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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 235 records · Page 13Linked to original sources
PubMed1996

Localization of an ovarian cancer tumor suppressor gene to a 0.5-cM region between D22S284 and CYP2D, on chromosome 22q.

The detection of loss of heterozygosity, indicative of the presence of a tumor suppressor gene, has been reported to occur frequently on chromosome 22q in human ovarian cancer. In this study, 110 sporadic ovarian tumors were analyzed using 8 polymorphic loci to define a minimum region of loss. Fifty-eight (53%) tumors showed loss of heterozygosity, and of these 6 exhibited partial loss, enabling the identification of two candidate tumor suppressor gene loci. One region, of less than 0.5 cM, is flanked by D22S284 and CYP2D, and a second region lies distal to D22S276. Analysis of loss of heterozygosity with respect to grade and stage suggests that chromosome 22q loss of heterozygosity is of more relevance in tumor progression rather than initiation.

Chromosome Deletion↗
PubMed1996

Refinement of two chromosome 11q regions of loss of heterozygosity in ovarian cancer.

Loss of heterozygosity on chromosome 11q23.3-qter is a frequent event in ovarian carcinoma, implying the existence of an important ovarian tumor suppressor gene(s) within the region. To refine a minimum region(s) of loss, 67 ovarian tumors were analyzed for loss of heterozygosity with eight microsatellite markers spanning 11q23.3-qter. Forty tumors (61%) demonstrated allelic losses. Twenty-seven of these had allelic losses on only part of 11q23.3, which enabled the identification of two distinct regions likely to harbor ovarian tumor suppressor genes. The proximal region, flanked by markers D11S925 and D11S1336, is less than two megabases while the second more distal region, flanked by markers D11S912 and D11S439, is approximately eight megabases. The refinement of these candidate tumor suppressor gene loci will facilitate future loss of heterozygosity studies and enable the isolation of candidate genes from these regions.

Alleles↗
PubMed1996

Facilitation of glutamate receptors reverses an age-associated memory impairment in rats.

The accuracy of memory for recent events is reported to decay between young adulthood and middle age in humans (Crook et al., 1990; Crook and West, 1990; Thomas et al., 1977) due to impairments in acquisition and/or retention (Craik, 1977; Huppert and Kopelman, 1989). Effects of this kind are also found in comparisons of middle-aged (12-18 months) vs. young adult (3 months) rats in tests requiring retention of recently sampled spatial cues (Kadar et al., 1990a; Kadar et al., 1990b; Goudsmit et al., 1990; Weiss and Thompson, 1991). The causes of such changes in memory processing are unknown but might be expected to involve age-related losses in forebrain glutamate receptors (Bahr et al., 1992; Magnusson and Cotman, 1993; Wenk et al., 1991); these receptors mediate fast excitatory transmission in many brain regions and play an essential role in the production of long-term potentiation (LTP), a form of synaptic plasticity that has been implicated in memory encoding (Landfield and Lynch, 1977; Moore et al., 1993). In the present communication we report results indicating that a drug that enhances AMPA-type glutamate receptors acts centrally to selectively increase hippocampal spatial cell firing and improves both acquisition performance and memory retention in middle-aged rats to levels equivalent to those found in young adult animals.

Age Factors↗
PubMed1996

Zn(2+)-induction of metallothionein in myotomal cell nuclei during somitogenesis of Xenopus laevis.

The localization of metallothionein in control and Zn-exposed embryos of Xenopus laevis was studied by whole-mount immunohistochemical staining. The embryos were grown according to the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) protocol from N/F stage 8 to stage 47, with or without addition of ZnCl2 (300 microM) to the medium. At stages 27, 38, 42, 45 and 47, control and Zn-exposed embryos were fixed in buffered formalin, and whole mounts were stained by an immunoperoxidase technique, using monoclonal murine antibody to equine metallothionein. Staining of metallothionein was evident in myotomal cell nuclei of developing somites by stage 27, stomatodeum, oropharynx, and gills by stage 38, developing kidneys (mesonephros) by stage 45, and liver by stage 47. The staining of metallothionein at these sites was more intense in Zn-exposed embryos than controls. The central nervous system (especially the spinal cord) and the yolk mass were faintly stained for metallothionein in controls and Zn-exposed embryos. Staining of metallothionein in myotomal cell nuclei was most prominent at stage 38, diminished at stages 42 and 45, and practically disappeared by stage 47. This is the first report that metallothionein is expressed in myotomal cell nuclei of Xenopus embryos during normal somitogenesis and becomes increased when the embryos are exposed to teratogenic levels of Zn2+.

