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Biomedical subjects

S Pettit

Publications and source records attributed to S Pettit.

16 recordsLinked to original sources

Outbreak of tuberculosis at a Newcastle public house: the role and effectiveness of contact screening.

We report an outbreak of tuberculosis (TB) that originated in a public house, involving 12 cases. The presumed index case was a regular patron. Initial screening of close contacts identified no further cases. Six cases of TB then presented symptomatically among other regular patrons. Contact screening was extended to include all regular patrons and bar staff. In total, 110 individuals were screened. One case was detected and three children were placed on chemoprophylaxis. Transmission of M. tuberculosis between patrons of a public house may cause community outbreaks of TB. Where cases present outside a close-contact screening program, extended contact screening must be considered.

Adult↗

Proteolytic processing of the p2/nucleocapsid cleavage site is critical for human immunodeficiency virus type 1 RNA dimer maturation.

Differences in virion RNA dimer stability between mature and protease-defective (immature) forms of human immunodeficiency virus type 1 (HIV-1) suggest that maturation of the viral RNA dimer is regulated by the proteolytic processing of the HIV-1 Gag and Gag-Pol precursor proteins. However, the proteolytic processing of these proteins occurs in several steps denoted primary, secondary, and tertiary cleavage events and, to date, the processing step associated with formation of stable HIV-1 RNA dimers has not been identified. We show here that a mutation in the primary cleavage site (p2/nucleocapsid [NC]) hinders formation of stable virion RNA dimers, while dimer stability is unaffected by mutations in the secondary (matrix/capsid [CA], p1/p6) or a tertiary cleavage site (CA/p2). By introducing mutations in a shared cleavage site of either Gag or Gag-Pol, we also show that the cleavage of the p2/NC site in Gag is more important for dimer formation and stability than p2/NC cleavage in Gag-Pol. Electron microscopy analysis of viral particles shows that mutations in the primary cleavage site in Gag but not in Gag-Pol inhibit viral particle maturation. We conclude that virion RNA dimer maturation is dependent on proteolytic processing of the primary cleavage site and is associated with virion core formation.

Dimerization↗

Selection of metastatic tumour phenotypes by host immune systems.

Metastasis and the processes underlying this phenomenon make epithelial cancers so malignant. Local control of cancers by surgery is sometimes possible but locoregional and distant recurrence commonly lead to the failure of treatment with ensuing morbidity and mortality. Tumour cells express a range of new antigens during growth and there are opportunities for the host immune system to interact with these antigens. This immune interaction eliminates the tumour or allows selection of phenotypic variants. Cell phenotypes selected by an incomplete immune response resemble the cell type commonly associated with metastases. Thus we propose that the host immune system may be responsible for selection of this phenotype and progression of the disease.

Animals↗

Effects of microwaves on three different strains of rats.

Confounding factors influencing the sensitivity of biological indicators of microwave exposure--lethality, colonic temperature (Tco), decreased body mass (dW), corticosterone (CS), thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), and prolactin (PRL) concentration--were studied in Long-Evans (LE), Wistar-Kyoto (WKY), and spontaneous hypertensive (SHR) rats. The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Test power density ranged from 1 to 50 mW/cm2 for 2 h. In contrast to the LE and WKY rats, the SHR rats were characterized by intolerance (death) between 40 and 50 mW/cm2 (9.2 to 11.5 W/kg). The lowest lethal Tco was 41.1 degrees C. Survivors including all the LE and WKY rats were capable of maintaining Tco lower than 41.0 degrees C. In general, strain of rat seemed to influence other bioindicators and to interact with power density on these bioindicators. Except for Tco and PRL, baseline for the various bioindicators varied among the different strains of rats. Responses of T4 and FT4 were limited in magnitude and inconsistent among strains of rats. In general, the magnitude of Tco increase was more pronounced in SHR than in WKY. Differences between SHR and LE, however, could be noted only at 1, 10, and 50 mW/cm2. Increased Tco, increased magnitude of Dw, increased CS, decreased TSH, and increased PRL (stress reactions) could be noted in rats exposed to 30 mW/cm2 (approximately 6 W/kg) or higher, irrespective of strain. At least two of three strains of rats (WKY and SHR) exposed to 20 mW/cm2 (approximately 4 W/kg) showed changes in Tco, CS, TSH, and PRL. At 10 mW/cm2 (2 W/kg), increased Tco could be found in all three strains of rats accompanied by changes in dW and TSH in LE, TSH in WKY, and dW and CS in SHR. At 1 mW/cm2 (0.2 W/kg), increased Tco could be noted in two of three strains (LE and SHR) and increased PRL in LE only. The smallest Tco increases for a consistent response (increased magnitude of response with power density) were 1.59 degrees C for dW, 0.70 degrees C for CS, 0.24 degrees C for TSH, and 0.97 degrees C for PRL. Tentatively, the threshold intensity for response to microwave exposure for rats could be considered as 2 W/kg or a 0.24 degrees C increase at 24 degrees C ambient temperature.

