Biomedical subjects

R Busch

Publications and source records attributed to R Busch.

At least 55 records · Page 3Linked to original sources

PubMed1998

Formation of a highly peptide-receptive state of class II MHC.

Peptide binding to class II MHC proteins occurs in acidic endosomal compartments following dissociation of class II-associated invariant chain peptide (CLIP). Based on peptide binding both to empty class II MHC and to molecules preloaded with peptides including CLIP, we find evidence for two isomeric forms of empty MHC. One (inactive) does not bind peptide. The other (active) binds peptide rapidly, with k(on) 1000-fold faster than previous estimates. The active isomer can be formed either by slow isomerization of the inactive molecule or by dissociation of a preformed peptide/MHC complex. In the absence of peptide, the active isomer is unstable, rapidly converting to the inactive isomer. These results demonstrate that fast peptide binding is an inherent property of one isomer of empty class II MHC. Dissociation of peptides such as CLIP yields this transient, peptide-receptive isomer.

Amino Acid Sequence↗

PubMed1998

[Perceptive and instrumental examination of voice quality in patients with lip-jaw-palate clefts].

BACKGROUND: In Anglo-American literature, prevalences as high as 41% are reported for voice disorders in cleft lip and palate (CLP) patients. Because of considerable variability in the reported findings and because no prevalence data are available for the German-speaking area, a screening study was conducted. METHOD: 154 patients with CLP were examined. Voice quality was assessed perceptively according to the rbh-system (roughness, breathiness, hoarseness). Suprasegmentals and nasal resonance were also assessed. Using a new computer programme for the apparative analysis of voice quality, data for pitch, intensity and pertubation (jitter and shimmer) were obtained for 4 sustained vowels. RESULTS: Based on perceptual analysis, we found that the prevalence of severe voice disorders in CLP patients was 6.5% which is lower than reported in most other studies. The incidence of voice disorders in CLP patients is numerically only slightly higher than in the normal population. The acoustic measurements confirm the results of perceptual analysis. Since the prevalence of severe voice disorders was low, none of the pertubation quotients differentiated between modal and disordered voices. A weak correlation was found between jitter and the ratings for hoarseness. CONCLUSIONS: 1. While it is appropriate to assume a higher potential risk for vocal dysfunction in CLP patients the actual prevalence in the patients examined is numerically only slightly higher than in normals. 2. For patients with voice disorders, apparative diagnostics of voice quality is a useful and practical adjunct to perceptual analysis which helps profiling individual patients and helps the professional to make decisions for therapy.

Adolescent↗

PubMed1998

Prognostic factors in resected primary small bowel tumors.

We report a retrospective analysis of 71 patients, operated for primary small bowel tumors (SBT): 47 malignant (66.2%) and 24 benign (33.8%) tumors. Of the malignant tumors, adenocarcinomas predominated (38.3%), followed by neuroendocrine tumors (31.9%), Non-Hodgkin lymphomas (NHL) (12.8%), leiomyosarcomas (10.6%) and other rare entities (6.4%). Morbidity of surgical treatment was 16. 9%, 30-day mortality 7%. The estimated 5-year survival rate in malignant lesions was 31.8%. Univariate analysis identified the presence of distant metastasis and the resection status (R status) as prognostic factors (p = 0.034 and p = 0.001). There was no influence of T, N status or grading on survival. A complete macroscopic and microscopic tumor resection has to be the aim of any curative surgical approach in patients with SBT.

Adenocarcinoma↗

PubMed1998

[Psychological comorbidity in patients with alarming chest pain symptoms].

