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Biomedical subjects

M Ritter

Publications and source records attributed to M Ritter.

At least 91 records · Page 5Linked to original sources
PubMed1997

Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compared with polymerase chain reaction: results of a prospective investigation.

In order to determine whether the polymerase chain reaction (PCR) is more suitable for the detection of inversion (16) as compared with standard cytogenetics, we prospectively investigated a total of 132 cases of de novo acute myeloid leukaemia (AML) (n = 121) and secondary AML after myelodysplastic syndromes (MDS) (n = 11) using a sensitive and nested PCR procedure to detect the fusion transcripts CBFbeta-MYH11. All patients were recruited within 10 months in an ongoing multicentre AML-trial. In addition, several cases from a retrospective molecular analysis were included. The data were compared with standard cytogenetics performed in a central laboratory. Of the 132 prospective AML cases, five patients (3.7%) harboured inv(16) upon conventional cytogenetics. In all cases fusion transcripts CBFbeta-MYH11 were detected using PCR. In addition in two patients fusion transcripts were detected, although cytogenetics revealed a normal karyotype. In the group of patients analysed retrospectively, four patients harboured fusion transcripts specific for CBFbeta-MYH11; cytogenetics were normal in one case, and could not be evaluated in two cases. These data show that PCR may be a better means to detect inv(16) in AML. Since inv(16) may have prognostic impact in AML, detection of this aberration seems important in the clinical management of AML patients.

Acute Disease↗
PubMed1997

Plasmid-homologous sequences in the chromosome of plasmidless Coxiella burnetii Scurry Q217.

Chromosomal DNA from Coxiella burnetii Scurry Q217 was screened for the presence of plasmid-homologous sequences. Total DNA from Scurry Q217 was digested with NotI, and the resulting DNA fragments were separated by contour-clamped homogeneous electric field pulsed-field gel electrophoresis (CHEF-PFGE). Following hybridization with biotin-labeled QpH1 plasmid as a probe, two DNA fragments of 40 and 170 kb were identified as targets. These fragments were cloned, and subclones containing QpH1-homologous sequences were completely sequenced. The physical mapping of DNA fragments was achieved by PCR with primers derived from adjacent fragments, and a total of 18,360 bp was sequenced. Within the QpH1-homologous region spanning 16,624 bp, homology was as high as 99%. Deletions were identified within EcoRI fragments A(H)-C(H)-K(H)-B(H) (13,490 bp) and J(H)-G(H)-E(H)-L+-D(H) (6,509 bp) and in fragment A(H) alone (619 bp). An insertion of 744 bp was identified within the JDc region of Scurry Q217. A search for putative coding regions identified a total of 17 open reading frames (ORFs). Compared to plasmid QpH1, 6 ORFs were identical, 5 ORFs were different in size, 6 ORFs were newly generated, and 25 ORFs were lost. It was found that plasmid-homologous sequences in Scurry Q217 were of chromosomal origin.

Base Composition↗
PubMed1997

Is the polymerase chain reaction or cure of Helicobacter pylori infection of help in the differential diagnosis of early gastric mucosa-associated lymphatic tissue lymphoma?

PURPOSE: The differential diagnosis of early gastric mucosa-associated lymphatic tissue (MALT) lymphoma based on Helicobacter pylori gastritis may be difficult when lymphoepithelial lesions are not detected. The aim of the present study was to investigate the question whether the polymerase chain reaction (PCR) or cure of H pylori infection may be of help in this respect. PATIENTS AND METHODS: Twenty patients with suspected low-grade gastric MALT lymphomas were treated in a double-blinded, randomized, crossover trial with 2,250 mg of either amoxicillin or placebo, both in combination with omeprazole, for 14 days with the aim to cure H pylori infection. PCR was performed using primers specific for the CDR3 region to detect monoclonal B cells. RESULTS: In five of 20 patients, MALT lymphomas were finally diagnosed. Three of these five patients went into complete remission, while two were referred to surgery. In the 15 patients with gastritis, complete regression was observed in all cases. With respect to PCR, monoclonal bands were detected in all four of the analyzed lymphoma patients before histology showed lymphoma. In addition, monoclonal bands were found in three patients with gastritis. In the patients with gastritis and monoclonal PCR, complete regression took longer as compared with the remaining 12 patients with polyclonal PCR and gastritis (P = .0209). Successful H pylori eradication was associated with earlier diagnosis of the MALT lymphoma (P = .0237). CONCLUSION: CDR3-PCR may be of help in the differential diagnosis of early gastric MALT lymphoma. Furthermore, H pylori eradication may lead to earlier diagnosis.

