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Biomedical subjects

C Finch

Publications and source records attributed to C Finch.

At least 37 records · Page 2Linked to original sources

Estrogen enhances uptake of amyloid beta-protein by microglia derived from the human cortex.

In recent years, inflammatory mechanisms have been increasingly appreciated as important steps in the pathology of Alzheimer's disease (AD). There are two pathological defects in AD: chronic inflammation and impaired clearance of amyloid beta-peptide (Abeta). In the periphery, estrogen both increases macrophage phagocytosis and has antiinflammatory effects. If estrogen had a similar effect in the CNS, it could reverse inflammatory defects in AD. Although microglia are a key component of the immune system and help clear Abeta deposits in the AD brain, little is known about the effects of estrogen on CNS microglia. Therefore, we sought to determine the relationship between estrogen treatment and internalization of Abeta by microglia by quantifying the internalization of aggregated Abeta by human cortical microglia. Abeta uptake was found to be dose- and time-dependent in cultured microglia. Increased Abeta uptake was observed at 1.5 and 24 h after addition of aggregated Abeta (50, 100, or 1,000 nM: Abeta), and this uptake was enhanced by pretreatment with estrogen. The expression of estrogen receptor (ER) beta (ER-beta) was also up-regulated by estrogen treatment. Cells cotreated with ICI 182,780, an ER antagonist, showed significantly reduced internalization of Abeta in cultured microglia. These results indicate that microglia express an ER-beta but that the effect of estrogen on enhancing clearance of Abeta may be related to the receptor-independent action of estrogen or to nonclassical ER effects of estrogen. Thus, stimulation of the ER might contribute to the therapeutic action of estrogen in the treatment of AD.

Amyloid beta-Peptides↗

The relation between dopamine D2 receptor density and personality: preliminary evidence from the NEO personality inventory-revised.

OBJECTIVE: To examine the relation between dopamine (DA) D2 receptor-specific binding and personality, we assessed the relation between DA D2 binding and the NEO Personality Inventory-Revised (NEO PI-R). BACKGROUND: Previous studies have demonstrated a relation between DA D2 receptor-specific binding and a personality trait involving personal detachment as defined by the Karolinska Scales of Personality: A subsequent study using a different measure of personal detachment failed to replicate this finding, suggesting that metric properties of the personality scale may be important. To further examine this issue, we assessed the relation between DA D2 binding and a third personality measure, the NEO PI-R. METHODS: Eighteen adult subjects completed the NEO PI-R and participated in an 11C-raclopride positron emission tomography study to quantify striatal DA D2 receptor binding. RESULTS: We did not find a significant relation between binding and detachment-like traits on the NEO PI-R; however, we found a significant relation between DA D2 receptor binding and the NEO PI-R personality facet of Depression (r = 0.75, p <0.0001). CONCLUSIONS: The results fail to replicate the findings of previous studies reporting an association between DA D2 receptor density and personal detachment, suggesting that the relation is relatively specific to the trait defined by the Karolinska Scales of Personality. The relation between a nonclinical personality trait of depression and DA D2 binding, if replicated, may help to elucidate the role of dopamine in depression.

Adult↗

Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.

INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.

Adolescent↗

MAO-A and MAO-B localisation in human lung and spleen.

Localisation of MAO-A and -B in human lung and spleen was studied by immunohistochemistry. The primary antibodies used were mouse monoclonal anti-human MAO-A (6G11/E1) and anti-human MAO-B (3F12/G10/2E3). Samples of lung and spleen were obtained from 6 routine autopsy cases. Both immunoreactivities showed a homogeneous distribution in lung, where all cell types had both MAO-A and -B staining. In spleen MAO-A and -B showed a very weak immunoreactivity, which was restricted to smooth muscle cells and reticular cells of the white pulp. These data represent the most comprehensive study of MAO-A and -B localisation in the two tissues.

Aged↗

Sports participation, sports injuries and osteoarthritis: implications for prevention.

