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Biomedical subjects

T Jelinek

Publications and source records attributed to T Jelinek.

At least 73 records · Page 4Linked to original sources

Japanese encephalitis vaccine in travellers. Is wider use prudent?

Vaccination against Japanese encephalitis has been carried out extensively in many Asian countries for the past 20 years and is also increasingly recommended for travellers to endemic areas. Although the currently available vaccine, manufactured from mouse brain, is generally considered to be highly effective and of low reactogenicity, approximately 50% of vaccinees report experiencing usually mild adverse effects following vaccination. Concern has been raised regarding potential neurological adverse effects but the incidence of such effects appears to be very low (around 1 to 2.3 per 1000000 vaccinations). Routine vaccination of all travellers to endemic areas is clearly not beneficial at this moment and use of the vaccine should remain restricted to persons spending a month or longer in endemic areas, especially rural areas, during the transmission season. However, when counselling individual travellers, it has to be kept in mind that the possibility of Japanese encephalitis can never be ruled out completely when travelling to endemic areas, and that such an infection can prove disastrous for the individual concerned.

Animals↗

[Cross reactions of patients with acute dengue fever to tick-borne encephalitis].

Sera from 20 patients with acute dengue fever were tested on their cross reactivities to other flaviviruses, especially against tick-borne encephalitis (TBE). One of the test systems used, indirect immunofluorescence (IIFT), was shown to exhibit strong cross reactivity. The reactivity pattern of sera from patients with pre-existing vaccine-induced antibodies against TBE or yellow fever was found similar to dengue secondary antibody response. In plaque reduction neutralization tests (PRNT) no cross reactions between different flaviviruses were found. The results show that PRNT is the most specific test system for differentiation of flavivirus antibodies.

Acute Disease↗

[Determination of actual risk factors for malaria infection for travelers by means of measurement of circumsporozoite antibodies].

Measurement of antibodies to circumsporozoite (CS) antigen of Plasmodium falciparum can be used as reliable indicator of malaria transmission in endemic areas. Sensitivity and specificity of an ELISA testkit for the detection of CS antibodies were assessed. In a second step, in order to estimate the actual rate of malaria infection, the prevalence of CS antibodies in serum was investigated in a selected population of travellers returning from sub-Saharan Africa and presenting without any clinical sign of malaria by use of an ELISA. CS antibodies could be detected in 47 out of the 222 investigated patients (21.2%), while 175 (78.8%) tested negative. Both groups did not differ in sex, age, destination or duration of journey or symptoms after return. There was, however, a considerable difference in travel type noticeable: 134 out of the 175 CS-negative patients (76.6%) travelled on a package tour, while this was only true for 8 out of the 47 CS-positive patients (17%, p < 0.001). These data demonstrate the importance of adequate malaria chemoprophylaxis in non-immune travellers to highly endemic areas.

Animals↗

Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by src.

The insulin-like growth factor type I (IGF-I) receptor can become tyrosine phosphorylated and enzymatically activated either in response to ligand or because of the activity of the Src tyrosine kinase (Peterson, J. E., Jelinek, T., Kaleko, M., Siddle, K., and Weber, M. J. (1994) J. Biol. Chem. 269, 27315-27321). The goal of the present study was to analyze the mechanistic basis and functional significance of the Src-induced phosphorylation and activation of the IGF-I receptor. 1) We mapped the sites of IGF-I receptor autophosphorylation to peptides representing three different receptor domains: tyrosines 943 and 950 in the juxtamembrane region; tyrosines 1131, 1135, and 1136 within the kinase domain; and tyrosine 1316 in the carboxyl-terminal domain. The juxtamembrane and kinase-domain peptides were phosphorylated both in vivo and in vitro. The carboxyl-terminal site, although phosphorylated in vitro and in src-transformed cells, was not a major site of ligand-induced phosphorylation in vivo. 2) We determined that the sites of Src-induced phosphorylation of the IGF-I receptor are the same as the ligand-induced autophosphorylation sites and that the Src kinase can catalyze these phosphorylations directly. 3) We showed that cells cultured from mice in which the IGF-I receptor has been knocked out by homologous recombination are defective for morphological transformation by src. Thus, the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF-I receptor, and this receptor phosphorylation and activation are essential for transformation by src.