About 1/3 of patients with chest pain undergoing coronary arteriography (CA) have no coronary artery disease (CAD). Individuals with non-CAD chest pain may be younger and more likely to be female; they may express higher degrees of neuroticism. Are those features stable enough to justifi; exclusion from CA if present? To investigate this issue, data on psychodiagnostic parameters (depression, anxiety, somatic complaints) were obtained in patients before this were referred to CA. Inclusion criteria were a chief complaint of chest pain with episodes of angina-like pain at rest, suspicious enough to warrant cardiac catherisation; and no prior history of CAD or other organic heart disease. The sample consisted of 77 patients, recruited from 89 eligible patients. 12 patients were excluded because CA findings were missing for multiple reasons. CA was conducted by Judkins technique. Patients were labeled as CAD (-) if no stenosis were detectable. In 50 (65%) of cases CA findings were positive and in 27 (35%) findings were negative. CAD+ were significantly older (p < 0.05); the superiority in both groups were male. Prevalence of emotional disorders was markedly more pronounced in both groups in comparison to the normal population and to a group of male myocardial infarction survivors. However, those features did not discriminate between the groups. Long acting chest pain was predictive for high degrees of emotional disability (relative risk 5.33; 95% Kl 1.6-61.6; p < 0.012). Chest pain at rest is a major source of anxiety, depression and subsequent somatic preoccupation despite its ischaemic or functional origin. It leads to clinically relevant adjustment disorders in a significant proportion of chest pain patients and triggers emotional disstress. These factors may thus have less impact on risk stratification than expected.

Adult↗

PubMed1997

Selective binding of bacterial toxins to major histocompatibility complex class II-expressing cells is controlled by invariant chain and HLA-DM.

Bacterial superantigens (SAgs) bind to major histocompatibility complex (MHC) class II molecules and activate T cells in a Vbeta-restricted fashion. We recently identified subsets of HLA-DR1 molecules that show selectivity for SAgs. Here, we extend these observations by showing that different cell lineages demonstrate distinct SAg-binding specificities although they all express HLA-DR1. Indeed, B cells bind staphylococcal enterotoxin A (SEA) and toxic shock syndrome toxin 1 (TSST-1) with high affinity while staphylococcal enterotoxin B (SEB) binding is barely detectable. In contrast, DR1-transfected HeLa cells show efficient binding of SEB, but not of SEA or TSST-1. We investigated the class II maturation events required for efficient interaction with SAgs and found that the ability of cells to bind and present the toxins can be drastically modulated by coexpression of the class II-associated invariant chain (Ii) and HLA-DM. SEA binding to DR1 molecules required coexpression of Ii, whereas TSST-1 binding was selectively enhanced by DM. Binding of SEB was affected by cell type-specific factors other than Ii or DM. The selectivity of SAgs for different MHC class II populations was minimally affected by HLA-DR intrinsic polymorphism and could not be explained by binding to alternative sites on DR molecules. Our results indicate that SAgs are sensitive to structural heterogeneity in class II molecules, which is consequent to the differential regulation of expression of antigen processing cofactors. Therefore, we speculate that Staphylococcus aureus have retained the ability to express numerous SAgs in adaptation to the micro-heterogeneity displayed by MHC class II molecules and that this may relate to their ability to infect different tissues.

Antigen Presentation↗

PubMed1997

[Incidence and prognostic significance of epithelioid cell reactions and microcarcinoses in regional lymph nodes in stomach carcinoma].

The frequency and prognostic relevance of sarcoid-like lesions and microcarcinosis in regional lymph nodes in gastric cancer (n = 113; pT1-3, pN0-1, pM0, R0) were investigated; the prognostic value was compared with pT and pN stage, grading and Laurén's tumor classification with Cox's multivariate regression-model. Sarcoid like lesions were found in 34% of the cases (n = 113). Statistical analysis did not indicate that they had any prognostic value or showed whether or not microcarcinosis or metastasis was present; they were independent of pT stage, histological tumor type, tumor grading, and the clinical course of disease. Microcarcinosis (defined as scattered carcinoma cells within lymph node sinuses or pulp without adjacent stromal reaction) was revealed by immunohistochemistry in 90% of pN0 cases; the presence of 3 or more tumor cells per lymph node section in over 10% of sampled lymph nodes per case carried a significant prognostic value. In microcarcinosis without evidence of metastasis, the number of tumor cells and the number of involved lymph nodes are of prognostic value. In pN1 cases microcarcinosis was found as well as the metastases in 97% and had no additional prognostic value. Microcarcinosis alone has a different significance from lymph node metastasis for prognosis.

