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Biomedical subjects

R E Watson

Publications and source records attributed to R E Watson.

At least 19 recordsLinked to original sources
PubMed2006

The case for integrating low dose, beneficial responses into US EPA risk assessments.

When conducting risk assessments, the US Environmental Protection Agency (EPA) does not currently consider the beneficial effects from exposure to concentrations of agents below the no observed adverse effect level (NOAEL). If such benefits were observed, and if the beneficial and toxicological mechanisms of action were identical, this would probably be represented as a 'j-shaped' hormetic dose-response curve. If such data are available, they should be considered when assigning uncertainty factors for safe exposure calculations. However, when such data are not readily available, as is likely the case when the mechanism of action of the benefit differs from that of toxicity, current US EPA methods appear adequate.

Dose-Response Relationship, Drug↗
PubMed2005

Extension of the BLOCH T(3/2) law to magnetic nanostructures: Bose-Einstein condensation.

We report a newly observed phenomenon, namely, the observation of a visible anomaly in the Bloch T(3/2) law for the temperature dependence of magnetization of nanostructured ferromagnets, for which we give a thermodynamic explanation. Our interpretation extends the Bloch law by introducing the system's chemical potential and assumes a finite Bose-Einstein condensation temperature T(BE) of the magnons. Our extension involves accounting for the possibility of a magnon or magnetic entropy term, leading to a magnon chemical potential (hitherto omitted in the traditional derivation) which varies with temperature. The result is a subtle upturn of the magnetization curves of ferromagnetic nanoparticles in the 10 to 50 K temperature range. Here we show experimental data for nanomaterials and an outline of the extended theory which includes T(BE).

Journal Article↗
PubMed2002

Role of sensory nervous system vasoactive peptides in hypertension.

The goal of the present research was to elucidate the roles and mechanisms by which the sensory nervous system, through the actions of potent vasodilator neuropeptides, regulates cardiovascular function in both the normal state and in the pathophysiology of hypertension. The animal models of acquired hypertension studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN-salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension during pregnancy in rats. The genetic model was the spontaneously hypertensive rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP play compensatory roles to buffer the blood pressure (BP) increase. Their synthesis and release are increased in the DOC-salt model but not in the SN-salt model. This suggests that the mechanism by which both models lower BP in SN-salt rats is by increased vascular sensitivity. CGRP functions in a similar manner in the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could contribute to the BP elevation in this model. The CGRP gene knockout mouse has increased baseline mean arterial pressure. The long-term synthesis and release of CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several animal models, sensory nervous system vasoactive peptides play a role in chronic BP elevation. In the acquired models, they play a compensatory role. In the genetic model, their decreased levels may contribute to the elevated BP. The roles of CGRP and SP in human hypertension are yet to be clarified.

Animals↗
PubMed2001

Distribution and expression of type VI collagen in photoaged skin.

BACKGROUND: Several of the characteristic clinical features of photoaged skin, including wrinkling, are thought to be dependent on changes in the dermal matrix brought about by chronic sun exposure. Such changes include reductions in collagens I, III and VII, an increase in elastotic material in the reticular dermis and a marked reduction in the microfibrillar glycoprotein fibrillin. OBJECTIVES: To examine whether type VI collagen, a microfibrillar collagen necessary for cell-cell and cell-matrix communication, is affected by the photoageing process. METHODS: Six healthy volunteers with moderate to severe photoageing were enrolled into the study. Immunohistochemistry and in situ hybridization histochemistry were used to examine the levels of type VI collagen in photoprotected and photoaged sites. RESULTS: In photoprotected skin, type VI collagen was concentrated in the papillary dermis immediately below the dermal-epidermal junction, around blood vessels, hair follicles and glandular structures. The distribution of type VI collagen was unchanged in photoaged skin, although we observed an increase in the abundance of the alpha3 chain of collagen VI in the upper papillary dermis, at its junction with the dermal-epidermal junction (P < 0.05). No alterations were observed for any alpha chain at the mRNA level. CONCLUSIONS: These studies suggest that chronic sun exposure (photoageing) has little or no effect on either the distribution, abundance or levels of expression of type VI collagen in human skin. Thus, type VI collagen, unlike other matrix components so far studied, appears to be relatively unaffected by the photoageing process.

