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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 1,063 records · Page 59Linked to original sources
PubMedDate not supplied

X chromosome inactivation in fibroblasts of mentally retarded female carriers of the fragile site Xq27.3: application of the probe M27 beta to evaluate X inactivation status.

Over 30% of female carriers of the fragile X [fra(X)] syndrome are clinically affected. A nonrandom X chromosome inactivation in these cases could be a plausible explanation. A review of previous studies addressing this question showed inconclusive results; thus, we analysed the X inactivation pattern in fibroblasts of 4 unrelated, mentally retarded fra(X) carriers with a high expression of the fragile site Xq27.3. Using Southern analysis with a highly polymorphic probe M27 beta that recognizes methylation differences between the active and inactive X chromosome we found a 50/50 inactivation pattern in 2 cases and skewed patterns in the other 2. As biased patterns were also observed in control females we conclude that at present no evidence exists for a nonrandom X chromosome inactivation in the fra(X) syndrome in females.

Blotting, Southern↗
PubMedDate not supplied

A pipette method for rapid karyotyping in prenatal diagnosis.

The "pipette method' is introduced as a method of prenatal diagnosis which is in competition with the "in situ' and the "trypsinization' technique. It is sufficiently standardized for routine diagnosis and the banding techniques currently used in prenatal diagnosis (G, Q, C-banding and NOR) have been adapted for it. In 180 cases from 27 different centres, the "pipette method' was employed for chromosomal harvesting in order to save time. An average of 6 X 6 days was taken to achieve a result. There was a pathological karyotype in 28 cases (16.1 per cent) and this high proportion can be related to cases where ultrasound scan has led to a diagnosis of "suspected chromosomal abnormality.' This technique is also of use in advanced stages of pregnancy. The early recognition of the fetal karyotype can contribute to the future management of the pregnancy. The "pipette method' can also be used in chromosomal harvesting of tumour cells and fibroblast cultures.

Chromosome Aberrations↗
PubMedDate not supplied

Three genes with different functions in transformation are regulated by c-Myb in myeloid cells.

The proto-oncogene c-myb is constitutively expressed in murine leukemia virus-induced myeloid leukemia (MML) due to the integration of virus at this locus. Our recent focus has been the determination of genes regulated by this transcription factor that may be involved in transformation. Data presented here, using conditional expression of Myb in myeloid cells, show that c-Myb directly transactivates the endogenous c-myc and Bcl-2 genes, which explains at least in part how c-Myb regulates proliferation and survival. In addition, c-Myb prevents expression at the RNA level of the tumor suppressor INK4b gene. This gene encodes a cyclin-dependent kinase inhibitor, p15INK4b, that is normally upregulated at the mRNA level during myeloid differentiation and promotes growth arrest. The MMLs are generally characterized as differentiated monocytic tumors and possess the phenotype that is normally associated with p15INK4b expression. c-Myb inhibits expression of this gene, however, and therefore acts to promote a pathway which is abnormal in mature cells. This activity of c-Myb collaborates with its maintenance of c-myc expression to promote growth.

Animals↗
PubMedDate not supplied

Four-year experience with a recombinant hepatitis B vaccine.

Three hundred and forty-three healthy adults were vaccinated with five different lots of recombinant hepatitis B vaccine. Three hundred and forty (99.1%) individuals produced antibodies against hepatitis B surface antigen (anti-HBs). Peak anti-HBs concentrations were significantly higher in females and younger individuals. All anti-HBs positive individuals developed antibodies to the common determinant "a" of HBsAg. The vaccine was well tolerated, without severe side reactions. Persistence of anti-HBs was followed in 130 individuals for 3, and in 15 for 4 years after the first vaccination of these two groups. 21.7% and 32.3%, respectively, no longer had protective levels of anti-HBs after this time. The persistence of anti-HBs was dependent on peak anti-HBs levels, with consistent kinetics of anti-HBs decline. Revaccination of individuals whose specific antibody levels had fallen below 10 IU/l led to a prompt anti-HBs response. Comparison with individuals vaccinated with plasma-derived hepatitis B vaccine revealed no substantial differences between the two vaccines.

Adolescent↗
PubMedDate not supplied

Can MR measurement of renal artery flow and renal volume predict the outcome of percutaneous transluminal renal angioplasty?

PURPOSE: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA. METHODS: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold, cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm3). RESULTS: Clinical success was observed in patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm3 predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm3 identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001). CONCLUSION: A combination of cine phase-contrast MR renal flow and parenchymal volume measurements enables identification of patients benefiting from PTRA with a high sensitivity and NPV, but only moderate specificity and PPV.

Aged↗
PubMedDate not supplied

Treatment of inoperable tracheobronchial obstructive lesions with the Palmaz stent.

