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Biomedical subjects

M Schmitz

Publications and source records attributed to M Schmitz.

At least 19 recordsLinked to original sources

The human mdr1 (multidrug-resistance) gene harbours a long homopyrimidine.homopurine sequence next to a cluster of Alu repeated sequences in intron 14.

In order to identify specific DNA sequences useful as 'genetic landmarks' in the construction of a complete map of the human mdr1 (multidrug-resistance) gene, we investigated the introns in the central region. In intron 14, we identified a long stretch of a homopyrimidine.homopurine sequence most probably adopting an unconventional DNA conformation, followed by a cluster of three Alu repeated sequences in an inverted orientation. Here, we describe the structure, formation and nucleotide sequence of these DNA elements.

ATP Binding Cassette Transporter, Subfamily B, Mem

Children's anticipation of and response to colposcopic examination.

Just prior to and following general physical and colposcopic anogenital exams, 43 mothers and daughters (3-15 years), referred because of allegations of sexual abuse, were interviewed separately to determine their knowledge of and feelings about the exam. Children were not retraumatized by the examination of their anogenital anatomy. Although poorly prepared for it, children reported medical staff touch to their genitals, anus, and buttocks at a higher rate than touch to all other body locations, 84.5% versus 16%, but did not rate that touch as more painful. Children were significantly less distressed after the exam; mothers were not.

Adaptation, Psychological

Screening for sinus disease in patients with asthma: a computed tomography-controlled comparison of A-mode ultrasonography and standard radiography.

BACKGROUND: Paranasal sinus disease and bronchial asthma are frequently associated. Patients with asthma often have chronic inflammatory changes of the paranasal mucosa rather than acute bacterial sinusitis. Our aim was to compare the rankings of A-mode ultrasonography and standard radiography as routine screening procedures in the diagnostic workup of these patients. METHODS: We compared the evaluation of the maxillary sinuses by A-mode ultrasonography and standard radiographs. Computed tomography served as a gold standard in 19 patients with asthma who had no history of sinus surgery. RESULTS: Computed tomography showed at least some minimal mucosal thickening in any of the paranasal sinuses in 74% and of the maxillary sinuses in 61% of the patients. Compared with the results of computed tomography, plain-view radiography gave a specificity of 86.7% for the maxillary sinuses. Although all cases of severe mucosal thickening were detected, sensitivity for minimal mucosal hyperplasia was low, at 52.2%. In contrast, A-mode ultrasonography demonstrated a sensitivity of 70% but a specificity of only 22%. CONCLUSIONS: Even symptom-free patients with asthma show a high prevalence of at least limited mucosal thickening in the paranasal sinuses. Acute sinusitis is not a common finding. A-mode ultrasonography does not allow sufficient evaluation of this mucosal hyperplasia and is therefore not suitable for initial screening in these patients. It may prove helpful as a follow-up in selected patients with known anatomic characteristics, however, especially when antral fluid is involved. For routine screening in patients with asthma, a conventional Waters' view radiograph should be used in conjunction with direct visualization of the ostial-meatal area by fiberoptic or rigid rhinoscopy. This combination provides information about the degree of mucosal hyperplasia as well as mucosal inflammation and secretion.

Adult

Lipidized medulloblastoma in adults.

We describe the clinical, imaging, histologic, immunohistochemical, and ultrastructural features as well as the DNA ploidy analysis of two primitive neuroectodermal neoplasms demonstrating prominent cytoplasmic lipid accumulation originating in the posterior fossa of adults. These two tumors most likely exemplify a variant of medulloblastoma with heavily lipidized cells and support the postulated pluripotentiality of primitive neuroectodermal neoplasms. Recognition of this entity as a phenotypic variant of medulloblastoma will militate against diagnostic confusion with other entities that may contain cells with lipoblastic or adipocytic differentiation.

Cerebellar Neoplasms

Soybean trypsin inhibitor(s) reduce absorption of exogenous and increase loss of endogenous protein in miniature pigs.

