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Biomedical subjects

L Goodman

Publications and source records attributed to L Goodman.

At least 19 recordsLinked to original sources

Immortalized rat whisker dermal papilla cells cooperate with mouse immature hair follicle buds to activate type IV procollagenases in collagen matrix coculture: correlation with ability to promote hair follicle development in nude mouse grafts.

An in vivo nude mouse graft model and an in vitro collagen matrix culture system were used to study interactions of immature hair follicle buds from newborn mice with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell lines. Of the 19 available dermal papilla cell lines, four consistently supported good hair follicle development and hair growth in grafts. Seven cell lines were clearly negative in this assay, and the remaining eight cell lines yielded poor to moderate hair growth. As a correlate to in vivo extracellular matrix remodeling accompanying hair follicle development, type IV collagenase activity in the medium from cocultures of dermal papilla cells and hair follicle buds was analyzed by gelatin zymography. Hair follicle buds cultured alone secrete primarily the 92-kDa type IV procollagenase. Cocultivation of hair follicle buds with eight of the dermal papilla cell lines resulted in activation of this proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases produced by the dermal papilla cells. Seven of these eight dermal papilla cell lines support hair growth in the graft system. In the absence of dermal papilla cells, several growth factors induced activation of the 92-kDa procollagenase secreted by hair follicle buds cultured in serum-free medium: epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor, and keratinocyte growth factor. The current working hypothesis is that a) hair follicle epithelial cells interact with dermal papilla cells in coculture by mutual induction of growth factors and cytokines that stimulate the release and activation of matrix remodeling proteases; and b) the ability of dermal papilla cells to interact with hair follicle epithelial cells in this way may be crucial for controlled dermal matrix remodelling during HF development.

Animals

Basal and induced amounts of interleukin-6 mRNA decline progressively with age in human fibroblasts.

Interleukin-6 (IL-6) is a multi-functional cytokine that plays a role in the body's response to injury and infection. IL-6 expression is induced in young human diploid fibroblasts (HDF) in response to a number of agents including fetal bovine serum, 12-O-tetradecanoylphorbol-13-acetate, double-stranded RNA, and forskolin. In contrast, we find that senescent HDF are markedly deficient in their ability to express IL-6 in response to serum, double-stranded RNA, and 12-O-tetradecanoyl-phorbol-13-acetate, whereas forskolin is still an effective inducer for senescent cells. Thus, specific pathways for stimulating IL-6 expression appear to be blocked in senescent HDF. The basal amount of IL-6 mRNA in unstimulated senescent HDF is also much lower than in unstimulated young quiescent HDF. Likewise, the amount of IL-6 protein produced by senescent HDF is decreased at least 10-fold. Both the basal and induced levels of IL-6 declined progressively with aging of the HDF in culture, e.g. IL-6 cannot be induced above the young basal level by approximately 65% of life-span completed. If a similar decrease in IL-6 expression takes place in HDF in vivo, it could contribute to the decline in wound healing and the increase in the number and severity of infections experienced by aged individuals.

Blood

Co-administration of progabide inhibits haloperidol-induced oral dyskinesias in rats.

Vacuous chewing movements in rats may be an animal analogue of the human motor disorder, tardive dyskinesia. The movements are phenomenologically and pharmacologically similar to tardive dyskinesia. The pathophysiology of these involuntary oral movements, and perhaps of tardive dyskinesia, are likely to include both dopamine receptor changes, and alterations in GABA (gamma-aminobutyric acid) system function. In an attempt to test the involvement of GABA system dysfunction in these movements, we treated rats chronically with water alone, haloperidol alone, the GABA agonist progabide alone, and haloperidol plus progabide. Sprague-Dawley rats received haloperidol (1.5 mg/kg per day) in their drinking water and progabide (100 mg/kg per day) in their food for 12 months. After 12 months of treatment, haloperidol had induced vacuous chewing movements when administered alone, but the prevalence of the movements was decreased by 40% with the coadministration of progabide. Moreover, the haloperidol-progabide-treated animals did not merely demonstrate movement suppression but actual inhibition of movement onset, as determined by an additional progabide-withdrawal experiment. These data would suggest that progabide and perhaps other GABAmimetic compounds can prevent the development of tardive dyskinesia in man.

Administration, Oral

Homelessness as psychological trauma. Broadening perspectives.

Most mental health literature on homelessness has focused on characteristics that may be risk factors for homelessness. The authors of this article argue that homelessness itself is a risk factor for emotional disorder and use the construct of psychological trauma--focusing on social disaffiliation and learned helplessness--to understand the potential effects of homelessness. Psychological trauma is likely among homeless individuals and families for three reasons. (a) The sudden or gradual loss of one's home can be a stressor of sufficient severity to produce symptoms of psychological trauma. (b) The conditions of shelter life may produce trauma symptoms. (c) Many homeless people--particularly women--become homeless after experiencing physical and sexual abuse and consequent psychological trauma. