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Biomedical subjects

T Hayes

Publications and source records attributed to T Hayes.

At least 19 recordsLinked to original sources

HIV-related deaths from selected infectious diseases among persons without AIDS in New Jersey.

This study sought to quantify HIV-related deaths among persons not classified as having AIDS, in an area where AIDS incidence among injecting drug users (IDUs) is high. Death certificates of persons who were aged 25-44 years at death, died in 1987 in two New Jersey counties, and had certain infectious conditions were compared with names in the AIDS Registry. Hospital and/or Medical Examiner records were reviewed for nonmatching cases. Cases were considered as confirmed HIV infection if there was laboratory evidence of such infection and as suggestive HIV infection if the decedent had oral thrush or a combination of certain other clinical findings were present. Of 412 deaths meeting the above criteria, 165 (40.0%) were in the AIDS Registry. We investigated 205 of the remainder; of these, 7.3% were found to have AIDS, 21.5% had confirmed HIV infection without AIDS, and 15.1% had suggestive HIV infection. This increased the HIV-related mortality in excess of deaths due to AIDS in this age group by 9.2% for confirmed HIV infections and 15.6% for both confirmed and suggestive HIV infections, with deaths among IDUs increasing 12.3% for confirmed HIV infections and 18.9% for both confirmed and suggestive HIV infections. Thus, in addition to AIDS indicator diseases, a variety of other infectious conditions can lead to death in HIV-infected persons, particularly in IDUs; however, the extent of such deaths may be less than previously described.

Adult

Mechanisms regulating cell number and type in the mammalian central nervous system.

In the developing brain, neurons are derived from multipotential precursor cells in a precise sequence, where the time when a neuron becomes postmitotic is closely linked to the differentiated function of the neuron. Work from our group (1) identifies the Nes+ neuronal precursor state, (2) defines growth factors that regulate the proliferation of Nes+ precursor cells and their differentiation into neurons, and (3) establishes immortal cell lines that may be useful models for the terminal differentiation of Nes+ cells into neurons and astrocytes. These results suggest that the basic technical requirements are now in place to define the signals that control the transition from a precursor cell to a postmitotic neuron in the mammalian CNS. Control of this terminal differentiation is a key step in generating the large numbers and types of cells in the CNS.

Animals

Development and decay of systemic thermotolerance in rats.

The development and decay of thermotolerance to the lethal effect of systemic hyperthermia was investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats into a temperature-controlled water bath. Survival was determined in rats challenged for periods of 10 to 90 min at 42.5 C, 24 to 144 h after a sublethal conditioning exposure of 41.8 C for 1 h. Survival curves of various exposure times at 42.5 C lethal to 50% of the animals (LD50) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (TTR-LD50 for conditioned animals at various times after sublethal conditioning exposure divided by the LD50 for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro and for tissues heated locally in vivo. Pretreatment of rats at 41.8 C for 1 h resulted in an increase in the LD50 when rats were challenged 24 to 96 h later, with a maximum increased noted at 48 h (56.5 vs. 25.0 min for control; TTR = 2.3). The animals remained relatively resistant to the second heat treatment at 96 h and returned to control levels of heat sensitivity by 120 h. The development and kinetics of thermotolerance to lethality induced by whole-body hyperthermia need to be considered when multiple-fraction hyperthermia treatment plans are designed.

Adaptation, Physiological

An outbreak of acute histoplasmosis in a family.

Acute pulmonary histoplasmosis was diagnosed in three members of a New Mexico family that had recently attended a family reunion in Iowa. The treating physicians rapidly documented an outbreak of atypical pneumonia in the family. The clinical features and epidemiology of the outbreak suggest histoplasmosis was contracted during exposure in an abandoned barn. Fever, chills and myalgia were the most common symptoms; shortness of breath occurred frequently.

Adolescent

Recognition of positive and negative bandpass-filtered images.

A study is reported in which the significance for vision of low- and high-spatial-frequency components of photographic positive and negative images was investigated by measuring recognition of bandpass-filtered photographs of faces. The results show that a 1.5 octave bandpass-filtered image contains sufficient visual information for good recognition performance, provided the filter is centred close to 20 cycles facewidth-1. At low spatial frequencies negatives are more difficult to recognize than positives, but at high spatial frequencies there is no difference in recognition, implying that it is the low-frequency components of negatives which present difficulties for the visual system.

Color Perception

Production of systemic hyperthermia in the rat.

The design of clinical trials employing whole-body hyperthermia in cancer therapy has been hampered due to lack of a suitable animal model. We describe a technique for reproducibly and efficiently inducing whole-body hyperthermia in Sprague-Dawley rats, using halothane and oxygen anesthesia and immersion in a hot water bath. Core body temperatures of between 41.5 and 43 degrees C were induced and maintained for periods of up to 200 min and survival curves were determined. The time of exposure at a given temperature that resulted in death in 50% of the animals within 24 hr after heating (LD50/24 hr) was calculated by linear logistic regression analysis. LD50 24 hr values of 115, 61, 57, 25 and 16 min were obtained for temperatures of 41.75, 42.0, 42.25, 42.5 and 42.75 degrees C respectively. This heating technique is compared to several more toxic methods for inducing whole-body hyperthermia with respect to possible pharmacological and physiological differences.

Anesthesia, Inhalation

Potential synthetic codeine substitutes: (-)-3-O-aryl-N-methylmorphinans.

A series of novel O-aryl-N-methylmorphinans (7-19) were synthesized by the Ullmann reaction from levorphanol (4) in our search for a synthetic codeine (2) substitute with reduced addition liability. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, (-)-3-phenoxy-N-methylmorphinan (7) is an orally active analgesic comparable in potency to codeine (2), which exhibits decreased physical dependence liability and longer duration of action.