PURPOSE: The treatment of inoperable tracheobronchial stenoses with Palmaz stents is analyzed in terms of the clinical effect, typical complications, and long-term follow-up. METHODS: Twenty-seven Palmaz stents were placed in 22 patients with the help of a rigid bronchoscope. RESULTS: Stents were implanted in the distal trachea, the main bronchi, and the lower lobe bronchi. Twenty-one of 22 patients reported an immediate subjective improvement in their respiratory situation. The mean survival time was 12 months; in two patients the stents were well tolerated for up to 40 months. A redilation of three stents was successful up to 33 months. In three cases a dislocation of the stent was observed; after bronchoscopic retraction a new stent was successfully implanted in each case. CONCLUSIONoff Treatment of inoperable tracheobronchial stenoses with the Palmaz stent is a safe procedure that provides an immediate improvement of the patient's pulmonary situation. The Palmaz stent shows a minimal complication rate in the long-term follow-up.

Adult↗
PubMedDate not supplied

Pulmonary hemorrhage: imaging with a new magnetic resonance blood pool agent in conjunction with breathheld three-dimensional magnetic resonance angiography.

PURPOSE: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. METHODS: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30 degrees ) were acquired breath-held over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. RESULTS: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. CONCLUSION: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.

Adult↗
PubMedDate not supplied

[Alprostadil (PGE 1) and cyclosporin A in treatment of vasculitis in rheumatoid arthritis].

A 56-year old female patient with rheumatoid arthritis and histologically verifiable vasculitis with necrosis around the nail bed and distal phalanx gangrene on both hands as well as skin ulcers on both thighs was treated over 16 weeks with Cyclosporin A, glucocorticoids and Alprostadil. This immunosuppressive therapy resulted in a clinically relevant improvement of acral microperfusion with complete remission of nail bed necrosis and of gangrenous distal phalanxes. Due to improved tissue perfusion the deep ulcers on both thighs could granulate and were closed by proliferative connective tissue, and the high-positive immunological parameters CIC, CRP and the number of activated T-cells normalized.

Alprostadil↗
PubMedDate not supplied

Effect of phenylephrine bolus administration on left ventricular function during postural hypotension in anesthetized patients.

STUDY OBJECTIVE: To investigate the effect of intravenous (IV) phenylephrine (PHE) bolus administration on left ventricular function in patients who developed postural hypotension during isoflurane anesthesia in the head-up tilt (reverse Trendelenburg) position. DESIGN: Prospective "before-after" trial. SETTING: Operation theater of a university medical center. PATIENTS: 15 ASA physical status I and II patients without cardiovascular disorders. INTERVENTIONS: The anesthetized patients were tilted from a supine horizontal to a 30-degree reverse-Trendelenburg position. Once a steady state was achieved, PHE 3 micrograms/kg was administered as an IV bolus dose. MEASUREMENTS AND MAIN RESULTS: Transesophageal echocardiography was used to assess left ventricular function. We measured blood pressure (BP); heart rate; left ventricular end-systolic and end-diastolic area, diameter, and wall thickness; and ejection time at baseline and after tilt, immediately before and for a period of 3 minutes after PHE injection. We calculated fractional area change (FAC), mean velocity of circumferential fiber shortening (mVcf), and end-systolic wall stress. Head-up tilt caused a reduction of mean arterial pressure [from 68 to 54 mmHg (mean)], end-systolic and end-diastolic left ventricular area (from 9.7 to 6.5 cm2 and from 19.2 to 13.1 cm2, respectively) and end-systolic wall stress (from 56 to 33 10(3).dyne/cm2). FAC and mVcf remained unaltered. PHE administration restored baseline values or overcompensated the changes caused by tilt. FAC slightly decreased in response to PHE (from 0.51 to 0.43), end-systolic wall stress increased to 83 10(3).dyne/cm2, and mVcf remained unchanged. CONCLUSION: PHE bolus administration effectively restored BP and cardiac filling, which were reduced after head-up tilt, without causing a relevant impairment of left ventricular function or an increase in end-systolic wall stress above the upper normal limit.

Adult↗
PubMedDate not supplied

The relationship between fibromyalgia and interstitial cystitis.

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and fibromyalgia respectively, both disorders share a number of features, including similar demographics, "allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were questioned regarding current symptomatology. A dolorimeter examination was also performed in the three groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder.

Adult↗
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Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome.

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

Adolescent↗
PubMedDate not supplied

Characterisation of recombinant human IgE-Fc fragments expressed in baculovirus-infected insect cells.

