Biomedical subjects

E Lang

Publications and source records attributed to E Lang.

At least 19 recordsLinked to original sources

PubMed1992

Fmoc-protected, glycosylated asparagines potentially useful as reagents in the solid-phase synthesis of N-glycopeptides.

1-Amino 1-deoxy derivatives of unprotected O-beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyrano se, 2-acetamido-2-deoxy-D-galactose, D-galactose, lactose, D-fucose, D-mannose, and 2-deoxy-D-arabino-hexose were prepared and acylated with N-fluorenylmethoxycarbonylaspartic acid alpha-tert-butyl ester. The anomeric configuration of the N-glycosyl bond (including that of the mannose derivative) in each of the purified compounds was shown to be beta. The probable stability of the N-glycosyl and glycosidic bonds during the conditions of solid-phase peptide synthesis was investigated by treatment of the glycosylated asparagine derivatives with different concentrations of trifluoroacetic acid. Based on their stability, we found that Fmoc-Asn(sugar)-OH derivatives are excellent candidates for automated synthesis of biologically active glycopeptides.

Asparagine↗

PubMed1992

Expression of retinoic acid nuclear receptors in the mouse embryonal carcinoma cell line PCC7-Mz1.

Mouse embryonal carcinoma cell line PCC7-Mz1 can serve as a model of mammalian neural development [1989, J. Cell. Biol. 109, 2481-2493]. Upon exposure to all-trans retinoic acid (RA), Mz1 cells differentiate into a stable pattern of neurons, astroglia and fibroblasts whereas variants of the parental cell line either are restricted in their patterns of derivatives or do not respond at all to RA. Using gene probes specific for the alpha 1, alpha 2 and beta 2 isoforms of the retinoic acid nuclear receptor, we have studied by Northern blot analysis the expression of these transcription factors in uninduced and induced cells of clone Mz1 and in variants with different developmental potential. alpha 1-RAR is expressed constitutively in all variants independent of whether RA is present or not. Soon after addition of 10(-7) M RA, alpha 2-RAR is induced in RA-responsive cells reaching within a few hours a plateau level that remains unchanged throughout the developmental process. In contrast, the beta 2 isoform is expressed only transiently after RA-induction despite the continuous presence of RA. Other RAR isoforms are expressed only in trace amounts.

Animals↗

PubMed1992

A serine-->proline change in the Alzheimer's disease-associated epitope Tau 2 results in altered secondary structure, but phosphorylation overcomes the conformational gap.

Monoclonal antibody Tau 2 was raised against bovine tau protein, was reported to recognize a conformational epitope, and stained tau was found in neurofibrillary tangles of Alzheimer's disease, but not normal human tau. We synthesized tetradeka peptides corresponding to the original bovine sequence, its serine-->proline substituted analog, the genuine human sequence of this region, and the bovine epitope phosphorylated on the crucial serine. The secondary structure of the peptides was determined by circular dichroism. It was found that only the original bovine epitope showed a tendency to form the beta-pleated sheets characteristic of the neurofibrillary tangles. The spectra of the human peptide, its analog, and the phosphorylated bovine sequence were very similar, featuring a weak, helical beta-turn character. Eventual phosphorylation of epitopes of this otherwise heavily phosphorylated protein may overcome inter-species conformational gaps.

Amino Acid Sequence↗

PubMed1992

Immunological and conformation characterization of a phosphorylated immunodominant epitope on the paired helical filaments found in Alzheimer's disease.

The immunological recognition pattern of one of the most commonly used monoclonal antibodies, PHF-1, which detects the paired helical filaments of Alzheimer's disease, exhibits a high degree of similarity with the recognition of a polyclonal antibody, anti-T3P, raised against a synthetic phosphopeptide, GAEIVYKS(Phospho)PVVSGD, corresponding to amino acids 389-402 of the microtubule-associated protein tau. A panel of 16 synthetic non-phosphorylated and phosphorylated peptides, excised from different regions of tau and peptide analogs thereof, were used to show that PHF-1 is indeed directed against the T3 fragment. Circular dichroism spectroscopy shows that the phosphorylated peptide exhibits a limited propensity to form intramolecular beta-pleated sheets, and alteration is found in the reverse-turn structure that dominates the middle section of the molecule. The shift in the turn-forming amino acids may also allow a stacking procedure, may interfere with microtubule assembly, and, consequently, may be accountable for deposit formation.

Alzheimer Disease↗

PubMed1992

Reversible beta-pleated sheet formation of a phosphorylated synthetic tau peptide.

