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Biomedical subjects

H Wilson

Publications and source records attributed to H Wilson.

At least 55 records · Page 3Linked to original sources

Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels.

Atracotoxins are novel peptide toxins from the venom of Australian funnel-web spiders that slow sodium current inactivation in a similar manner to scorpion alpha-toxins. To analyse their interaction with known sodium channel neurotoxin receptor sites we determined their effect on scorpion toxin, batrachotoxin and saxitoxin binding. Nanomolar concentrations of delta-atracotoxin-Hv1 and delta-atracotoxin-Ar1 completely inhibited the binding of the scorpion alpha-toxin AaH II to rat brain synaptosomes as well as the binding of LqhalphaIT, a scorpion alpha-toxin highly active on insects, to cockroach neuronal membranes. Moreover, delta-atracotoxin-Hv1 cooperatively enhanced batrachotoxin binding to rat brain synaptosomes in an analogous fashion to scorpion alpha-toxins. Thus the delta-atracotoxins represent a new class of toxins which bind to both mammalian and insect sodium channels at sites similar to, or partially overlapping with, the receptor binding sites of scorpion alpha-toxins.

Amino Acid Sequence↗

Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes.

Cyclic ADP-ribose (cADPR) is a cyclic metabolite of NAD+ synthesised in cells and tissues expressing ADP-ribosyl cyclases. Although it was first discovered in sea-urchin egg extracts as a potent calcium mobilizing agent, subsequent studies have indicated that it may have a widespread action in the activation of calcium-release channels in such diverse systems as mammalian neurones, myocytes, blood cells, eggs, and plant microsomes. In this review we focus on recent work suggesting that cADPR enhances the sensitivity of ryanodine-sensitive calcium-release channels (RyRs) to activation by calcium, a phenomenon termed calcium-induced calcium release (CICR). Two roles for cADPR in calcium signaling are discussed. The first is as a classical second messenger where its levels are controlled by extracellular stimuli, and the second mode of cellular regulation is that the levels of intracellular cADPR may set the sensitivity of RyRs to activation by an influx of calcium in excitable cells. These two possible actions of cADPR are illustrated by considering the signal transduction events during the fertilization of the sea-urchin egg and the modulation of CICR during excitation-coupling in isolated guinea-pig ventricular myocytes, respectively.

Adenosine Diphosphate Ribose↗

Sex steroid control of mood, mental state and memory.

1. Sex steroid hormones exert profound effects on mood and mental state. Thus, in women, oestrogen is thought to protect against depression and delay the onset of schizophrenia and Alzheimer's disease. 2. Our studies in the female rat show that oestradiol, in its positive feedback mode for gonadotrophin release, increases the expression of genes for the 5-hydroxytryptamine 5-HT2A receptor and the serotonin transporter (SERT) in the dorsal raphe nucleus and the density of 5-HT2A receptor and SERT sites in regions of the forebrain that, in the human, are concerned with cognition, mental state, emotion and memory. 3. In the male rat, castration decreases while oestrogen and testosterone, but not 5 alpha-dihydrotestosterone (5 alpha-DHT), increase the density of 5-HT2A receptors in forebrain. The fact that 5 alpha-DHT has no effect suggests that the action of testosterone depends on its conversion to oestradiol by aromatase. 4. In intact rats, the density of 5-HT2A receptors in cerebral cortex is significantly higher in pro-oestrous female than in male and dioestrous female rats, showing that the spontaneous, preovulatory surge of oestradiol that reaches a peak at 12.00 h of pro-oestrus also increases the density of 5-HT2A receptors in cortex. 5. Oestrogen and testosterone (by way of its conversion to oestrogen) also stimulate the expression of the arginine vasopressin gene in the bed nucleus of the stria terminalis of the rodent, a mechanism that plays a key role in olfactory memory. 6. These actions of sex steroid hormones are discussed in the context of genomic versus non-genomic mechanisms, the recent discovery that there are two oestradiol receptors with different distributions in brain, the significance of our findings for our understanding of the control of mood, mental state and memory and the mechanism by which oestrogen stimulation of the 5-HT2A receptor could delay the onset of Alzheimer's disease.

Affect↗

Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain.

The aim of the present study was to determine the effect of estradiol-17 beta (E2), in its positive feedback mode for gonadotropin release, on the serotonin transporter (SERT) in female rat brain. Levels of SERT mRNA were determined by in situ hybridization and SERT-binding sites were measured by quantitative [3H]paroxetine receptor autoradiography. The injection of estradiol benzoate (EB) in acutely ovariectomized rats increased significantly (approximately 50%) the numbers of cells that expressed SERT mRNA in the dorsal raphe nucleus and the density of SERT-binding sites in lateral septum (90%), basolateral amygdala (20%), ventral nucleus of thalamus (250%) and ventromedial hypothalamic nucleus (250%). SERT-binding sites in EB-treated rats were significantly lower in periaqueductal central grey (15%). These findings indicate that effects on SERT gene expression may be involved in the E2-induction of the gonadotropin surge. Together with our previous findings, they also suggest that the sex differences in depression and the apparent psychotropic effect of E2 may be due to the action of E2 on the serotonin transporter as well as 5-HT2A receptors.