There is increasing concern that too much physical activity may lead to osteoarthritis. The continuous stress that physical activity places on the joints can result in microtrauma and degeneration of the articular cartilage. However, the onset of osteoarthritis appears to depend on the frequency, intensity and duration of physical activity. Research has shown that individuals of all ages can tolerate moderate amounts of exercise without adverse consequences or accelerated development of osteoarthritis. However, excessive participation in high impact sports, particularly over a long period of time and at an elite level, can increase the risk of developing osteoarthritis. Participants may also be at risk if they have abnormal joint anatomy or alignment, joint instability, underlying muscle weakness or imbalance, or if they are overweight and engage in significant amounts of exercise. Individuals who have experienced sports injuries to joints, or macrotrauma, may also be at risk of accelerated development of osteoarthritis. Certain types of surgery for the treatment of severe sports injuries, particularly to the knee, also appear to be associated with an increased risk. If surgery to the knee is required, continuous passive motion is an ideal form of rehabilitative treatment, as it promotes healing of the articular cartilage, ligaments and tendons. Moreover, athletes who have undergone surgery should return slowly to sporting activities to ensure they do not place too much stress on their injured joint(s). Further research into the causes of osteoarthritis is required; in particular, prospective and retrospective cohort studies are needed to confirm the association between exposure to risk factors and the development of osteoarthritis.

Animals↗

Extensive lipomatous metaplasia in bilateral macronodular adrenocortical hyperplasia.

OBJECTIVE: We describe a case of macronodular hyperplasia with marked adrenal enlargement in which mature adipose tissue was a significant component. To our knowledge, this condition has not been reported previously. METHODS: A 42-year-old woman with newly diagnosed Cushing's syndrome underwent endoscopic bilateral adrenalectomy to remove bilateral adrenal masses. RESULTS: Both adrenal glands displayed features of macronodular hyperplasia with marked adrenal enlargement, and abundant mature adipose tissue was identified in some nodules of both glands. CONCLUSIONS: Lipomatous metaplasia is histologically demonstrated in a case of macronodular hyperplasia with marked adrenal enlargement. This distinctive change may be secondary to metaplastic transformation of either stromal cells or adrenocortical cells. The presence of lipomatous metaplasia would appear to indicate adrenocortical process, since, to our knowledge, it has never before been described in the adrenal nodule.

Adipose Tissue↗

What do adult squash players think about protective eyewear?

OBJECTIVE: To determine the attitudes of adult squash players towards protective eyewear. METHODS: A survey of 197 competition and social squash players from seven squash centres in the outer eastern suburbs of Melbourne, Australia was conducted in September to October 1995. Information about participation in squash, previous injuries, use of protective eyewear, barriers towards eyewear use, and attitudes towards protective eyewear was obtained by a self report questionnaire. RESULTS: Squash is a popular sport in Australia. Of the players surveyed, 6% played in junior competitions, 67% in senior competitions, and 27% were social players. Most had been playing for more than ten years. Some 15% of players had previously suffered an eye injury, most commonly caused by a racquet. Less than 10% of players reported that they wore protective eyewear when they played squash, and 35% of these wore prescriptive lenses which they considered to be protective. The major reason for not wearing protective eyewear was the perception that it was unnecessary. Poor vision and a lack of comfort were also stated as reasons by a significant number of players. More than half (57%) of the respondents agreed that more players should wear protective eyewear, yet only 16% thought it should be compulsory for all players. There was considerable support for protective eyewear use by junior players, however. CONCLUSIONS: The rate of protective eyewear use is low among competition and social squash players in Melbourne. The major areas that need to be addressed are the ignorance of the need for protective eyewear among social and experienced players and the mistaken belief that prescription lenses provide adequate protection on a squash court.

Adolescent↗

Sport and active recreation injuries in Australia: evidence from emergency department presentations.

OBJECTIVE: Despite the rise in specialist clinical services for the management of sports and active recreation injury, many patients attend hospital emergency departments for treatment. The purpose of this study was to describe sports injury cases presented to selected hospital emergency departments around Australia for the period 1989-1993. METHODS: Routinely collected emergency department injury presentation data from the Australian National Injury Surveillance Unit were examined. Data on 98,040 sports and active recreation emergency department presentations were analysed. Sports and active recreation activities were ranked according to frequency of presentation. Relative proportions of injury type and body region injured were determined. Data are presented separately for children (<15 years of age) and adults (>15 years of age). RESULTS: Among the 10 activities that most commonly led to a sports or active recreation injury presentation for all ages were cycling, Australian football, basketball, soccer, cricket, netball, and rugby. For children, injuries were also commonly associated with roller skating/blading, skateboarding, and trampolining. Hockey, martial arts, and dancing injuries were frequent in adults. Most sporting injuries occurred during organised competition or practice whereas the active recreation injuries occurred in a variety of settings. Fractures, strains, and sprains, particularly to the lower and upper extremities, were common types of injury. CONCLUSION: The rich, but nevertheless limited, information available about sports and active recreation injuries from data collected in emergency departments indicates that these activities are a common context for injury at the community level in Australia.

Adolescent↗

Sporting and recreational injuries. In a general practice setting.

