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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 559 records · Page 31Linked to original sources

SLACS retrotransposon from Trypanosoma brucei gambiense is similar to mammalian LINEs.

We have characterized a retrotransposon in Trypanosoma brucei gambiense uniquely associated with the spliced-leader (SL) RNA gene cluster (Spliced Leader Associated Conserved Sequence, SLACS). There are nine copies of SLACS and DNA sequence analysis of one shows the hallmarks of Line-1 like elements. SLACS has generated a 49 bp target DNA duplication at its insertion site and its 3'-end is preceded by a poly(A) stretch. Two putative open reading frames (ORFs) span 75% of the element. ORF1 has CysHis motif associated with the retroviral gag polypeptide while ORF2 shows homology with reverse transcriptase sequences. Its 5'-end contains a repeated segment of a 185 bp that varies in copy number in different SLACS insertions. Retrotransposon-like sequences inserted into the SL-RNA genes occur in several hemoflagellates. These elements may represent a related family which has maintained its target site specificity.

Amino Acid Sequence↗

Spinal c-fos induction by sensory stimulation in neonatal rats.

C-fos immunocytochemistry was used to investigate the functional connectivity between primary afferent nociceptive fibres and second-order neurons in the spinal cord of the anaesthetised neonatal rat. Subcutaneous injection of 50 mg/kg capsaicin potently induced c-fos in the spinal cord on the first postnatal day (P1), whilst plantar injection of dilute formalin was much less effective until P3. In contrast with the adult, there was no c-fos response of the neonatal rat spinal cord to cutaneous application of the C-fibre irritant, mustard oil. It is concluded that spinal c-fos expression induced by noxious sensory stimulation can occur before the development of mature functional synaptic contact with first-order neurones.

Animals↗

Changing patterns of c-fos induction in spinal neurons following thermal cutaneous stimulation in the rat.

Patterns of neuronal activity in the lumbar spinal cord of the anaesthetized rat were mapped by immunocytochemical localization of the c-fos gene product, Fos protein, at different timepoints following brief noxious stimulation of one hindpaw (20 s immersion in water at 52 degrees C). After 2 h, Fos-immunoreactive neurons were seen mainly in the superficial laminae of the ipsilateral dorsal horn, with maximum somatotopic organization in lamina II. Subcutaneous injection of dilute formalin produced a similar pattern of immunostaining at 2 h, with a greater proportion of Fos-positive neurons in laminae III-VIII than with heat. With a survival time of 8 h following formalin injection, Fos immunoreactivity was virtually absent from the spinal cord. Eight hours after heat stimulation, however, the superficial pattern had given way to the appearance of a population of immunoreactive cells in the deeper laminae. The pattern of this "second wave" of heat-induced Fos-positive cells had a marked contralateral component, and was still present after 24 h, having become even more diffuse and symmetrical. The number of Fos-positive cells seen at 8 h was increased by local anaesthetic blockade of the peripheral nerve after stimulation, and reduced by continuous barbiturate anaesthesia. These findings suggest that the early stages of thermal injury trigger a complex pattern of molecular events within the spinal cord, which are initially monosynaptic and closely related to primary afferent terminal depolarization, and in the longer term the result of an induced pattern of synaptic activity set up within the spinal cord.

Anesthesia↗

Membrane properties of interneurons in stratum oriens-alveus of the CA1 region of rat hippocampus in vitro.

The membrane properties of interneurons situated near the border of stratum oriens and the alveus of the CA1 region were examined with intracellular recording and staining in rat hippocampal slices in vitro. Cellular staining with Lucifer Yellow indicated that the somata of these interneurons were multipolar and their dendrites projected horizontally along the alveus and vertically toward stratum lacunosum-moleculare. Intrinsic properties (input resistance, action potential amplitude, time constant) and spike after-potentials were typical of non-pyramidal cells. Action potential duration, however, was of relatively medium duration (1.15 ms) and slow afterhyperpolarizations followed depolarization-induced trains of action potentials. Spontaneous activity of interneurons was prominent and of either of two types: single action potentials or high frequency bursts of action potentials. Interneurons displayed marked, voltage- and time-dependent inward rectification and anodal break excitation. Analysis of the slope of the charging function of hyperpolarizing transients, suggested that these interneurons were electrically compact (dendrite to soma conductance ratio, p approximately 2.7; and electrotonic length constant, L approximately 1.1). Characteristically, interneurons sustained high frequency repetitive firing during long depolarizing pulses. The slope of the frequency-current relation was 442 Hz/nA for the first interspike interval and 117 Hz/nA for later intervals (no. 60), suggesting the presence of spike frequency adaptation. Physiologically, these interneurons resembled more closely basket cells of stratum pyramidale than stellate cells of stratum lacunosum-moleculare.