Aged↗
PubMed2001

Activation of oral keratinocytes by mercuric chloride: relevance to dental amalgam-induced oral lichenoid reactions.

BACKGROUND: Despite the benefits of mercury-containing amalgam dental fillings there are growing concerns regarding the potential adverse health effects arising from exposure to mercury released from fillings. In some individuals this process may result in a local lichenoid reaction of the oral mucosa. OBJECTIVES: The aim of this study was to investigate the possibility that mercury salts released from amalgam fillings might act directly on oral keratinocytes to induce changes that could promote the development of such lesions. METHODS: In vitro experiments were performed in which normal oral and cutaneous keratinocytes were cultured in the presence of mercuric chloride (HgCl2). ICAM-1 expression and the release of cytokines was determined by enzyme-linked immunosorbent assay techniques. T-cell binding to HgCl2-pretreated keratinocytes was assessed using a colorimetric method. RESULTS: Subcytotoxic concentrations of HgCl2 induced a concentration-related increase in ICAM-1 expression and consequent T-cell binding on oral, but not cutaneous, keratinocytes. HgCl2 also stimulated the release of low levels of tumour necrosis factor-alpha and interleukin-8 (but not RANTES), and inhibited the release of interleukin-1alpha by oral keratinocytes. CONCLUSIONS: This study provides evidence that oral keratinocytes may play an integral part in initiating the pathogenesis of amalgam-induced lichenoid reactions.

Cell Adhesion↗
PubMed2001

A short-term screening protocol, using fibrillin-1 as a reporter molecule, for photoaging repair agents.

Photoaged skin is characterized by coarse and fine wrinkles. The mechanisms of wrinkle formation are undetermined, but appear to be due to changes within the matrix of the dermis and at the dermal-epidermal junction. Previous studies have identified marked reductions in procollagens I and III, collagen VII, and the fibrillin-rich microfibrillar apparatus in this area. Topically applied all-trans retinoic acid can repair photoaged dermal matrix, but this takes at least 6 mo of treatment. In this study, we have examined the abundance and distribution of fibrillin-1 prior to, and following, 192 wk of all-trans retinoic acid treatment. We have further developed a short-term protocol to determine the utility of potential repair agents, using fibrillin-1 as the marker for outcome. Individuals with clinically assessed severe photoaging were recruited to the study (n = 8). 0.025% all-trans retinoic acid, 5% sodium lauryl sulfate (irritant control), or vehicle were applied under occlusion to photoaged extensor forearm. A fourth control area was also occluded. After 96 h, punch biopsies were taken under local anesthesia and processed for either transmission electron microscopy or snap frozen. Frozen sections were prepared for immunohistochemistry and in situ hybridization immunohistochemistry. Electron microscopy revealed aberrant elastic fibers in the papillary dermis of photoaged forearm skin, with sparse microfibrillar apparatus and interstitial collagen. After application of 0.025% all-trans retinoic acid, there was increased deposition of both these dermal matrix components, with the aberrant elastic fibers no longer apparent. Significant increases (p < 0.05) were observed at the protein and mRNA levels for fibrillin-1 following all-trans retinoic acid and sodium lauryl sulfate treatments, with all-trans retinoic acid having a significantly greater effect than irritant control (p < 0.001); however, neither application had significant effect on the abundance of collagen VII or its mRNA. Investigation of collagen I synthesis revealed no difference following treatments. To ascertain the clinical relevance of using fibrillin-1 as a marker for photoaging, facial skin was biopsied at baseline and after long-term (192 wk) topical all-trans retinoic acid treatment (n = 5). Biopsies were wax-embedded and sections prepared for immunohistochemistry for fibrillin-1. Significant increases in the abundance of the microfibrillar apparatus was observed proximal to the dermal- epidermal junction (p < 0.001) following long-term all-trans retinoic acid application. This study indicates that all-trans retinoic acid can significantly affect fibrillin-1 content in photoaged skin. Furthermore, fibrillin-1 can be used as a "reporter" molecule in short-term protocols for testing the utility of topical agents in the repair of photoaged skin.