It was the purpose of this study to define whether trypsin inhibitors impair protein digestibility via enhanced loss of exogenous or endogenous protein by quantifying those losses using the homoarginine technique, recently developed in this laboratory. Pigs fitted with permanent ileal T-cannulas were fed test meals containing homoarginine-labeled protein. The meals contained casein and increasing doses of trypsin inhibitors (Experiment 1) or alternatively either heat-treated or raw ground soybeans (Experiment 2). Following a casein meal (425 mmol nitrogen, no trypsin inhibitors), ileal protein was predominantly of endogenous rather than of exogenous origin (105 vs. 9 mmol nitrogen). Addition of isolated trypsin inhibitors (3000 mg) enhanced appearance of both endogenous and exogenous protein at the ileum (by 73 and 9 mmol nitrogen, respectively). Feeding raw instead of heat-treated soybeans in one single test meal caused a significant increase of endogenous protein from 217 +/- 42 to 263 +/- 47 mmol (mean +/- SEM) and of exogenous protein from 16 +/- 3 to 48 +/- 14 mmol. If fed continuously for 1 wk, a raw soybean diet caused endogenous protein loss to rise significantly from 221 +/- 26 to 432 +/- 85 mmol. We conclude that ingestion of food containing trypsin inhibitor affects nitrogen balance more by losses of amino acids of endogenous secreta than by losses of dietary amino acids.

Analysis of Variance

Base-pair probability profiles of RNA secondary structures.

Dynamic programming algorithms are able to predict optimal and suboptimal secondary structures of RNA. These suboptimal or alternative secondary structures are important for the biological function of RNA. The distribution of secondary structures present in solution is governed by the thermodynamic equilibrium between the different structures. An algorithm is presented which approximates the total partition function by a Boltzmann-weighted summation of optimal and suboptimal secondary structures at several temperatures. A clear representation of the equilibrium distribution of secondary structures is derived from a two-dimensional bonding matrix with base-pairing probability as the third dimension. The temperature dependence of the equilibrium distribution gives the denaturation behavior of the nucleic acid, which may be compared to experimental optical denaturation curves after correction for the hypochromicities of the different base-pairs. Similarly, temperature-induced mobility changes detected in temperature-gradient gel electrophoresis of nucleic acids may be interpreted on the basis of the temperature dependence of the equilibrium distribution. Results are illustrated for natural circular and synthetic linear potato spindle tuber viroid RNA respectively, and are compared to experimental data.

Algorithms

Frequency analysis of allergen-reactive T-lymphocytes in individuals allergic against the house-dust mite Dermatophagoides pteronyssinus.

We have investigated the frequencies of Dermatophagoides pteronyssinus (Dpt)-reactive circulating T cells in individuals allergic to this house dust mite and in asymptomatic controls. In allergic patients the median for frequencies of Dpt-reactive T cells (80/10,000 T cells) was significantly higher (p = 0.0001) than that in the controls (19/10,000 T cells). Frequencies of spontaneously proliferating T cells were also determined. Here too, marked differences (p = 0.0001) were observed between the allergics (median = 32/10,000 T cells) and the non-allergics (median = 7.5/10,000 T cells). The allergen-reactive T cells tended to occur at a higher frequency with increasing serum level of Dpt-specific IgE. Thus the median value for Dpt-reactive T cells in patients showing RAST class greater than or equal to 4 (176.5/10,000 T cells) was higher than that shown by patients with RAST class 3 (62/10,000 T cells). Frequency estimations of allergen-reactive T cells before, during and after the completion of hyposensitization therapy might help to clarify their possible role in the allergic symptoms.

Allergens

Pentafraction reduces the lung lymph response after endotoxin administration in the ovine model.

For the past half-century, several high molecular weight compounds have been used for volume expansion during cardiopulmonary resuscitation. However, the effectiveness and side effects of these different expanders are varied. We have compared plasma, pentastarch, and a new product, pentafraction, for effective plasma volume expansion before and after tissue injury with endotoxin administration. In each group, eight range ewes instrumented with a Swan-Ganz, arterial, and venous catheters, and lung and flank lymphatic cannulas were compared. Each group received 15 ml/kg of either 6% pentafraction, 6% pentastarch, or plasma followed two hours later by 1.5 micrograms/kg/0.5 hr E. Coli endotoxin over 30 min. Data were collected for an additional 24 hr after endotoxin administration. Our results indicated a plasma volume expansion in all three groups. However, the prior administration of pentafraction significantly attenuated the increase in the lung lymph flow and early evaluation of systemic vascular resistance noted with endotoxin in comparison to the other two groups.

6-Ketoprostaglandin F1 alpha

Formation of a thermodynamically metastable structure containing hairpin II is critical for infectivity of potato spindle tuber viroid RNA.

