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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 307 records · Page 17Linked to original sources
PubMed1993

Capillaritis: a manifestation of rheumatoid disease.

We present seven cases of capillaritis arising in patients with rheumatoid arthritis and suggest that it is primarily related to disease activity and not drugs. In the majority, the rash resolved spontaneously with the use of a topical steroid to treat the symptom of itch.

Administration, Topical↗
PubMed1993

Yohimbine-facilitated acoustic startle reflex in humans.

Preclinical studies have suggested the acoustic startle reflex (ASR) may be a useful animal model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals. The present investigation evaluated the effects of yohimbine on the ASR in healthy subjects. Seven healthy subjects received IV yohimbine (0.4 mg/kg) or saline placebo on two separate days in a randomized double blind placebo control design. A trial of 2 tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise, instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 sec, for a 30 ms duration. Startle testing was done 80 minutes post infusion and lasted 15-20 minutes. Sign rank testing indicated yohimbine caused an overall increase in startle amplitude, as well as significant augmentation of startle amplitude at 96, 102, 108, 114 decibels but not at the 90 dB intensity. Sign rank tests indicated a significant reduction of startle latency by yohimbine at only the 96 dB intensity. Significant correlations were observed between startle and peak anxiety, startle and plasma MHPG, peak anxiety and plasma MHPG. This study demonstrates in healty human subjects an excitatory effect of yohimbine on the magnitude of the ASR and a decrease in its latency. In the context of the key role of this reflex in the alarm response, this finding adds to the array of documented behavioral, biochemical and cardiovascular effects of yohimbine in humans which support the relationship between increased noradrenergic function and anxiety states.

Acoustic Stimulation↗
PubMed1993

Visual cortex ablations do not prevent extinction of fear-potentiated startle using a visual conditioned stimulus.

Following observations in the literature that sensory cortex ablations prevent extinction of conditioned fear, the present experiments tested the generality of this finding by examining whether visual cortex ablations would prevent extinction of conditioned fear as assessed by fear-potentiated startle using a visual conditioned stimulus. Consistent with previous reports, visual cortex ablations did not prevent the acquisition or expression of fear-potentiated startle to a visual conditioned stimulus. More importantly, visual cortex ablations did not prevent extinction of fear-potentiated startle to a visual conditioned stimulus, nor did they reverse preoperatively established extinction, indicating that sensory cortex is not required for extinction of conditioned fear in all situations.

Animals↗
PubMed1993

Infusion of the non-NMDA receptor antagonist CNQX into the amygdala blocks the expression of fear-potentiated startle.

The involvement of non-N-methyl-D-aspartate receptors in the amygdala in the expression of conditioned fear was examined using the fear-potentiated startle paradigm. Rats implanted with bilateral cannulae in the basolateral amygdaloid nuclei received 10 pairings of either a visual or auditory conditioned stimulus with footshock on each of 2 days. The next day, they were tested by eliciting the acoustic startle reflex in the presence or absence of the conditioned stimulus and divided into groups with equivalent levels of potentiation. One or two days later, rats were tested again following intra-amygdala infusion of vehicle or 0.025, 0.25, or 2.5 micrograms of 6-cyano-7-nitroquinoxaline-2,3-dione. The drug dose-dependently blocked the expression of potentiated startle in both sensory modalities, indicating that activation of non-NMDA receptors in the amygdala is necessary for the expression of conditioned fear.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Renal cell carcinoma.

Complete surgical resection of renal cell cancer confined to the kidney offers a hopeful prognosis of long-term remission or cure. Metastatic renal cell cancer is not effectively managed through the traditional modalities of surgery, chemotherapy, hormonal therapy, or radiation therapy. Quantum leaps in the understanding of immunobiology and molecular genetics, as well as the elucidation and application of biologic response modifiers, have created a climate of renewed enthusiasm for defining more active regimens for the management of metastatic renal cell cancer. As long-term remission and cure are highly unlikely for the majority of individuals presenting with advanced disease, attention to quality of life issues such as symptom control, cost containment, and honesty is appropriate. In diseases such as metastatic renal cell cancer where no effective standard of therapy has been demonstrated, participation in well-designed, carefully executed clinical trials with adequate reimbursement is encouraged for all eligible candidates. Individuals challenged with living with metastatic kidney cancer are aware of the gradual or precipitous nature of their declining process and generally do not harbor unrealistic hope for longterm survival. However, pain relief and comfort are reasonable hopes, and striving for and attaining an optimal quality of life will sustain both the individual and caregiver.