Serine416 of human tau protein is believed to be phosphorylated in Alzheimer neurofibrillary tangles. We synthesized a fragment of tau, consisting of amino acids 408-421 in both non-phosphorylated and serine416-phosphorylated forms. Circular dichroism in a trifluoroethanol-water mixture indicated a beta-turn----beta-pleated sheet conformational transition upon phosphorylation. The beta-structure formation is intermolecular and can be inhibited by addition of Ca2+ ions or a phosphorylated tripeptide, but not with its non-phosphorylated analog. The presence of the phosphorylated tau peptide did not facilitate the formation of beta-pleated sheets of a phosphorylated neurofilament fragment. Multivalent cations induced a conformational transition of this phosphorylated neurofilament peptide, but the effect was less specific than the transition induced in the tau fragment, and it could also be reversed with the competing phosphorylated tripeptide.

Amino Acid Sequence↗

PubMed1992

Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage-colony-stimulating factor therapy in a patient with Hurler's syndrome undergoing bone marrow transplantation.

Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases.

Bone Marrow↗

PubMed1992

A reciprocal whole-arm translocation, rcp(1;6)(1p6p;1q6q) in a boar, localization of the breakpoints, and reassignment of the genes for glucose phosphate isomerase (GPI) and calcium release channel (CRC).

A reciprocal whole-arm translocation between chromosomes 1 and 6 in a Swiss Large White boar with reduced fertility was identified by the use of different staining techniques in mitotic metaphase cells, synaptonemal complex analyses, and meiotic chromosome preparations. The karyotype of this boar was demonstrated to be 38,XY,rcp(1;6)(1p6p;1q6q). To further localize the breakpoints more precisely and determine the precise gene locations, several in situ hybridization experiments were performed with a chromosome 1 centromere-specific probe and two other gene probes. The breakage and reunion points of both chromosomes were located in the centromeric regions. The genes for glucose phosphate isomerase and calcium release channel were mapped to 6cen----q12.

Animals↗

PubMed1992

The relationship between license type and alcohol-related problems attributed to licensed premises in Perth, Western Australia.

Drink-driving offenses, alcohol-related traffic accidents and number of assault charges were used as indicators of the degree of alcohol-related problems associated with individual licensed premises in the Perth Traffic Police region of Western Australia. These indicators were used to rank five main categories of licensed premises according to the levels of harm experienced by their customers while controlling for the amounts of alcohol sold in each category. Nightclubs, taverns and hotels emerged as "high-risk" in comparison with clubs and restaurants. The role of such factors as different customer characteristics, opening hours, types of entertainment, restrictions on clientele and provision of meals are discussed as possible explanations underlying this finding.

Accidents, Traffic↗

PubMed1992

Efficacy, tolerability and pharmacokinetics of teicoplanin in patients undergoing breast surgery.

In a prospective open trial, 21 female patients undergoing breast surgery received a single intravenous bolus injection of teicoplanin, 400 mg, 30 minutes before the operation. During surgery, (1 hour after teicoplanin administration), samples of breast and fat tissue and serum were collected; 24 hours and 48 hours after dosing, samples of wound exudate were taken. Teicoplanin concentrations were determined using the RASA method. Teicoplanin levels were lowest in fat tissue. Teicoplanin levels in wound exudate were found to be satisfactorily high. However, teicoplanin levels in fat and breast tissue and in wound exudate exceeded the MIC90 for various staphylococcus strains, such as S. aureus and S. epidermidis. No local or systemic adverse reactions were observed during the trial. Teicoplanin was well tolerated. Preliminary results from this trial, therefore, indicate that teicoplanin may be a suitable antibiotic for use in the prophylaxis of infection in breast surgery.

Adult↗

PubMed1992

[Perioperative risk of surgical therapy of Crohn disease].

301 patients, operated for Crohn's disease in a ten-year period (1980-1989) were analyzed retrospectively, regarding perioperative risk of bowel resection (n = 336). The overall mortality rate was 0.6% (elective 0, emergency 6%). The reasons of this low mortality rate are of different nature. Very important is a meticulous perioperative treatment and a standardized operative approach.

Adolescent↗

PubMed1991

Drinking locations of drink-drivers: a comparative analysis of accident and nonaccident cases.

This study utilizes data collected by the Perth (Australia) Traffic Police on the last drinking location of persons arrested for drink-driving either as a consequence of their being involved in a road traffic accident or as a result of failing a roadside breath test. A comparison of these data has found that significantly more persons involved in traffic accidents had been drinking at unlicensed locations, that is at private residences or in public places such as parks, than at licensed premises. It was also found that accident cases were more likely to involve males under 25 years; for those involved to have, on average, significantly higher blood alcohol levels than was the case for nonaccident drink-driving cases; and for most accidents to occur late at night and early morning. The significance of these findings were confirmed by logistic regression. A surprise incidental finding was that considerably more women had been arrested for drink-driving than had been previously reported in other studies, both in Australia and overseas.

