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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 109 records · Page 6Linked to original sources

Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime.

Human immunodeficiency virus (HIV) vaccine candidates were previously constructed as a string of cytotoxic T lymphocyte (CTL) epitopes delivered and expressed using DNA and modified virus Ankara (MVA; an attenuated vaccinia virus) vectors. These vaccines were shown to induce interferon (IFN)-gamma-producing and cytolytic CD8+ T cells after a single vaccine administration. In the course of this work, immunization protocols were sought which would improve the levels of induced HIV-specific T cells. It was found that previous immunological exposure to MVA reduced the efficiency of subsequent priming and boosting using the same vaccine vehicle. However, a combined regime whereby the animals were first primed with the DNA vaccine and then boosted with MVA was the most potent protocol for the induction of both interferon-gamma-producing and cytolytic T cells against two CTL epitopes simultaneously. The general applicability of this novel vaccination method for induction of major histocompatibility complex class I-restricted T cells is discussed.

Animals↗

Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara.

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.

Animals↗

Primordial role of CD34+ 38- cells in early and late trilineage haemopoietic engraftment after autologous blood cell transplantation.

In order to better define which cell subset contained in graft products might be the most predictive of haemopoietic recovery following autologous blood cell transplantation (ABCT), the relationships between the amounts of reinfused mononuclear cells (MNC), CFU-GM, total CD34+ cells and their CD33 and CD38 subsets. and the successive stages of trilineage engraftment kinetics, were studied in 45 cancer patients, using the Spearman correlation test, a linear regression model and a log-inverse model. No relationship was found between the infused numbers of MNC, CD33+ and CD33- subsets observed and the numbers of days to reach predetermined absolute neutrophil (ANC), platelet and reticulocyte counts. The infused numbers of CFU-GM, CD34+ and CD34+ 38+ cells correlated inconstantly with haemopoietic recovery parameters. The strongest and the most constant correlations were significantly observed between the infused numbers of CD34+ 38- cells and each trilineage engraftment parameter. The log-inverse model determined a threshold dose of 0.05 x 10(6) (= 5 x 10(4)) CD34+ 38- cells/kg, below which the trilineage engraftment kinetics were significantly slower and unpredictable. Post-transplant TBI-conditioning regimens increased the low cell dose-related delay of engraftment kinetics whereas post-transplant administration of haemopoietic growth factors (HGF) seemed to abrogate this delay. This would justify clinical use of HGF only in patients transplanted with CD34+ 38- cell amounts lower than the proposed threshold value. This study suggests that the CD34+ 38- subpopulation, although essentially participating in late complete haemopoietic recovery, is also composed of committed progenitor cells involved in early trilineage engraftment.

ADP-ribosyl Cyclase↗

Millard repair of unilateral isolated cleft lip: a 25-year follow-up.

Twenty-five patients with isolated unilateral cleft lip took part in a follow-up study at a mean age of 28.6 years. All had had a primary, Millard lip repair, at a mean age of 4.6 months. In 20 patients, at least one secondary correction had been undertaken during adolescence. The overall long-term outcome was thought to be good, leaving a fairly inconspicuous fine lip scar and acceptable nose configuration. In half the patients, however, the lip was slightly elongated and the nostrils were still asymmetrical. These findings concurred with the patients' subjective assessments, which showed that appearance of the lip and nose were rated good by 20 (80%) and 16 (64%), respectively. The findings of this study provide a baseline for future evaluation of the results achieved with lip closure by Johanson's technique.

Adolescent↗

Morphometry in digital photographs: a promising technique for assessing patients with cleft lip and palate.

As digital photography is being increasingly used in clinical medicine, we devised a software program for 'on screen' image analysis, which allows distance, angle, and area to be measured. In this study, 30 photos were evaluated by 10 observers, so 3000 observations were used to test the reproducibility of the measurements. The results showed excellent reproducibility within observer, between observers, and between photographs. The coefficient of variation (CV) ranged from 0 to 1.3% for distance, from 0.6 to 2.3% for angle, and from 1.5 to 7.7% for area. The system could be particularly useful for assessing patients with cleft lip and palate.

Cleft Lip↗

Clinical examination compared with morphometry of digital photographs for evaluation of repaired cleft lips.