The functional relevance of a hairpin II-containing structure of viroid RNA was studied by site-directed mutagenesis, thermodynamic calculations, experimental denaturation curves and infectivity tests. Hairpin II is formed during thermal denaturation of circular viroids or as part of a metastable structure during synthesis of viroid replication intermediates. In potato spindle tuber viroid (PSTVd), eight single-site mutations were generated in the segments which form hairpin II. From the mutated viroid cDNA clones, linear RNA transcripts of PSTVd unit length were synthesized. The relevance of hairpin II for the mechanism of denaturation was confirmed quantitatively by optical denaturation curves and temperature-gradient gel electrophoresis. Infectivity tests showed that the mutations in the core region of hairpin II reverted to the wild type sequence whereas the mutations in the peripheral regions of hairpin II remained genetically stable. These data are in accordance with the natural variance of hairpin II in other viroids of the PSTVd class. Thus, the integrity of the core of hairpin II is critical for infectivity. Hairpin II exhibits a strong similarity in sequence as well as in three-dimensional structure to certain DNA GC-clusters found in the 5'-upstream regions of some genes in man, animals, viruses and plants. A hypothesis about a function of hairpin II as a binding site for host cell transcription factors is proposed.

Base Composition

Homoarginine labeling is suitable for determination of protein absorption in miniature pigs.

Intestinal proteolysis and absorption of dietary protein was followed using a chemical label of the lysine side-chain. Protein-bound lysine was transformed into homoarginine (HA), an amino acid that is not used for protein synthesis. Disappearance in the intestinal tract of HA originating from labeled casein and soybean isolate and appearance in peripheral blood was followed in four miniature pigs fitted with permanent T-cannulas at the proximal jejunum and ileum. Less than 0.2% of HA appeared in the digesta at the ileum when up to 13.5 mmol of HA was infused either into the jejunum or jugular vein. Several factors suggest that HA in fact traces the exogenous (dietary) protein: 1) the quick postprandial appearance of HA in plasma; 2) the high (greater than 97%) oro-ileal absorption of HA-labeled casein and soybean isolate; 3) the similarity of chymotryptic proteolysis in vitro of guanidinated and native casein; 4) the fact that only trace amounts of the marker reenter the intestinal lumen from the blood. Therefore HA-label is suitable for the differentiation of exogenous and endogenous protein in the chyme and thus the measurement of oro-ileal protein absorption and irreversible loss of endogenous protein in the chyme of the small intestine.

Animals

[Postprandial plasma variations of 3-methylhistidine compared to those of lysine, homoarginine and xylose on the normal conditions and in malabsorption in the suckling calf].

We have studied the absorption of 3-methylhistidine (3MH) in vitro and changes in its plasma concentration in preruminant calves after ingestion of milk containing 3MH under normal and malabsorptive conditions. Changes in 3MH concentration were compared to those in lysine, homoarginine (as a component of guanidinated caseine) and xylose, also added to milk. The absorption of 3MH in vitro was dose-dependent and was inhibited by leucine, indicating that 3 MH was transported in the same manner as neutral amino acids. After the ingestion of milk supplying 2.5-20 mumols (3MH)/kg body weight, 3MH increased dose-dependently within 1.75 h and reached maximal levels between 3 and 8 h. Lysine concentration initially parallelled the course of blood 3MH levels but dropped sooner. Homoarginine concentration did not increase until 2-4 h postprandially, probably as a consequence of the time needed for casein degradation. Xylose concentration increased as rapidly as 3MH and lysine concentration. Feeding a diet containing soybean protein for 36 d and administration of neomycine for 5 d to newborn calves induced malabsorption of xylose. However, 3MH absorption and caseine digestion, which increased after homoarginine absorption were not reduced.

Animal Feed

[Experiences with a combination therapy of methylprednisolone and troleandomycin in severe bronchial asthma requiring high-dose corticoids].

Although treatment comprising a combination of methylprednisolone (MP) and troleandomycin (TAO) has been employed to treat cases of severe bronchial asthma requiring high doses of corticosteroids, for about 20 years, now, it has always been associated with major adverse reactions (1). A new protocol avoids these adverse effects by a rapid reduction in the dose of MP to alternating administrations and low TAO dosage (250 mg). Nineteen patients were treated using this protocol, 16 of whom for more than two months (maximum 21, minimum 4 months). Three patients were taken out of the study as early non-responders in the initial phase. Five patients must be considered to be late non-responders, or were discharged from the study on account of pathological liver parameters. In 8 patients who showed good tolerance, an appreciable reduction in the dose of steroids, with stabilisation of the asthma, was observed.