Aged↗
PubMed2001

Do race and gender influence the use of invasive procedures?

OBJECTIVE: To assess the influence of race and gender influence on the use of invasive procedures in patients with acute myocardial infarction (AMI) in community hospitals. DESIGN: Prospective, observational. SETTING: Five mid-Michigan community hospitals. PATIENTS: All patients (838) identified with AMI between January 1994 and April 1995 in 1 of these hospitals. MEASUREMENTS AND MAIN RESULTS: After adjusting for age, hospital of admission, insurance type, severity of AMI, and comorbidity, using white men as the reference group, the rate of being offered cardiac catheterization (CC) was 0.88 (95% confidence interval [95% CI], 0.60 to 1.29) for white women; 0.79 (95% CI, 0.41 to 1.50) for black men; and 1.14 (95% CI, 0.53 to 2.45)for black women. Among patients who underwent CC, after also adjusting for coronary artery anatomy, the rate of being offered angioplasty, using white men as the reference group, was 1.22 (95% CI, 0.75 to 1.98) for white women; 0.61 (5% CI, 0.29 to 1.28, P =.192) for black men; and 0.40 (95% CI, 0.14 to 1.13) for black women The adjusted rate of being offered bypass surgery was 0.47 (95% CI, 0.24 to 0.89) for white women; 0.36 (95% CI, 0.12 to 1.06) for black men; and 0.37 (95% CI, 0.11 to 1.28)for black women. CONCLUSIONS: Our study shows that white women are less likely than white men to be offered bypass surgery after AMI. Although black men and women with AMI are less likely than white men to be offered percutaneous transluminal coronary angioplasty or coronary artery bypass grafting in both unadjusted and adjusted analyses, these findings did not reach statistical significance. Our study is limited in power due to the small number of blacks in the sample.

Black or African American↗
PubMed2000

The use of angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction in community hospitals. Michigan State University Inter-Institutional Collaborative Heart (MICH) Study Group.

BACKGROUND: Previous studies documenting underutilization of angiotensin-converting enzyme inhibitors (ACEIs) in acute myocardial infarction (AMI) have been limited to Medicare populations. HYPOTHESIS: This study examines ACEI prescription rates and predictors in a community sample of hospitalized patients with AMI. METHODS: The charts of 1163 community patients with AMI, prospectively identified at admission between January 1, 1994, and April 30, 1995, were reviewed. RESULTS: Only 64 of 158 (40%) patients considered ideal candidates for ACEI prescription were discharged with a prescription for an ACEI. In a multivariate logistic regression model, prior ACEI utilization [adjusted odds ration (OR) = 3.26; 95% confidence interval (CI) = 2.05-5.20], presence of congestive heart failure (OR = 2.33; CI = 1.50-3.61) and black race (OR = 2.20; CI = 1.34-3.64) were identified as positive predictors of ACEI prescription. Conversely, lack of left ventricular ejection fraction (LVEF) measurement (OR = 0.46; CI = 0.28-0.75), LVEF > 40 ( OR = 0.27; CI = 0.18-0.40), and acute renal failure (OR = 0.08; CI = 0.01-0.44) were negative predictors. Women were also less likely to be discharged with an ACEI prescription (OR = 0.71; CI = 0.48-1.05). Furthermore, women were significantly less likely to have LVEF measured prior to discharge than were males (77 vs. 85%, p = 0.001). CONCLUSION: This study underscores the need for improvement in the utilization of ACEI in eligible patients with AMI. It also identifies opportunities for improvement in prescription rates, especially in women.

Adult↗
PubMed1999

Detection of bovine immunodeficiency virus DNA in the blood and semen of experimentally infected bulls.

