Biomedical subjects
Publications and source records attributed to G Heinze.
alpha-2,3-Sialyltransferase mutants of three genetically and phenotypically diverse Neisseria meningitidis strains were compared with regard to resistance to human serum and systemic spread in the infant rat. Lipopolysaccharide sialylation was found to be of minor importance for the resistance of serogroup B and C meningococcal disease isolates to complement attack.
OBJECTIVE: To help clinicians more accurately predict outcomes of treatment for depression, variables associated with recurrence of depression in the year after treatment were examined in a group of patients who completed treatment for an index episode of depression. METHODS: Forty-two depressed patients who participated in a double-blind pharmacological treatment study were followed for one year after treatment was discontinued. Length of treatment for the index episode was determined by clinicians and ranged from eight to 76 consecutive weeks. Eighteen patients who had a recurrent episode (43 percent) and 24 patients who did not (57 percent) were compared on sociodemographic and clinical variables, including scores on the Eysenck Personality Questionnaire (EPQ). RESULTS: A combination of three variables predicted recurrence of depression in 90 percent of cases. They were an elevated EPQ score on the neuroticism subscale, a short duration of treatment of the index episode, and a slow onset of response to treatment of the index episode. CONCLUSIONS: The findings suggest that personality traits, treatment duration, and variations in response to treatment might have an impact on long-term treatment outcome. Clinicians should consider these factors when making treatment decisions for depressed patients.
BACKGROUND: Adhesion molecules have been demonstrated to be involved in placental growth and development in normal pregnancy. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate serum levels of the adhesion molecule Leukocyte Functional Antigen (LFA)-3 in healthy, non pregnant, female controls, healthy pregnant women, and preeclamptic women. METHODS: In our study we included 45 healthy, non pregnant, female controls, 45 healthy pregnant women, and 45 preeclamptic women. An enzyme-linked immunosorbent assay was used to determine serum levels of LFA-3. Results were correlated to clinical data. RESULTS: The median LFA-3 serum level in healthy, non pregnant, female controls was 0.2 (range 0 to 8.6) ng/mL. LFA-3 serum levels in healthy pregnant women were 4.8 (range 0 to 18) ng/mL and were significantly elevated compared to healthy, non pregnant, female controls (Mann-Whitney U-test, p=0.004). A cut-off level of 4.8 ng/mL was selected according to the 75th quantile of serum levels measured in the panel of healthy, non pregnant, female controls. In preeclamptic women, whose pregnancies had to be terminated due to exacerbation of preeclamptic symptoms, LFA-3 serum levels above the cut-off level were seen in 14/27 (52%) cases. In contrast, preeclamptic women, who went into spontaneous labor showed elevated LFA-3 serum levels in 17/18 (95%) cases (chi-square test, p=0.002). LFA-3 serum levels revealed a statistically significant influence on the odds of termination of pregnancy due to exacerbation of preeclamptic symptoms (unconditional logistic regression, p=0.02) with an odds ratio of 0.1 (95% CI, 0.006 to 0.7) by every doubling of LFA-3 values. CONCLUSIONS: Our results suggest that LFA-3 expression is upregulated in healthy pregnant women compared to healthy, non pregnant, female controls. Failure of LFA-3 upregulation in preeclampsia is associated with an increased risk for termination of pregnancy due to exacerbation of preeclamptic symptoms.
This study sought to compare the efficacy and safety of intravenous flecainide and sotalol for immediate cardioversion of atrial fibrillation. We performed a prospective, randomized, single-blind, multicenter trial, including 106 hemodynamically stable patients with atrial fibrillation, stratified according to duration of the arrhythmia. Exclusion criteria included severely reduced left ventricular systolic function, recent antiarrhythmic therapy, and hypokalemia. Patients were randomly assigned to receive either intravenous flecainide or intravenous sotalol. Trial medication was given at a dose of 1.5 mg/kg body weight (maximum 150 mg). Overall, 28 of 54 patients (52%) given flecainide and 12 of 52 patients (23%) given sotalol converted to sinus rhythm during the first 2 hours after start of the infusion (p = 0.003). Multivariate analysis confirmed that treatment allocation to flecainide, an arrhythmia duration of < or = 24 hours, higher plasma magnesium level at baseline, higher age for men, and lower age for women independently increases the probability of conversion. The frequency of adverse effects was not significantly different in the 2 treatment groups.