Amino Acid Sequence↗

Risk Factors for Typhoid Fever in Travelers.

Background: The incidence of typhoid fever in the developing world remains high and has been estimated at 540 cases per 100,000 of the population per year. International travelers to such areas are at risk of infection, especially if they travel under low hygienic standards. Methods: In order to identify the risk factors leading to infection in travelers and expatriates, travel histories, anamnestic and clinical features of 31 patients with typhoid fever, who presented to a German travel clinic, were investigated. Results: Compared to the total patient population of the outpatient clinic during the period of investigation (n = 17,029 patients), patients who presented with typhoid fever were older (39 years versus 31 years, p <.001) and traveled longer (58 days versus 19 days, p <.001). While only 19.2% of the total patient population had traveled to the Indian subcontinent prior to referral, 35.4% of the patients with typhoid fever had acquired the infection there (p <.001). Similar results were obtained for South East Asia and Indonesia: twenty percent of the total patient population traveled there in contrast with 32.2% of patients with typhoid fever (p <.001). Latin America was visited by 16.3% of all patients, but only 6.4% of patients with typhoid (p <.001).

Journal Article↗

Schistosomiasis in Travelers and Expatriates.

Background: Several outbreaks of schistosomiasis among travelers, expatriates, and military serviceman have been reported in recent years. Methods: The travel histories and anamnestic and clinical features of 62 patients with schistosomiasis, who presented to a German outpatient clinic specializing in infectious and tropical diseases, were investigated to identify risk factors that could lead to infection in travelers and expatriates. Results: All patients remembered incidents that led to a likely exposure to cercariae of Schistosoma sp. Fifty nine patients (95%) acquired infection in Africa, two (3%) in South America, and one each (2% each) in Iraq and the Mekong River, respectively. The highest proportion of infection (45%) was imported from West Africa. Patients returning from West Africa reported either contact with tributaries of the Niger (including freshwater pools in the Dogon country, Mali) or with waters of the Volta River, notably Lake Volta and/or its delta. Six patients (10%) acquired infection in little-visited areas such as Central Africa and the Congo Basin. East Africa (especially Lake Victoria) and Lake Malawi contributed 14 patients (22%) to our study group; a further nine patients (14%) became infected after contact with waters of the Zambezi River. Conclusions: The most sensitive method for detection of possible infection with schistosomiasis appeared to be a combination of thorough travel history and serologic testing by indirect hemagglutination (IHA), immunofluorescence antibody test (IFAT), and enzyme-linked immunosorbent assay (ELISA). Most infections were acquired by travelers on lengthy and adventurous journeys or by expatriates venturing outside their normal areas of activity. Most patients knew that they had traveled in an area endemic for schistosomiasis, but were uninformed about behavioral risks they had taken in specific settings.

Journal Article↗

Evaluation of an antigen-capture enzyme immunoassay for detection of Entamoeba histolytica in stool samples.

In order to identify the prevalence of Entamoeba histolytica in tourists with diarrhoea returning from countries of the developing world, sensitivity and specificity of a commercially available enzyme immunoassay (EIA) kit for the detection of Entamoeba histolytica coproantigen in stool were evaluated. Five hundred seventy-seven specimens from 469 patients were examined by microscopy and EIA. Sixty-two specimens from 49 patients were considered positive for Entamoeba histolytica. Compared with microscopic examination of stool samples, the EIA was found to be slightly more sensitive (90.3% vs. 87.1%) and was 97.7% specific for Entamoeba histolytica.

Animals↗

Adverse reactions to Japanese encephalitis vaccine in travellers.