Action Potentials↗

Genomic analysis of a mouse zinc finger gene, Zfp-35, that is up-regulated during spermatogenesis.

Zinc finger genes are a class of eukaryotic regulatory genes that encode sequence-specific nucleic acid-binding proteins. Members of this large gene family are required for growth and development in a wide range of organisms. We previously identified a mouse zinc finger gene, Zfp-35, that was up-regulated during spermatogenesis at the pachytene spermatocyte stage of development. We now describe the genomic organization of this gene, including its intron-exon structure, the sequence of its flanking regions, and its assignment to a region encompassing bands B3 to C of chromosome 18. The transcription unit has three exons. Intron 1 is within the 5' untranslated region and exon 3 contains the block of all 18 zinc fingers. These two features are common to a number of zinc finger genes. We also show that Zfp-35 is conserved in some placental mammals and that it is a member of a subfamily of related mammalian zinc finger genes.

Amino Acid Sequence↗

Differential expression of immediate early genes in the hippocampus and spinal cord.

We have demonstrated that immediate early genes can be differentially activated within the central nervous system. We examined the effects of tetanic stimulation in the hippocampus and of noxious sensory stimulation of the spinal cord on the expression of eight immediate early genes. Induction of long-term potentiation (LTP) in the dentate gyrus resulted in an increase in mRNA and protein for NGFI-A (also termed Zif/268, Egr-1, or Krox 24), and less consistently for jun-B mRNA. No increase was seen for c-fos, NGFI-B, c-jun, jun-D, SRF, or PC4 mRNAs. Blockade of the NMDA receptor prevented the induction of both LTP and NGFI-A mRNA in the dentate gyrus. However, commissural stimulation, which prevented the induction of LTP, resulted in bilateral activation of all the genes examined, including NGFI-A. No change was seen in animals trained in a water maze. These results suggest that no simple relationship exists between LTP, spatial learning, and immediate early gene induction. Stimulation of sensory fibers resulted in an increase in mRNA for NGFI-A, c-fos, SRF, NGFI-B, and c-jun in spinal cord neurons. Blockade of the NMDA receptor had no effect on immediate early gene induction in the spinal cord.

Animals↗

Clonidine inhibits fluid absorption in the rabbit proximal convoluted renal tubule.

Previous studies have shown that norepinephrine (NE) and the beta-adrenoceptor agonist, isoproterenol (I), enhance fluid absorption (JV) in isolated, perfused proximal convoluted tubule segments (PCT). Pretreatment of PCT with the beta-adrenoceptor antagonist, propranolol, inhibited the action of NE and produced a significant decline in JV, suggesting modulation of JV by both alpha- and beta-adrenoceptors. The present studies further characterize the alpha-adrenoceptor control of JV in isolated perfused PCT using specific agonists and antagonists. Basal JV declined significantly with the addition of the alpha 2-adrenoceptor agonist, clonidine (10(-4) M), to the bath; however, it was unchanged with the addition of the alpha 1-adrenoceptor agonist, methoxamine (10(-6) or 10(-4) M). With the addition of 10(-6) M isoproterenol JV increased significantly, and returned to control values with the subsequent addition of clonidine (10(-6) or 10(-4) M). Pretreatment of PCT with the alpha 2-adrenoceptor antagonist, yohimbine (10(-5) M), or with pertussis toxin (100 ng/ml) did not interfere with the stimulation of JV by isoproterenol, but abolished the inhibition of isoproterenol-stimulated JV by clonidine. Thus, clonidine inhibits JV in PCT via an alpha 2-adrenoceptor. This effect is mediated by a pertussis toxin inhibitable GTP-binding protein, but not one that is coupled to adenylyl cyclase.