OBJECTIVE: To evaluate the clinical and hormonal response of topically applied cyproterone acetate, oral cyproterone acetate, and placebo lotion in women with acne. DESIGN: Placebo-controlled, randomized study. SETTING: Patients were recruited from the Institute of Endocrine Cosmetics, Vienna, Austria. PATIENTS: Forty women with acne. INTERVENTIONS: Treatment with oral medication consisting of 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate (n=12), 20 mg of topical cyproterone acetate lotion (n=12), and placebo lotion (n=16) was offered. Patients were assessed monthly for 3 months. MAIN OUTCOME MEASURES: Clinical grading according to acne severity and lesion counts as well as determinations of serum cyproterone acetate concentrations. RESULTS: After 3 months of therapy with topical cyproterone acetate, the decrease of mean facial acne grade from 1.57 to 0.67 was significantly better (P<.05) compared with placebo (which showed a change from 1.57 to 1.25), but not compared with oral medication (1.56 to 0.75) (P>.05). Lesion counts also decreased from 35.9 to 9.1 in the topical cyproterone acetate group compared with oral medication (45.4 to 15.5) (P>.05) and placebo (38.2 to 23.1) (P<.05). After topical cyproterone acetate treatment, serum cyproterone acetate concentrations were 10 times lower than those found after oral cyproterone acetate intake. CONCLUSIONS: The therapeutic effect of topically applied cyproterone acetate for acne treatment was clearly demonstrated. Topically applied sexual steroids in combination with liposomes are as effective as oral antiandrogen medication in acne treatment, while reducing the risk of adverse effects and avoiding high serum cyproterone acetate concentrations.
Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and poor prognosis. We investigated 23 cases of UPSC. p53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8 stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P = 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of 24% compared to 100% in those in stages I and II (log-rank, P = 0.018). Myometrial invasion, lymphatic space invasion, or lymph node involvement did not correlate with the 5-year OS of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P = 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.
OBJECTIVE: Our goal was to evaluate the effect of Escherichia coli, Bacteroides fragilis, Mycoplasma hominis, and Staphylococcus aureus on cytokine and prostaglandin production by amnion cells in vitro. STUDY DESIGN: Amnion cells were obtained from women undergoing elective cesarean section before the onset of labor and cultured in a primary cell culture. Confluent amnion cells were incubated with heat-inactivated bacteria in different concentrations (10(1) to 10(6) colony-forming units/ml) for 48 hours. Samples for quantification of interleukin-1 beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and prostaglandin E2 were collected at 6, 12, 24, and 48 hours. RESULTS: Under basal conditions, minor amounts of interleukin-6 and interleukin-8 were detectable. Incubation of amnion cells with E. coli enhanced the secretion of interleukin-8 and also induced an transient increase of prostaglandin E2 in a dose-dependent manner. B. fragilis produced an increase in the secretion of interleukin-6 and interleukin-8. M. hominis and S. aureus did not cause an increase in either interleukin-6, interleukin-8, or prostaglandin E2. CONCLUSION: The gram-negative bacteria E. coli and B. fragilis stimulated interleukin-6 and interleukin-8 to a greater degree than the other bacteria investigated in this study. This finding may be of clinical interest in the onset of preterm birth.