Adult↗
PubMed1997

Isolated noncompaction of the myocardium in adults.

OBJECTIVE: To describe the entity of isolated ventricular noncompaction (IVNC) and present a series of cases of this rare disorder in an adult population. MATERIAL AND METHODS: We review a 10-year experience with the diagnosis of IVNC and discuss the clinical, echocardiographic, and pathologic features of this condition. Echocardiographic diagnostic criteria included the absence of coexisting cardiac abnormalities, the presence of prominent and excessive trabeculations of one or more ventricular wall segments, and intertrabecular spaces perfused from the ventricular cavity. Pathologic examination focused on regions with exaggerated trabeculations and deep intertrabecular spaces. RESULTS: IVNC is an unexplained arrest of myocardial morphogenesis previously encountered mainly in pediatric patients. Among 37,555 transthoracic echocardiographic studies performed at our hospital between January 1984 and October 1993, 17 cases of IVNC were identified in adult subjects (14 men and 3 women, 18 to 71 years of age). The mean time from onset of symptoms to correct diagnosis was 3.5 +/- 5.7 years, and the mean duration of follow-up was 30 +/- 28 months. Common clinical symptoms were heart failure, ventricular arrhythmias, and a history of embolic events. Two-dimensional echocardiography revealed 10 patients with left ventricular and 7 (41%) with biventricular IVNC. During a 6-year follow-up period, eight patients died and two underwent heart transplantation. CONCLUSION: Although the diagnosis of IVNC in an adult population is often delayed because of similarities with more frequently diagnosed conditions, two-dimensional echocardiography will facilitate the diagnosis of IVNC in this subset of patients. Because of the high incidence of heart failure, ventricular arrhythmias, and embolization in adults with IVNC, early diagnosis is important.

Adult↗
PubMed1997

Activation of Na+/H(+)-exchanger by transforming Ha-ras requires stimulated cellular calcium influx and is associated with rearrangement of the actin cytoskeleton.

Expression of the Ha-ras oncogene in NIH 3T3 fibroblasts (+ras cells) results in growth factor-independent proliferation and marked alteration of cytoskeletal architecture including breakdown of actin stress fiber network. Compared to identical cells not expressing the oncogene (-ras cells), +ras cells exhibit a more alkaline intracellular pH (pHi) and a larger cell volume (CV), both of which are important mitogenic elements. They are due to a set point shift for activation of the Na+/H(+)-exchanger. Moreover +ras cells respond to stimuli like 0.5% fetal calf serum or bradykinin with sustained oscillation of the cell membrane potential (PD) due to stimulated Ca2+ entry which triggers pulsatile release of calcium from internal stores and subsequent activation of calcium-sensitive K+ channels. 10 mumol/l bepridil inhibit oscillations of PD and protect +ras cells against actin stress fiber depolymerization. It is shown that bepridil blocks both cellular calcium entry as measured by Mn2+ quenching of fura-2 fluorescence and activation of the Na+/H(+)-exchanger following expression of the Ha-ras oncogene. Inhibition of the Na+/H(+)-exchange with 10 mumol/l HOE 694, on the other hand, does not significantly alter Ha-ras stimulated calcium entry or cytoskeletal rearrangement. In -ras cells ionomycin (0.1 mumol/l) leads to a transient increase in Cai. This effect is paralleled by a transient depolymerization of actin stress fiber network which cannot be inhibited by HOE 694. Disruption of the actin cytoskeleton in -ras cells by cytochalasin D does not alter steady state cell volume or Na+/ H(+)-exchange activity. However, stimulation of cytochalasin-treated -ras cells with bradykinin leads to cell swelling which can be blunted by HOE 694. The results show that both cytoskeletal rearrangement and activation of the Na+/H(+)-exchanger following expression of the Ha-ras oncogene require stimulated calcium influx and Cai oscillations. The depolymerization of the actin cytoskeleton is permissive for the Na+/ H(+)-exchanger to cause cell swelling upon stimulation with bradykinin.