Vaccination against Japanese Encephalitis (JE) has been carried out extensively in many Asian countries for the past 20 years. The vaccine was generally considered to be effective and of low reactogenity. However, since 1989 an unusual number of systemic reactions characterized mainly by generalized urticaria and/or angioedema following JE vaccination were reported from Australia, Canada and Denmark, 860 travellers were recruited during a period of 16 months for a prospective study with the aim to investigate the type and incidence of side effects following JE vaccination (JEV) in German travellers. 826 received a primary immunization (2 injections at days 0 and 7-14) and 34 received a single booster injection. A detailed standardized questionnaire was distributed to all vaccinees after the first injection. A total of 509 questionnaires could be evaluated, which represents a return rate of 59.2%. 46% of the vaccinees reported about no adverse events at all. 54% reported about one or more adverse effects. Local reactions at the injection site were observed by 209 vaccinees, while 65 reported about systemic side effects like headache, fever, dizziness and generalized rash. There was no significant difference following first or second injection of the primary immunization or the booster injection, respectively, regarding incidence, severity or type of side effects. 2.2% of the vaccinees reporting reactions sought medical advice and 1.8% were judged unfit for work for an average of 2.2 days. The amount of systemic reactions might indicate a potential hazard of serious anaphylactic reactions. Unlike hepatitis A. Japanese encephalitis is an extremely rare disease in travellers. Therefore, the risk of acquiring the disease when travelling to affected areas without prior immunization should be considered against the risk of developing serious side effects after vaccination. We conclude that JEV should remain restricted to travellers with an increased risk of acquiring JE.

Adolescent↗

High prevalence of antibodies against circumsporozoite antigen of Plasmodium falciparum without development of symptomatic malaria in travelers returning from sub-Saharan Africa.

Circumsporozoite (CS) antibodies, indicating that falciparum malaria infection has occurred, have been shown to be reliable indicators of transmission in malaria-endemic areas. In order to estimate the actual rate of malaria infection, the prevalence of CS antibodies in serum was investigated by ELISA in a selected population of travelers returning from sub-Saharan Africa without any clinical sign of malaria. Sera from 39 (48.8%) of 80 individual travelers were positive, while this was only true for 8 (5.6%) of 142 travelers who took package tours. The risk of malaria infection was therefore 8.7 times greater for individual tourists than for package-tour travelers. These data demonstrate the importance of adequate malaria chemoprophylaxis in nonimmune travelers to areas with highly endemic disease.

Adolescent↗

Parasite-specific lactate dehydrogenase for the diagnosis of Plasmodium falciparum infection in an endemic area in west Uganda.

The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.

Humans↗

Human dirofilariasis.

BACKGROUND: Subcutaneous and pulmonary dirofilariasis in humans appears to be a frequent disease in endemic areas, notably the Mediterranean region. Following increased air travel in recent years, the incidence of human dirofilariasis has increased in tourists as well. METHODS: The clinical and parasitologic aspects in a series of six patients with cutaneous and pulmonary dirofilariasis, seen in a German unit for infectious and tropical diseases, are reviewed. RESULTS: Four patients presented with subcutaneous tumors due to infection with Dirofilaria repens, whereas two patients had pulmonary infiltrates due to the canine heartworm, D, immitis. All infections were acquired in the Mediterranean region. Symptoms were only slight and nonspecific. Eosinophilia in the blood was absent in all patients. The serum IgE levels were normal and signs of a specific humoral response to antigens of Dirofilaria spp. were absent, although slightly elevated antibody levels to antigens of Onchocerca volvulus could be demonstrated in all patients. The diagnosis was established in all patients by the surgical removal of adult worms from the lesions. Oral treatment with diethylcarbamazine (DEC) (2 mg per kg t.i.d.) over a period of 4 weeks was added to the surgical treatment in all patients. In one patient this therapy was preceded by oral ivermectine (150 mg per kg). CONCLUSIONS: Dirofilariasis has to be considered as a differential diagnosis in patients presenting with subcutaneous or pulmonary tumors after travels to endemic areas within the last few years. Effective therapy is possible by surgical removal of the adult worms and oral ivermectine plus diethylcarbamazine.

Adult↗

Ras-induced activation of Raf-1 is dependent on tyrosine phosphorylation.