Animals↗

Specific monoclonal antibody raised against the p33ING1 tumor suppressor.

An IgG1 mouse monoclonal antibody (CAb1) was produced against human recombinant p33ING1. The antibody is able to recognize native and denatured antigen in ELISA and Western blot protocols, respectively. CAb1 can be used to specifically detect the p33ING1 protein in dot blot and Western immunoblot protocols of both human and mouse cell lysates. In addition, this antibody is also useful for cellular localization of native and ectopically overexpressed p33ING1 protein by indirect immunofluorescence.

Animals↗

Integration specificities of two lambdoid phages (21 and e14) that insert at the same attB site.

It was shown previously that phage 21 and the defective element e14 integrate at the same site within the icd gene of Escherichia coli K-12 but that 21 integrase and excisionase excise e14 in vivo very infrequently compared to excision of 21. We show here that the reverse is also true: e14 excises itself much better than it excises an adjacent 21 prophage. In vitro integrase assays with various attP substrates delimit the minimal attP site as somewhere between 366 and 418 bp, where the outer limits would include the outermost repeated dodecamers suggested as arm recognition sites by S. J. Schneider (Ph.D. dissertation, Stanford University, Stanford, Calif., 1992). We speculate that the reason 21 attP is larger than lambda attP (240 bp) is because it must include a 209-bp sequence homologous to the 3' end of the icd transcript in order to allow icd expression in lysogens. Alteration of portions of 21 attP to their e14 counterparts shows that 21 requires both the arm site and core site sequences of 21 but that replacements by e14 sequences function in some positions. Consistent with Schneider's in vivo results, and like all other known integrases from lambdoid phages, 21 requires integration host factor for activity.

Bacterial Proteins↗

PBMA (programme budgeting marginal analysis)--its role in the future purchasing arrangements for health care services.

The movement of the purchasing process in health care from a central to local level has to be accompanied by an accountability process which makes local purchasers accountable within an agreed national and area framework for their decisions and implementation of change. This paper focuses on PBMA and its applicability to health boards and general practitioner fundholders in future purchasing arrangements. It is argued that it is a useful tool which may provide a basis for more rational discussion about use of resources, both at a micro and macro level, than the current arrangements.

Budgets↗

The American Urological Association symptom index: does mode of administration affect its psychometric properties?

PURPOSE: We determine whether self-administration and interviewer administration of the American Urological Association (AUA) symptom index are equivalent. MATERIALS AND METHODS: The AUA symptom index was administered twice to 41 visually impaired or illiterate men. Men who were able were randomized to self-administration first and then interviewer administration (43) or the reverse (40). RESULTS: The scores in each group were reliable. However, because we could not reject a differential carryover effect, the nonsignificant test of mode effect in the crossover design may have been invalid. At time 1 there was no significant difference between group mean scores for randomized patients (p = 0.13). CONCLUSIONS: Although the AUA symptom index should be self-administered when possible, interviewer administration appears to be acceptable.

Aged↗

Can phage defence maintain colicin plasmids in Escherichia coli?

We examined the role of plasmid-based phage defence in maintaining plasmids, using colicin plasmids in Escherichia coli as a model system. Experimental data indicated that the possession of a colicin plasmid can confer limited protection against bacteriophages. A continuous culture model, using these experimental values, indicated that the observed limited protection alone could selectively maintain colicin plasmids, without requiring a competitive advantage due to colicinogeny. Phage defence might explain the current maintenance of colicin plasmids, given the naturally occurring high levels of resistance to colicins. This model also suggests that many plasmids might be maintained in natural populations, in part, by phage resistance, including 'cryptic' plasmids for which no phenotype is known.

Bacteriocin Plasmids↗

The development of astrocytes immunoreactive for glial fibrillary acidic protein in the mediobasal hypothalamus of hypogonadal mice.