3T3 Cells↗
PubMed1997

Allele-specific PCR amplification of factor V Leiden to identify patients at risk for thromboembolism.

Resistance to activated protein C is the most common hereditary cause of thrombophilia and is significantly linked to factor V Leiden. We designed primers in order to identify factor V Leiden by allele-specific PCR amplification. Amplification specificity for factor V was ensured by a 3' primer located at the intron 9/exon 10 border of the gene. One sense and two antisense primers were used in two separate primer mixes specific for factor V ARG506 (wild-type) or factor V GLN506 (factor V Leiden). In each PCR reaction a pair of primers amplifying a fragment of the human growth hormone gene was included as an internal positive amplification control. The presence or absence of specific PCR amplification allowed definite allele assignment without the need for any postamplification specificity step. The internal positive control primers indicate a successful PCR amplification, allowing the assignment of homozygosity. In a prospective study 126 patients with thromboembolic events were analyzed using this technique and PCR-RFLP. The concordance between these methods was 100%. In 27 patients a heterozygous factor V GLN506 mutation was detected, whereas 1 patient with recurrent thromboembolism was homozygous. No false-positive or false-negative results were observed in the homozygous as well as heterozygous samples. Additionally, in 15 samples identified to carry the point mutation by allele-specific PCR amplification, automatic sequencing has confirmed the heterozygous or homozygous point mutation. Due to its time- and cost-saving features allele-specific amplification should be considered for screening of factor V Leiden.

Alleles↗
PubMed1997

Outcome implications for the timing of bilateral total knee arthroplasties.

Health Care Financing Administration data from 1985 to 1990 revealed 339,152 total knee arthroplasties of which 62,730 (18.6%) were bilateral procedures (simultaneous 112,922; staged 6 weeks, 4354; staged 3 months, 4524; staged 6 months, 9829; and staged 1 year 31,401). Medicare beneficiaries undergoing bilateral procedures were an average of 73 years of age; demographics revealed that among the various simultaneous and staged groups 57% to 69% were females, 90% were white, 85% to 90% had a diagnosis of osteoarthritis, and 30% to 40% were performed in rural hospitals. Between 1985 and 1990, surgical and vascular complications ranged from 2.4% to 4% and 4.1% to 6.8%, respectively, for all types of bilateral staged and simultaneous total knee arthroplasties. All differences were statistically significant. After controlling statistically for demographic variables and diagnoses, a surrogate for case mix, it was found that individuals electing simultaneous bilateral arthroplasties experienced twice the number of intensive care days than those choosing staged procedures. Days in the intensive care unit were double when done simultaneously instead of staged (0.48 versus 0.21). Nosocomial infections were similar within groups (10% versus 13%); however, wound infections were nearly half when done simultaneously (0.5% versus 1%) versus in a staged fashion. Length of stay and cost were much less for the simultaneous procedure group who were sicker as measured by the number of diagnoses. Mortality at 30 days was highest for the simultaneous procedure group (.99%) versus staged 3 or 6 months (0.30%); however, by 2 years it was close to 4% for all groups. Staging the procedure 3 to 6 months seems to offer the fewest disadvantages, is only slightly more expensive, and has the lowest mortality rate.

Age Factors↗
PubMed1996

Antigen presentation by T cells inhibits IL-2 production and induces IL-4 release due to altered cognate signals.

