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Biomedical subjects

D M White

Publications and source records attributed to D M White.

At least 19 recordsLinked to original sources

Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase.

We have cloned and characterized the human gene for the 21-kDa brain form of prostaglandin D2 synthase. The gene was isolated from a human genomic lambda library and spans 3600 base pairs. It consists of seven exons and six introns. Southern blot analysis indicates that there is a single copy of the gene in the haploid genome. The transcriptional start site was mapped to a G residue 74 base pairs 5' of the ATG initiation codon. A TATA box-like element (ATAAATA) is situated 21 base pairs upstream of the mRNA start site. The gene was mapped to chromosome 9 bands q34.2-q34.3. The gene bears close resemblance to the genes for murine major urinary protein and ovine beta-lactoglobulin.

Amino Acid Sequence

Risk level, knowledge, and preventive behavior for human papillomaviruses among sexually active college women.

During the past decade, there has been mounting scientific evidence linking human papillomavirus (HPV) with cervical cancer and, at the same time, a great increase in physician consultations for HPV infections. HPV infection risk factors include multiple sex partners, early age at first intercourse, history of sexually transmitted diseases (STDs), and smoking. This study surveyed 263 sexually active college women and concluded that (1) they are at considerable risk for contracting HPV, (2) they lack awareness of HPV, and (3) they are not practicing preventive behaviors that could reduce their risk of HPV and its serious consequences.

Adolescent

Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas.

Normal nociceptors are sensitized by hyperalgesic mediators such as eicosanoids and tachykinins. The possibility that these mediators contribute to hyperalgesic pain associated with neural injury was investigated by examining their effects on the excitability of injured afferent nerve endings. In amounts that sensitize normal nociceptors and are hyperalgesic in normal skin, the eicosanoids prostaglandin I2 (PGI2), and 8(R),15(S)-dihydroxyicosatetraenoic acid (8(R),15(S)-diHETE) both excited some C-fibers in chronic neuromas of rat sciatic nerve. In contrast, the selective tachykinin-receptor agonists septide and senktide did not excite C-fibers. None of the mediators affected A-fibers. We conclude that PGI2 and 8(R),15(S)-diHETE may contribute to post-injury pain and hyperalgesia by an action on injured afferent endings.

Animals

Increased responsiveness of sensory neurons in the saphenous nerve of the streptozotocin-diabetic rat.

1. This study examined sensory neurons in the saphenous nerve of rats treated with streptozotocin to induce diabetes (STZ-D). Several physiological properties of sensory neurons were not significantly different in STZ-D compared with control (CON) rats, including percentage and rate of spontaneous activity seen in the whole nerve and mechanical and thermal thresholds of individual C-fibers. 2. The response of STZ-D and CON C-fibers to a sustained (1 min) mechanical stimulus of threshold force was similar. However, during the 5 min immediately after removal of this stimulus, there was a much greater afterdischarge in STZ-D rats (STZ-D: n = 35; 14.6 +/- 5.1 action potentials/5 min, mean +/- SE; CON: n = 34; 3.9 +/- 0.7 action potentials/5 min). The number of action potentials during a sustained (1 min) suprathreshold mechanical (445 g) stimulus was also significantly greater in the C-fibers from STZ-D rats (STZ-D: n = 44; 149.7 +/- 18.4 action potentials; CON: n = 45; 84.7 +/- 12.2 action potentials). The afterdischarge during the 5 min immediately after removal of the sustained suprathreshold stimulus was also greater in C-fibers from STZ-D rats (STZ-D: 38.7 +/- 13.1 action potentials/5 min; CON: 9.3 +/- 2.3 action potentials/5 min). 3. There was a significant difference between C-fibers from STZ-D and CON rats with respect to the distribution among certain sensory classes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Neurologic syndrome in 25 workers from an aluminum smelting plant.

BACKGROUND: This article expands on an earlier series of three patients with a neurologic syndrome, who had all worked in an aluminum smelting plant. METHODS: Twenty-five symptomatic workers from the same plant were referred for a standardized evaluation, including completion of a health questionnaire, neurologic examination, and neuropsychologic evaluation. An exposure index was calculated for each worker based on level and duration of exposure in the potroom, where exposures were the greatest. This index was correlated with symptoms, signs, and neuropsychologic test scores. RESULTS: Twenty-two (88%) of the patients reported frequent loss of balance, and 21 (84%) reported memory loss. Neurologic examination revealed signs of incoordination in 21 (84%) of the patients. Neuropsychologic test results showed preservation in certain spheres of functioning, such as verbal IQ, with substantial impairment in others, particularly memory functioning. On memory tests, 70% to 75% showed mild or greater impairment. The majority (17 of 19 tested, or 89%) showed depression on the Minnesota Multiphasic Personality Inventory. The exposure index was significantly correlated with signs and symptoms of incoordination. CONCLUSIONS: This study and others in humans and animals support the existence of a syndrome characterized by incoordination, poor memory, impairment in abstract reasoning, and depression. Aluminum exposure in the potroom seems the most likely cause.