Twenty-four adult patients who had been operated on as infants for isolated cleft lip underwent clinical examination combined with photographic documentation using a digital camera. The same predetermined protocol comprising 20 variables describing nasolabial appearance was used for both the clinical examination and the computerised evaluation of the images. The correlation between the two methods is described in the present study. The results obtained with the two methods agreed closely. For metric variables the mean coefficient of correlation was 0.73 and when all measurements were combined, it reached 0.98. Likewise, discrete variables showed a close correlation, with a mean kappa value of 0.72. Variables related to muscular dynamics of the lip can for obvious reasons not be judged from photographs. However, the computerised photographic evaluation was able to detect more precisely even minor angular deviations of the nose and to measure areas such as the areas of the nostrils. We conclude that morphometry of digital photographs is a new valuable clinical tool for the assessment of the nasolabial appearance in patients with cleft lip and palate.

Adult↗

Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

A vaccine against human immunodeficiency virus (HIV) is still awaited. Although the correlates of protection remain elusive, it is likely that CD8+ T cells play an important role in the control of this infection. To firmly establish the importance of these cells in protective immunity, a means of efficient elicitation of CD8+ T cell responses in the absence of antibody is needed and, when available, might represent a crucial step towards a protective vaccine. Here, a novel vaccine candidate was constructed as a multi-cytotoxic T lymphocyte (CTL) epitope gene delivered and expressed using modified vaccinia virus Ankara (MVA). The immunogen consists of 20 human, one murine and three rhesus macaque epitopes. The non-human epitopes were included so that the vaccine can be tested for immunogenicity and optimal vaccination doses, routes and regimes in experimental animals. Mice were immunized intravenously (i.v.) or intramuscularly (i.m.) using a single dose of 10(6) p.f.u. of the recombinant MVA and the induction of CTL was assessed. It was demonstrated that both administration routes induced specific CTL responses and that the i.v. route was moderately more immunogenic than the i.m. route. The frequencies of ex vivo splenocytes producing interferon-y upon MHC class I-restricted peptide stimulation were determined using an ELISPOT assay. Also, the correct processing and presentation of some HLA-restricted epitopes in human cells was confirmed.

AIDS Vaccines↗

Birth weight, body length, and cranial circumference in newborns with cleft lip or palate.

OBJECTIVE: This paper reports on birth weight, body length, body mass index, and cranial circumference at birth of infants with cleft lip and/or palate born between 1973 and 1992. METHODS: Data were obtained from two nationwide Swedish health registries. Infants with syndromes, twins, and infants with immigrant parentage were excluded from the study. Comparisons were made with all singleton births with the same exclusion criteria (n = 2,031,140). RESULTS: The body dimensions of infants with isolated cleft lip (n = 865) were found not to differ from those of control subjects, but infants with isolated cleft palate (n = 811) or cleft lip and palate (n = 1139) were found to be lighter and shorter than control subjects. Also, infants with the Pierre Robin sequence (n = 121) had a tendency to be lighter and shorter than control subjects, but these differences did not reach statistical significance despite the large study population.

Birth Weight↗

A US experience: consumer responsive quality of life measurement.

OBJECTIVE: In the United States, interest in quality of life and social disabilities associated with mental illness intensified in the wake of the deinstitutionalization of the late '60s and '70s. Although mental health professionals in the United States have begun to recognize the importance of quality of life considerations to patient management and treatment outcomes, review of the literature shows there is minimal research in mental health on this important topic. As a result, little theoretical or methodological progress has been made. Quality of life has not been clearly conceptualized or defined and there are no agreed-upon standards or criteria for measurement. This presentation will: (a) review important conceptual issues in quality of life research, (b) discuss the benefits of and obstacles to incorporating consumer values in judgments of quality of life, and (c) present data from the Wisconsin Quality of Life Index (W-QLI; Becker et al., 1993) to illustrate the usefulness of a consumer responsive model of quality of life and the importance of incorporating consumer values in the assessment of quality of life of persons with schizophrenia. METHODS: The W-QLI was administered to a convenience sample of psychiatric outpatients with a DSM-IV diagnosis of schizophrenia. The W-QLI is a self-administered individually preference-weighted index that measures nine separate domains encompassing quality of life. The W-QLI scoring method results in separate scores for each domain and allows for the relationships among separate domains to be studied. The nine separate domains include: (a) satisfaction level for different objective quality of life indicators, (b) occupational activities, (c) psychological well-being, (d) physical health, (e) social relations, (f) economics, (g) activities of daily living, (h) symptoms, and (i) goal attainment. RESULTS: Study findings are consistent with previous theory and empirical research which supports the independence of component quality of life domains. Results show that while consumers' and clinicians' judgments of outcome correlated, there were important differences. Clinicians systematically rated function higher and social relations lower than did consumers, and there were significant differences in consumer and provider goals for improvement with treatment. Overall ratings of quality of life and function are only weakly correlated with psychopathology. The findings support the importance and feasibility of incorporating consumer values and judgments of quality of life in outcome measurement.

