PubMed Health⌕ Search

Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 145 records · Page 8Linked to original sources
PubMed1987

A modified nicotinic acetylcholine receptor lacking the 'ion channel amphipathic helices'.

Antibodies to a synthetic peptide from the 'amphipathic helix' of the alpha-chain of the nicotinic acetylcholine receptor (nAChR) bound both to detergent-solubilised and membrane-bound nAChR, indicating that this region, suggested as a component of the transmembrane ion channel in one model, is not buried in the membrane. Trypsinisation of membranes prior to affinity purification yielded preparations lacking the amphipathic helices of the alpha- and beta-chains and probably also of the gamma- and delta-chains. Such material should allow direct testing, by reconstitution experiments, of the importance of these regions for channel activity.

Animals↗
PubMed1987

Mapping the main immunogenic region and toxin-binding site of the nicotinic acetylcholine receptor.

The alpha-chain of the nicotinic acetylcholine receptor carries the binding sites both for cholinergic ligands and for most experimentally induced or naturally occurring antibodies to the native receptor. By means of expression cloning in Escherichia coli, fusion proteins were derived from specific fragments of a complementary DNA encoding the mouse alpha-chain, allowing the mapping of the toxin-binding site to residues 160-216 and the main immunogenic region to residues 6-85. This approach permits the independent study of different functional domains of a complex receptor molecule and should be generally applicable to other proteins for which complementary DNA clones are available.

Amino Acid Sequence↗
PubMed1987

Haemorrhagic shock-encephalopathy syndrome: plasmapheresis as a therapeutic approach.

We present the case of a 4.5-week-old boy with acute encephalopathy, shock, intestinal bleeding and disseminated intravascular coagulation. The clinical course and typical laboratory parameters were compatible with a diagnosis of haemorrhagic shock-encephalopathy syndrome (HSE). Immediate shock treatment, repeated haemodialysis and plasmapheresis did not prevent a fatal outcome 4 days after the onset of clinical symptoms.

Brain Diseases↗
PubMed1987

Renal and cerebral necrosis in survivor after in utero death of co-twin.

A newborn with bilateral renal cortical necrosis and severe cerebral damage in association with a macerated stillborn twin is reported. The alterations in the kidneys and brain of the twin born alive suggest that the primary event took place before birth. Thromboplastic material and embolizing particles derived from the dead fetus may have passed the monoamnionic-monochorionic twin placenta and caused disseminated intravascular coagulation in the living twin, followed by infarction in other organ systems.

Brain Diseases↗
PubMed1987

Anxiety disorders and psychiatric referral in the general medical emergency room.

A retrospective chart review of patients seen in the medical emergency room between July 1983 and July 1984 indicated that only one third of the patients who received a final diagnosis that included anxiety were referred for psychiatric follow-up. This was in sharp contrast to the referral pattern from the ER of depressed or psychotic patients. In the present study, referred and nonreferred patients were compared on 17 variables to determine those factors that influenced decision to refer. Among the five factors that discriminated between the criterion groups were age, depression, and lack of concomitant medical findings.

Adolescent↗
PubMed1987

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes.

A group of trimethoprim (TMP) analogues containing 3,5-dialkyl(or halo)-4-alkoxy, -hydroxy, or -amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably similar for rat, Neisseria gonorrhoeae, and Plasmodium berghei enzymes in all three series, although somewhat different for Escherichia coli DHFR, leading to the conclusion that the hydrophobic pockets are similar for the first three isozymes. Optimal substitution was reached with 3,5-di-n-propyl or 3-ethyl-5-n-propyl groups. Branching of chains at the alpha-carbon, which resulted in increased substituent thickness, was detrimental to E. coli DHFR inhibition in particular. MR is an inadequate parameter for use in correlating such substituent effects. Conformational changes of the more bulky inhibitors can be invoked to explain some differences in inhibitory pattern. Although log P explains simple substituent effects with the vertebrate DHFRs very well, it is insufficient in the more complex cases described here, where shape is clearly involved as well. Solvent-accessible surface areas were measured for TMP in E. coli and chicken DHFRs, where the coordinates are now known. The environment is more hydrophobic in the latter case; this can also be postulated for rat DHFR, which has a very similar activity profile. As with the mammalian isozymes, N. gonorrhoeae DHFR contains an active site phenylalanine replacing Leu-28 of E. coli DHFR, thus creating a more hydrophobic pocket. A similar replacement may also occur in the P.berghei isozyme. Selectivity for bacterial DHFR is dependent on the nature of the 4-substituent, being low for polar 4-hydroxy compounds but high for polar 4-amino analogues, possibly as a result of solvation differences. With complex substituents, the environment of each atom in the active site must be taken into account to adequately explain structure-activity relationships.