Conflicting results of the effects of Ag presentation by MHC class II-expressing T cells have been described. In some studies class II-expressing T cells have been shown to act as effective APCs, while others have reported that the recognition of Ag on the surface of another T cell inactivates IL-2 production. In this study we have investigated the mechanisms involved in Ag presentation by T cells. The results obtained suggest that 1) lack of costimulation is not responsible for the inhibitory effects of T cell Ag presentation on IL-2 production; the provision of costimulation by immobilized anti-CD28 Ab or by the addition of accessory cells failed to reverse the effects of T cell Ag presentation, but restored the response to immobilized anti-CD3; 2) T cell Ag presentation induced a minimal increase in intracellular Ca2+ compared with that induced by antigen-pulsed B cells; this difference in the calcium response is not explained by quantitative differences in ligand density between B cells and T cells; and 3) despite the weak calcium signal, T cell presentation supported IL-4 release in the absence of IL-2 production. Taken together these data suggest that T cell Ag presentation leads to altered TCR/CD3-transduced signals, which biases the T cell towards a Th2 phenotype.

Animals↗
PubMed1996

Marine lipids normalize cholesteryl ester transfer in IDDM.

Patients with insulin-dependent diabetes mellitus (IDDM) have a pathological increase in cholesteryl ester transfer (CET) that enriches the apolipoprotein B-containing lipoproteins with cholesteryl ester and increases their atherogenicity. Since we have shown earlier that omega-3 (n-3) fatty acids present in marine lipids normalize both CET and lipoprotein composition in non-diabetic patients with hypercholesterolaemia, we sought to determine whether the same beneficial effects could be achieved in nine normolipidaemic (triglycerides 1.10; cholesterol 4.94, high density lipoprotein 1.10 mmol/l) IDDM patients (fructosamine 424 +/- 156; normal 174-286 mumol/l) treated for 2 months with n-3 fatty acids (4.6 g/day). Before treatment, CET measured by both mass and isotopic assays was abnormally accelerated (p < 0.001). While marine lipids modestly decreased triglyceride levels (-14%; p < 0.05 ), CET fell dramatically in all subjects (mass assay: -97% at 1 h; isotopic assay: -58%; p < 0.001) to below control levels with no change in glycaemic control (fructosamine 408 +/- 103 mumol/l). The mass of cholesteryl ester transfer protein paradoxically increased significantly (pre-treatment: 2.04 +/- 0.86 vs post-treatment 2.48 +/- 0.97 micrograms/ml; p < 0.05). Since it is believed that accelerated CET promotes the formation of atherogenic cholesteryl ester-enriched apo B-containing lipoproteins, the capacity of marine lipids to reverse this functional abnormality without altering glycaemic control suggests that these agents may have an adjunctive role to play in the nutritional therapy of IDDM.

Adult↗
PubMed1996

The role of fundoplication in the treatment of type II paraesophageal hernia.

OBJECTIVES: The role of fundoplication in patients with pure type II paraesophageal hiatal hernia remains controversial. Conventional thinking suggests that because the lower esophageal sphincter is located within the abdomen, it is competent, and fundoplication is unnecessary. Few studies have used objective evaluation to guide the addition of an antireflux procedure. METHODS: Fifteen consecutive patients with type II paraesophageal hernia were treated between May 1991 and July 1994. All had radiographic criteria of pure type II hernias. Preoperative evaluation included upper intestinal endoscopy, esophageal manometry, and 24-hour ambulatory pH monitoring. The lower esophageal sphincter was considered incompetent if any of the following criteria were present: a resting pressure less than 7 mm Hg, an overall sphincter length less than 2 cm, or an intraabdominal length less than 1 cm. Primary symptoms responsible for surgery were related to the hernia in 73% of patients: dysphagia or postprandial abdominal pain in six patients, abdominal distension or vomiting in four patients, and bleeding in one patient. Symptoms typical of gastroesophageal reflux were present in four patients: heartburn and regurgitation in two each. RESULTS: Objective evidence of gastroesophageal reflux was present in the majority of patients. Five patients (31%) had evidence of esophageal injury: esophagitis in three patients, stricture in one, and esophageal ulcer in one. In 11 of 15 patients (69%), pathologic esophageal acid exposure was detected by 24-hour pH monitoring. Twelve patients (75%) had a defective lower esophageal sphincter, usually the result of an inadequate intraabdominal length (8/12, 66%). Hernia reduction, crural closure, and Nissen fundoplication were performed in 14 patients (one patient awaits surgery). Symptomatic relief was excellent in all cases. No patient has had hernia recurrence at an average of 14 months' follow-up (range 2 to 39 months). CONCLUSION: Objective evaluation reveals that gastroesophageal reflux accompanies type II paraesophageal hernia in a high proportion of patients, usually because of an incompetent lower esophageal sphincter. Appropriate treatment includes reduction of the hernia, crural closure, and fundoplication in most, if not all, patients.

