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S Brenner

Publications and source records attributed to S Brenner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Something fishy in the rat brain: molecular genetics of the hypothalamo-neurohypophysial system.

The brain peptides vasopressin and oxytocin play crucial roles in the regulation of salt and water balance. The genes encoding these neurohormones are regulated by cell-specific and physiological cues, but the molecular mechanisms remain obscure. New strategies, involving the introduction of rat transgenes into rats, are being used to address these issues, but the complexity of the rat genome has hampered progress. By contrast, the pufferfish, Fugu rubripes, has a "junk-free" genome. The oxytocin homologue from Fugu, isotocin, has been introduced into rats and is expressed in oxytocin neurons, where it is upregulated by physiological perturbations that upregulate the oxytocin gene. The Fugu and rat lineages separated 400 million years ago, yet the mechanisms that regulate the isotocin and oxytocin genes have been conserved. Fugu genome analysis and transgenesis in the physiologically tractable rat host are a powerful combination that will enable the identification of fundamental components of the neural systems that control homeostasis.

Animals↗
PubMed1998

Biological computation.

It is argued that biological systems can be viewed as special computing devices. This view emerges from considerations of how information is stored in and retrieved from the genes. Genes can only specify the properties of the proteins they code for, and any integrative properties of the system must be 'computed' by their interactions. This provides a framework for analysis by simulation and sets practical bounds on what can be achieved by reductionist models.

Computational Biology↗
PubMed1998

A stage of change approach to addiction in the medical setting.

Despite recent advances in its understanding and treatment, addiction remains a difficult challenge for clinicians within medical settings such as the general hospital. The use of single, traditional paradigms (disciplinary, therapeutic, educational, or libertarian) for approaching addiction-related problems have often failed to embrace the complexity of the patients' motivation to change. Prochaska and DiClemente's [7] stage of change model offers a realistic, practical, and broadly applicable means by which clinicians can facilitate behavioral change from the stage of denial (precontemplation) through that of sustained recovery (maintenance). Clinicians can help addicted individuals to move from precontemplation to contemplation by enhancing their ambivalence; from contemplation to preparation by considering their history of change; from preparation to action by flexibly intervening based on this understanding; and from action to maintenance by evaluating the outcomes of these interventions. A stage of change model is also useful in understanding the process of change in clinicians' own approaches to patients with substance use disorders.

Adult↗
PubMed1998

Different patterns of in vitro acantholysis in normal human skin samples explanted from different sites of the body.

BACKGROUND: The factors that contribute to a preferential anatomic localization of pemphigus lesions are not well known. In particular, the question arises as to whether certain skin areas may be more acantholysis-prone than others. OBJECTIVE: To verify whether, in pemphigus patients, a different susceptibility to acantholysis exists among different cutaneous regions, the technique of tissue cultures was used. METHODS: Normal human skin explants from two distinct anatomic regions (back and buttocks) of two former pemphigus patients were cultured in vitro in the presence of enalapril (6 mM) or cystamine (10 mM), two substances with a proven biochemical acantholytic effect. After 4 days of culture, the tissues were processed for standard histology. RESULTS: Diffuse acantholysis, with large intraepidermal splits, was observed in the explants taken from the backs of both subjects and cultured with either enalapril or cystamine. Mild to moderate acantholytic changes were detected in the explants taken from the buttocks of both subjects and cultured with either enalapril or cystamine. No structural changes were seen in the control cultures. CONCLUSIONS: Pemphigus patients present different thresholds of acantholysis in different areas of their bodies. This might explain, at least in part, certain preferential anatomic localizations of pemphigus lesions.

Acantholysis↗
PubMed1998

Dorfman-Chanarin syndrome: morphologic studies and presentation of new cases.

Dorfman-Chanarin syndrome, or neutral lipid storage disease with ichthyosis, is a rare inherited metabolic disorder characterized by accumulation of neutral lipids in different tissues. Variability in dermatologic severity is not understood. We report two new cases, compare their features with other reported cases, and examine the possible relationship between the severity of the dermatologic condition and lipid accumulation in various types of skin cells. The localization of lipid droplets was determined in various dermal and epidermal cells by light microscopy of epoxy resin semithin sections and electron microscopy in four cases of Dorfman-Chanarin syndrome. Lipid droplets in the dermis were detected in fibroblasts, Schwann cells in both myelinated and unmyelinated nerves, smooth muscle cells, and sweat gland cells, but not in endothelial cells of blood capillaries. The droplets were not surrounded by a membrane. Findings indicate that there is no correlation between the clinical severity of the disease and the microscopic findings.