Adenylate Cyclase Toxin↗

Diagnostic value of clinical examination for the identification of children in need of orthodontic treatment compared with clinical examination and screening pantomography.

Ninety children in the 5th school grade (means age = 11.9 years) participated in this investigation. As part of the orthodontic screening examination, pantomograms of all children had been performed as a routine procedure. Prior to assessment of the pantomograms each child was assigned to one of the following treatment categories based on clinical examination: -T (no indication for orthodontic treatment), O (observation of dentition development) and +T (indication for orthodontic treatment). Children, in whom clinical symptoms gave rise to a radiographic examination, were selected and their pantomograms assessed. Finally, the pantomograms of all children were interpreted, and the clinically established treatment categories re-evaluated on basis of the findings on the pantomograms. Fifteen children were selected for pantomography, but only one changed treatment category (from O to +T) due to observation of developmentally missing premolars. Three of the children not selected for pantomography changed categories from -T; two to O and one to +T. Clinical examination with selective pantomography was thus able to correctly identify 97 per cent of children in need of immediate orthodontic treatment, while it was able to correctly exclude 94 per cent of the healthy children. On the basis of these results, routine screening pantomography may be omitted.

Anodontia↗

Comparative therapy with cefpirome alone and in combination with rifampin and/or gentamicin against a disseminated Pseudomonas aeruginosa infection in leukopenic mice.

Treatment of disseminated Pseudomonas aeruginosa infection in leukopenic mice was evaluated using cefpirome alone and in combination with gentamicin and/or rifampin. Mice were made leukopenic with cyclophosphamide and infected through a skin incision with an inoculum of 1250 organisms (13 LD50). Antibiotics were administered subcutaneously for 48 h. Although the addition of cefpirome to gentamicin and/or rifampin improved survival significantly at 48 h compared with untreated controls (84.6%-100% vs. 38.5%), therapy with these combinations did not improve survival significantly from that achieved with cefpirome alone. Quantitative blood and tissue (liver, spleen, kidney, lung) cultures in mice treated with cefpirome alone or including rifampin were lower than in infected controls or groups receiving therapy that excluded cefpirome. Highest counts were observed in mice receiving cefpirome plus gentamicin. Except for the cefpirome plus gentamicin group, which demonstrated areas of acute tubular necrosis, the cefpirome group had less tissue pathology than infected controls.

Animals↗

Efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome.

The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome. In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion. On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected. An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls. During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin. Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo. Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides. These changes were associated with complete ablation of diarrhea (p less than 0.001). Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping. Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05). Chronic daily treatment with octreotide acetate resulted in minimal side effects. These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period. In addition most patients were able to resume employment. The long-acting somatostatin analog, octreotide acetate, is highly effective in preventing the development of symptoms of severe dumping syndrome, both vasomotor and gastrointestinal.

Adult↗

Risk factors for behavioral and emotional disorder in preadolescent children.

The relationship between risk factors and behavioral and emotional disorder was examined in 792 11-year-old children. Background characteristics such as sex, maternal depression, marital status of the parents, and reading problems distinguished between children with and without disorder. It also appeared that disorder was related to the number of risk factors experienced. This study, like others, failed to provide strong support for differences in background characteristics among children with different diagnoses. This may reflect the degree of overlap among disorders, because even children with only a single disorder may not be entirely free of the symptomatology of other disorders. For this reason it is important to assess children for multiple disorders or at least consider impaired functioning in other dimensions.

Affective Symptoms↗

DSM-III disorders in a large sample of adolescents.

The prevalence of DSM-III disorders was studied in 943 adolescents aged 15 years from a general population. Prevalence rates of disorder of 25.9% for girls and 18.2% for boys were found. The most prevalent disorders were overanxious disorder, nonaggressive conduct disorder, and simple phobia. Marked differences were noted among the disorders in terms of associated social competence, with multiple disorders and primarily "externalizing" disorders being related to poorer competence. A model of parental confirmation of disorder was developed suggesting that confirmation was more likely where the mother was depressed, the family low in social support, and the adolescent less socially competent.

Adolescent↗

The polymorphic human DNA sequence D8S8 assigned to 8q13-21.1, close to the carbonic anhydrase gene cluster, by isotopic and nonisotopic in situ hybridization and by linkage analysis.