Animals↗

Effects of microwaves on the adrenal cortex.

Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.

Adrenal Cortex↗

Neuroendocrine parameters in the rat exposed to 60-Hz electric fields.

This study was designed to assess the neuroendocrine response of male Long-Evans rats to sustained or intermittent 60-Hz electric fields when exposed for 1 or 3 h at 100 kV/m. No significant differences were noted in corticosterone, prolactin, or thyrotropin levels between exposed and sham-exposed rats. A statistically significant increase (P less than .01) in growth hormone was noted in rats exposed to intermittent electric fields for 3 h. Emphasis was placed on good experimental design and the need to avoid standard laboratory stressors (excessive handling, temperature extremes, transportation, noise, etc.) known to be present in many biomedical studies. The importance of avoiding reactions due to extraneous factors in experiments predicated on investigating physiological function in relation to electric field exposure is discussed.

Animals↗

Who goes home? Predictive factors in stroke recovery.

One hundred and seventy two stroke patients were assessed two weeks post-stroke by a multi-disciplinary team. The predictive ability of a number of variables, including social, psychological and physical factors, was estimated for four outcome groups. Highly significant factors for good and bad outcome for one year were identified.

Activities of Daily Living↗

Serum-thyroxine levels in microwave-exposed rats.

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The relationship of decreased serum thyrotropin and increased colonic temperature in rats exposed to microwaves.

Although decreased serum thyrotropin (TSH) concentration has been found to be part of the endocrine response pattern in rats exposed to microwaves and other stimuli, the response of individual endocrine organs was not activated simultaneously by a given irradiance. Therefore, analytical evaluation of the function of endocrine organs individually as well as collectively is required to characterize the extent of biological involvement in microwave exposure. We have studied the changes in TSH concentration in unanesthetized rats exposed to 2.45 GHz amplitude modulated (120 Hz) microwaves in the far field for 2 and 4 h, between 0 and 55 mW/cm2, and from 1 to 10 times to demonstrate any possible cumulation, acclimation, or sensitization process. Ether inhalation was administered to test the responsiveness of TSH in groups of rats that failed to respond to microwave exposure by lowering TSH concentration. In addition, groups of rats were sampled 24 h after microwave exposure to test the persistency of the microwave effect on serum TSH concentration. Results showed that TSH concentration decreased in rats after microwave exposure. Influence of microwave exposure on serum TSH concentration was independent of the number of exposures indicating absence of cumulation, acclimation, or sensitization. The microwave effect on serum TSH could be dependent on duration of exposure. Decreased TSH concentration was usually accompanied by increased colonic temperature. For 4-h exposure, the lowest irradiance was 20 mW/cm2 or a 0.3 degree C increase in colonic temperature independent of the number of exposures. For 2-h exposure, the lowest irradiance was 30 mW/cm2 or a 1.1 degree C increase in colonic temperature regardless of the number of exposures. All the rats exposed at 10 mW/cm2 for 2 h had a lower TSH concentration than those of sham-exposed rats. Occasionally, significant reduction in TSH concentration could not be found in rats exposed to 20 or 25 mW/cm2 for 2 h. None of the rats exposed at an irradiance lower than 10 mW/cm2 had any change in TSH concentration. Failure of change in TSH concentration in response to microwave exposure was not a reflection of a deficiency since these rats responded to ether inhalation by lowering their TSH concentration. The effect of microwave exposure on TSH concentration was not persistent after exposure. The relation between TSH concentration and colonic temperature was curvilinear (exponential). From these results, two mechanisms and their implications for man were discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Endogenous avidin-binding activity in human lymphoid tissue.

