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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 397 records · Page 22Linked to original sources

Is insulinlike growth factor I associated with diabetic retinopathy?

Insulinlike growth factor I (IGF-I) is the mediator of the growth-promoting effects of growth hormone and has been suspected of playing a role in the pathogenesis of proliferative diabetic retinopathy (PDR). However, previous attempts to correlate IGF-I levels with PDR have yielded conflicting results. We determined IGF-I levels in a large population-based study of 682 early-onset (diagnosed before 30 yr of age) adult (greater than or equal to 18 yr old) insulin-taking diabetic subjects. PDR was found in 25% of the population. IGF-I levels were measured by radioimmunoassay. The mean serum level of IGF-I was 277 +/- 108 micrograms/L (mean +/- SD). Spearman rank correlations showed statistically significant negative correlations between IGF-I levels and age (r = -0.51, P less than 0.0001), duration of disease (r = -0.36, P less than 0.0001), and glycosylated hemoglobin (r = -0.09, P less than 0.05). There was a significant trend (P less than 0.001) toward decreasing risk of PDR with increasing IGF-I. However, after controlling for duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, and the presence of proteinuria and/or creatinine greater than or equal to 265 microM in a multiple logistic regression model, IGF-I was not significantly associated with PDR. These data suggest that IGF-I may not be a risk factor for the development of PDR.

Adolescent↗

Laboratory evidence of active HIV-1 infection in Canadians with hemophilia associated with administration of heat-treated factor VIII.

Heat-treated factor VIII has been implicated in the transmission of HIV to hemophiliacs. Previously, evidence has been limited to documenting cases of seroconversion following administration of heat-treated factor VIII. Here, we present evidence of active HIV infection, i.e., infected and not merely sensitized following factor VIII injections. Six Canadians with hemophilia had seroconverted during a longitudinal study of their HIV immune status. Two of the three patients tested by this method demonstrated HIV gag-specific sequences upon amplification by polymerase chain reaction. In addition, HIV-1 virus was isolated from peripheral blood lymphocytes of one of these two persons as shown by reverse transcriptase activity of culture supernatants as well as neutralizable p24 antigen. This, we believe, is the first evidence of active HIV infection following administration of 60 degrees C, 30 h heat-treated factor VIII.

Canada↗

Pharmacological and anatomical analysis of fear conditioning.

The potentiated startle paradigm measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety, since it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Lesion and electrical stimulation studies on fear-potentiated startle and startle increased by electrical stimulation of the amygdala are being used to define the neural pathways necessary for a visual conditioned stimulus to alter the acoustic startle reflex. The current working hypothesis is that the conditioned stimulus activates the central nucleus of the amygdala through a pathway involving the lateral geniculate nucleus and insular cortex. The central nucleus of the amygdala may then project directly to the acoustic startle pathway, modulating the startle response. More work has to be done to define conclusively the relevant neural pathways involved in fear-potentiated startle. Nonetheless, by combining behavioral, anatomical, physiological, and pharmacological approaches, it will be possible to determine each step along the pathway that mediates the ability of a stimulus signaling fear to alter behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways to affect behavior. Eventually, this approach should help to determine where plastic changes take place along these pathways to mediate the conditioned effects that are being measured and the biochemical processes that are involved.

Amygdala↗

Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions.

Monoclonal antibody was conjugated to N-glutaryl-phosphatidylethanolamine in the presence of octylglucoside by using N-hydroxysulfosuccinimide as a carboxyl-activation reagent. The conjugated antibody was then incorporated into liposomes by a simple dialysis method. The method is mild and is compatible with various lipid compositions of the liposomes. We have prepared immunoliposomes containing a lung endothelium-specific monoclonal antibody and showed excellent target binding (approximately 75% injected dose) of the immunoliposomes in mouse. Immunoliposomes can be prepared to contain other acidic lipids such as phosphatidylserine and various amounts of cholesterol. The presence of 20% or more cholesterol in liposomes resulted in high level of target binding. We have used in these experiments a new radioactive lipid-phase marker, 111In-DTPA-SA, which was very stable in vivo. The halflife of clearance in mouse exceeded 3 weeks.