Adenocarcinoma↗

PubMed1997

Management of 219 consecutive cases of postcatheterization pseudoaneurysm.

OBJECTIVES: We attempted to evaluate nonsurgical methods of treating postcatheterization pseudoaneurysm. BACKGROUND: The value of reapplication of a compression bandage, ultrasound-guided compression repair (UGCR) and awaiting spontaneous thrombosis in the treatment of postcatheterization pseudoaneurysms is unsettled. METHODS: We followed a stepwise treatment strategy of primarily conservative management using 1) reapplication of a compression bandage, followed by 2) UGCR, if needed, and 3) observation of the natural course. Surgical repair was reserved for patients with a rapidly expanding or complicated lesion. RESULTS: Reapplication of a compression bandage was performed in 128 patients and was successful in 32%. The success rate correlated inversely with anticoagulant therapy and the size of the aneurysm. In case of failure this pretreatment with a compression bandage significantly enhanced the success rate of subsequent UGCR (p = 0.04). UGCR was performed in 124 cases with a success rate of 84%. In 54 patients with a stable lesion, refraining from any (further) active measures resulted in spontaneous thrombosis of the aneurysm in 50 patients (93%) after 1 to 180 days (median 40 days). The course of the remaining four femoral artery aneurysms was uneventful. Definitive repair by operation or collagen plug implantation was required in only 20 patients (9%). CONCLUSIONS: The first measure performed in the treatment of pseudoaneurysms should be reapplication of a compression bandage, followed, if necessary, by UGCR. After failure of UGCR, spontaneous healing occurs in the majority of patients. Operation can be reserved for progressive and complicated lesions.

Adult↗

PubMed1997

Optimized differential diagnosis of breast lesions by combined B-mode and color Doppler sonography.

To optimize the sensitivity and specificity of gray-scale imaging and color Doppler in breast tumor diagnosis, alone and in combination, 89 women with palpable breast masses were scanned preoperatively and standard parameters were determined in both modes. Parameters significant for differentiation of benign and malignant tumors identified using univariate analysis were combined and weighted using multivariate analysis (multiple logistic regression). Histologically 59 tumors were malignant and 30 benign. Gray-scale sonography alone achieved a sensitivity of 88% and a specificity of 96% using the parameters of wall structure and posterior acoustic attenuation. Color Doppler achieved a sensitivity of 85% and a specificity of 79% using resistance index and pulsatility index as parameters. Combination of both methods yielded an accurate diagnosis in 84/87 patients (sonographic lesion correlates were absent in two cases), equivalent to a sensitivity of 97% and a specificity of 96%. Thus the individual diagnostic performance of gray-scale imaging and color Doppler sonography in palpable breast disease is further enhanced using multiple logistic regression to combine independently significant parameters.

Adult↗

PubMed1997

Eradication of Helicobacter pylori in peptic ulcer disease with amoxycillin, 2.0 g, and omeprazole, 80 or 120 mg: a prospective randomized trial.

BACKGROUND: The appropriate dose of proton pump inhibitors needed for eradicating Helicobacter pylori by dual therapy is still controversial. DESIGN: The study was conducted as a single-blind, single-centre trial. METHODS: Fifty-four patients with active duodenal ulcers were treated with amoxycillin tablets, 750 mg three times daily, and omeprazole, either 40 mg twice daily (group 1) or 40 mg three times daily (group 2), for 14 days in a prospective randomized trial. H. pylori eradication was assessed 10 weeks after starting treatment. Biopsies were taken for rapid urease tests and histological analysis and 13C-urea breath tests were ordered. RESULTS: In both groups ulcer healing was complete in 96.3% of patients after 10 weeks. Ten weeks after starting treatment, Helicobacter pylori was eradicated in 76.9% of the patients in group 1 and 74.1% of those in group 2, as shown by rapid urease tests and histological analysis. In the subgroup of fully compliant patients (n = 49) the eradication rates were 80% and 79.2%, respectively. Hyperacidity significantly reduced the eradication rates. Patients showing successful H. pylori eradication were significantly older (59 +/- 14.0 years vs. 49 +/- 15.6 years; P = 0.025). Eradication rates were lower in smokers than in non-smokers (36.4% vs. 83.9%; P = 0.006). CONCLUSION: It is concluded that higher omeprazole doses should be reserved for younger patients and smokers; in others they are not needed.

