: evidence for environmental transmission

Hepatitis B virus (HBV) serum markers (HBsAg, anti-HBs, anti-HBc) and antihepatitis C antibody (anti-HCV) were prospectively followed in haemodialysis and CAPD patients. From January 1987 to January 1990, 185 patients on haemodialysis and 124 on CAPD were analysed. Among patients susceptible to HBV (69 on haemodialysis and 70 on CAPD), there were 17 HBsAg seroconversions on haemodialysis (0.19/patient-year) and 1 on CAPD (0.01/patient-year). A Cox proportional hazards model showed that haemodialysis treatment was the only risk factor significantly associated with HBV infection, thus suggesting transmission through the environment. Regarding hepatitis C, 83 anti-HCV-negative patients on haemodialysis and 46 on CAPD were followed. There were 18 seroconversions on haemodialysis (0.15/patient-year) and two seroconversions on CAPD (0.03/patient-year). Haemodialysis treatment was also the only risk factor significantly associated with a higher risk of HCV infection. The hazard ratio for HCV infection in haemodialysis patients was 5.7 compared to CAPD patients. Nevertheless, for one patient on CAPD treatment transfusions were the only possible source of HCV infection. In conclusion, both viruses were transmitted mainly through the haemodialysis environment, but the role of transfusions could not be excluded.     

Judgmental overshadowing: further evidence of cue interaction in contingency judgment

We investigated a phenomenon called judgmental overshadowing. Subjects predicted whether each of several patients had a disease on the basis of whether or not the patient had each of two symptoms. For all the subjects, the presence of the disease was moderately contingent on the presence of one of the symptoms (S1). In Condition 1 of our first experiment, the presence of the disease was highly contingent on the presence of the other symptom (S2). In Condition 2, the presence of the disease was independent of S2. Judgmental overshadowing occurred in that the S1-disease contingency was judged to be stronger in Condition 2 than in Condition 1. Subsequent experiments showed that judgmental overshadowing depends little on the form of the judgment, is not due to a response bias or contrast effect, and does not depend on subjects' actively diagnosing each patient. These results are consistent with, and are generally predicted by, an associative-learning model of contingency judgment.     

High prevalence of Helicobacter pylori antibodies in an institutionalized population: evidence for person-to-person transmission

OBJECTIVE: To evaluate the prevalence of H. pylori antibodies in mentally and physically handicapped adults living together in a long-term care facility. METHODS: One hundred twenty-two institutionalized subjects from six living areas were compared to a normal representative Caucasian population obtained by random sampling from the urban population area of Melbourne. Serum samples from 1977 and 1989 from 122 subjects were tested for H. pylori antibody by an ELISA technique. The data were analyzed by Student's t test, chi 2 test and logistic regression. RESULTS: Ninety-two of the 122 subjects (75%) from whom sera was collected in 1989 were seropositive for H. pylori, compared with only 23% in age- and sex-matched control subjects (p < 0.0001). The prevalence of H. pylori antibodies in 1977 was 34% (42/122). Of the remaining 80 seronegative subjects, 51 (61.4%) converted to became positive in the 12-yr interval. The annual seroconversion rate was 7.4%, with an average of 4.25 newly positive subjects each year. The prevalence of H. pylori in 1989 was significantly higher than in 1977 after adjustment for age (odds ratio 2.39, 95% CI 1.1-5.3, p = 0.03). CONCLUSIONS: H. pylori antibodies are significantly more prevalent in institutionalized adults compared with controls from the general population. These data support the hypothesis that H. pylori is acquired by either fecal-oral or oral-oral transmission.     

Fecal-oral transmission of viral hepatitis

The cumulative, subchronic and chronic toxicity of B-193 were studied on the rats and mice. It was found that this compound exerted weak tendency to cumulation in the body. Only the highest doses of B-193 (70, 40 mg/kg po for 12 weeks) caused the increase of animals mortality. Studies on subchronic and chronic toxicity have demonstrated, that B-193 administrated po or ip for 3 weeks, and po for 12 weeks, in general, neither affects the body weight gain nor the mass and morphology of heart, liver and kidneys, as well as spontaneous locomotor activity of animals. The weak depressant effect of B-193 on peripheral blood morphology was seen only after 3 weeks po or ip treatment with this compound. The moderate effect of B-193 on activity of alanine and aspartate transaminases (A1At and AspAt) and serum protein level found after 3 weeks of treatment, was no longer observed after 12 weeks of treatment. This could indicate that above effects of B-193 are reversible.     

Diphenylhydantoin-induced hepatitis: a case report

This case report is of a 25-year old man with severe diphenylhydantoin-induced hepatitis, fever, rash and generalized lymphadenopathy. Hepatic histology and lymphocyte transformation tests strongly supported the diagnosis. He made an uneventful recovery with supportive therapy.     