Animals↗
PubMed1996

Characterization of pNiXa, a serpin of Xenopus laevis oocytes and embryos, and its histidine-rich, Ni(II)-binding domain.

A Ni(II)-binding serpin, pNiXa, is abundant in Xenopus oocytes and embryos. Kinetic assays show that purified pNiXa strongly inhibits bovine alpha-chymotrypsin (Ki = 3 mM), weakly inhibits porcine elastase (K1 = 0.5 microM), and does not inhibit bovine trypsin. The reversible, slow-binding inhibition of alpha-chymotrypsin by pNiXa is unaffected by Ni(II). Ovochymase in egg exudates is inhibited by pNiXa, but to a limited extent, even at high pNiXa concentrations. An octadecapeptide that models the His-rich domain (-HRHRHEQQGHHDSAKHGH-) of pNiXa forms six-coordinate, octahedral Ni(II)-complexes when the N-terminus is acetylated, and a square-planar Ni(II)-complex when the N-terminus is unblocked. Spectroscopy reveals two distinct types of octahedral Ni(II)-coordination to the N-acetylated octadecapeptide, involving, respectively, 3-4 and 5-6 imidazole nitrogens; the octadecapeptide undergoes partial, reversible precipitation in pH- and Ni(II)-dependent fashion, suggesting an insoluble, Ni(II)-coupled (Hx)n-dimer. Such (Hx)n-peptide interaction is confirmed by an enzyme-linked biotinavidin assay with N-biotin-KHRHRHE-amide and N-acetyl-KHRHRHE-resin beads, which become coupled after adding Ni(II) or Zn(II). H2O2 oxidation of 2'-deoxyguanosine to mutagenic 8-hydroxy-2'-deoxyguanosine is enhanced by the octahedral Ni(II)-octadecapeptide complex, although the effect is more intense with the square-planar Ni(II)-octadecapeptide complex. Immunoperoxidase staining of whole mounts with pNiXa antibody shows that pNiXa is distributed throughout gastrula-stage embryos and is localized during organogenesis in the brain, eye, spinal cord, myotomes, craniofacial tissues, and other sites of Ni(II)-induced anomalies. Patterns of pNiXa staining are similar in controls and Ni(II)-exposed embryos. Binding of Ni(II) to pNiXa may cause embryotoxicity by enhancing oxidative reactions that produce tissue injury and genotoxicity. Although the natural target proteinases for pNiXa inhibition have not been established, pNiXa may be an important regulator of proteolysis during embryonic development.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Pattern of basic life support ambulance use in an urban pediatric population.

To evaluate the pattern of use of basic life support (BLS) ambulances in a pediatric population, emergency medical service (EMS) and pediatric emergency department (PED) records from an urban hospital PED for all children transported to PED by ambulance during a 1-month study period were retrospectively reviewed. Excluded were: (1) advanced life support transport, (2) transport from other medical facility, (3) patients with chronic medical disability without acute decompensation, and (4) patients in police custody. BLS transport was considered inappropriate if: (1) no intervention by BLS technicians, (2) minimal to no intervention in the PED, and (3) discharge without prescription medication. Of 376 ambulance transports evaluated, 238 (63%) met entry criteria, and 105 (44%) transports met criteria for being inappropriate. The mean charge for appropriate transport was $240.68, and for inappropriate, $237.12 (P = .2). The total charge for inappropriate transports was $26,523.20. Patients on federal assistance had a significantly higher rate of inappropriate transport (51%) compared with patients who had commercial insurance (30%) and those who self paid (42%). Trauma was the most common cause for transport, 48% of which was inappropriate. It was concluded that inappropriate BLS transport of pediatric patients is common. This use is costly and may disrupt the delivery of EMS care to the remainder of the community. Efforts aimed at public education and providing alternative means of transport may significantly reduce charges and improve the delivery of EMS care.

Ambulances↗
PubMed1996

Lack of a temporal gradient of retrograde amnesia following NMDA-induced lesions of the basolateral amygdala assessed with the fear-potentiated startle paradigm.

M. Kim and M. Davis (1993b) previously reported that electrolytic lesions of the central nucleus of the amygdala, made 6 or 30 days after training, completely blocked the expression of fear-potentiated startle in rats. The present study shows that excitotoxic lesions of the basolateral amygdala also block fear-potentiated startle and do so whether the lesions are made soon (i.e., 6 days) or long (i.e., 30 days) after training. The relevance of these findings to various theories of amygdala function is discussed.

Amygdala↗
PubMed1996

The role of the nurse practitioner in a urology service.