Adult↗

PubMed1997

Long-term results of the Stamey bladder neck suspension procedure: a patient questionnaire based outcome analysis.

PURPOSE: Reported success rates of the Stamey bladder neck suspension procedure vary from 39 to 91%. The disparity is substantially influenced by the methods used to assess the surgical outcome, with best results being found consistently in retrospective chart review studies. We assessed the true long-term outcome of the Stamey bladder neck suspension with a patient questionnaire based outcome analysis using strict definitions for cure and recurrence. MATERIALS AND METHODS: Of 172 consecutive patients 138 (80.2%) returned a questionnaire designed to assess the outcome of the procedure and the subjective satisfaction with the operative result. To our knowledge we report the longest mean followup for this procedure (66 months). RESULTS: Of 130 evaluable patients with hypermobility or intrinsic sphincter deficiency leading to urinary stress incontinence 65 (50.0%) remained completely continent, 15 (11.5%) never became continent and 50 (38.5%) had recurrence 6 to 90 months after initial operative success. However, approximately two-thirds of the patients believed they were cured or substantially improved more than 5 years postoperatively. CONCLUSIONS: Despite the considerable failure rate, the substantial improvement in the quality of life of almost two-thirds of the patients during long-term followup and the lack of superior techniques qualify the Stamey bladder neck suspension as a treatment of choice for urinary stress incontinence in women. We strongly emphasize the need for standardized questionnaire based outcome analyses for the evaluation of incontinence surgery.

Adult↗

PubMed1996

[Comparison of the quality of life after subtotal and total gastrectomy for stomach carcinoma].

OBJECTIVE: To compare quality of life after subtotal gastrectomy (STG) and total gastrectomy of various types, in view of the fact that, with T1 and T2 gastric carcinoma of intestinal type in the distal third of the stomach, subtotal gastrectomy is similar to total gastrectomy regarding the extent of lymphadenectomy and prognosis. PATIENTS AND METHODS: Quality of life was measured by standardised questionnaires given to 36 patients after subtotal gastrectomy (22 men, 14 women; mean age 63 [27-79] years): general physical complaints (GPC); contentment with life (CL); psychosocial stress (PSS). The results were compared with those previously obtained in 58 patients with total gastrectomy (46 men, 12 women; mean age 63.4 [36-74] years) and oesophagojejunostomy (OJS) (n = 29) or oesophagojejunoplication and pouch (OJPP) (n = 29). RESULTS: Weight loss of patients after OJPP was not significantly different from that of patients after STG, but it was significantly higher after OJS (13.5 +/- 8.6 kg; P < 0.0006). Patients with STG had significantly more general complaints (P < 0.05) and greater discontent with life (P < 0.05) than those with OJPP. Specific analysis of gastric complaints showed greatest dissatisfaction with gastrointestinal functions in patients after STG (P < 0.0004), less also after OJS compared with OJPP (P < 0.01). CONCLUSIONS: Subtotal gastrectomy for gastric carcinoma has no advantages over total gastrectomy with oesophagojejunoplication and pouch as regards weight loss, gastrointestinal complaints, psychosocial stress and general contentment. The poor quality of life seems to have its functional correlate in increased intestino-oesophageal reflux with incompetent cardia and after Billroth II reconstruction.

Adult↗

PubMed1996

Invariant chain protects class II histocompatibility antigens from binding intact polypeptides in the endoplasmic reticulum.