Numbers of astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) are markedly increased in the mediobasal hypothalamus (MBH) of adult hypogonadal (hpg) mice. The astrocytosis cannot be reversed by administration of gonadal steroids. To investigate whether the glial changes are established in the perinatal period, when crucial developments occur in rodent brain, we determined the distribution of GFAP-IR astrocytes in normal and hpg mouse brain from birth to adulthood. The period up to 3 weeks of age was characterized by the gradual disappearance of radial glia and the increase in mature astrocytes in some brain regions, for example hippocampus. However, there were no apparent differences in GFAP-IR elements between normal and hpg brains and very few astrocytes in the MBH. From age 1 month, increased numbers of GFAP-IR astrocytes were apparent in the hypothalamus in hpg mice and this difference was more obvious at 2 months. By 4 months of age the characteristic astrocytosis in the MBH had been attained and this did not change in older hpg mice. These observations provide no evidence for upregulation of the GFAP gene during the first 2 postnatal weeks when its transcription is highest and astrocytes are proliferating most rapidly. It is more likely that the astrocyte response in the MBH in hpg mice reflects permanent differences in steroid-induced neuronal connectivity, caused by the hypogonadism.

Animals↗

Antigenicity and immunogenicity of equine influenza vaccines containing a Carbomer adjuvant.

Equine influenza vaccines containing inactivated whole virus and Carbomer adjuvant stimulated higher levels and longer lasting antibody to haemagglutinin in ponies than vaccines of equivalent antigenic content containing aluminium phosphate adjuvants. Five months after the third dose of vaccine containing Carbomer adjuvant, ponies were protected against clinical disease induced by an aerosol of virulent influenza virus (A/equine/Newmarket/79, H3N8). In contrast ponies which received vaccine containing aluminium phosphate adjuvant were susceptible to infection and disease. There was an inverse correlation between prechallenge levels of antibody detected by single radial haemolysis (SRH) and duration of virus excretion, pyrexia and coughing. All ponies with antibody levels equivalent to SRH zones of > or = 154 mm2 were protected against infection and all those with levels > or = 85 mm2 were protected from disease.

Acrylic Resins↗

Nitrite inhalants: history, epidemiology, and possible links to AIDS.

Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal.

Acquired Immunodeficiency Syndrome↗

Human herpesvirus 6 is present in lesions of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a disease characterized by Langerhans cell infiltration of skin and bone, with its most severe form manifested by multifocal infiltration of many organs. The etiology is unknown, although viral infection has been proposed as a potential pathogenic factor. Human herpesvirus 6 (HHV-6), a recently described member of the human herpesvirus family, has been associated with atypical or malignant lymphocytic processes, and immune disorders. Based on these observations, we suspected that HHV-6 may play a role in the pathogenesis of LCH. Lesional tissue of 30 patients with LCH was retrospectively examined for the presence of HHV-6 by using the polymerase chain reaction. Tissue specimens from 63 patients with other benign and malignant histiocytic and lymphocytic diseases served as controls. In addition, all specimens were examined with control primers specific for herpes simplex virus (HSV). HHV-6 DNA was detected in lesions of 14 of 30 patients with LCH (47%). On clinical subgroup analysis, HHV-6 DNA was found in 10 of 16 patients with extraosseous disease (63%) and in four of 14 patients with disease limited to bone (29%). In each case, the prevalence of HHV-6 in LCH lesions was statistically significant, when compared to the control population. HSV DNA was not found in any of the LCH or control specimens. Although the presence of a virus alone does not establish a causal role in the disease, it supports the possibility of an etiologic relationship. From this study, we emphasize the need for further investigation of the potential HHV-6-mediated pathogenesis of LCH.

Adolescent↗

Peripheral neuroepithelioma of the soft tissues. A retrospective analysis of fifteen pediatric patients.

PURPOSE: The purpose of this study was to determine the clinical outcome for pediatric patients with peripheral neuroepithelioma treated with combined modality therapy and followed long enough to account for late relapses. PATIENTS AND METHODS: Fifteen patients, ages 3 3/12 to 19 10/12 years, with peripheral neuroepithelioma (median follow-up 91 months) were diagnosed at The Children's Hospital, Denver, Colorado over the period 1980-1989. All of these malignancies originated in the soft tissues. A critical review of these cases was performed with particular consideration given to the site and stage of the tumor and to the radiographic findings at presentation. Thirteen patients had bulk (> 5 cm in the greatest dimension) or metastatic disease. Four patients had primary tumors involving the chest wall. All patients received chemotherapy, which included at least doxorubicin, vincristine, and cyclophosphamide. Definitive surgical resections were performed on 13 of 15 patients. RESULTS: Five patients relapsed. Three were late relapses 24-44 months after diagnosis. Three of the five patients who relapsed had chest wall primaries. There were three deaths in this series due to peripheral neuroepithelioma and one due to sepsis. The overall survival was 68.5%, and the recurrence-free, survival 55.2%. Two patients with pulmonary relapses were treated with surgery and intensive chemotherapy and remain free of disease > 51 months following recurrence. CONCLUSIONS: Combined treatment modalities appear to be important for optimal outcome. This series represents the first report of favorable outcome of peripheral neuroepithelioma using a series with follow-up that is long enough to account for late relapses.

Adolescent↗