OBJECTIVE: To collect data on sporting and recreational injuries presenting to a general practice clinic in metropolitan Melbourne, to gain better knowledge about the range of these injuries commonly seen in general practice and in the community. METHOD: A survey was conducted for four, 2 week periods, at 3 monthly intervals, over approximately 1 year, at a general practice clinic in metropolitan Melbourne. All patients who presented with a new sporting or recreational injury were asked to complete a questionnaire, seeking information on the nature, circumstances, risk factors and severity of their injury, as well as why they had chosen to present to a general practice clinic, in preference to a hospital emergency department. It was completed by both the patient and the treating doctor. RESULTS: The main findings of the survey were that patients who presented to the clinic with a sporting or recreational injury were most likely to be male and in their twenties. The most common sports that had been played prior to injury were Australian rules football, soccer and hockey. The majority of injuries were relatively mild, with sprains and bruises accounting for 78% of injuries, while 89% of patients required conservative forms of treatment. The ankle, fingers and knee were the most common body parts affected. CONCLUSION: Data from general practice provides important information about the epidemiology of sporting and recreational injuries in the community.

Adolescent↗

Methylation of the glial fibrillary acidic protein gene shows novel biphasic changes during brain development.

The gene for glial fibrillary acidic protein (GFAP) was analyzed in the rat for developmental changes in methylation of cytosine at CpG sequences as a correlate of the onset of GFAP mRNA expression and for the effect of methylation on GFAP promoter activity. The methylation of nine CpG sites in the GFAP promoter and ten sites in exon 1 was analyzed in F344 rats by a quantitative application of ligation-mediated polymerase chain reaction. Whole rat brain poly(A)+ RNA showed an exponential increase of GFAP mRNA after embryo day 14 that reached stable adult levels by postnatal day 10. During development, only the seven CpG sites in the far-upstream promoter showed large changes in methylation; these sites constitute the brain-specific domain of methylation described in adult rats (Teter et al: J Neurosci Res 39:680, 1994). These seven CpG sites showed a cycle of demethylation during the onset of GFAP transcription in the embryo (between embryonic day 14 and postnatal day 10) followed by remethylation at later postnatal ages when GFAP mRNA remains prevalent. The minimum levels of methylation across these CpG sites displayed a gradient with the lowest minima at the 3' sites. This demethylation/remethylation cycle is a novel phenomenon in DNA methylation during perinatal development. The demethylation/remethylation cycle during development was also shown by the opposite-strand cytosines. Two cytosines in this region that are conserved in rat and mouse also undergo the same demethylation/remethylation cycle in the mouse GFAP gene during development, implying evolutionary conservation and functional significance. As a further test of functional significance, a Luciferase reporter gene assay was evaluated in primary cultured astrocytes; the activity of the GFAP promoter was reduced when it was methylated at one or all CpG sites. Therefore, the GFAP promoter may be activated in rodent development by transient demethylation of a conserved brain-specific methylation domain.

Animals↗

Capacity of the store-regulator in maintaining iron balance.

There is evidence that iron stores alter iron absorption to meet body iron needs. In this study, quantitative aspects of this regulation of iron balance are examined. Two male subjects, one with low and one with average iron stores, were given additional dietary iron over 500 days. Changes in iron stores were monitored by plasma ferritin measurements, and the ferritin estimate of stores was validated at the end of the study by bleeding to the point of iron deficiency. The subject with low iron stores increased his ferritin by 39 micrograms/L or 0.8 mg/day, whereas the subject with average iron stores had no significant change. It is concluded that the mechanism by which stores regulate food iron absorption has a capacity of about 1 mg/day, sufficient to meet usual physiological needs, with the exception of pregnancy, as well as the ability to resist increase in stores above normal despite an iron rich diet.

Adult↗

Receptor binding and signal transduction are dissociable functions requiring different sites on follicle-stimulating hormone.