Unlike class I histocompatibility (MHC) antigens, most newly synthesized MHC class II molecules fail to be loaded with peptides in the endoplasmic reticulum (ER), binding instead to the invariant chain glycoprotein (Ii). Ii blocks the class II peptide binding groove until the class II:Ii complexes are transported to endosomes where Ii is removed by proteolysis, thus permitting loading with endosomal short peptides (approximately 12-25 amino acids). Ligands from which the groove is protected by Ii have not yet been identified; theoretically they could be short peptides or longer polypeptides (or both), because the class II groove is open at both ends. Here we show that in Ii- deficient cells, but not in cells expressing large amounts of Ii, a substantial fraction of class II alpha beta dimers forms specific, SDS-resistant 1:1 complexes with a variety of polypeptides. Different sets of polypeptides bound to H-2Ak, Ek, Ed and HLA-DR1 class II molecules; for Ak, a major species of Mr 50 kDa (p50) and further distinct 20 and 130 kDa polypeptides were detectable. Class II binding of p50 was characterized in detail. Point mutations within the Ak antigen binding groove destabilized the p50:class II complexes; a mutation outside the groove had no effect. A short segment of p50 was sufficient for association with Ak. The p50 polypeptide was synthesized endogenously, bound to Ak in a pre-Golgi compartment, and was transported to the cell surface in association with Ak. Thus, Ii protects the class II groove from binding endogenous, possibly misfolded polypeptides in the ER. The possibility is discussed that polypeptide binding is an ancestral function of the MHC antigen binding domain.

Animals↗

PubMed1996

Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases.

A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1-3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.

Adult↗

PubMed1996

Overexpression of human nucleolar proteins in insect cells: characterization of nucleolar protein p120.

Nucleolar p120 is a proliferation-associated protein, which becomes detectable early in the G1 phase of the cell cycle and peaks early in the S phase. A variety of human malignant tumor cells contain much higher levels of p120 than normal resting cells. The cellular functions of p120 are unknown, and little information is available on the structural characteristics of the human p120 protein. For biochemical characterization, human p120 protein was expressed in a baculovirus system and purified to approximately 95% purity. By indirect immunofluorescence, most of the recombinant human p120 as well as recombinant human B23, C23, or fibrillarin were localized to insect cell nucleoli and to large globular nuclear inclusions. Like endogenous p120 in HeLa cells, recombinant p120 expressed in insect cells was phosphorylated. On sucrose density gradients, p120 from HeLa cells sedimented in the 60-80S region, in which preribosomal particles sedimented using similar extraction and centrifugation procedures. The sedimentation of p120 shifted to the 5-10S region by treatment with 1 M KCl or with RNAse which suggests that p120 is bound to RNA.

Amino Acid Sequence↗

PubMed1996

Apolipoprotein E type 4 allele and Alzheimer's disease: effect on age at onset and relative risk in different age groups.

The effect of the apolipoprotein E (apoE) genotype on the age at onset of Alzheimer's disease (AD) and the relative risk conferred by the apoE epsilon 4 allele were studied in 91 patients and 69 healthy age-matched controls. According to the age of presentation, which varied from 44 to 95 years, subjects were divided into four groups. The inheritance of at least one epsilon 4 allele was associated with a significant reduction of the age at onset by 7.7 years among patients who were 83 years or older when examined. A weaker inverse relationship between the epsilon 4 allele and the age at onset was also observed among patients who were aged 44-63 years at presentation. The effect of the epsilon 4 allele was minimal or absent in the two intermediate age categories. The relative risk of AD conferred by the inheritance of at least one epsilon 4 allele showed no consistent age-related pattern. The overall risk expressed as an odds ratio was 5.0 (95% CI 2.4-10.5). With respect to the limitations of the study, we tentatively conclude (1) that the effect of the apoE epsilon 4 allele on the age at onset is not restricted to AD patients of a particular age, in accordance with current hypotheses on the role of apoE gene products in the biology of AD; (2) that the relative risk of AD associated with the epsilon 4 allele is not significantly modulated by age. Although the apoE epsilon 4 allele is an important susceptibility factor for AD occurring in middle age as well as in later life, it is of limited value in routine clinical diagnosis and should not be used for predictive testing in asymptomatic individuals.

