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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 217 records · Page 12Linked to original sources
PubMed1994

One armed PCR (OA-PCR): amplification of genomic DNA from a single primer domain.

One-armed PCR (OA-PCR) is a novel technique that allows amplification of genomic DNA from a single region of known sequence. Previously described methods are either limited to cDNA or require extensive manipulation of template prior to amplification. In OA-PCR, DNA from a small insert phage Fugu genomic library is amplified using two sequence-specific primers and a tailed vector primer. Single, specific products of between 70 bp and 1.9 kb (mean 600 bp) have been obtained following two rounds of amplification and directly sequenced without cloning. The optimum parameters have been investigated: primer pairs of 18-24 bp, separated by between 0 and 500 bp, have successfully amplified a specific product. OA-PCR represents a rapid, simple method to extend genomic sequence into noncoding and regulatory sequences. In addition, degenerate OA-PCR primer pairs have allowed cross-species amplification of novel Fugu gene homologues.

DNA, Viral↗
PubMed1994

A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1.

Within the Hoxb homeobox gene complex, Hoxb-1 is the earliest member expressed in the mesoderm and neuroectoderm of primitive streak and presomite embryos, preceding rhombomere-restricted expression in the hindbrain. Ectopic exposure of embryos to retinoic acid alters spatial aspects of Hox gene expression patterns. However, the role of retinoids in regulating these genes during normal development is unclear. We have now identified two enhancers, 3' of the mouse Hoxb-1 gene, which together reconstruct the early endogenous expression pattern and mediate the early ectopic response to retinoic acid. Furthermore, these regions are functionally conserved in both chicken and pufferfish (Fugu rubripes) Hoxb-1 genes. The enhancer that controls the retinoic acid response, and regulates expression predominantly in neuroectoderm, contains a retinoic acid response element (RARE). Point mutations in the RARE abolish expression in neuroectoderm. Therefore, this RARE is not only involved in the ectopic response to retinoic acid, but is also essential for establishing aspects of the early Hoxb-1 expression pattern.

Animals↗
PubMed1994

Lambda foo: a lambda phage vector for the expression of foreign proteins.

This work describes a lambda phage expression system, lambda foo, that produces foreign proteins fused to the surface of the virus particle. The lambda foo vector has multiple cloning sites for the insertion of a foreign DNA fragment and color selection for recombinants. Foreign proteins are fused to the C terminus of a truncated phage tail protein, pV, by a peptide linker. Conditional chain termination allows the assembly and fusion of multisubunit proteins. We have attached the complete Escherichia coli beta-galactosidase and the plant Bauhinia purpurea agglutinin by cloning their genes into the vector. The constructs express functionally active proteins on the phage particle surface and have been purified by affinity chromatography with an antibody for beta-galactosidase and a mucin as a ligand for Bauhinia purpurea agglutinin.

Amino Acid Sequence↗
PubMed1994

Subtraction hybridisation and shot-gun sequencing: a new approach to identify symbiotic loci.

Traditionally, new loci involved in the Rhizobium-legume symbiosis have been identified by transposon mutagenesis and/or complementation. Wide dispersal of the symbiotic loci in Rhizobium species NGR234, as well as the large number of potential host-plants to be screened, greatly reduces the efficiency of these techniques. As an alternate strategy designed to identify new NGR234 genes involved in the early stages of the symbiosis, we combined data from competitive RNA hybridisation, subtractive DNA hybridisation and shot-gun sequencing. On the assumption that the expression of most nodulation genes is triggered by compounds released by the host-plant, we identified, in the ordered cosmid library of the large symbiotic plasmid pNGR234a, restriction fragments that carry transcripts induced by flavonoids. To target genes not present in the closely related strain R. fredii USDA257, we selected fragments that also carried sequences purified by subtractive DNA hybridisation. Shot-gun sequencing of this subset of fragments lead to the identification of sequences with strong homology to diverse prokaryotic genes/proteins. Amongst these, a symbiotically active ORF from pNGR234a, is highly homologous to the leucine responsive regulatory protein of Escherichia coli (Lrp), is induced by flavonoids, and is not present in USDA257.

Amino Acid Sequence↗
PubMed1994

Eosinophilic pustular folliculitis: a sterile folliculitis of unknown cause?