Animals↗

Effects of N,N-dimethylglycine on cardiorespiratory function and lactate production in thoroughbred horses performing incremental treadmill exercise.

In a crossover study, either a placebo paste or N,N-dimethylglycine was administered orally at a dose rate of 1.2 mg/kg twice daily for five days to six thoroughbred horses, with bodyweights ranging from 424 to 492 kg. Using previously determined regression equations for oxygen uptake (VO2) against speed for each horse, a standardised exercise test was given with speeds equivalent to fixed percentages of the maximum oxygen uptake (VO2max). The test consisted of two minutes at speeds equivalent to approximately 40 per cent and 50 per cent VO2max, and one minute at speeds that produced approximately 60, 70, 80, 90 and 100 per cent VO2max. During the last five seconds of each exercise stage, the values of VO2, carbon dioxide production (VCO2), heart rate, arterial blood and plasma lactate concentrations, arterial blood gases and pH were measured. Before and immediately after the exercise test, muscle biopsies were collected from the middle gluteal muscle to determine the muscle lactate concentrations. The administration of N,N-dimethylglycine produced no significant differences in any of the measured values, and it is concluded that the compound has no beneficial effects on cardiorespiratory function or lactate production in the exercising horse.

Animals↗

Double-pulse stimulation of startle-like responses in rats: refractory periods and temporal summation.

A startle-like response was evoked by electrical stimulation with one pulse in several brainstem sites of the primary acoustic startle circuit. If a second pulse was delivered 0.4-10 ms after the first pulse, a stronger response or a decreased current threshold resulted. The facilitatory effect of the second pulse increased as interpulse (C-T) interval increased from 0.4 to 2.0 ms in cochlear nucleus or ventral lateral lemniscus sites. In caudal pontine reticular formation sites, the effect of the second pulse increased sharply from 0.3 to 0.5 ms. These results suggest that very short refractory period axons mediate electrically elicited startle in reticular formation, and that longer refractory period axons mediate startle in cochlear nucleus or ventral lateral lemniscus. In reticular formation sites, the effect of the second pulse declined nearly exponentially from 2.0 to 50 ms with a time constant of about 4 ms. Stimulation of similar reticular formation sites in cats evokes monosynaptic EPSPs in spinal motoneurons with an almost identical time course, as reported by other investigators. This suggests that the startle response evoked from the reticular formation results from monosynaptic activation of spinal motoneurons. Temporal summation declined more slowly and irregularly in cochlear nucleus and ventral lateral lemniscus sites, suggesting that these sites are not monosynaptically connected with spinal motoneurons, a conclusion consistent with anatomical data. In reticular formation sites near the facial nerve, a second peak in the two-pulse curve was observed at a C-T interval of 10 ms. The second peak was blocked by local anesthesia of the face ipsilateral to the stimulating electrode, suggesting that a single twitch of facial muscles facilitates startle.

Action Potentials↗

Selective postoperative radioactive iodine treatment of thyroid carcinoma.

In a consecutive series of 234 patients with differentiated thyroid carcinoma of follicular cell origin (Hürthle cell tumors excluded), a radioactive iodine (131I) scan was obtained 3 to 6 months after thyroidectomy and 4 weeks after cessation of thyroid hormone treatments, only if extrathyroidal tumor extension or nodal or distant metastases were present. Twenty-one patients (9%) with 131I uptake of 3% or more (group 1) were treated with 150 to 200 mCi of 131I. Forty-four patients (19%) with less than 3% uptake (group 2) and 169 patients (72%) without evidence of metastases or extrathyroidal spread (group 3) were treated only with thyroid hormone. All patients initially underwent total thyroidectomy and modified neck dissection if cervical lymph node metastases were present. Three patients in group 1 and one patient in group 2 had recurrent tumor with a mean follow-up of 8.9 and 8.4 years. There were no recurrences in group 3 with a mean follow-up of 7.2 years. Death rate from thyroid carcinoma was 5% in group 1 (one patient) and 0% in groups 2 and 3. In conclusion, 131I scanning and therapy may be omitted in patients with differentiated thyroid carcinoma in the absence of local tumor extension or regional or distant metastases. Therapy with 131I is not demonstrated to be of benefit in this population of patients.