Five 18- to 24-month-old bulls were inoculated with either a cell suspension containing bovine immunodeficiency virus (BIV-FL112; 3 bulls) or a BIV-free cell suspension (2 bulls). Blood and semen specimens were collected once a week for 14 weeks, and seroconversion was confirmed by indirect immunofluorescent antibody (IFA) testing. The presence of BIV in blood and semen was determined by virus isolation and/or polymerase chain reaction (PCR) assays. Antibodies to BIV were detected in the 3 experimentally infected bulls as early as day post inoculation (DPI) 17, and levels peaked at DPI 37-58. BIV was isolated from the peripheral blood mononuclear cells (MNCs) of the infected bulls at DPI 9 (2 bulls) and DPI 23 (1 bull), and could be isolated from one animal up to DPI 65. PCR analysis of MNC DNA, using BIV pol gene primers, detected virus in all three of the experimentally infected bulls from DPI 9 until the termination of the experiment at DPI 98. Efforts to isolate a significant number of non-spermatozoal cells (NSC) by gradient separation from the semen of the experimentally infected bulls were unsuccessful. Two methods for the extraction of total NSC DNA from up to 2 ml of non-extended semen were employed; however, no BIV pol fragment was amplified from these DNA preparations. Additionally, 30 bulls from artificial insemination (AI) centers were evaluated for BIV infection by PCR. No amplification products were obtained from MNC DNA from the AI submissions using primer sets for both the BIV pol and env genes.

Animals↗
PubMed1999

Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction.

Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal-epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity.

Adult↗
PubMed1998

Fibrillin microfibrils are reduced in skin exhibiting striae distensae.

Striae distensae (striae: stretch marks) are a common disfiguring condition associated with continuous and progressive stretching of the skin--as occurs during pregnancy. The pathogenesis of striae is unknown but probably relates to changes in those structures that provide skin with its tensile strength and elasticity. Such structures are components of the extracellular matrix, including fibrillin, elastin and collagens. Using a variety of histological techniques, we assessed the distribution of these extracellular matrix components in skin affected by striae. Pregnant women were assessed for the presence of striae, and punch biopsies were obtained from lesional striae and adjacent normal skin. Biopsies were processed for electron microscopy, light microscopy and immunohistochemistry. For histological examination, 7 microns frozen sections were stained so as to identify the elastic fibre network and glycosaminoglycans. Biopsies were also examined with a panel of polyclonal antibodies against collagens I and III, and fibrillin and elastin. Ultrastructural analysis revealed alterations in the appearance of skin affected by striae compared with that of normal skin in that the dermal matrix of striae was looser and more floccular. Light microscopy revealed an increase in glycosaminoglycan content in striae. Furthermore, the number of vertical fibrillin fibres subjacent to the dermal-epidermal junction (DEJ) and elastin fibres in the papillary dermis was significantly reduced in striae compared with normal skin. The orientation of elastin and fibrillin fibres in the deep dermis showed realignment in that the fibres ran parallel to the DEJ. However, no significant alterations were observed in any other extracellular matrix components. This study identifies a reorganization and diminution of the elastic fibre network of skin affected by striae. Continuous strain on the dermal extracellular matrix, as occurs during pregnancy, may remodel the elastic fibre network in susceptible individuals and manifest clinically as striae distensae.

Actin Cytoskeleton↗
PubMed1998

All-trans retinoic acid compromises desmosome expression in human epidermis.

An undesirable side-effect of retinoid treatment is skin fragility. As desmosomes are important in maintaining the cohesion of epidermal keratinocytes, we investigated whether all-trans-retinoic acid (RA) compromises desmosome expression in human epidermis, thereby predisposing skin to fragility. Solutions containing 0.025% RA, 5% sodium dodecyl sulphate (SDS) as an irritant control, or vehicle alone were applied to three sites on the buttocks of normal volunteers (n = 9). Treated sites were occluded for 4 days, and biopsies taken under local anaesthesia. Cryostat sections were stained with a panel of antibodies to desmosomal proteins and visualized by immunofluorescence microscopy. Stained sections were randomized and assessed for intensity of staining. The epidermal thickness of each treated site was quantified by image analysis. Western blots of epidermal desmocollins were quantified by densitometry. RA and SDS treatments significantly, but equivalently, increased epidermal thickness compared with vehicle. Immunohistochemically, both RA and SDS were shown to reduce epidermal staining for desmoplakin, desmoglein 1, plakophilin 1 and desmocollin 3 equally compared with vehicle-treated skin (P < 0.001). RA produced a greater reduction in desmocollin 1 staining compared with SDS (P < 0.001). Similar reductions in desmocollins were found by Western blot analysis. Reduced desmocollin expression may indicate compromised desmosomal adhesion, leading to the skin fragility that results from retinoid treatment.