Treatment of chronic hepatitis C with interferon-alpha: a preliminary report

Interferon alpha (IFN-alpha) has been indicated to be dramatically effective in some but not all patients with chronic hepatitis C virus (HCV) infection. We investigated prospectively 27 patients of chronic hepatitis C, 12 females and 15 males, treated with IFN-alpha for a better regimen of the therapy and for any effective predictor of response to the treatment. All patients were treated with 3 to 6 million units (MU) of recombinant IFN-alpha 2b (n = 15) or lymphoblastoid IFN-alpha (n = 12) given 3 times weekly for 12 to 36 weeks. Patients with normal alanine aminotransferase (ALT) value during therapy, who sustained this response throughout 6 months follow-up after treatment was completed, were grouped into the complete responders. Patients with normal ALT value during therapy but who relapsed after treatment completed, were grouped as partial responders. Non-responders were defined as patients without normal ALT value during therapy. The rates of complete response, partial response, and non-response were 29.6%, 40.8%, and 29.6%, respectively. The degree of response to IFN-alpha therapy was not related to age, sex, type of IFN-alpha, history of blood transfusion, the state of liver pathology, or pretreatment level of ALT value. The complete responsive rate to IFN-alpha was higher in patients treated with total dose above 215 MU [38.1% (8/21) vs. 0% (0/6), p = 0.06], in patients treated for at least 24 weeks [40% (8/20) vs. 0% (0/7), p < 0.05], and in patients with non-genotype 1b/II HCV infection [40% (8/20) vs. 0% (0/7), p < 0.05]. We concluded that IFN-alpha was effective in the treatment of chronic HCV infection, particularly in those other than HCV genotype 1b/II. A high-dose, and long-duration regimen may be recommended for better response of chronic hepatitis C to IFN-alpha therapy.     

Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence

A case report of lethal distant myonecrosis with gas gangrene is presented. Cultures from blood and suppuration of our patient revealed Clostridium septicum. At obduction the patient appeared to have a necrotic metastasis of a known ovarian carcinoma in the cecum wall. Predisposing conditions for this type of infection are hematologic malignancies, colon carcinoma, neutropenia, diabetes mellitus, and disruption of the bowel mucosa. Clostridium septicum is highly associated with the presence of a malignancy, either known or occult at the time infection occurs. Occult tumors are mostly situated in the cecal area of the bowel. Clinical symptoms of the syndrome and therapeutic options are discussed.     

Reading epilepsy: report of five new cases and further considerations on the pathophysiology

Liposomes, microscopic lipid vesicles consisting of concentric phospholipid bilayers enclosing discrete aqueous spaces, have been investigated extensively as carries for drugs in attempts to achieve selective deposition and/or reduced toxicity. Liposomes radiolabeled with gamma emitters (67Ga, 111In and 99mTc) have been used for imaging purposes. Liposomes as formulated in the past, are rapidly taken up by cells of the mononuclear phagocyte system, primarily those located in liver and spleen. However, it has been shown during the last two decades that the in vivo behavior of liposomes can be modulated by modifying their formulation. The size and the lipid composition have a major influence on the blood clearance rate, hepatic uptake and splenic uptake of liposomes. The development of long circulating liposomes, in particular coating of the bilayer with polyethyleneglycol (PEG) resulted in liposomes that oppose recognition by the MPS, thus displaying even longer circulatory half-lives. By carefully adjusting the liposomal formulation, the in vivo characteristics of liposomes can be tailored such that they become suitable vehicles for imaging various pathological processes in vivo. Liposomes have been proposed for tumor imaging, for infection imaging and as blood pool markers. Here, the factors that determine the in vivo behavior of liposomes and the current status of liposome-based radiopharmaceuticals are reviewed.     

Vertical transmission of hepatitis E virus

Little is known about vertical transmission of hepatitis E virus from infected mothers to their infants. We studied eight babies born to mothers infected with hepatitis E in third trimester. One baby was icteric at birth with elevated transaminases and four babies had anicteric hepatitis. Two babies were born with hypothermia and hypoglycaemia and died within 24 h; one had massive hepatic necrosis. Hepatitis E virus RNA was detected by PCR in cord or birth blood samples of five infants. Six infants had evidence of hepatitis E infection. We conclude that hepatitis E virus is commonly transmitted from infected mothers to their babies with significant perinatal morbidity and mortality.     

Lexical and conceptual processing in Chinese-English bilinguals: further evidence for asymmetry

According to the asymmetry model of bilingual representation (Kroll & Stewart, 1994), the first language (L1) lexicon is closely tied to an underlying conceptual memory, whereas second language (L2) items are mostly associated with their L1 equivalents. An outcome of this architecture is that L1-to-L2, or forward, translation must be mediated by the conceptual memory, whereas L2-to-L1 (backward) translation takes a direct lexical path. Some predictions derived from this hypothetical structure were tested in the present study, which took into account, through analysis of covariance, variations in response production time, concept retrieval time, and some other characteristics associated with the individual test items. Proficient Chinese-English bilinguals were tested on delayed production (Balota & Chumbley, 1985), picture naming, word translation, and category matching. The expected asymmetrical pattern of translation latencies (i.e., forward > backward) was demonstrated, although it could be statistically explained by the item characteristic of familiarity; matching an L1 item to a category name was faster than matching an L2 item, suggesting relatively strong L1 conceptual links. The present results are best accommodated by a form of asymmetry that allows for nondominant L2-concept linkage, the use of which is conditional upon the familiarity of the test item to the bilingual.     

Labor force participation of working mothers and family formation: some further evidence

This paper offers additional insight and evidence on the well-documented inverse relationship between female employment and fertility. Interviews with 388 working mothers from a probability sample in Robeson County, North Carolina, provide the data for testing the hypothesized relationships. Generally, the results indicate that lower fertility, lower desires and expectations, and earlier use of birth control are associated with work before the first birth and with employment of the longest duration. The timing of the first birth was not differentiated by variations in work experience. The results are conditional in that the relationships hold more for whites than for blacks or Indians.     

Pyoderma gangrenosum associated with active chronic hepatitis: report of two cases

In two patients, active chronic hepatitis was complicated by the development of pyoderma gangrenosum. The favorable response of the pyodermatous lesions to azathioprine therapy suggests that this drug may be of value in treating this disorder in patients for whom corticosteroid therapy produces no benefit or is contraindicated because of side effects. Azathioprine, too, is a potentially toxic drug and may need to be discontinued. Possible causal relationships between pyoderma gangrenosum and active chronic hepatitis are discussed.