Adolescent↗
PubMed1998

Contact dermatitis with systemic symptoms from Agave americana.

BACKGROUND: Twelve cases of contact dermatitis provoked by Agave americana are described, 10 with systemic signs and symptoms and 8 with abnormal laboratory results. RESULTS: Patient history revealed a background of intentional exposure among soldiers seeking sick leave. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24 h of hospitalization and regression of cutaneous manifestations in 7-10 days. CONCLUSION: The importance that dermatologists be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants is stressed, especially to A. americana. Systemic signs are not rare accompanying findings with this plant.

Adolescent↗
PubMed1998

Classic Kaposi's sarcoma: low-dose interferon alfa treatment.

BACKGROUND: Classic Kaposi's sarcoma, a rare form of cancer, has no definitive cure. A beneficial effect of low-dose interferon (IFN) alfa was indicated by some case reports. In the present report, we summarize the results of our experience with subcutaneous low-dose IFN alfa treatment of 11 patients with extensive classic Kaposi's sarcoma and review the literature. DESIGN: Eleven patients, 56-96 years old, were treated: 10 men, 1 woman, 3 of whom had an associated malignancy. Subcutaneous injections of IFN alfa were given, starting with 3 million units 5 times a week, and modified according to side effects and response after 2 weeks (2-6 million units, 3-6 times a week). This treatment was continued for 6 months, except for 1 patient who died after 4 months and another who stopped treatment at 4 months due to surgery but was treated again after recurrence. Treatment was continued after 6 months when a partial response was noted, but further improvement was desired (1 patient). RESULTS: In 9 out of the 11 patients, initial response was noted after 3-13 weeks of treatment. This was manifested by a reduction of lesion size and fading of color, leading to a partial resolution. Maximum response was achieved after 4-6 months. Remission lasted 4-72 months. Recurrences were retreated, with additional remissions after only 5-8 weeks of treatment. Side effects included fever and fatigue, which were overcome by dose reduction. CONCLUSION: Whereas in AIDS-related Kaposi's sarcoma patients become refractory to IFN, this was not observed in our patients with classic Kaposi's sarcoma. Moreover, unlike AIDS-related Kaposi's sarcoma, continuous treatment was not needed in classic Kaposi's sarcoma, and recurrences were responsive to retreatment.

Aged↗
PubMed1998

Peeling skin syndrome with hair changes.

A 13-year-old boy with typical peeling skin syndrome (PSS) is described. The clinical picture corresponded to the inflammatory variant of PSS (type B). In addition, the patient had gross and microscopic hair anomalies such as trichorrhexis invaginata-like changes, irregular hair shaft torsions and moniliform hair shaft diameter reductions. The observed dysmorphic hair changes are discussed and interpreted as being an integral component of the dermatosis in this case. To the best of our knowledge, such hair anomalies have not yet been described in PSS.

Adolescent↗
PubMed1998

Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate.

The generation of anterior-posterior polarity in the vertebrate brain requires the establishment of regional domains of gene expression at early somite stages. Wnt-1 encodes a signal that is expressed in the developing midbrain and is essential for midbrain and anterior hindbrain development. Previous work identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence which is necessary and sufficient for Wnt-1 expression in vivo. Using a transgenic mouse reporter assay, we have now identified a 110 base pair regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate stages. Multimers of this element driving Wnt-1 expression can partially rescue the midbrain-hindbrain phenotype of Wnt-1(-/-) embryos. The possibility that this region represents an evolutionarily conserved regulatory module is suggested by the identification of a highly homologous region located downstream of the wnt-1 gene in the pufferfish (Fugu rubripes). These sequences are capable of appropriate temporal and spatial activation of a reporter gene in the embryonic mouse midbrain; although, later aspects of the Wnt-1 expression pattern are absent. Genetic evidence has implicated Pax transcription factors in the regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory element in vitro, the location of the binding sites could not be precisely established and mutation of two putative low affinity sites did not abolish activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory region. Our analysis of the 110 base pair minimal regulatory element suggests that Wnt-1 regulation is complex, involving different regulatory interactions for activation and the later maintenance of transgene expression in the dorsal midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.