Although Rafs play a central role in signal transduction, the mechanism(s) by which they become activated is poorly understood. Raf-1 activation is dependent on the protein's ability to bind Ras, but Ras binding is insufficient to activate Raf-1 tyrosine phosphorylation to this Ras-induced activation, in the absence of an over-expressed tyrosine kinase. We demonstrate that Raf-1 purified form Sf9 cells coinfected with baculovirus Ras but not Src could be inactivated by protein tyrosine phosphatase PTP-1B. 14-3-3 and Hsp90 proteins blocked both the tyrosine dephosphorylation and inactivation of Raf-1, suggesting that Raf-1 activity is phosphotyrosine dependent. In Ras-transformed NIH 3T3 cells, a minority of Raf-1 protein was membrane associated, but essentially all Raf-1 activity and Raf-1 phosphotyrosine fractionated with plasma membranes. Thus, the tyrosine-phosphorylated and active pool of Raf-1 constitute a membrane-localized subfraction which could also be inactivated with PTP-1B. By contrast, B-Raf has aspartic acid residues at positions homologous to those of the phosphorylated tyrosines (at 340 and 341) of Raf-1 and displays a high basal level of activity. B-Raf was not detectably tyrosine phosphorylated, membrane localized, or further activated upon Ras transformation, even though B-Raf has been shown to bind to Ras in vitro. We conclude that tyrosine phosphorylation is an essential component of the mechanism by which Ras activates Raf-1 kinase activity and that steady-state activated Ras is insufficient to activate B-Raf in vivo.

3T3 Cells↗

Geographic differences in the sensitivity of a polymerase chain reaction for the detection of Plasmodium falciparum infection.

The amplification of target DNA by highly specific probes using the polymerase chain reaction (PCR) provides a highly sensitive and specific method for the detection of malaria infection. The use the of PCR in settings with varying endemicity within one survey area has not been investigated intensively. Therefore, a cross-sectional study was conducted in the districts of Kabarole and Bundibugyo in western Uganda using material from three villages with different epidemiologic situations regarding malaria and DNA primers for a PCR that had shown satisfactory sensitivity and specificity in previous trials. The sensitivity of the PCR varied significantly (P < 0.001) in the three survey villages (between 63.2% and 83.9% for the primer pair K1-14-1 and between 37.9% and 69.9% for the primer pair MSP-1) and was highly linked to geographic differences and social exchanges of the inhabitants with other areas of the district. According to the results of this investigation, it is advisable not to use a single primer pair in epidemiologic field studies for the detection of falciparum malaria. The use of combined primer pairs and the frequent confirmation of the results by microscopy are recommended.

Animals↗

Giardiasis in travellers: evaluation of an antigen-capture ELISA for the detection of Giardia lamblia-antigen in stool.

Diagnosis of giardiasis relies largely on the microscopical detection of trophozoites or cysts in feces. However, this method is labour- and time-intensive and depends highly on the skill of an experienced microscopist. In order to identify the prevalence of Giardia lamblia in travellers returning from overseas, we evaluated sensitivity and specificity of a commercially available ELISA kit for the detection of Giardia-lamblia-antigen in stool. Nine hundred seventy-eight stool samples from 795 patients were examined by microscopy (iron-hematoxyilin-stain, SAF-concentration) and ELISA. Altogether, Giardia infection could be detected in 74 subjects. On evaluation of all samples, the ELISA turned out to be more sensitive than microscopy (95.5% vs. 81.8%) and 99.7% specific for Giardia lamblia. Especially with microscopy, the examination of more than one stool specimen did improve diagnostic sensitivity. It seems therefore advisable to retain the practise of examining at least three stool samples before considering a patient as not infected. The coproantigen-ELISA is especially advantageous in situations where only a single stool sample can be examined. It should not, however, replace microscopical examination of stool specimens for ova and parasites since other potential pathogens would otherwise escape detection.

Animals↗

[Severe protracted cholestasis after general anesthesia in a patient with Alagille syndrome].

A 27-year-old female patient with partial Alagille's syndrome (hypoplasia of the intrahepatic bile ducts, typical facial dysmorphism and skeletal anomalies) developed a marked cholestasis (total bilirubin 59 mg/dl), decrease of liver synthesis tests and ascites four weeks after gynecological surgery with general anesthesia involving propofol, isoflurane and nitrous oxide. Slow recovery could be achieved under treatment with ursodeoxycholic acid, spironolactone and substitution of fat-soluble vitamins A, D, E and K. Four months after admission the ascites had disappeared, liver synthesis had increased and the total bilirubin level had dropped to 3.8 mg/dl. Since all other possible causes were excluded during the hospital stay, the prolonged episode of cholestasis in this patient is best explained by the preceding general anesthesia with propofol which is known to be metabolized in the liver and impedes hepatic cytochrome P450 and hepatic blood flow.

Adult↗

Retrospective Immunodiagnosis of Malaria in Nonimmune Travelers Returning From the Tropics.