BACKGROUND: Eosinophilic pustular folliculitis (EPF) was initially defined as a sterile folliculitis of unknown cause. Because attempts to demonstrate bacterial organisms have been unsuccessful, and antibiotic therapy is usually ineffective, a bacterial infection is not considered a plausible causative factor for this disease. OBJECTIVE: Our purpose was to describe five patients with the clinical and histologic characteristics of EPF and to report the results of bacterial cultures. METHODS: Biopsy specimens were examined and pustules were cultured. RESULTS: In three of the five patients, Pseudomonas infection of the hair follicle was the cause of the disease as proven by repeated cultures and the response to specific therapy. Three patients had a systemic disorder known to cause immunologic alteration: AIDS in one and a myeloproliferative disorder in two. CONCLUSION: Although EPF was initially defined as a sterile folliculitis of unknown origin, three of our patients had an identifiable and treatable cause. We believe that these cases warrant the diagnosis of EPF.

Adult↗
PubMed1994

Contact dermatitis in Israeli soldiers.

This report consists of an evaluation of 41 soldiers from the infantry, armored, and artillery division, who developed hand dermatitis from their contact with oils and fuel. A special "tailored" supplementary tray with five reagents relevant to their field of work and environment was performed. The reagents that were used were gun oil, hydraulic oil, automotive lubricant (oil) 20/50, white spirit, and car petrol (gasoline). Seven of the 41 patients (17%) showed one or more positive tests to the supplementary tray. The fact that none of the control group of 64 patients not exposed to these substances showed a positive result to the supplementary tray indicates that false positive results are, at least, not probable. It is suggested that soldiers with occupational hand dermatitis should be tested with supplemental aimed trays that are relevant to their work and environment, in addition to the standard trays.

Dermatitis, Contact↗
PubMed1994

Induction of psoriasiform changes in guinea pig skin by propranolol.

BACKGROUND: The ability of beta-adrenergic blocking agents to induce psoriasis as an adverse effect prompted us to use such an agent to induce psoriasis in guinea pigs. METHODS: Thirty female albino guinea pigs were divided into four groups. Group 1 received propranolol, 0.1 mg/day, dissolved in 2 mL of normal saline, orally by gavage for 30 days. Group 2 was given the same treatment, but in addition intradermal injections of propranolol with Freund's complete adjuvant, injected at weekly intervals. Group 3 (five animals) received 2 mL saline, and group 4 additional injections of adjuvant without propranolol. Groups 3 and 4 served as normal controls. RESULTS: All animals of group 2 (which received propranolol orally and in addition intradermal injections of adjuvant) developed psoriasiform epidermal hyperplasia with acanthosis. Parakeratosis, papillomatosis, and formation of microabscesses, all characteristic signs of psoriasis, have not been seen in any of the skin samples of this group. Skin samples from group 1 animals receiving propranolol orally showed normal epidermis and dermis. They showed exactly the same histologic picture as the control groups 3 and 4. CONCLUSIONS: Beta-blockers given orally for 30 days do not cause any significant skin changes in guinea pigs. When given with a weekly intradermal injection of Freund's complete adjuvant, they cause psoriasiform epidermal hyperplasia. Although the overall histologic appearance of the skin of group 2 resembled psoriasis, it lacked important histologic features characteristic of this disease. It seems, therefore, that the model, per se, does not fulfill the initial expectations as an experimental model for psoriasis; however, this model has potential in the study of adverse drug reactions. Perhaps by introducing modifications to the experimental protocol, we may succeed also in developing a better model for experimental psoriasis.

Abscess↗
PubMed1994

Canine, human, and rat plasma insulin responses to galanin administration: species response differences.

Previous studies demonstrated that porcine galanin is a potent inhibitor of insulin secretion in many species but fails to alter human insulin secretion. To resolve whether this discrepancy was due to the use of a heterologous peptide or to a true species response difference, we studied the effect of a synthetic replicate of human galanin on glucose-stimulated insulin secretion in rats, dogs, and humans. On administration into rats, human and rat galanin significantly inhibited glucose-induced insulin responses to a similar degree. Similarly, porcine and human galanin significantly elevated canine plasma glucose and inhibited canine plasma insulin responses. In contrast, plasma glucose and insulin responses to glucose administration in humans were unaltered by the addition of human galanin at or above the maximum effective dose employed in dogs. Possible effects of galanin administration were seen on human glucagon and pancreatic polypeptide responses to glucose at the highest dose of human galanin infused. We conclude that galanin probably does not play a major role in modulating human beta-cell function.

Adult↗
PubMed1994

An active amide group in the molecule of drugs that induce pemphigus: a casual or causal relationship?

