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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 145 records · Page 8Linked to original sources
PubMed2000

A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates.

A human immunodeficiency virus (HIV) vaccine that will be useful in diverse geographic regions will need to induce a broad immune response characterized by cross-clade immunity. To test whether a clade B-based HIV candidate vaccine could induce interclade humoral responses, including neutralizing activity against primary HIV-1 isolates, sera were tested from recipients of a vaccine consisting of recombinant canarypox virus vCP205 and recombinant gp120(SF2). Serum antibodies exhibited strong immunochemical cross-reactivity with V3 peptides from clades B, C, and F, with weaker activity for several V3 peptides from clades A, D, G, and H; essentially no reactivity could be demonstrated with V3 peptides from clades E and O. Extensive cross-clade reactivity was also documented by enzyme-linked immunosorbent assay with all nine recombinant HIV envelope glycoproteins tested from clades B, D, and E. In addition, vaccinees' sera displayed significant neutralizing activity against 5 of 14 primary isolates tested, including one X4 virus and two dualtropic viruses (from clade B) and two R5 viruses (from clades B and C). This is the first demonstration of the induction by a candidate HIV vaccine constructed from clade B laboratory strains of HIV of neutralizing activity against R5 and clade C primary isolates. The data suggest that, by virtue of their ability to induce cross-clade immune responses, appropriately formulated HIV vaccines based on a finite number of HIV isolates may ultimately be able to protect against the wide range of HIV isolates affecting the populations of many geographic regions.

AIDS Vaccines↗
PubMed2000

[Frequency of cesarean sections in Austria].

OBJECTIVE: While there exist detailed reports on the frequency of cesarean sections in many European countries, there are only selective data of single centers available in Austria. Thus this study aims at evaluating the present frequency of cesarean sections in Austria. METHODS: To achieve this aim, we analyzed all births during the years 1996 (n = 89,208), 1997 (n = 84,408) and 1998 (n = 81,568). Along with the general mean rate of sections, we also describe the influences of the duration of pregnancy, of the birth weight, and of the number of paturitions. The data were statistically evaluated by chi-square test. RESULTS: During the study period, the frequence of sections rose from 13.08% (1996) to 14.0% (1997) and to 14.55% (1998). This rise proved to be statistically significant (p = 0.0001). 47% of premature births (< or = 35th week of gestation) are delivered by cesarean section. This rate drops to only 13.24% after the 35th week of gestation. Yet, more than half of pregnancies with dystrophic children (<2,000 g) are delivered by cesarean section even after the 35th week of gestation. Primigravidae have to expect section in 17% of the cases (1998); the section rate diminishes continuously, however, with increasing number of pregnancies. CONCLUSIONS: Following the general trend, the frequency of cesarean sections is continuously rising in Austria too. The present study can serve as a basis for international comparisons as well as for measures of intradepartmental quality control.

Austria↗
PubMed2000

The thioredoxin boxes of thyroglobulin: possible implications for intermolecular disulfide bond formation in the follicle lumen.

Multimerization of thyroglobulin (TG) takes place extracellularly in the thyroid follicle lumen and is regarded as a mechanism to store TG at high concentrations. Human thyroglobulin (hTG) has been shown to multimerize mainly by intermolecular disulfide cross-links. We recently noted that TG of various mammalian species contains three highly conserved thioredoxin boxes (CXXC). This sequence is known to underlie the enzymatic activity of protein disulfide isomerase (PDI). As hTG formed intermolecular disulfide bonds in the absence of other proteins depending on the redox conditions and hTG concentration, the CXXC-boxes of TG might provide the structural basis for self-assisted intermolecular cross-linking. To test this hypothesis we prepared a recombinant TG fragment containing the three thioredoxin boxes. This fragment exhibited a redox activity amounting to about 10% of the activity of PDI at redox conditions supposed to be present in the extracellular space. This activity might be supplemented by the oxidizing system of the apical cell surfaces of thyrocytes facing the follicle lumen. Indeed, incubation of hTG with peroxidase and H202 resulted in intermolecular disulfide bridge formation. Our results suggest a combined mechanism of self-assisted and peroxidase-mediated disulfide bond formation leading to the intermolecular cross-linking of lumenal hTG.

Animals↗
PubMed2000

Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death.

Recently, we have demonstrated that human platelet antigen 1b (HPA-1b or P1A2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-lb does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-lb on the outcome in patients after coronary-artery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronary-artery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-lb was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA-1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-lb had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Aged↗
PubMed2000

Reconstruction of the contracted ocular socket with free full-thickness mucosa graft.

Patients who have undergone enucleation of the eye can be treated with glass eye prostheses, provided retention is adequate. Inadequate retention due to contraction of the conjunctival mucosa is a common problem which frequently affects the lower fornix first. This can be corrected using a free full-thickness buccal mucosa graft. Indications, operative procedures and postoperative results are presented.

Adult↗
PubMed2000

Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study.

AIM: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. METHODS: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy or clinical follow-up. RESULTS: Group I: out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. CONCLUSION: Further studies are required to demonstrate if WB PET can become a reliable non-invasive alternative to surgery in the characterization of the SLN. WB PET is important as a baseline in primary localized melanoma and decisively impacts patient management in metastatic melanoma.

Adult↗
PubMed2000

Mental fatigue and task control: planning and preparation.