Restriction fragment length polymorphism at the D8S8 locus is explained by the occurrence of at least two alternative alleles at two separate TaqI sites; TaqI-A allele frequencies 0.73 and 0.27 and TaqI-B allele frequencies 0.94 and 0.06. The D8S8 locus has been assigned to 8q13-21.1, near to the carbonic anhydrase (CA) gene cluster, by in situ hybridization to metaphase chromosomes using both tritium and immunofluorescently labelled probes. Linkage analysis using the CEPH family DNA panel indicates a close genetic linkage between D8S8 and CA3, with a lod score of +7.80 at theta = 0.05 in males.

Alleles↗

Muscarinic depression of synaptic transmission at the hippocampal mossy fiber synapse.

1. The action of muscarine was studied in the CA3 region of the rat hippocampal slice with single-electrode voltage-clamp techniques. 2. Bath application of 1 or 10 microM muscarine produced an increase in the input resistance of these cells and reduced the slow afterhyperpolarization (sAHP) response. Changes in input resistance were more pronounced around the resting potential of the cell (-50 to -60 mV), but in many cells an effect was also seen at -80 mV. These effects were absent when cesium chloride-containing microelectrodes were used. 3. At 1 microM, muscarine had little effect on synaptic transmission, causing a 0 +/- 7% (mean +/- SE, n = 19) change in excitatory postsynaptic potential (EPSP) and decreasing the excitatory postsynaptic current (EPSC) by 11 +/- 6% (n = 14); neither change was statistically significant. 4. In contrast, 10 microM muscarine produced a reliable depression of both the EPSP and EPSC. This effect was independent of the electrolyte used: with KCl the EPSP was depressed 23 +/- 4% (n = 5) and the EPSC 35 +/- 5% (n = 4); for CsCl the EPSP was depressed 23 +/- 10% (n = 7) and the EPSC 34 +/- 5% (n = 7). 5. Muscarine did not alter the reversal potential of the synaptic current but merely produced a decrease in slope conductance (37 +/- 5%, n = 6). 6. Muscarine did not significantly alter the shape of the EPSC waveform. This was assessed by comparing the 10-90% rise time and the half decay time of the current before and after muscarine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluating expansion of traditional home care agencies.

In a changing health care environment, it is important for home care agencies to regularly review their mission and goals and evaluate the services offered in the community. The participation of the entire home care team is essential in this process. For American Nursing Care in Cincinnati, a strong focus on teambuilding and mission development has resulted in the successful expansion of services and branch offices.

Community Health Nursing↗

Monoclonal antibodies 323/A3 and Ca1 identify a paracrine function of breast carcinoma on adjacent benign histological components.

The 323/A23 monoclonal antibody (MAb) is expressed with increasing breast atypia, whilst Ca1 has been suggested as a marker of cancer risk in benign breast disease. To establish whether they would be useful as markers of malignancy the staining characteristics in benign tissue components associated with malignant biopsies have been compared with the staining patterns of benign biopsies from patients with no known malignancy. Staining with 323/A3 and Ca1 MAb was carried out on formalin-fixed paraffin-embedded tissue sections using ABC Vectastain Reagents (Vector Laboratories) and diaminobenzidine as the chromogen. All biopsies contained ductolobular tissues. Apocrine metaplasia was present in 35 of 79 malignant biopsies, in 42 of 77 selected and 20 of 50 prospective unselected benign biopsies. The 323/A3 MAb stained strongly the cytoplasm of apocrine metaplasia in breast carcinoma biopsies in 18 of 35 cases, in the selected benign group this was two out of 42 (P less than 0.001) and in the prospective benign group one of 19 (P less than 0.01). No differences in staining were noted for ductolobular tissue. The Ca1 MAb showed strong apical staining in ductolobular tissue in 66 of 79 invasive carcinoma biopsies, in 20 of 50 prospective benign biopsies and 53 of 77 selected biopsies. The prospective and selected benign group staining was significantly different from that of the invasive carcinomas (P less than 0.005 and less than 0.05 respectively). These data suggest that 323/A3 staining of apocrine metaplasia and Ca1 staining of ductolobular tissue is affected by a paracrine function of breast cancer.

Antibodies, Monoclonal↗