Adult↗
PubMed1996

Spontaneous obliteration of a pseudo-aneurysm complicating an aortic homograft.

Pseudoaneurysm formation after aortic homograft replacement in patients with active endocarditis is a common observation and usually occurs at the site of a former abscess or paravalvular leak in case of prosthetic valve endocarditis. A 53-year-old man with prosthetic endocarditis underwent aortic valve homograft replacement and developed a pseudoaneurysm at the right and noncoronary aortic sinus which was documented by Doppler echocardiography. Follow-up examination ten months after operation unexpectedly revealed a complete obliteration of the previously echo free space between the homograft and the native aortic root and, thus, spontaneous obliteration of the pseudoaneurysm.

Aneurysm, False↗
PubMed1996

Loss of interleukin 4 receptor-associated molecule gp200-MR6 in human breast cancer: prognostic significance.

Several in vitro studies stress a potentially important role of interleukin 4 (IL-4) and the related gp200-MR6 molecule in the immunological response to cancer and in tumour proliferation. In the present study, we assessed the expression of gp200-MR6 in primary breast cacrinomas using the MR6 monoclonal antibody. Results were correlated with tumour parameters (T-,N-stage, histology, grade, oestrogen and epidermal growth factor (EGF) receptors), and the impact on survival was assessed. Twenty-four out of 110 cases (22%) were positive for gp200-MR6, 62 out of 110 (56%) expressed weak staining and 24 out of 114 (22%) did not stain. The normal breast epithelia were invariably stained for gp200-MR6 showing that down-regulation or loss of this molecule occurred during the evolution of breast cancer. Gp200-MR6 loss was independent from differentiation, nodal positivity and oestrogen receptor levels as well as patients' age. Loss of the gp200-MR6 molecule was more frequent in lobular cases (P=0.03). The overall survival was better, although not reaching statistical significance, in patients with positive gp200-MR6 expression (92% alive at 5 years compared with 70% for those with weak or no expression, P=0.1). The local relapse-free survival was independent of gp200-MR6 status. It is concluded that loss of gp200-MR6 may be one of the mechanisms through which breast cancer cells escape immune surveillance, resulting in an increased metastatic potential and poorer outcome. Evidence of down-regulation of the gp200-MR6 molecule has implications for IL-4-linked toxin therapy and, as IL-4 is an inhibitor of breast epithelial growth, may represent loss of a tumour-suppression mechanism.

Analysis of Variance↗
PubMed1996

Leaking giant aneurysm of the aortic root due to cystic medial necrosis with pericardial tamponade mimicking type-A aortic dissection.

The diagnosis of acute type-A aortic dissection is predominantly based on the demonstration of an intimal tear or a dissection membrane. We describe another pathogenetic mechanism in a patient with the typical features of acute aortic dissection with pericardial tamponade, and a giant aneurysm of the ascending aorta. However, no dissection membrane, rupture site, or intimal tear could be demonstrated by transesophageal echocardiography, intraoperatively, or histologically. The histological work-up showed an extreme form of cystic medial necrosis with intramural hemorrhages consistent with a leaking aneurysm. Hence, in a patient with a symptomatic aneurysm of the aortic root and pericardial tamponade, obvious intimal dissection or rupture does not always have to be present echocardiographically or intraoperatively. A different presentation can occur in the setting of an extreme medial necrosis, where blood leaks through the aortic wall causing intramural hemorrhages with intimal leaks invisible to the surgeon's or echocardiographer's eye. This process is clinically indistinguishable from type-A aortic dissection.