Adult

Different mechanical transduction mechanisms for the immediate and delayed responses of rat C-fiber nociceptors.

1. In this electrophysiological study, action potentials from single C-fibers were recorded in fine filaments teased from the rat saphenous nerve. We evaluated the effect of pharmacological agents on the responses of C-fiber mechanoheat nociceptors (C-MH; n = 53) after sustained suprathreshold and subthreshold stimuli. 2. Sustained suprathreshold mechanical stimuli elicit an immediate burst of activity that quickly adapts to a low-level firing that is maintained during the stimulus. Sustained subthreshold stimuli activate C-MHs after a delay and elicit a constant, low-level firing. 3. Gentamicin, a known suppressor of mechanosensory cell activity, blocked the initial rapid burst response to suprathreshold stimuli (n = 11) but had no effect on the adaptive low-level firing. The latency of the delayed activation of C-MHs induced by sustained subthreshold stimuli was not affected by gentamicin. 4. Sphingosine, a protein kinase inhibitor, increased the latency of the delayed activation of C-MHs (n = 7) to sustained subthreshold stimuli; phorbol 12-myristate 13-acetate (TPA), a protein kinase C activator, decreased the latency of the delayed activation of C-MHs (n = 9); and 4 alpha-phorbol, an inactive isomer of TPA, had no effect on the latency of the delayed activation (n = 7). Sphingosine, TPA, and 4 alpha-phorbol had no affect on the initial burst response induced by suprathreshold stimuli. 5. K+ channel blockers, 4-aminopyridine (n = 9) and noxiustoxin (n = 5), decreased the latency of the delayed activation of C-MHs to sustained subthreshold stimuli but had no effect on the initial burst response of C-MHs to suprathreshold stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine

Delayed activation of nociceptors: correlation with delayed pain sensations induced by sustained stimuli.

1. In this study we used psychophysical experiments in humans and behavioral and electrophysiological studies in rats to evaluate nociceptive and C-fiber mechanoheat nociceptor (C-MH) responses to sustained mechanical stimuli that are initially nonpainful or nonnoxious. 2. In normal rat skin, sustained subthreshold mechanical stimuli activate C-MHs (n = 36) with a delayed onset that parallels the delayed pain sensation recorded in human psychophysical tests. 3. The subthreshold stimuli did not induce a decrease in mechanical threshold (n = 11), and the effect of the subthreshold stimulus on latency to firing of C-MHs (n = 6) persists for a very short time after the stimulus is removed (less than 10 s). 4. Intradermal injection of prostaglandin E2 (PGE2; 100 ng), which induced a significant decrease in the mechanical threshold of C-MHs (n = 7), had no effect on the latency of the delayed activation of C-MHs. Also, indomethacin, which inhibits the synthesis of prostaglandins, had no effect on the latency of the delayed paw-withdrawal response in the behavioral test. 5. Intradermal injection of the calcium ionophore A23187 significantly reduced the latency of the delayed activation of C-MHs (n = 6) the calcium chelator Quin 2 (n = 6) significantly increased the latency. A23187 and Quin 2 had similar effects on the latencies to paw withdrawal in behavioral tests. The sensitization of C-MHs (n = 9) by PGE2 was not, however, affected by Quin 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines

Effects of chronic exposure to ozone on pulmonary lipids in rats.