IgE mediates its effector functions through the Fc region and it has been demonstrated that structures in the Cvarepsilon3-domain are crucial for FcvarepsilonR-binding. In order to further study structures of importance for the function of IgE, such as the carbohydrates, fragments with unmodified amino acid sequence were blunt-end cloned and expressed in baculovirus-infected Sf9 cells. Two fragments of human IgE, one encompassing the entire Fc-region (rCvarepsilon2-4) and a smaller one comprising the second and third domain (rCvarepsilon2-3), were produced and characterised with respect to epitope expression, glycosylation and FcvarepsilonR-binding. N-terminal analysis showed the expected VCSRDF-sequence of the Cvarepsilon2-domain, confirming correct cleavage of the secretion signal. Immunoblotting and gel permeation chromatography demonstrated that rCvarepsilon2-4 mainly formed a dimer, whereas rCvarepsilon2-3 also existed as monomers and oligomers. Endoglycosidase-treatment revealed that both fragments were N-glycosylated. In inhibition ELISA, rCvarepsilon2-4 and myeloma protein IgE(DES) reacted in a near equimolar way with monoclonal antibodies against the Cvarepsilon2-, Cvarepsilon3- and Cvarepsilon4-domains, whereas rCvarepsilon2-3 only reacted with anti-Cvarepsilon2 mAbs. Moreover, in FACS analysis rCvarepsilon2-4 interacted with two cell-lines constitutively expressing FcvarepsilonRI or FcvarepsilonRII, whereas rCvarepsilon2-3 lacked reactivity. A substantial reduction in the ability of rCvarepsilon2-4, following endoglycosidase treatment, to react with recombinant alpha-chain of the high affinity receptor for IgE in sandwich ELISA, indicated a role of N-linked oligosaccharides in stabilising receptor binding structures. Taken together, our results show that rCvarepsilon2-4, but not rCvarepsilon2-3, will be useful in studies of structure-function relationships of IgE, including the role of N-glycosylation, since it demonstrated appropriate epitope expression, conformation and ability to bind Fcvarepsilon-receptors.

Animals↗
PubMedDate not supplied

Saccade-induced activity of dorsal lateral geniculate nucleus X- and Y-cells during pharmacological inactivation of the cat pretectum.

The influence of neurons projecting from the pretectal nuclear complex to the ipsilateral dorsal lateral geniculate nucleus (LGNd) was investigated in awake cats. Responses from relay cells in the A-laminae of the LGNd were extracellularly recorded and analyzed during saccadic eye movements and visual stimulation in association with reversible inactivation of the ipsilateral pretectum with the GABA agonist, muscimol. Pretectal inactivation (PTI) resulted in spontaneous nystagmic eye movements in the dark with slow phases directed away from the injected side. In the control situation, all Y-cells and about two thirds of X-cells were excited during saccades or saccade-like visual stimulation but one third of X-cells were inhibited. During PTI all recorded X-cells were inhibited, either during saccades or saccade-like visual stimulation. The PTI-associated inhibition was stronger than in inhibited X-cells in control experiments only during saccades but not during stimulation with a moving pattern while the eyes were stationary. In Y-cells a reduction in the response peak width at half-height was seen during PTI, again only during saccades but not during stimulation with a moving pattern. These results indicate that during saccades the pretecto-geniculate pathway has a stronger influence on X LGNd relay cells than on Y-cells. The findings are discussed in terms of saccadic suppression and postsaccadic facilitation.

Animals↗
PubMedDate not supplied

New global communication process in thermodynamics: impact on quality of published experimental data.

Thermodynamic data are a key resource in the search for new relationships between properties of chemical systems that constitutes the basis of the scientific discovery process. In addition, thermodynamic information is critical for development and improvement of all chemical process technologies. Historically, peer-reviewed journals are the major source of this information obtained by experimental measurement or prediction. Technological advances in measurement science have propelled enormous growth in the scale of published thermodynamic data (almost doubling every 10 years). This expansion has created new challenges in data validation at all stages of the data delivery process. Despite the peer-review process, problems in data validation have led, in many instances, to publication of data that are grossly erroneous and, at times, inconsistent with the fundamental laws of nature. This article describes a new global data communication process in thermodynamics and its impact in addressing these challenges as well as in streamlining the delivery of the thermodynamic data from "data producers" to "data users". We believe that the prolific growth of scientific data in numerous and diverse fields outside thermodynamics, together with the demonstrated effectiveness and versatility of the process described in this article, will foster development of such processes in other scientific fields.

Chemistry↗
PubMedDate not supplied

Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Adenocarcinoma↗
PubMedDate not supplied

CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated antigens provided by HPV 16 E7.

OBJECTIVE: In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. MATERIAL AND METHODS: Flow-cytometric cell sorted CD8+CD45RA+CD28- and CD8+CD45RA+CD28-T-cells were obtained from patients with cervical cancer and tested for recognition of HLA-A2 restricted peptides derived from the human papillomavirus (HPV)16-E7 gene product using ELISA. HPV DNA in tumor tissue was detected by PCR. RESULTS: We show that the effector CD8+CD45RA+CD28-T-cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with cervical cancer, but also in PBL from patients with an acute mycobacterial infection. CD8+T-cells from 3/6 cancer patients showed a peptide-specific immune response which could be segregated in peptide epitopes which elicited either a strong TNF-alpha production, or GM-CSF and IL-2 secretion. Peptide-reactivity could exclusively be detected in the ex vivo freshly isolated CD8+CD45RA+CD28-T-cell population. A similar situation was found to be true for HLA-A2 presented peptide epitopes derived from M. tuberculosis-associated antigens presented to T-cells obtained from patients with tuberculosis. CONCLUSIONS: The sorting of CD8+CD45RA+CD28-T-cells enables to determine the fine specificity of CD8+ effector T-cells without the need for in vitro manipulation and aids to define the most appropriate target epitopes for novel vaccine designs.

Amino Acid Sequence↗