Adult↗

[Contribution to the treatment of displacement of the ascendant colon in the spleen-kidney area].

Objective to this field study was to find an alternative to rolling a colic patient with left dorsal displacement under general anesthesia. For that purpose a total of 49 horses with a complete nephrosplenic entrapment out of 542 colic patients presented at the Tierklinik Kerken in 1996 were retrospectively evaluated. Having performed a preliminary colic examination and initial treatment if needed, horses which did not undergo surgery immediately where left loose in a small sized arena to move and roll themselves under observation. According to the results of further exams, horses were left in the arena until the displacement was corrected and were only treated if needed or underwent surgery. In 42 (85.7%) out of the 49 horses that were sent in for left dorsal displacement, the entrapment resolved itself within a period of 30 minutes to 48 hours (phi 12.1 +/- 10.4 hours) through walking and rolling themselves. Seven horses (14.3%) needed surgery (midline laparotomy) due to worsening of the general condition, repeated overload of the stomach or more dramatic colic symptoms. Two horses (4.1%) developed a gastroduodenojejunitis or thyphlocolitis postoperatively and were euthanized. The results showed that individual rolling of colic patients versus rolling under general anesthesia as a means of therapy in cases of nephrosplenic entrapment has higher success rates and also reduces the risk for the horses as no general anesthesia is necessary.

Animals↗

Orthotopic liver transplantation for hepatic associated metabolic disorders.

Hepatic associated metabolic disorders represent 5% of the indications for orthotopic liver transplantation (OLTX) according to the European Liver Transplant Registry. We studied the outcome of this group at our institution after OLTX and combined liver/kidney transplantation. Between September 1988 and January 1997, 837 OLTXs were performed in 735 patients. Patient survival and graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr, range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7), hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n = 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1), ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering from primary hyperoxaluria type I received combined liver/kidney grafts. Survival rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant lymphoma 5 months after transplantation. One patient required retransplantation 2 months after OLTX following arterial thrombosis and ischemic type biliary lesion. One year after OLTX, all patients demonstrated good graft function, liver grafts (ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/- 15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX, respectively combined OLTX/NTX, represent a successful therapy for hepatic associated metabolic disorders. Survival rates and graft function are similar to those in liver graft recipients for established indications at our institution. OLTX seems to be an excellent treatment for hepatic based therapy resistant neurological disorders.

Adolescent↗

Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma.

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.

Adenocarcinoma↗

Cloning and sequencing of ribosomal protein L27a and a gene similar to human GS1 in Drosophila.

Two closely linked genes were identified and characterized in the 24F region on the left arm of chromosome 2 in Drosophila. One cDNA predicts a protein of 231 amino acids, with a molecular mass of 25.7 kDa. The predicted amino-acid sequence of this protein is 47.2% identical to that of the previously reported human GS1 protein, which is encoded by a gene that is of interest because it is one of the few X-linked genes that escapes X-inactivation. We have accordingly named our gene GS1like (GS1l). The second cDNA begins 383 bp proximal to the first. This cDNA encodes a protein of a predicted 149 amino acids and a molecular mass of 17.0 kDa. This protein represents a homolog of ribosomal protein L27a; thus, we have named the gene RpL27a. This gene might be responsible for the Minute mutation located at 24F. An rpL27a gene was previously localized to 87F/88A; thus, this gene might be present in two locations in Drosophila.

Amino Acid Sequence↗