Adult↗
PubMed1993

Electrolytic lesions of the amygdala block acquisition and expression of fear-potentiated startle even with extensive training but do not prevent reacquisition.

Lesions of the amygdala have been shown to block the expression of fear-potentiated startle (increased acoustic startle in the presence of a cue previously paired with shock). In the present study, bilateral lesions of the central nucleus of the amygdala given after extensive training totally blocked the expression of fear-potentiated startle but did not prevent reacquisition. In contrast, when the lesions were made before any training, the lesioned rats did not show potentiated startle even with extensive training. Thus, the central nucleus of the amygdala normally seems to be required for the initial acquisition and expression of potentiated startle regardless of the degree of learning. However, reacquisition of potentiated startle can occur without the central nucleus, which implies the presence of a secondary brain system that can compensate for the loss of the central nucleus of the amygdala under some circumstances.

Amygdala↗
PubMed1993

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

It is well known that lesions of the hippocampal formation produce a temporally graded retrograde amnesia for certain types of memory. A similar pattern of results has been reported with amygdaloid lesions in avoidance learning (K.C. Liang et al., 1982). The present study examined the effects of posttraining amygdaloid lesions using a Pavlovian conditioning task, fear-potentiated startle, in which the amplitude of the acoustic startle reflex is increased when elicited in the presence of a cue (e.g., a light) previously paired with footshock. Electrolytic lesions of the amygdala given either 6 or 30 days after training blocked the expression of potentiated startle, indicating no temporal gradient of amnesia over these intervals in this paradigm. The effects of amygdaloid lesions on different measures of aversive learning are discussed.

Amygdala↗
PubMed1993

Unusual DQA-DR haplotypes in rheumatoid vasculitis.

DQA and DQB variants and HLA haplotypes were defined in Caucasian subjects with rheumatoid arthritis (RA), in a rheumatoid subset characterized clinically by extra-articular features of major vasculitis, and in controls. DQ variants were defined using a panel of sequence specific oligonucleotide probes. In RA subjects without extra-articular features the frequency of DQB*0301 was significantly increased but this was secondary to the main association with DR4. In rheumatoid vasculitis by contrast, DQB*0302 rather than DQB*0301 was increased in frequency, in addition to an increase of C4A null alleles. Family studies showed that DR4 negative haplotypes had an increased frequency of unusual DR-DQA combinations as compared to other rheumatoid subsets. These findings are in keeping with the concept that genes within the MHC other than DR4 have a disease-modifying role in rheumatoid subsets. HLA haplotypes were defined in a family where the proband has RA and Felty's syndrome and an affected sister has rheumatoid vasculitis. These siblings share a DR4 bearing haplotype typing for DQB*0301, and the sister with rheumatoid vasculitis has a DR4 negative haplotype carrying a C4A null allele and an unusual DR-DQA combination.

Arthritis, Rheumatoid↗
PubMed1993

Antibodies to type II collagen in early rheumatoid arthritis.

Antibodies to native and denatured type II collagen were investigated in a group of 79 patients with rheumatoid arthritis (RA) of disease duration less than 12 months (median 8 months; range 3-12 months). Using a solid-phase ELISA to measure these antibodies, the incidence of patients with levels above the upper limit of normal (mean of normal plus 3 SD) was low as compared to previous findings in patients with established disease. The majority of positive sera contained small amounts of IgM antibodies to denatured type II collagen whilst a few had IgG antibodies to native and denatured type II collagen. These findings suggest that the production of high levels of serum anti-type II collagen antibodies in patients with RA is a secondary phenomenon, which may exacerbate the disease rather than be a primary cause of disease.

Adult↗
PubMed1993

Temporal and spatial association of histone H2A variant hv1 with transcriptionally competent chromatin during nuclear development in Tetrahymena thermophila.