OBJECTIVE: To evaluate the role of the nurse practitioner in urology and to determine the impact on the work of junior doctors. METHODS: Written criteria were defined before the postholder was appointed and subsequent performance was assessed against these criteria. Training was provided and the quality of work was assessed by direct observation. Senior House Officers (SHOs) were asked whether the post had increased their opportunities to attend theatre, outpatients and post-graduate training sessions and had decreased the number of 'inappropriate' tasks they had to perform. RESULTS: The nurse practitioner accomplished all the tasks that were defined before the appointment. The assessment of patients in pre-admission and haematuria clinics was satisfactory. The continuity of information, care of patients and counselling for patients receiving complex surgery were improved. Sixty-three per cent of all patients seen in the pre-admission clinic and all patients in a haematuria clinic were assessed initially by the nurse practitioner. Because the nurse practitioner was involved in setting up intravenous drug administration and infusions, administrative tasks and in obtaining results from the laboratory, the number of 'inappropriate' tasks performed by the SHOs decreased and they were able to attend more sessions of training and education. CONCLUSIONS: The nurse practitioner in clinical urological practice constitutes an effective use of resources and relieves junior medical staff from other tasks, allowing them to receive a more focused training. In addition, the quality of patient care was thought to be improved in some areas. The framework of a job plan for a nurse practitioner is described.

Humans↗
PubMed1996

Endobronchial brachytherapy with high-dose-rate remote afterloading for recurrent endobronchial lesions.

PURPOSE: To evaluate toxicity and efficacy of endobronchial brachytherapy with high-dose-rate (HDR) after-loading of iridium-192 for recurrent endobronchial lesions. MATERIALS AND METHODS: From 1988 to 1993, 81 patients with lung cancer previously treated with external beam radiation therapy were treated with palliative HDR endobronchial brachytherapy for symptoms due to relapse or persistent tumor of endobronchial bronchogenic origin. For most patients, Ir-192 was delivered in a dose of 3,000 cGy at 6 mm in two fractions over 2 weeks. RESULTS: Sixty-eight patients (84%) achieved some response: Twenty-six (32%) had excellent, 25 (31%) had moderate, and 17 (21%) had minimal symptomatic improvement with HDR endobronchial brachytherapy. Eleven patients had no change, and two became worse. The median duration of responses was 4.5 months. Those patients with an excellent response had a significantly better survival (13.3 months) compared with that of the other patients (5.4 months) (P = .01). There were two fatal complications, which were due to fistula and tracheal malacia. CONCLUSION: HDR endobronchial brachytherapy is an effective method to relieve airway obstruction promptly for patients with recurrent endobronchial lesions and may be considered as a boost for obstructive lesions before chemotherapy and external beam radiation therapy.

Brachytherapy↗
PubMed1996

Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder.

OBJECTIVE: Exaggerated startle reflex is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to assess the magnitude of the acoustic startle reflex in Gulf War veterans with PTSD. METHOD: The eye-blink component of the startle reflex was measured in response to six blocks of pseudorandomized 40-msec white noise bursts of varying intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD, seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD. RESULTS: The magnitude of the first startle response, as well as the magnitude of startle response averaged across blocks of testing, was significantly greater in Gulf War veterans with PTSD than in veteran and civilian comparison groups. CONCLUSIONS: Consistent with some clinical studies investigating the startle response in Vietnam veterans with PTSD, this investigation provides evidence for exaggerated startle response in this disorder. Preclinical studies of shock sensitization of the startle response suggest that the higher levels of startle response seen in the PTSD subjects may reflect a sensitization of the fear/alarm response created by the stress of combat trauma.

Acoustic Stimulation↗
PubMed1996

Acute day hospitalization as an alternative to inpatient treatment.

OBJECTIVE: This paper describes the administrative process by which the Ottawa General Hospital (OGH) closed 6 beds and used the staff and space resources thus released to set up an acute day hospital (ADH) for the treatment of 8 acutely ill psychiatric patients. Outcome data are presented on the first 160 patients admitted to the ADH. METHODS: Demographic and clinical information including diagnostic (DSM-III-R; Global Assessment of Functioning [GAF]) and questionnaire data (Symptom Checklist-90 Revised [SCL-90R]; Beck Depression Inventory [BDI]; State-Trait Anxiety Inventory [STAI]; patient satisfaction) were obtained from 160 ADH patients at admission and discharge. Forty-two of these patients provided follow-up data 3 to 6 months postdischarge. The outcome of ADH patients was compared with that of a retrospectively obtained random sample (n = 100) of inpatients on selected diagnostic and demographic variables. RESULTS: On clinician-rated and self-report clinical scales, ADH patients showed significant clinical improvement reflected in higher GAF scores and less psychological distress, depression, and anxiety at discharge relative to admission. There were no significant group differences in outcome indices except for shorter length of stay in the ADH group compared with inpatients. The ADH group rated the program highly in help received and quality of service. Short-term follow-up showed that gains made during treatment were maintained 3 to 6 months later. CONCLUSIONS: These results show that a time-limited day hospital program is clinically effective for acutely ill psychiatric patients and leads to a more efficient use of inpatient resources. We believe that partial hospitalization for the treatment of acute psychiatric disorders may have wide application in psychiatric hospital practice.