Adenocarcinoma↗

Esophageal carcinoma multiplex with gastric metastasis.

We describe here the radiographic findings in a patient with multiple synchronous squamous carcinomas of the esophagus with a large metastasis to the gastric cardia. Radiographic documentation of this constellation of tumor involvement has not previously been reported. The mechanisms of esophageal metastasis are reviewed.

Carcinoma, Squamous Cell↗

Lymphomatous polyposis of the colon.

Lymphoma of the colon is rare and has different radiographic presentations. The least common of these presentations is diffuse polyposis. Here we describe 4 cases of diffuse lymphomatous polyposis of the colon, each having a distinct radiographic appearance.

Aged↗

Disparate effects of two herpesvirus [corrected] immediate-early gene trans-activators on the HIV-1 LTR.

The BMLF1 region of the Epstein-Barr virus (EBV) genome and the immediate-early (IE) region of human cytomegalovirus (HCMV) both encode proteins which can trans-activate heterologous promoter/chloramphenicol acetyl transferase (CAT) constructs, including a human immunodeficiency virus type-1 promoter/CAT construct. We demonstrate here that this trans-activation by the EBV BMLF1 gene product, which we have previously shown to be largely post-transcriptional, is reporter gene dependent. In contrast, trans-activation by the HCMV-IE gene product(s), previously shown to be mediated at the RNA level, is seen regardless of whether CAT, human growth hormone, or beta-galactosidase is used as the reporter gene. Mutational analysis revealed no specific cis-acting sequences within the HIV-1 promoter which were required for trans-activation by the HCMV-IE gene product(s).

Carcinoma↗

Spinal vs. supraspinal sites of action of the alpha 2-adrenergic agonists clonidine and ST-91 on the acoustic startle reflex.

Previous work has shown that stimulation of alpha 2-adrenergic receptors depresses the startle responses in rats. The present study suggests that this depressant effect involves supraspinal rather than spinal alpha 2-adrenergic receptors because intraventricular but not intrathecal infusion of the hydrophilic alpha 2-adrenergic agonist ST-91 depressed the acoustic startle reflex. To determine the point in the acoustic startle pathway where alpha 2-adrenergic receptor activation might ultimately alter neural transmission, startle responses were elicited electrically from different points along the acoustic startle pathway after systemic administration of clonidine. Clonidine depressed acoustically-elicited startle and startle elicited by electrical stimulation of the ventral cochlear nucleus to a comparable magnitude and over a similar time course. It also partially depressed startle elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC). Taken together, these data suggest that alpha 2-adrenergic stimulation depresses startle by acting on supraspinal receptors, but that this effect is ultimately expressed, at least in part, by actions at both spinal and brainstem levels of the acoustic startle response pathway. The results are compared to other drugs known to affect the startle reflex.

Acoustic Stimulation↗

Definition of subchromosomal intervals around the myotonic dystrophy gene region at 19q.

The localization to 19q of the gene causing myotonic dystrophy (DM) has been defined more precisely by refinement of the physical location of several linked markers. A somatic cell hybrid mapping panel from cells with t(1;19), t(12;19), and t(X;19) translocation products was constructed to define five different intervals across 19q. In addition, we have derived a series of cell hybrids by irradiation of a der(19)-only hybrid to further subdivide the cen-q13.1 region. Using an array of 36 cloned genes, anonymous DNAs, and enzyme markers, we have tested the location of the panel breakpoints and refined the regional assignment of several of these markers. All markers tightly linked to DM are localized mainly within 19q13.2, thus suggesting that the DM gene is also close to this region.

Animals↗