Vegetative cells of the ciliated protozoan Tetrahymena thermophila contain a transcriptionally active macronucleus and a transcriptionally inactive micronucleus. Although structurally and functionally dissimilar, these nuclei are products of a single postzygotic division during conjugation, the sexual phase of the life cycle. Immunocytochemical analyses during growth, starvation, and conjugation were used to examine the nuclear deposition of hv1, a histone H2A variant that is found in macronuclei and thought to play a role in transcriptionally active chromatin. Polyclonal antisera were generated using whole hv1 protein and synthetic peptides from the amino and carboxyl domains of hv1. The transcriptionally active macronuclei stained at all stages of the life cycle. Micronuclei did not stain during growth or starvation but stained with two of the sera during early stages of conjugation, preceding the stage when micronuclei become transcriptionally active. Immunoblot analyses of fractionated macro- and micronuclei confirmed the micronuclear acquisition of hv1 early in conjugation. hv1 staining disappeared from developing micronuclei late in conjugation. Interestingly, the carboxy-peptide antiserum stained micronuclei only briefly, late in development. The detection of the previously sequestered carboxyl terminus of hv1 may be related to the elimination of hv1 during the dynamic restructing of micronuclear chromatin that occurs as the micronucleus enters a transcriptionally incompetent state that is maintained during vegetative growth. These studies demonstrate that the transcriptional differences between macro- and micronuclei are associated with the loss of a chromatin component from developing micronuclei rather than its de novo appearance in developing macronuclei and argue that hv1 functions in establishing a transcriptionally competent state of chromatin.

Amino Acid Sequence↗
PubMed1993

Measuring the time course of anticipatory anxiety using the fear-potentiated startle reflex.

The time course of the facilitation of the acoustic startle reflex induced by anticipation of electric shocks was measured in 20 normal volunteers. Shocks could be administered during the last 10 s of 45-s threat conditions but not during 50-s no-threat conditions, each condition being signaled by a different light. Consistent with previous data, overall eyeblink startle levels were higher during the threat than during the no-threat conditions. However, the magnitude of this fear-potentiated startle effect became progressively larger in the threat condition the longer the light was on and then abruptly decreased with the onset of the light signaling the no-threat condition. These effects of the threat of shock on startle were interpreted in terms of anticipatory anxiety. Other interpretations, such as changes in selective or generalized attention, were also discussed. This paradigm provides a method to assess the time course of anticipatory anxiety in humans.

Acoustic Stimulation↗
PubMed1993

A point mutation in the human cytomegalovirus DNA polymerase gene confers resistance to ganciclovir and phosphonylmethoxyalkyl derivatives.

Ganciclovir-resistant mutant 759rD100 derived from human cytomegalovirus strain AD169 contains two resistance mutations, one of which is in the UL97 gene and results in decreased ganciclovir phosphorylation in infected cells [V. Sullivan, C. L. Talarico, S. C. Stanat, M. Davis, D. M. Coen, and K. K. Biron, Nature (London) 358:162-164, 1992]. In the present study, we mapped the second mutation to a 4.1-kb DNA fragment containing the DNA polymerase gene and showed that it confers ganciclovir resistance without impairing phosphorylation. Sequence analysis of the 4.1-kb region revealed a single nucleotide change that resulted in a glycine-to-alanine substitution at position 987 within conserved region V of the DNA polymerase. Recombinant viruses constructed to contain the DNA polymerase mutation but not the phosphorylation defect displayed intermediate resistance (4- to 6-fold) to ganciclovir relative to the original mutant 759rD100 (22-fold); the recombinant viruses also displayed resistance to ganciclovir cyclic phosphate (7-fold), 1-(dihydroxy-2-propoxymethyl)-cytosine (12-fold), and the phosphonylmethoxyalkyl derivatives (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (8- to 10-fold). However, the recombinant viruses remained susceptible to certain related compounds. These results imply that the human cytomegalovirus DNA polymerase is a selective target for the antiviral activities of ganciclovir, certain of its derivatives and phosphonomethoxyalkyl derivatives; support a role for region V in substrate recognition; and suggest the possibility of clinical resistance of human cytomegalovirus to these compounds because of polymerase mutations.

Amino Acid Sequence↗
PubMed1993

Routine quality assurance of high frequency ultrasound breast scanners in a screening context.

The use of frequencies above 5 MHz for medical imaging is now commonplace and one example is in the context of routine breast screening. No satisfactory quality assurance (QA) procedures have been agreed for these systems hitherto but it is clear that techniques developed for lower frequencies are not necessarily relevant. The National Breast Screening Programme therefore commissioned the production of a new protocol for this purpose and this is described here. The work is divided between an experienced tester, equipped with a commercial test object (RMI 414B) and the routine user who is provided with a specified perspex block to provide routine measurements of certain parameters in a relative manner.

Breast Neoplasms↗