Biotin-avidin systems can be used as an alternative to indirect antibody sandwich methods in the detection of T lymphocyte subsets in cryostat sections of human lymphoid tissue. Appreciable endogenous avidin binding activity (EABA) has been found, however, in human lymph nodes and tonsils. Such EABA can be a source of false positive staining when biotin-avidin detection systems are used to identify cells in cryostat sections. The finding that avidin binding cells may also contain endogenous peroxidase activity and are morphologically similar to histiocytes suggests that such cells may be of histiocytic lineage. EABA is not seen in intrafollicular "tingible body" macrophages, however, and only rarely in medullary sinus histiocytes. Thus further studies are necessary to identify the lineage of avidin binding cells in lymphoid tissues. EABA can be effectively blocked by treatment of cryostat sections with 1% avidin followed by 0.01% biotin before specific staining with biotinylated antibodies and avidin-peroxidase or avidin-fluorochrome conjugates.

Avidin↗

Increased serum enzyme activity in microwave-exposed rats.

Heat stable serum enzymes were studied in rats exposed to microwaves (2.45 GHz, 120 Hz amplitude modulated) 24 hr after a single 4-hr exposure or immediately after 3 and 10 exposures to 0.1 to 55 mW/cm2. In addition, stable colonic temperature at 41.5 degrees C for 30 min was maintained by microwave exposure in a group of five rats under barbiturate anesthesia. Alkaline phosphatase and lactic dehydrogenase did not increase as a result of microwave exposure. Increased serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were noted in the 41.5 degrees C group 24 hr after exposure. A threshold body temperature for acute cellular injury after microwave exposure was demonstrated. The acute cellular injury could be in the liver. These mild elevations in the serum enzyme levels (mean +/- SE, GOT = 167 +/- 40 U/liter: GPT = 74 +/- 26 U/liter) indicated that the injuries were not accompanied by any significant sequelae in the rat. From this threshold and colonic temperature (41.5 degrees C for 30 min) in barbiturate-anesthetized, microwave-exposed rats, we derived a tentative threshold for the whole-body average absorption rate at 14 W/kg (70 mW/cm2 at 2.45 GHz for adult rats) for 4 hr. This tentative threshold is subject to changes by duration of exposure and by compounding variables influencing maintenance of body temperature.

Alanine Transaminase↗

A rapid and simple procedure for the preparation of human lactate dehydrogenase-2 from erythrocytes using an ion-exchange mini-column.

We describe a simple ion-exchange chromatography technique for the rapid preparation of lactate dehydrogenase-2 from lysed human erythrocytes obtained either from plasma or serum clots. The procedure appears capable of scale-up to larger columns thus making it ideal as an initial step in a more extensive purification scheme.

Chromatography, Ion Exchange↗

Delineating acute neuroendocrine responses in microwave-exposed rats.

One hundred and eighteen male rats (Long-Evans) were acclimated to experimental procedures (i.e., handling, transferring from and back to "home" cage, body weight and colonic temperature determinations) for 2 wk and then subjected to cage confinement for 3 days before microwave (MW) exposure to 2,450 MHz for 1-, h, at 1-70 mW.cm-2 or sham exposure at ambient temperature of 24 +/- 1 degree C. Colonic temperature increased after exposure to power densities greater than or equal to 20 mW.cm-2 and was the most sensitive parameter measured. Inverse relationships between corticosterone and thyrotropin or growth hormone were noted after exposure for 1 h at 50 mW.cm-2 and above. Pituitary-thyroid function was inhibited after exposure to 20 mW.cm-2 for 2-8 h. Changes in other hormones were transient or inconsistent. Corticosterone, thyrotropin, and growth hormone levels could be correlated with power density or colonic temperature in rats exposed to MW for 1 h; corticosterone and thyrotropin levles correlated with colonic temperatures in shams. Body temperature influences adenohypophysial hormones in studies of MW biological effects.

Animals↗