Accidents, Traffic↗

PubMed1991

[Perforation in Crohn disease as a complication in pregnancy].

The manifestation of Crohn's disease with perforation in pregnancy has been described in one case only. In our case, a 25-year-old woman in the 28th week of pregnancy was admitted to our hospital with signs of an acute abdomen. Due to deterioration of the maternal and foetal situation, the child was delivered by a Caesarean section. Subsequently, exploration of the abdomen showed an ileum perforation with diffuse fibrinous peritonitis. In this case, the definitive diagnosis could not be made prior to laparotomy. The aim of surgical therapy in such cases should be the limited resection with end to end anastomosis. In diffuse peritonitis, discontinuous resection and secondary reconstruction after three to six months is preferred.

Abdomen, Acute↗

PubMed1991

[The rating box--a new instrument for ambulatory detection of subjective variables].

For the acquisition of subjective variables in outpatients and inpatients, a new device--the Rating Box--has been designed. The Rating Box provides a standardized, date- and time-logged documentation of symptoms by the patient and rapid transfer of data to a personal computer. The simultaneous acquisition of several symptoms using different types of scales is possible. The acoustic alarm of the Rating Box reminds the patient to enter data at preselected times. The device is easy to handle, even by older patients, and has been successfully tested in the acquisition of pain variables in patients with a variety of painful conditions.

Data Collection↗

PubMed1991

[Local excision of early stages of rectal cancer].

59 patients with rectal cancer were treated by local excision. In 17 of these patients a radical resection was performed afterwards. In one of 21 local excised "low risk" T1-carcinomas a recurrence was observed. Five of 11 local treated patients with "high risk" tumours developed a recurrence. In the group of the radically treated patients two recurrences were seen. Regarding our results the local excision of "low risk" T1-carcinomas seems to be justified, if final histological workup reveals an adequate margin of healthy tissue.

Aged↗

PubMed1991

[Significance of arrhythmias in advanced age].

Tachycardiac and bradycardiac arrhythmias increase with age. Because cardiac arrhythmias at an advanced age are almost always caused by organic disease, one must face more frequently electrical complications (e.g. ventricular fibrillation). Owing to the decrease of arterial flow volume as well as mean arterial pressure, bradycardiac and tachycardiac arrhythmias result in cerebral symptoms more often in elderly than younger persons. The causes of this observation are the disturbed cerebral autoregulation of blood pressure, but also the insufficient capacity of adaptation of the ageing circulation. In this situation it is more frequently necessary in old people than in younger ones to treat cardiac arrhythmias by antiarrhythmic drugs. The cardiodepressant effect of most antiarrhythmic drugs must be taken into account in this context.

Aged↗

PubMed1990

A clinical trial on efficacy and safety of teicoplanin in combination with beta-lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation.

Early institution of empiric therapy with a broad-spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous bone marrow transplant. Ceftazidime in combination with an aminoglycoside, i.e. netilmicin, has been established as a combination schedule offering low or even avoiding therapy-related toxicity. We evaluated teicoplanin for suspected Gram-positive infections after inadequate response to initial beta-lactam and aminoglycoside combination therapy. All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML), non-Hodgkin lymphoma (NHL, high grade) or other malignant diseases. All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g, i.v., t.i.d., netilmicin 400 mg once daily). All 11 patients responded to therapy, 10 patients were clinically cured, one patient improved under therapy. The therapeutic regimen was well tolerated and adverse drug reactions did not occur. We have not observed any delayed take of prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy. Our preliminary results suggest that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

Adolescent↗

PubMed1990

Chemosensitivity of fine afferents from rat skin in vitro.

1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1990

High spinal anesthesia does not depress central nervous system function as measured by central conduction time and somatosensory evoked potentials.

Short-latency somatosensory evoked potentials (SSEPs) in response to median nerve stimulation were recorded from the neck and the scalp before and during diagnostic high spinal anesthesia (touch T3, pinprick C8) in six patients with chronic pain. The central conduction time--the time difference between the neck-recorded N13 and the scalp-recorded N20--and the amplitudes of the SSEPs did not change in a statistically significant way during high spinal anesthesia. However, latencies of the neck-recorded N13 and the scalp-recorded N20 and P25 increased slightly. This may have been due to a local anesthetic effect on those spinal roots of the median nerve in which segmental pinprick analgesia occurred. Because high spinal anesthesia did not depress central nervous function, as measured by central conduction time, and SSEP amplitudes, it is concluded that scalp-recorded SSEPs during high spinal anesthesia measure the effects of local anesthetics in the cerebrospinal fluid on neuronal pathways outside the brain.

Adult↗