The effects of mental fatigue on planning and preparation for future actions were examined, using a task switching paradigm. Fatigue was induced by "time on task," with subjects performing a switch task continuously for 2 hr. Subjects had to alternate between tasks on every second trial, so that a new task set was required on every second trial. Manipulations of response-stimulus intervals (RSIs) were used to examine whether subjects prepared themselves for the task change. Behavioral measurements, event-related potentials (ERPs), and mood questionnaires were used to assess the effects of mental fatigue. Reaction times (RTs) were faster on trials in which no change in task set was required in comparison with switch trials, requiring a new task set. Long RSIs were used efficiently to prepare for the processing of subsequent stimuli. With increasing mental fatigue, preparation processes seemed to become less adequate and the number of errors increased. A clear poststimulus parietal negativity was observed on repetition trials, which reduced with time on task. This attention-related component was less pronounced in switch trials; instead, ERPs elicited in switch trials showed a clear frontal negativity. This negativity was also diminished by time on task. ERP differences between repetition and switch trials became smaller with increasing time on task.

Adolescent↗
PubMed2000

[Primary aortoenteric fistula].

Aortoenteric fistulas are a very unlikely cause of digestive bleeding. We present the case of a fifty six year old patient with a primary aortoduodenal fistula who consulted because of melena and a pulsating abdominal mass. He underwent three digestive endoscopies without arriving at any diagnosis. A computed axial tomography and an angiography showed an aneurysm of the abdominal aorta. With an exploring laparotomy a fistula was identified between the aneurysm and the fourth portion of the duodenum. An aortoaortic bypass was carried out followed by a surgical fix of the duodenum. The patient was released six days after the operation.

Aortic Aneurysm, Abdominal↗
PubMed1999

Echovirus 9 strain barty non-structural protein 2C has NTPase activity.

Non-structural protein 2C is known to play a fundamental role in the replication of picornaviruses. Sequence analyses revealed that 2C belongs to a rapidly expanding group of proteins containing a consensus sequence for nucleotide binding (NTB). We report that echovirus 9 polypeptide 2C displays NTPase activity in vitro. In our experiments, several P2 genes were expressed in Escherichia coli as fusion proteins linked to glutathione S-transferase (GST) prior to purification close to homogeneity. In contrast to GST-2B, both GST-2C and GST-2BC showed ATPase as well as GTPase activity indicating that the site for NTB binding and splitting is located in 2C.

Acid Anhydride Hydrolases↗
PubMed1999

Lymphadenectomy in primary carcinoma of the Fallopian tube.

OBJECTIVE: The bad prognosis of primary carcinoma of the Fallopian tube is ascribed to early lymphogenous metastasis. Due to the rarity of cases, there exist only few and divergent results on the importance of lymph node metastasis in the relevant literature. Thus, our study aimed at detecting the incidence of lymph node metastases and their influence on overall survival, as well as at evaluating the therapeutic effect of radical lymphadenectomy. METHODS: We studied 158 cases of primary carcinoma of the Fallopian tube in a retrospective multicenter analysis. Group I (n = 38) consisted of patients who were subjected to radical pelvic and para-aortic lymphadenectomy in addition to total abdominal hysterectomy, bilateral adenectomy and omentectomy. The control group II (n = 71) underwent the same surgical procedures but without radical lymphadenectomy. Patients who received post-operative irradiation (n = 49) were excluded from the study. RESULTS: On average, 38 lymph nodes (range 12-68) were extirpated. In group I 42.1% of the cases showed lymph node metastases. Lymphatic dissemination was observed only after the carcinoma had spread beyond the organ (intraabdominal stage II); the incidence of lymph node metastases rose significantly (P = 0.02) with growing intraperitoneal tumour masses. Pelvic and para-aortic metastases occur simultaneously. Overall survival with tumour of equal size is markedly, but not significantly reduced (P = 0.18) if the lymph nodes are involved. If, however, radical lymphadenectomy is performed (group I) the median survival time increases to 43 months (95% confidence-interval 20-66), compared with 21 months (95% confidence-interval 10-32) in group II (P = 0.095). CONCLUSION: Correct staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy. Radical lymphadenectomy in tumours of equal size may markedly prolong survival.

Carcinoma↗
PubMed1999

AIDS and HIV vaccines.

In spite of extensive prevention programs, the HIV epidemics is still spreading worldwide, in particularly in developing countries where clade C viruses predominate. WHO estimates that there are 16, 000 new cases of HIV infection daily and that 100 M individuals will be infected by the end of the next decade. In spite of its spectacular results in seropositive patients, high-activity antiretroviral therapy (HAART) cannot eradicate the virus and is faced with side-effects, problems of compliance and the emergence of drug-resistant viruses. Furthermore, its prohibitive cost severely limits its use in developing countries. Therefore, the development of a preventive vaccine remains the best strategy to control the HIV-1 epidemics and a public health priority. However, the development of such a vaccine remains a formidable challenge to both the industry and the scientific community (Burton DR, More JP. Why do we not have an HIV vaccine and how can we make one? Nat Med 1998;4:495-8).

AIDS Vaccines↗
PubMed1999

Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer.

BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.

Aged↗
PubMed1999

Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS).

There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine.

Adolescent↗
PubMed1999

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

AIDS Vaccines↗