Aortic Dissection↗
PubMed1996

Blockade of swelling-induced chloride channels by phenol derivatives.

1. In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as ICln, a protein isolated from a cDNA library derived from Madin Darby canine Kidney (MDCK) cells. ICln expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and NPPB (5-nitro-2-(3-phenylpropylamino)-benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD. 2. RVD in NIH3T3 fibroblasts and MDCK cells is temperature-dependent. 3. RVD, the swelling-dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB. 4. The cyclic AMP-dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium-activated chloride current in fibroblasts is insensitive. 5. The binding site for the two phenol derivatives onto ICln seems to be distinct but closely related to the nucleotide binding site identified as G x G x G, a glycine repeat located at the predicted outer mouth of the ICln channel protein.

3T3 Cells↗
PubMed1996

Calcium entry stimulated by swelling of Madin-Darby canine kidney cells.

Cell swelling in Madin-Darby canine kidney (MDCK) cells by reduction of extracellular osmolarity (omission of 70 ad 150 mmol/l mannitol, respectively) leads to the activation of anion of channels and Ca2+ sensitive K+ channels. The K+ channel activation leads to an initial transient hyperpolarization of the cell membrane potential (PD) followed by a sustained depolarization due to activation of anion channels. The present study elucidates the role of intracellular calcium (Ca2+i) in regulatory cell volume decrease (RVD) of MDCK cells. While reduction of extracellular osmolarity by omitting 70 mmol/l mannitol did not lead to a detectable change in Ca2+i, severe cell swelling by omitting 150 mmol/l mannitol led to a transient rise in Ca2+i. PD changes, on the other hand, were not different under either condition. In addition, the response of PD to cell swelling was not altered by treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate diester, pertussis toxin or cholera toxin. In the nominal absence of extracellular Ca2+, reduction of extracellular osmolarity did not lead to an increase in Ca2+i and no initial transient hyperpolarization was observed, whereas addition of 10 mumol/l ATP still led to a significant hyperpolarization. Omission of extracellular Ca2+ was followed by a strong decrease in cell membrane resistance (Rm) due to activation of a depolarizing cation conductance. Subsequent readdition of Ca2+ caused a marked increase in Ca2+i due to Ca2+ influx. This Ca2+ entry was further stimulated by cell swelling. RVD was significantly blunted in the absence of extracellular Ca2+. The results suggest that cell swelling stimulates a Ca2+-permeable pathway in the cell membrane favoring Ca2+ entry into the cell with subsequent activation of Ca2+-sensitive K+ channels.

Animals↗
PubMed1996

Simple and rapid detection of factor V Leiden by allele-specific PCR amplification.

Resistance to activated protein C is the most common hereditary cause for thrombosis and significantly linked to factor V Leiden. In this study, primers were designed to identify the factor V mutation by allele-specific PCR amplification. 126 patients with thromboembolic events were analysed using this technique, PCR-RFLP and direct sequencing. The concordance between these techniques was 100%. In 27 patients a heterozygous factor VGln506 mutation was detected, whereas one patient with recurrent thromboembolism was homozygous for the point mutation. Due to its time- and cost-saving features allele-specific amplification should be considered for screening of factor VGln506.

Alleles↗
PubMed1996

Ventricular laceration and cardiac tamponade during laparoscopic Nissen fundoplication.

Laparoscopic fundoplication is now accepted as an excellent alternative to long term medical therapy for select patients with gastroesophageal reflux disease. Morbidity is uncommon and usually not life threatening. The procedure requires retraction of the left lateral segment of the liver, which has emerged as one of the most troubling technical aspects. This case report represents an uncommon, albeit dramatic, complication involving traumatic injury to the right ventricle thought secondary to trauma from a non-disposable, fan shaped, liver retractor.

Aged↗