Traditionally, drugs that are capable of inducing pemphigus are divided into two main groups according to their chemical structure, in particular, the existence of a sulfhydryl group in their molecule. Thus, two groups are formed: (1) drugs containing a sulfhydryl radical (thiol drugs or SH drugs) and (2) nonthiol or other drugs. Much emphasis has been put on the role of the sulfhydryl group in the pathogenesis of drug-induced pemphigus. The effects of this group have been extensively studied, and a logical paradigm on the mode of its action has been created. However, no attempt has been made to search for other biochemical radicals which might have an influence on the activation/triggering of this disease. The aim of the present report is to draw attention to a chemical group common to the molecule of several drugs that have been associated with the induction of pemphigus. Careful analysis of the chemical structure of nonthiol drugs known to induce pemphigus revealed that several of them share an active amide group in their molecule. We believe that this group might be responsible for the induction of the disease; thus, a third group of drugs capable of triggering pemphigus can be formed, namely drugs containing an active amide group. Several drugs of this group are discussed.

Amides↗
PubMed1994

Possible nutritional factors in induced pemphigus.

Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus. Some plants, in particular those belonging to the Allium group, contain several active compounds with stable disulfide and thiol groups in their molecule. The Allium group contains many important vegetables like onion, leek and garlic. Examples of molecules with an active thiol group are: CH2 = CH-CH2-S-S-CH2-CH = CH2 (diallyl disulfide) or CH2 = CH-CH2-S(O)S-CH2-CH = CH2 (allicin). It is suggested that some foods, in particular vegetables of the Allium group that contain active thiol groups in their molecule, could contribute to the induction of pemphigus. In general, nutritional factors should be added to the list of exogenous factors that are capable of inducing pemphigus.

Allium↗
PubMed1994

Histamine effect on human cutaneous blood flow: regional variations.

Different reactivities of small blood vessels to the histamine released by exogenous and endogenous substances may play a role in the regional variations of the elicited cutaneous response. To study the regional dependence of cutaneous blood flow in response to histamine, the compound was administered intradermally (prick introduction), thereby bypassing the spatially dependent penetration process. The induced response was quantified with cutaneous blood flow measurements utilizing laser Doppler flowmetry. Extent of response and time parameters were compared. Three anatomical sites, the back, volar side of the forearm, and ankle, were studied on 20 volunteers (10 men and 10 women, age 24-34). For comparison, topical administration was also performed. Significant differences in the measured responses at the three sites were observed: the increase of the cutaneous blood flow on the back was greater than the forearm (p < 0.01 prick test, p < 0.05 topical application), and that of both sites was greater than the ankle (p < 0.01 prick test, p < 0.05 topical application). There were no significant differences among the different sites in time parameters and no gender variations. As expected, the time required to reach maximum response was shorter for the intradermal method as compared to the topical application on the back (p < 0.001) and forearm (p < 0.05). On the other hand, the time required to decrease to 50% of maximum response was not different for the intradermal and topical methods of histamine application. These blood vessel response observations may provide initial insight into inherent functional differences influencing cutaneous manifestations of endogenous and exogenous diseases.

Administration, Topical↗
PubMed1994

Leukocytoclastic vasculitis: another coumarin-induced hemorrhagic reaction.

A 67-year-old male developed a hemorrhagic eruption 4 weeks after initiation of coumarin therapy. Examination revealed a well-demarcated, purple patch with a central hemorrhagic bulla on the anterior aspect of the leg, surrounded by small petechiae. Histological examination of the purple plaque revealed leukocytoclastic vasculitis. It is suggested that leukocytoclastic vasculitis be considered in the differential diagnosis of coumarin-induced hemorrhagic reactions.

Aged↗
PubMed1994

Psoriasiform eruption induced by anticonvulsants.

We present findings from three patients who experienced a psoriasiform eruption apparently due to the antiepileptic agents sodium valproate and carbamazepine. The causal relationship between the drug and the eruption has been based mainly on circumstantial evidence and is further strengthened by the positive result of one or two in vitro tests: the macrophage migration inhibition (MIF) test and the indirect rat mast cell degranulation (MCD) test. Sodium valproate and carbamazepine, antiepileptic drugs that are associated with a relatively low rate of adverse cutaneous reactions, should be added to the growing list of drugs that produce psoriasiform eruptions. A drug-induced psoriasiform eruption due to these drugs seems to be more common than previously reported. Physicians should be aware of this type of reaction. Early detection of these cases has practical importance since the identification and elimination of the causative drug is essential for therapy success.

Adult↗