Animals↗
PubMed1998

Screening for tumour suppressor p16(CDKN2A) germline mutations in Israeli melanoma families.

Approximately ten percent of patients with malignant melanoma have family histories of the disease, suggesting a genetic predisposition. Germline mutations in tumour suppressor p16 gene have been implicated as disease causing mutations in some of the melanoma families. The frequency of families with p16 germline mutations among melanoma prone families varies from eight to fifty percent. The range of the variability is influenced apparently by the number of melanoma affected individuals within the family, as well as by other, yet unidentified factors. Ethnic background is known to determine both the frequency and the nature of germline alterations. Recently, specific mutations in tumour suppressor genes involved in breast cancer and in colon cancer were found at elevated frequency among Ashkenazi Jews. This report describes results of a screening for p16 germline alterations in a collection of Israeli melanoma families. We have analyzed genomic DNA from thirty one Ashkenazi and non-Ashkenazi Jewish melanoma families, as well as from thirty melanoma patients without an apparent family history of the disease. The entire coding region of the p16 gene was screened by single strand conformation polymorphism analysis and direct DNA sequencing. We have detected a number of carriers with the Ala148 Thr polymorphism at the end of the second exon and several instances of 500(G=>C) substitution at the 3' untranslated portion of the gene.

Female↗
PubMed1998

Duodenal ulcer patients exhibit a greater skin response to histamine.

BACKGROUND: Histamine is considered a major mediator in the process of gastric acid secretion. When acid peptic activity overpowers the mucosal defense mechanism, peptic ulceration may develop. Is the hyperreactivity of patients with duodenal ulcer to histamine also expressed in the skin? OBJECTIVE: The aim of the present study was to assess the reactivity of patients with duodenal ulcer to histamine as reflected in the skin, by comparing the erythema and the cutaneous blood flow response to histamine in duodenal ulcer patients and healthy controls. METHODS: Twenty volunteers participated in the study: 10 duodenal ulcer patients and 10 age and gender matched healthy controls. Histamine was topically administered to the back and to the volar side of the forearm, and the induced response was quantified by spectrophotometry and laser Doppler flowmetry (LDF). The extent of the response and time parameters were compared. RESULTS: The maximum response, as measured by LDF, was greater in the peptic ulcer patients (P < 0.05) compared to healthy controls. Aging was accompanied by decreased responsiveness in both groups. CONCLUSION: The results suggest that some peptic ulcer patients exhibit a greater cutaneous response to topical application of histamine than healthy controls. As the methods used are non-invasive, simple and rapid, they might be useful in preclinical ulcer diagnosis and detection of patients at risk.

Administration, Topical↗
PubMed1997

Academic dynamics

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Journal Article↗
PubMed1997

Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes.

We have asked whether comparative genome analysis and rat transgenesis can be used to identify functional regulatory domains in the gene locus encoding the hypothalamic neuropeptides oxytocin (OT) and vasopressin. Isotocin (IT) and vasotocin (VT) are the teleost homologues of these genes. A contiguous stretch of 46 kb spanning the Fugu IT-VT locus has been sequenced, and nine putative genes were found. Unlike the OT and vasopressin genes, which are closely linked in the mammalian genome in a tail-to-tail orientation, Fugu IT and VT genes are linked head to tail and are separated by five genes. When a cosmid containing the Fugu IT-VT locus was introduced into the rat genome, we found that the Fugu IT gene was specifically expressed in rat hypothalamic oxytocinergic neurons and mimicked the response of the endogenous OT gene to an osmotic stimulus. These data show that cis-acting elements and trans-acting factors mediating the cell-specific and physiological regulation of the OT and IT genes are conserved between mammals and fish. The combination of Fugu genome analysis and transgenesis in a mammal is a powerful tool for identifying and analyzing conserved vertebrate regulatory elements.

Animals↗