Ozone is the most toxic component of photochemical oxidant air pollution. Exposure to high concentrations of ozone produces a variety of toxic effects in the lung, but it is not known to what extent prolonged exposure to low concentrations of ozone may contribute to the development of chronic lung disease. Phospholipids, important components of cellular membranes and surfactant, are necessary for the maintenance of normal lung structure and function. In order to test the effects of chronic exposure to environmentally relevant concentrations of ozone on phospholipid metabolism in the lung, rats were exposed to clean air or to 0.12, 0.25 or 0.50 ppm ozone for up to 18 months. The content and biosynthesis of phospholipids in both lung tissue and bronchopulmonary lavage fluid (surfactant) were measured. Incorporation of [14C]acetate into lung tissue phospholipids, an estimate of overall biosynthesis, decreased significantly at some time points in the study, while tissue phospholipid content tended to increase with both ozone concentration and with age. No changes were detected in phospholipid content of bronchopulmonary lavage fluid. These findings did not support the hypothesis that prolonged exposure of rats to environmentally relevant concentrations of ozone results in either qualitative or quantitative deficits in the pulmonary surfactant system.

Animals

Denervation-induced inflammation in the rat.

We report that section of the sciatic and saphenous nerves, in the hindlimb of the rat, evokes an inflammatory response in the denervated tissue that can be distinguished from the previously described peptide-mediated neurogenic inflammation. This novel form of neurogenic inflammation has a very delayed onset (9.75 +/- 2.1 h, mean +/- S.E.M., n = 8), persists for more than 30 h, and is characterized by a marked neutrophilic cellular infiltrate. These features cannot be mimicked by electrical stimulation of the peripheral nerve and are not prevented by either prior application of local anesthetics to the nerve lesion site or by neonatal treatment with capsaicin.

Animals

Morning vs evening light treatment for winter depression. Evidence that the therapeutic effects of light are mediated by circadian phase shifts.

Bright light exposure has been found to alleviate the symptoms of recurrent winter depression in many patients. The mechanism of light therapy may involve shifts in the timing (phase) of circadian rhythms. In this study, morning light exposure (which shifts rhythms earlier) was compared with evening light exposure (which shifts rhythms later) in a double-blind, crossover design. The onset of melatonin secretion in the evening was measured under dim light conditions as a marker for circadian timing (phase) before and after each treatment. Eight patients with winter depression and five control subjects were studied. Morning light was found to be significantly better than evening light in reducing depressive symptoms. At baseline, there was a trend for the onset of melatonin production to be later in the patients than in the controls. Morning light shifted the melatonin onset significantly earlier in the patients but not the controls. Our findings suggest that patients with winter depression have circadian rhythms that are abnormally delayed and that bright light therapy benefits winter depression by providing a corrective advance.

Adult

Cognition and metacognition at extreme altitudes on Mount Everest.

The FACTRETRIEVAL2 test battery, which assesses both retrieval of general information from memory and metacognition about that retrieval, was administered to people before and after a recent expedition to Mount Everest and at extreme altitudes above 6,400 m (higher than any mountain in North America or Europe). The major findings were as follows: First, the same extreme altitudes already known to impair learning did not affect either accuracy or latency of retrieval, and this robustness of retrieval occurred for both recall and forced-choice recognition. Second, extreme altitude did affect metacognition: The climbers showed a decline in their feeling of knowing both while at extreme altitude and after returning to Kathmandu (i.e., both an effect and an aftereffect of extreme altitude). Third, extreme altitude had different effects than alcohol intoxication (previously assessed by Nelson. McSpadden, Fromme, & Marlatt, 1986). Alcohol intoxication affected retrieval without affecting metacognition, whereas extreme altitude affected metacognition without affecting retrieval; this different pattern for extreme altitude versus alcohol intoxication implies that (a) hypoxia does not always yield the same outcome as alcohol intoxication and (b) neither retrieval nor metacognition is strictly more sensitive than the other for detecting changes in independent variables.

Adult

Psychosis following styrene exposure: a case report of neuropsychological sequelae.

A patient with a significant history of substance abuse was exposed to styrene and other solvents in the workplace. He became acutely psychotic, experiencing visual hallucinations. The psychosis was controlled with neuroleptic medications and avoidance of solvent exposure, but he continued to show significant deficits in visual-spatial and memory abilities. These deficits cleared with time away from the workplace. The case is of interest in terms of neuropsychological sequelae of solvent exposure and potential interaction of solvents with alcohol and recreational drugs.

Adult

Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases.

Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Androgens

AIDS/HIV education for preservice elementary teachers.

Professional preparation programs should provide future elementary teachers opportunities to develop competence in dealing with school-related AIDS issues. Curriculum writers and instructors of preservice elementary teachers could be more effective if they were aware of this groups' beliefs about school-related AIDS issues. A survey was conducted to assess the beliefs and opinions of preservice elementary teachers about school-related AIDS issues. Subjects (n = 157) generally agreed they would eventually have a child with AIDS in their classroom and agreed AIDS education should be included in the elementary grades, yet a substantial number did not believe they understood the basics about AIDS. Less than one-third indicated they knew how to clean up blood or body fluids safely. About one-third indicated they would feel personally threatened to teach a student with AIDS. These results are reflected in recommended AIDS educational content and resources for preservice elementary teachers and future research in this area.