The WT1 gene is expressed in 73-100% of patients with acute myelogenous leukemia (AML) and is thought to play a role in maintaining the viability of leukemic cells. WT1 has been proposed as a marker for minimal residual disease in leukemia. We obtained serial blood or bone marrow samples from patients with de novo AML at diagnosis, during therapy, and up to 95 months after diagnosis and analyzed for WT1 gene expression by RT-PCR to determine whether gene expression was predictive of relapse. Forty-four patients had WT1-positive AML and achieved a complete remission (CR) following chemotherapy and 24 patients underwent unrelated donor (n = 4), sibling donor (n = 13) or autologous (n = 7) marrow transplantation. After achieving CR 62% of the patients became WT1-negative, while 38% remained WT1-positive. There was no difference in the disease-free survival (DFS) and survival from remission between WT1-positive and -negative patients (P > 0.1). Following BMT, 32% of the patients analyzed in CR within the first 100 days after transplantation were WT1 PCR positive. Detection of WT1 transcripts within 100 days following BMT did not affect DFS and overall survival (OS) after transplantation (P > 0.1). Ten of 11 patients who are in continuous CR following chemotherapy or BMT for more than 3 years were transiently WT1-positive during the observation period. Four of these patients displayed the WT1 transcript at the last examination. Thirteen of 39 patients were WT1 PCR negative within 4 months before clinical onset of relapse and eight patients were WT1 PCR negative at time of relapse. These data indicate that: (1) achievement of WT1 negativity is not associated with longer DFS, survival from remission, or OS after transplantation; (2) not all patients who relapse become WT1 positive again; (3) long-term remitters frequently display the WT1 transcript. Thus, we conclude that the monitoring of WT1 gene expression by qualitative RT-PCR during treatment and CR is of very limited value.
The neisserial alpha-2,3-sialyltransferase, which is encoded by the lst gene, terminally links sialic acid to the lacto-N-neotetraose residue of neisserial lipooligosaccharide (LOS). We used the recently published nucleotide sequence of the neisserial lst gene to construct an isogenic serogroup B meningococcal lst mutant by insertion of a kanamycin resistance gene. The resulting lst mutant expressed the unsialylated lacto-N-neotetraose structure. Using bactericidal assays and an infant rat model of meningococcal infection, we were able to demonstrate that lst mutation, in contrast to galE mutation, which results in a truncated LOS, or to siaD mutation, which results in loss of the capsule, neither had an effect on resistance to normal human serum, nor did it impair the ability of meningococci to spread systemically in the non-immune host. The lst mutant was serum resistant despite of the fact that the central factor of complement activation, C3b, was deposited on the lst mutant as efficiently as it was on the galE mutant. Thus, the terminal sialic acid residue linked to the wild-type LOS inhibited C3b deposition on the meningocuccus. However, in contrast to the galE mutant, where C3b deposition is promoted by IgM binding, the lst mutant's surface is not a target for IgM molecules. Thus, the lacto-N-neotetraose residue of neisserial LOS alone, without the presence of terminal sialic acid, is sufficient to block IgM epitopes either on the LOS itself, or on other surface molecules. Our data provide further insight into the complex interplay of capsular and LOS sialic acids in serogroup B meningococci with host effector mechanisms, and suggest that LOS sialylation in meningococci is of a less central importance as it is in gonococci.
We examined the presence of WT1-specific mRNA in bone marrow samples of 125 patients with de novo acute myeloid leukemia at diagnosis by two-step RT-PCR. The sensitivity of the assay was 1:100 (first step) and 1:10000 (second step), respectively. WT1-specific mRNA was detected in 73% of patients. No correlation was found between WT1 gene expression and age, FAB type, LDH and karyotype at diagnosis. All patients were treated with standard induction chemotherapy. There was no difference in the CR rate between WT1-positive and -negative patients. Using Kaplan and Meier plot analysis we found no difference in disease-free survival (DFS) and overall survival (OS) between patients displaying the WT1 transcript and WT1-negative patients. Furthermore, no significant interactions between WT1 PCR results and age, FAB type, LDH and karyotype on DFS and OS were demonstrable using Cox regression analysis. Eight patients who were WT1 PCR positive at diagnosis and achieved complete hematological remission following chemotherapy were monitored during the course of the disease. Based on our limited data demonstrating a heterogeneity of WT1 PCR results in CR we cannot draw any conclusions regarding the usefulness of WT1 PCR analysis for the early detection of relapse. We conclude that WT1 gene expression at diagnosis is not associated with specific characteristics of AML blast cells and is not a prognostic factor for CR, remission duration and overall survival in acute myeloid leukemia.
BACKGROUND: Mice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that alpha beta T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice. AIM: To analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice. METHODS: Expression of beta-actin, IL-1 alpha, IL-1 beta, IL-6, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta 1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2-/-) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology. RESULTS: IL-2-/- mice had expressed low levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10, but not TGF-beta 1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-beta 1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IL-10, or IFN-gamma mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2-/- and IL-2+/+ mice. CONCLUSIONS: Bowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1 alpha, IL-1 beta, TNF-alpha, and IFN-gamma mRNA expression in colon tissue. Low levels of TGF-beta 1, but high levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.