Acute Disease↗
PubMed1995

Involvement of cyclic AMP at the level of the nucleus reticularis pontis caudalis in the acoustic startle response.

Rats were implanted with cannulas in the nucleus reticularis pontis caudalis (PnC), an obligatory part of the neural pathway that mediates the acoustic startle reflex. Following at least 1 week of recovery, rats were tested for acoustic startle amplitude before or after infusion of compounds known to alter the second messenger, adenosine cyclic 3', 5'-monophosphate (cAMP). Local infusion into the PnC of the cAMP analog, 8-bromo cAMP (0.125-1.0 micrograms), increased the amplitude of the acoustic startle response in a dose-dependent manner. In addition, local infusion of a phosphodiesterase inhibitor, rolipram (10 micrograms) or the water soluble adenylate cyclase activator, forskolin-DHA (2.5 micrograms), produced a significant enhancement of startle amplitude. These effects probably resulted from intracellular actions because cAMP itself, which does not readily penetrate lipid membranes, had no effect. Moreover, the effects seemed somewhat specific because the precursor of cAMP, ATP or 8-bromo cGMP, also failed to alter startle at doses where 8 bromo-cAMP did. The fact that a phosphodiesterase inhibitor elevated startle suggests that cAMP serves to tonically elevate startle at this level of the pathway. Hence, treatments that either increase (fear, sensitization) or decrease (habituation, pre-pulse inhibition) startle at the level of the PnC may do so via release of neurotransmitters either positively or negatively coupled to cAMP, which in turn may alter either sound evoked transmitter release, excitability of PnC neurons or both.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

LOH and mutation analysis of CDKN2 in primary human ovarian cancers.

The CDKN2 gene encodes a cell cycle regulatory protein and is located on chromosome 9p21, a region deleted in a wide variety of primary tumours. While mutations in the CDKN2 gene itself are frequently observed in tumour cell lines, they are less common in primary tumours. We have investigated the role of the CDKN2 gene in ovarian cancer by analysis for allelic loss of 9p21 and single-strand conformational polymorphism analysis of exons 1 and 2 of CDKN2 in 67 primary ovarian tumours. Loss of heterozygosity on 9p21 was frequently observed (24/50 informative tumours) and was common in early-stage tumours, suggesting that it is an early event in ovarian tumorigenesis. Homozygous deletion of the CDKN2 gene was detected in only 1 tumour. No somatic or germline mutations were observed in CDKN2, though a codon 140 polymorphism was detected in 2 cases. This suggests that CDKN2 is not involved in ovarian tumorigenesis and that another gene(s) may be the target of the frequent 9p allelic losses observed.

Base Sequence↗
PubMed1995

Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl alpha-ketobenzoxazoles.

A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in vitro potency (Ki = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vivo activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

Amino Acid Sequence↗
PubMed1995

Fear-potentiated startle in posttraumatic stress disorder.

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude was significantly greater during baseline and during shock anticipation in the PTSD subjects, compared to the controls. Habituation of the startle reflex was normal. Because other studies in the literature, as well as in our own laboratory, have failed to find exaggerated startle at baseline (i.e., absence of stress) in PTSD patients, it is unlikely that the present results reflect a chronic elevation of startle in this group. Instead, the higher levels of startle in the PTSD group probably resulted from a greater conditioned emotional response in this group, triggered by anticipation of electric shocks that generalized to the unfamiliar experimental context in which testing occurred. Hence, emotionally charged test procedures may be especially informative in distinguishing PTSD patients from other psychiatric diagnostic groups.

Adult↗
PubMed1995

Set up and run an objective structured clinical exam.

Objective structured clinical exams are increasingly used as a way of assessing a range of clinical skills at both undergraduate and postgraduate level. To those planning to introduce such assessments, this article provides basic guidance on their development and structure and the personnel required. For those already using the assessments, our article may provide new ideas or be the impetus for an exchange of ideas. For those who are facing such formal assessment as candidates, we hope this article shows the efforts that are made to achieve the necessary structure and objectivity in this type of examination.

Clinical Competence↗