Animals

Squamous carcinoma model of humoral hypercalcemia of malignancy.

Squamous carcinomas are the most common cause of humoral hypercalcemia of malignancy (HHM) in humans. To develop an animal model of this syndrome, CD-1 female mice were painted with dimethylbenzanthracene, which produced cutaneous squamous carcinomas in the majority of those painted. Greater than 90% of tumor-bearing mice developed a syndrome of hypercalcemia, hypophosphatemia, hypercalciuria, elevated plasma 1,25-dihydroxyvitamin D, normal immunoreactive PTH, elevated urinary cAMP, and accelerated bone resorption compared to control mice. Tumor excision reversed the hypercalcemia and hypophosphatemia, and autopsies revealed no evidence of skeletal or other metastases. Dietary calcium restriction did not affect the hypercalcemia in tumor-bearing mice. Extracts of tumor tissue contained potent bioactivity paralleling that of bovine (b) PTH in a PTH-sensitive canine renal cortical adenylate cyclase assay. The activity was trypsin sensitive and partially inhibitable by Nle, Tyr bPTH amide. The activity coeluted with chymotrypsinogen (mol wt, 25,700) on Sephacryl S-200 chromatography, well ahead of bPTH. This is the first description of an animal squamous carcinoma that produces HHM. With the exception of elevated plasma 1,25-dihydroxyvitamin D levels, the syndrome precisely mimics that seen in human HHM. The presence of a biologically active protein larger than PTH in tumor extracts, similar to that extracted from human tumors, suggests a common mode of pathogenesis. This model should be useful in further studying the pathophysiology of HHM.

Animals

Development and decay of systemic thermotolerance in rats.

The development and decay of thermotolerance to the lethal effect of systemic hyperthermia were investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats in a controlled-temperature water bath. Survival was determined for rats challenged for periods of 10 to 90 min at 42.5 degrees at intervals of 24 to 144 hr after a sublethal conditioning exposure of 41.8 degrees for 1 hr. Survival curves and times of exposure at 42.5 degrees lethal to 50% of the animals (LD50) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (LD50 for conditioned animals at various times after sublethal conditioning exposure divided by the LD50 for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro or for tissues heated locally in vivo. Pretreatment of rats at 41.8 degrees for 1 hr resulted in an increase in the LD50 for rats challenged 24 to 96 hr later, with a maximum increase noted at 48 hr (56.5 min compared with 25 min for control; thermotolerance ratio, 2.3). The animals remained relatively resistant to the second heat treatment at 96 hr and returned to control levels of heat sensitivity by 120 hr. The development and kinetics of thermotolerance to lethality induced by wholebody hyperthermia need to be considered in the design of multiple-fraction treatment plans.

Animals

Quantitative evaluation of fluorescein angiograms: microaneurysm counts.

This study describes a method for quantifying microaneurysms (MA) from fluorescein angiograms. The method was validated by the reproducibility of the number of MA in 30 angiograms read twice each by two independent observers; and by the absolute difference in MA counts between two readings by the same observer, and difference in numbers counted by two different observers. The precise location of each MA on two readings was also studied and the reproducibility of location varied from 60 to 71%, depending on the quality of the angiograms. Clinicians and technicians working in the same or in different centers obtained similar results. The coefficient of correlation between observers and between readings was satisfactory, r greater than 0.9. The method is easy to learn and the reproducibility allows for its use in clinical trials.

Aneurysm

Evaluation of periodate/lysine/paraformaldehyde fixation as a method for cross-linking plasma membrane glycoproteins.

Fixation by periodate/lysine/paraformaldehyde, a method purported to cross-link specifically plasma membrane glycoproteins, was evaluated using Novikoff rat ascites hepatocellular carcinoma cells. Cells were treated with periodate/lysine, periodate/glycine, and periodate/lysine/paraformaldehyde and subsequently reduced with NaB3H4. The glycoproteins labeled with 3H were resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and visualized by fluorography. The effects of reactant concentrations on 3H-labeling of cellular components, cell viability, and cross-linkage of 3H-labeled proteins were examined. The effect of increasing the localized density of plasma membrane glycoproteins on the extent of cross-linkage by periodate and lysine was investigated using cells in which patching of the plasma membrane glycoproteins had been induced by ferritin-conjugated concanavalin A/rabbit antiferritin antiserum. Also investigated was the periodate-independent to mixtures of periodate and lysine or glycine. Results of these studies did not support a mechanism of cross-linking involving reaction between the free base lysin and aldehyde groups on periodate oxidized carbohydrate residues but suggested a complex interaction between periodate oxidized plasma membrane glycoproteins and polymeric complexes of lysine and formaldehyde.U

Animals

Conductive coatings studied on inflated lung in the frozen-hydrated and freeze-dried states.

Evaporative coatings of platinum-carbon and gold on freeze-fractured mouse lung, preserved in frozen-hydrated and freeze-dried states, are studied in secondary emission mode by low temperature scanning electron microscopy. Unfixed, inflated frozen lung is freeze-etched in high vacuum, metal coated and observed frozen-hydrated and freeze-dried, to demonstrate sample shrinkage and coating deformation upon drying the sample. Buckling and cracking of the coatings occur as a result of freeze-drying. Correlative TEM thin film analysis of the coatings is used to estimate film thickness and reticularity. Freeze-drying biological samples is a common SEM preparative technique which causes morphological artifacts due to both freezing and drying. Frozen-hydrated low temperature-SEM investigation can selectively study these artifacts morphologically to distinguish between freezing and drying artifacts.

Animals