Animals↗
PubMed1987

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 8. The 3,4,5-triethyl isostere of trimethoprim. A study of specificity.

3,4,5-Triethylacetophenone was synthesized in 60% yield by a Friedel-Crafts reaction from 4-ethylacetophenone and converted to 2,4-diamino-5-(3,4,5-triethylbenzyl)pyrimidine (2), a trimethoprim (1) isostere, by standard techniques. This compound is more lipophilic than 1 by three log units (log P, octanol/water). Compound 2 was approximately equipotent with 1 in inhibiting Escherichia coli dihydrofolate reductase (DHFR), 2-fold more potent against P. berghei and N. gonorrhoeae DHFR, and 10 and 25 times better an inhibitor of rat and chicken liver DHFR, respectively. Although the 3,4-dimethoxy analogue 19 was 10-fold less inhibitory to E. coli DHFR than 1, it was 3-4 times more potent on the vertebrate isozymes, whereas the diethyl congener 10 followed 19 in its E. coli DHFR binding but was less active on rat and chicken DHFR. Therefore, a significant portion of the selectivity of 1 for bacterial, as opposed to vertebrate, DHFR, involves the methoxy functions. An analysis of the X-ray data on 1 and 2 complexed with chicken DHFR, coupled with kinetic data, led to the conclusion that the difference in binding energies of the methoxy and ethyl compounds probably involve desolvation factors, as well as direct energies of interaction with protein atoms. Thus, one cannot invoke lipophilicity or shape alone in explaining the relationship in properties of 1 and 2.

Animals↗
PubMed1986

A study of optimal length of flexible fiberoptic sigmoidoscopes for initial endoscopic training.

Eighteen trainees with no prior fiberoptic endoscopic experience performed a total of 305 fiberoptic sigmoidoscopies using a colonoscope. Basic training, consisting of reading materials, lecture instructions, practice on a colon model, and observation of procedures, was completed prior to beginning patient examinations. Additional instruction was given between examinations. The performance of these examinations was an individual effort on the part of the trainee without verbal or mechanical assistance from the instructor after the initial ten examinations. All were performed with an instructor viewing through a teaching attachment. Total insertion distance was greater than or equal to 30, greater than or equal to 40, greater than or equal to 50, greater than or equal to 60 cm in 65, 60, 46, and 20 percent of examinations, respectively. Overall performance was better in those with prior rigid sigmoidoscopic experience (20 examinations). The mean examination time was 11.8 minutes. These data help to define the appropriate length of fiberoptic sigmoidoscope recommended for use by inexperienced endoscopists.

Education, Medical, Undergraduate↗
PubMed1986

[Treatment tactics and late results in early infection following osteosynthesis].

UNLABELLED: On the basis of long term results (five to 29 years), the treatment of postoperative wound infection after internal fixation (40 shaft fractures) is outlined. Of decisive importance is the immediate surgical intervention as soon as the first clinical signs of infection become evident. PROCEDURE: opening of the wound, leaving stable implants in situ, temporary irrigation drainage. RESULTS: in 31 cases spontaneous bone healing without bone grafting. Only in nine cases a residual infected focus needed cancellous bone grafting (in five of these cases additional surgical stabilisation, in the other four cases the bone itself was already sufficiently stable). In 35 patients full restoration of working capacity; in 33 patients full functional repair.

Combined Modality Therapy↗