Explore the source record for details and available documents.
Moclobemide is the first of a new generation of reversible inhibitors of monoamine oxidase-A (RIMA) with no clinically relevant potentiation of the hypertensive actions of dietary tyramine. The present study was conducted to compare the efficacy and safety of moclobemide with an established irreversible monoamine oxidase inhibitor, tranylcypromine, in depressed patients. Patients were randomized to receive moclobemide (81 patients) or tranylcypromine (79 patients) at individually titrated doses (100-300 mg/day of moclobemide and 10-30 mg/day of tranylcypromine) under double-blind conditions for at least four weeks, in a multicenter trial. Antidepressant efficacy was assessed using items 1-17 of the Hamilton depression rating scale (HAMD-17), the von Zerssen 'Befindlichkeits' scales, a visual analog scale and the clinicians' global impression. Both treatments resulted in significant amelioration of depression as determined by all rating instruments. HAMD-17 scores were reduced by 63% and 58% with moclobemide and tranylcypromine respectively, although the difference between the groups was not significant. The other rating instruments yielded similar results, apart from the clinician's assessment of efficacy at day 28. In this assessment, efficacy was rated as very good/good in 78% of moclobemide treated patients and in 88% of the tranylcypromine treated patients; however, only patients who had not dropped out of the trial were included in this assessment. The tolerability of both drugs was good, although moclobemide appeared to possess a small advantage in this regard since only one patient in this group was prematurely withdrawn from the trial due to inadequate tolerability/adverse events, compared with nine withdrawals in the tranylcypromine group.(ABSTRACT TRUNCATED AT 250 WORDS)
The effector function of immunocompetent cells in the gut mucosa has not yet been defined. The cytotoxic function of these cells might be important in the normal immune response and could be relevant to the mucosal damage seen in inflammatory conditions. The cytotoxic function of isolated intraepithelial and lamina propria mononuclear cells in six and 18 hour assays after the addition of various stimuli that interact with the human leukocyte antigens CD2 and CD3 on the mucosal effector cells was investigated. T cell phenotypes were determined using CD4, CD8, and HML1 to characterise cells of the appropriate compartments. Anti-CD3 and phytohaemagglutinin can induce toxic activity of lamina propria lymphocytes in most individuals after six hours and in all individuals after 18 hours. Anti-CD2, anti-CD3, and phytohaemagglutinin are similarly effective at triggering lamina propria lymphocytes. Intraepithelial lymphocytes contain predominantly CD8 and HML1 positive T cells, differentiating phenotypically intraepithelial lymphocytes from lamina propria lymphocytes. Intraepithelial lymphocytes are not cytotoxic at six hours, but have a toxic function comparable with lamina propria lymphocytes after 18 hours with all three triggers. Intraepithelial lymphocytes from inflamed mucosa (Crohn's disease and diverticulitis) mediate significantly reduced cytotoxicity in vitro compared with normal mucosa, whereas lamina propria lymphocyte toxicity is not different. Reduced numbers of cytotoxic cells and reduced reactivity to the trigger substances used after in vivo activation or cold target inhibition could explain the observed differences between intraepithelial lymphocytes from inflamed and uninflamed mucosa. Changes in cell mediated cytotoxicity of intraepithelial lymphocytes and lamina propria lymphocytes may be involved in the mucosal damage in these inflammatory conditions.
Morphological data in humans and rodents and functional data of intraepithelial lymphocytes of mice support the idea that cytotoxic cells are a significant population of the human mucosa. Previously it was shown that human IEL have no spontaneous cell-mediated cytotoxicity and that human LPL cells have anti-CD3-mediated cytotoxicity. We confirm that most individuals have anti-CD3- or PHA-mediated cytotoxicity of LPL. In IEL we do not find cytotoxic function in short-term assays. There is no difference between patients with colon cancer and inflammatory bowel disease.
Explore the source record for details and available documents.
Explore the source record for details and available documents.