Age Factors↗

PubMed1996

Developing and shedding inhibitions: how MHC class II molecules reach maturity.

Over the past year, several important advances have been made in understanding the mechanisms by which class II MHC glycoproteins acquire endosomal peptides inside antigen-presenting cells. Recent progress in the study of class II antigen presentation includes the identification of ligands from which invariant chain protects class II molecules in pre-endosomal compartments, an improved understanding of how invariant chain inhibits antigenic peptide binding, and the appreciation that HLA-DM (a factor important for antigen presentation in vivo) can act as a catalyst for peptide exchange.

Antigen Presentation↗

PubMed1996

Interferon-alpha 2b (IFN alpha) for early-phase chronic lymphocytic leukaemia with high risk for disease progression: results of a randomized multicentre study.

The efficacy of interferon-alpha 2b (IFN alpha) to prolong progression-free (PFS) and/or overall survival (OS) in early B-CLL (Binet stage A) was examined in a risk-adapted phase III study. 99 previously untreated B-CLL patients were recruited. 44 patients with expected high risk for disease progression, defined by non-nodular bone marrow infiltration and lymphocyte doubling time < or = 12 months or serum thymidine kinase levels > or = 5 U/I, were randomized to either receive IFN alpha (group 1, n = 21) or not (group 2, n = 23). 55 low-risk patients were observed to evaluate this risk stratification (group 3). During a median observation time of 36 months, four patients in the IFN alpha group achieved a partial remission (PR), no patient had stable disease (SD), and 17 patients experienced progressive disease (PD). The four responders had less extensive disease at study entry and tended to exhibit a rise in serum IgG levels. In group 2, no PR, seven SD and 16 PD, whereas in group 3, no PR, 37 SD and 18 PD occurred. PFS in group 1 (6.7 months) was not different from group 2 (13.3 months, P = 0.22), but PFS of groups 1 and 2 differed from group 3 (37 months, P < or = 0.001). OS was 44.9 months (group 1), 43.1 months (group 2) and 57.9 months (group 3). OS was not significantly different for group 1 v 2, but was significant between groups 1 and 3 (P = 0.023). The higher percentage of PD in group 2 compared to group 3 (70% v 29%) shows that the selected risk factors allow the definition of CLL stage A patients at risk for disease progression within about a year. In conclusion, our data indicate that IFN alpha does not prolong PFS or OS in stage A CLL patients with high risk for disease progression.

Aged↗

PubMed1996

Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma.

Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably heterogeneous with regard to their clinical course. The current staging systems can distinguish prognostic subgroups, but do not seem to predict the risk of disease progression of an individual patient with sufficient accuracy. Given the increase of treatment options for CLL and IC, additional parameters are needed to decide which patients may benefit from early or intensified treatment. It has been shown that two biochemical markers, serum beta 2-microglobulin (s-beta 2M) and serum thymidine kinase (s-TK), might identify CLL and IC patients at high risk of disease progression. Therefore, the prognostic value of these two serum parameters was compared with a panel of several established prognostic factors in a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean age +/- SD 63.9 +/- 10.7 years) were included. The following parameters were determined: histopathological diagnosis (IC vs. CLL), age, sex, performance status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), s-beta 2M, s-TK, serum creatinine, number of lymph node areas involved, prior therapy, and the time from diagnosis to inclusion in the study. Univariate analyses showed that nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count, blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-beta 2M, and s-TK) significantly predicted progression-free survival. In a Cox regression model, only four of these parameters provided independent prognostic information on progression-free survival: 1. s-beta 2M, 2. Karnofsky index, 3. platelet count, and 4. s-TK. The results show that s-beta 2M and s-TK independently predict progression-free survival in patients with CLL and IC, and suggest that these prognostic factors may allow an improved prediction of progression-free survival, particularly in early disease stages.

Biomarkers, Tumor↗