Background: Since travelers are now frequently advised to carry emergency self medication for the treatment of suspected malaria, the issue of retrospective diagnosis of malaria in nonimmune patients has recently gained more importance. Reliable methods for evaluating the frequency and justifying the use of self medication in clinically suspected malaria are warranted. Methods: One hundred and eighty-five sera from 132 nonimmune travelers returning to a nonendemic area, and with a microscopically confirmed diagnosis of malaria, were investigated for the presence of antibodies against blood stages of Plasmodium falciparum or Plasmodium vivax, by the indirect fluorescence antibody test (IFAT). Eighty-eight patients suffered from infection with P. falciparum and 44 from the infection with P. vivax. In falciparum malaria, 97.1% of patients had positive reactions during a period of 15-60 days after onset of symptoms. During the same period after onset of symptoms, significant titers were demonstrated in 88.2% of patients with vivax malaria. Extended cross-reactions between the antigens used and a wide range of interindividual differences in antibody titers were observed. One hundred sera from Germans recovering from nonmalarial febrile illnesses were used as negative control group in the investigation, of which none resulted in a positive IFAT. Conclusions: We conclude from these results that the IFAT is a specific and sensitive tool for the retrospective confirmation of malaria in the differential diagnosis of fever imported from endemic areas by nonimmune travelers. Nevertheless, when dealing with the individual patient, a careful interpretation, with inclusion of all available clinical data, is mandatory. However, by using blood stage antigens, the IFAT can be considered a sensitive tool in epidemiologic surveys. The tool can be used with a high degree of reliability, even without access to additional clinical data.

Journal Article↗

[Epidemiology of echinococcosis in Bavaria].

OBJECTIVE: There are few and incomplete data about the epidemiology of echinococcosis in Germany. The aim of this retrospective study was to collect informations about frequency and distribution of this parasitosis in one of the main endemic regions (Bavaria). PATIENTS AND METHODS: Standardized questionnaires were sent to all Bavarian hospitals, requesting (anonymous) information about all patients with echinococcosis seen between 1985 and 1989. In addition, hospital statistics and archives were searched for echinococcosis cases. A total of 216 cases were found; sufficient data were available for 181 (87 males, 94 females; mean age 41 [4-79] years). There were 123 patients with cystic echinococcosis (infection with the larval stage of Echinococcus granulosus), 58 with the alveolar form (larval stage of Echinococcus multilocularis). In the remaining 35 the available information was inadequate for reliable differentiation. RESULTS: The data indicate a prevalence of echinococcosis in Bavaria of 1.9 per 100,000 inhabitants, 1.1 for Echinococcus granulosus and 0.5 for Echinococcus multilocularis. The mean annual incidence was 0.22 (Echinococcus granulosus 0.15; Echinococcus multilocularis 0.03). Dividing the patients by country of origin, 86.2% of those with Echinococcus multilocularis were German, while 68.3% of those with Echinococcus granulosus originated from outside Germany, mostly the Mediterranean area. The prevalence of Echinococcus multilocularis infection was highest in the District of Swabia (2.4/100,000) and Upper Bavaria (0.6/100,000). These are regions in which there is a proven significantly higher infestation of echinococcosis in foxes. Farmers were most at risk of being infected with alveolar echinococcosis.

Adolescent↗

Reversal of Raf-1 activation by purified and membrane-associated protein phosphatases.

The Raf-1 protein kinase participates in transduction of mitogenic signals, but its mechanisms of activation are incompletely understood. Treatment of human Raf-1 purified from insect Sf9 cells co-expressing c-H-Ras and Src(Y527F) (in which phenylalanine replaces tyrosine at residue 527) with either serine-threonine or tyrosine phosphatases resulted in enzymatic inactivation of Raf-1. Inactivation of purified Raf-1 was blocked by addition of either the 14-3-3 zeta protein or heat shock protein 90. Loading of plasma membranes from transformed cells with guanosine triphosphate (GTP) resulted in inactivation of endogenous or exogenous Raf-1; inactivation was blocked by inclusion of protein phosphatase inhibitors. These results suggest the existence of protein phosphatases in the cell membrane that are regulated by GTP and are responsible for Raf-1 inactivation.

14-3-3 Proteins↗