Adult↗
PubMed1997

The medial capsule of the human temporomandibular joint.

PURPOSE: Attachments of the medial capsule of the temporomandibular joint (TMJ) to structures other than the medial fossa wall are thought to exist and to have functional significance. This study evaluated these relationships. MATERIALS AND METHODS: The anatomic relationships between the medial capsule and other medial structures, the sphenomandibular ligament, discomalleolar ligament, and auriculotemporal nerve, were examined in 14 cadaver heads. RESULTS: The results showed that the sphenomandibular ligament attaches separately from the medial capsule of the TMJ and therefore has no functional significance to the biomechanics of the joint. The discomalleolar ligament was found to be a continuation of the retrodiscal tissues and minimally associated with the medial capsule. The auriculotemporal nerve was not found to be in a relationship with the medial aspect of the condyle to the extent that mechanical irritation is possible during TMJ movement or disc displacement.

Aged↗
PubMed1997

Clinical features of photodamaged human skin are associated with a reduction in collagen VII.

Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear microns of basement membrane (mean +/- SEM) were significantly lower in photodamaged skin (1.79 +/- 0.10) as compared with sun-protected hip (2.28 +/- 0.11) and upper inner arm skin (2.21 +/- 0.10) (P < 0.01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6.3 +/- 2.5) as compared with sun-protected hip (20.0 +/- 5.6) and upper inner arm skin (17.7 +/- 4.9) (P < 0.001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.

Aged↗
PubMed1997

Myers-Briggs Type Indicator and dental school performance.

The Myers-Briggs Type Indicator (MBTI) was administered to 256 dental students, representing four classes, at the University of Florida College of Dentistry. The results of this psychological instrument were then correlated with overall dental school performance based on results from the National Dental Board Examinations Part I and II (NB-I, NB-II), yearly class rank, and specific academic difficulties as measured by the Student Performance Evaluation Committee. Introverted students were found to display a significantly increased performance on NB-I (p = .038) and NB-II (p = .044). They were also found, however, to demonstrate a progressively lower class rank over the four-year period than extroverted students and were more likely to experience major academic difficulties as well. Judging and sensing individuals were found to earn a higher class rank over the four-year period than perceiving and intuitive students, respectively. Perceiving students were found to exhibit major difficulties or were placed on probation more often than judging individuals. These results may prove useful in counseling students to recognize potential problems before they commence their dental education or to anticipate and address specific weaknesses during the course of their education.

Achievement↗
PubMed1996

The hypothalamic ventromedial nucleus sends a met-enkephalin projection to the preoptic area's periventricular zone in the female rat.

The female but not the male rat possesses a dense network of methionine enkephalin (m-Enk) fibers in the periventricular zone of the preoptic area (pePOA). The potential source of these fibers was determined by injection of the tracer fluorogold, FAu, into the preoptic area of adult female rats. Twenty-four hours before they were killed, the rats were administered colchicine (intraventricularly) to enable immunocytochemical visualization of m-Enk cells. Upon examination of the brains with fluorescence microscopy, double-labeled cells showing fluorogold and immunofluorescence for m-Enk were consistently observed in the preoptic area, the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) and nearby medial tuberal area (MTA), the arcuate nucleus, periventricular area of the hypothalamus, perifornical area, and dorsomedial nucleus of the hypothalamus. A series of lesion and knife cut experiments using glass, Halasz, and wire knives determined that the pePOA m-Enk fibers arose from the hypothalamus, near or within the VMH. Ibotenic acid lesions further determined that the source of the m-Enk projection was the VMHvl with a possible additional contribution from the MTA.

Animals↗