Acquired Immunodeficiency Syndrome

The 15-lipoxygenase product, 8R,15S-diHETE, stereospecifically sensitizes C-fiber mechanoheat nociceptors in hairy skin of rat.

1. This study examined the effects of the 15-lipoxygenase product of arachidonic acid metabolism, (8R,15S)-dihydroxyicosa-(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on mechanical thresholds and thermal responses of saphenous nerve cutaneous C-fiber nociceptors that innervate the hairy skin of the rat hindpaw. Single C-fiber mechanoheat nociceptors (C-MH) that had von Frey hair (VFH) thresholds greater than 5 g and were activated by a noxious heat stimulus were chosen for study. We also studied the effects of prostaglandin E2 (PGE2), a cyclooxygenase product of arachidonic acid metabolism, on these nociceptors. 2. The 63 C-MHs studied had a conduction velocity of 0.82 +/- 0.03 m/s (mean +/- SE) and a mechanical threshold of 13.4 +/- 2.4 g. In a subgroup of these (n = 24), the thermal threshold was measured as (44 +/- 1 degree C) (mean +/- SE). 3. 8R,15S-diHETE produced a significant decrease in mechanical threshold of C-MHs (n = 33). The 8R,15S-diHETE-induced sensitization of C-MHs to mechanical stimuli was completely antagonized by coadministration with a stereoisomer, 8S,15S-diHETE (n = 10). 4. The mechanical threshold of C-MHs (n = 10), previously injected with the combination of 8R,15S-diHETE and 8S,15S-diHETE, was significantly reduced by a subsequent injection of PGE2. In a separate group of C-MHs (n = 7), PGE2 was co-injected with 8S,15S-diHETE, which failed to antagonize the sensitizing effect of PGE2 on mechanical threshold. 5. 8R,15S-diHETE also sensitized C-MHs (n = 9) to a thermal stimulus consisting of 37 degrees C for 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

The localization and release of substance P and calcitonin gene-related peptide at nerve fibre endings in rat cutaneous nerve neuroma.

This study uses radiological and immunocytochemical techniques to investigate the localization, content, transport and release of substance P- and calcitonin gene-related peptide-like immunoreactivity (SP-LI and CGRP-LI, respectively) in nerve fibre endings in 1-, 3- and 5-week-old cutaneous nerve neuromas. Neuromas were induced by ligating and transecting the saphenous nerve in anaesthetized Sprague-Dawley rats. The content of both neuropeptides in 3-week-old saphenous nerve neuroma was significantly reduced compared to that in normal saphenous nerve. At 5 weeks the levels of the peptides in the neuromas had returned to normal but remained reduced in the nerve just proximal to the neuroma. Following a 24-h ligation of the nerve proximal to 3-week-old neuromas there was a diminished immunocytochemical staining for SP-LI and CGRP-LI both proximal and distal to the ligature when compared to that seen at ligations of normal nerves. This indicates a decreased transport of the neuropeptides both to and from the 3-week-old neuromas. The density of neuropeptide staining at ligatures of nerves with 5 week or older neuromas had increased, but still remained less than that seen at ligations of normal nerve. Both a basal and a bradykinin-induced release of SP-LI and CGRP-LI from nerve fibre endings in the neuroma was demonstrated. The basal release was demonstrated by exposing the neuromas, in situ, to solutions containing 50 microM morphine plus 2 mM CoCl2 for 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Safety and first aid behavioral intentions of supervised and unsupervised third grade students.

This study assessed the safety and first aid behavioral intentions of 285 third grade students. Of the participants, 19% were left at home unsupervised by someone older than age 12 at least three days a week. Students responded to a survey instrument that described situations related to stranger safety, fire safety, accident prevention, and first aid. Stranger safety items received the most correct responses, with females scoring significantly higher than males. Most responses to fire safety items were inappropriate, and 40% of accident prevention items received a dangerous response most frequently. First aid items received more dangerous responses than appropriate ones. Supervised students scored significantly higher than unsupervised students in accident prevention and first aid. Results indicated students' behavioral intentions often were dangerous for situations requiring judgments about safety or application of first aid.

Accident Prevention