Separate sites for glycoprotein hormone receptor binding and signal transduction have yet to be elucidated. In general, certain peptide regions are thought to be critical for receptor binding, whereas the oligosacharides are thought to be important for signal transduction. Using site-directed mutagenesis of FSH, we made selective amino acid substitutions and oligosaccharide alterations to try and identify specific sites mediating receptor binding distinct from signal transduction and vice versa. We substituted Lys or Asp for beta Arg35 in the purported receptor binding loop between cysteine-32 and -51, and we substituted Gln for alpha Asn52, alpha Asn78, beta Asn7, or beta Asn24, the attachment sites for each of the oligosaccharide side-chains. We determined the binding and signal-transducing activity of wild-type and mutant human FSH at the human FSH receptor, as recent data suggest that glycoprotein hormone-receptor interactions are species specific. The binding activities of FSH with Lys or Asp substituted for beta Arg35 were reduced 71% and 98%, respectively, but their signal transduction, at equivalent levels of binding activity, was unaffected. The binding activity of FSH lacking the oligosaccharide at alpha Asn52 was enhanced 2- to 3-fold, but its signal-transducing activity, at equivalent levels of receptor binding, was decreased 72%. In contrast, the binding and signal-transducing activities of FSH lacking the alpha Asn78, or alpha Asn7, or beta Asn24 oligosaccharide were unaffected. Thus, a specific amino acid (beta Arg35) is important for high affinity binding, but is not involved in signal transduction, whereas a specific oligosaccharide (alpha Asn52) is important for signal transduction, but is not required for high affinity binding. Therefore, receptor binding and signal transduction are dissociable functions involving different sites on the FSH glycoprotein.

Follicle Stimulating Hormone↗

Blood pressure, hypertension and other cardiovascular risk factors in six communities in Papua New Guinea, 1985-1986.

Surveys of noncommunicable diseases were performed in six communities in Papua New Guinea during 1985-1986. Results are reported here with respect to blood pressure and associated factors in adults. Mean systolic and diastolic blood pressures were lowest, and hypertension was rarest (less than 2%), in three rural/semirural villages on Karkar Island, Madang Province. Intermediate values for blood pressure and moderate prevalence of hypertension (3-6%) were observed in rural and urban Tolai communities in East New Britain Province. A periurban village in the Eastern Highlands Province displayed the highest mean blood pressures and prevalence of hypertension (12% in men and 5% in women). There was a modest rise in mean systolic blood pressure with age in most groups, but the age-related rise in diastolic pressure was much less pronounced. Other cardiovascular risk factors--body mass index (BMI), and plasma cholesterol, glucose and insulin concentrations--were lowest in the least developed rural villages on Karkar Island and highest in the urban Tolai and periurban highland communities. Both systolic and diastolic blood pressures were significantly (and positively) related to age, male sex, BMI and speaking a non-Austronesian language. It is concluded that there is now a considerable variation in the prevalence of hypertension, and the levels of blood pressure and other cardiovascular risk factors, in different communities in Papua New Guinea.

Adult↗

High, usual and impaired functioning in community-dwelling older men and women: findings from the MacArthur Foundation Research Network on Successful Aging.

The objective of this study is to determine the range of complex physical and cognitive abilities of older men and women functioning at high, medium and impaired ranges and to determine the psychosocial and physiological conditions that discriminate those in the high functioning group from those functioning at middle or impaired ranges. The subjects for this study were drawn from men and women aged 70-79 from 3 Established Populations for the Epidemiologic Study of the Elderly (EPESE) programs in East Boston MA, New Haven CT, and Durham County NC screened on the basis of criteria of physical and cognitive function. In 1988, 4030 men and women were screened as part of their annual EPESE interview. 1192 men and women met criteria for "high functioning". Age and sex-matched subjects were selected to represent the medium (n = 80) and low (n = 82) functioning groups. Physical and cognitive functioning was assessed from performance-based examinations and self-reported abilities. Physical function measures focused on balance, gait, and upper body strength. Cognitive exams assessed memory, language, abstraction, and praxis. Significant differences for every performance-based examination of physical and cognitive function were observed across functioning groups. Low functioning subjects were almost 3 times as likely to have an income of < or = $5000 compared to the high functioning group. They were less likely to have completed high school. High functioning subjects smoked cigarettes less and exercised more than others. They had higher levels of DHEA-S and peak expiratory flow rate. High functioning elders were more likely to engage in volunteer activities and score higher on scales of self-efficacy, mastery and report fewer psychiatric symptoms.

Activities of Daily Living↗

Endobronchial closure of a postpneumonectomy bronchopleural fistula.

Successful permanent endobronchial closure of a serious postpneumonectomy bronchopleural fistula is reported in a patient with a delayed diagnosis of Mycobacterium fortuitum-cheloni infection. Increasing experience, improved plugging agents, and a review of the literature suggest that in selected patients, this procedure can avoid complex repeat operations and reverse life-threatening situations. Although atypical mycobacterial infections occur with infrequency, they are difficult to treat and may lead, as in this patient, to a misdiagnosis. Operations on granulomatous tissues are prone to heal poorly, thus inviting tissue breakdown and chronic fistulas.

Bronchial Fistula↗