Administration, Oral

[Fatal injury in childhood. Analysis of 160 autopsies].

During the period from 1971 to 1987 160 deadly injured children were dissected at the Institute of forensic medicine in Hamburg-Eppendorf. 72.5% of the children died after a traffic accident. Injuries of the head as cause of death is the most detected reason. 62% of the children died because of a head injury, 13% in consequence of bleeding and 10.8% because of contusion of the medulla oblongata by injuries of the upper vertebral column. The majority of the children died by injuries of only one cavity (42%). It is conspicuous that the portion of infants (none to three years) is greater than we expected.

Abdominal Injuries

Selective recognition of mucosal lymphoid high endothelium by gut intraepithelial leukocytes.

Circulating precursors of mucosal immunoglobulin A plasma cells and T-cell immunoblasts migrate selectively into mucosal sites from the blood, but the mechanisms controlling this selective trafficking have not been determined. One possibility is that the site-specific extravasation of circulating effector cell populations is determined by organ-specific endothelial cell recognition mechanisms. Here we have assessed the ability of isolated mouse gut intraepithelial lymphocytes to recognize and bind to mucosal versus nonmucosal lymphoid organ high endothelial venules, vessels that support high levels of lymphocyte traffic in vivo. In an in vitro assay of lymphocyte interaction with high endothelial venules in frozen sections, intraepithelial leukocytes bind well to high endothelial venules in Peyer's patches but, unlike most circulating B and T lymphocytes, are unable to interact with peripheral lymph node high endothelial venules. Furthermore, we show by in situ immunohistology and in cell suspension immunofluorescence studies that intraepithelial leukocytes fail to stain with a monoclonal antibody, MEL-14, against putative lymphocyte receptors for lymph node high endothelial venules. Thus, they lack a cell surface glycoprotein required for homing to peripheral nodes. The demonstration of organ-specific recognition of endothelial cells by a normal mucosal effector lymphocyte population suggests that selective interactions with endothelium may play an important role in controlling the distribution of effector cells in vivo. The utilization of organ-specific endothelial cell recognition mechanisms by circulating precursors of mucosal effector cells could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from nonmucosal immune mechanisms.

Animals

Purification and characterization of the feline sarcoma virus tyrosine-specific kinase pp85gag-fes.

The transforming phosphoprotein pp85gag-fes of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) was purified in a form which exhibits tyrosine-specific kinase activity. Cell lysates of ST-FeSV-transformed mink nonproducer cells were applied to a column of DEAE-Sephacel and eluted with a linear gradient of NaCl in phosphate buffer. Kinase activity was found uncomplexed (pp85gag-fes) in the flow-through and was eluted with 200 mM NaCl in a complex with pp50 and pp90. The flow-through material was further fractionated by chromatography on hydroxylapatite, followed by phosphocellulose and a final gel filtration step using Sephacryl S200. The final preparation was specifically enriched 1400-fold, and tyrosine-specific kinase activity was increased by about 300-fold as determined by autophosphorylation or phosphorylation of casein. Pp85gag-fes kinase activity was inhibited by nicotinamide adenosine dinucleotide (NAD) and slightly inhibited by NADH, while quercetin, a strong inhibitor for pp60src-associated tyrosine kinase activity, had no inhibiting effect.

Animals

Relative effects of static muscle contraction on digital artery and nailfold capillary blood flow velocities.

Previous studies have shown that a decrease in blood flow to the finger is not necessarily accompanied by a corresponding change of blood flow in nailfold capillaries. The purpose of this study was to determine if nailfold capillary blood flow remains relatively stable during a decrease in finger blood flow induced by muscle contractions. Four male subjects 20 to 30 years of age exerted 2-min periods of static calf muscle contraction at levels of 7.5, 15, 30, and 45% of their maximum voluntary contractile force (MVC) while systemic blood pressure (BP), and flow velocities in the digital artery (VEL-A) and nailfold capillaries (VEL-C) were measured by, respectively, Doppler ultrasound and video densitometry. Each subject repeated the series five times. There was a significant linear decrease in VEL-A with increasing force of contraction for each subject individually (P less than or equal to 0.009) and for the group as a whole (P less than or equal to 0.0001); whereas VEL-C did not significantly change during muscle contraction. These results indicate that the initial cutaneous constrictor response in the finger during the onset of leg muscle exercise is not reflected to the nailfold capillaries.

Adult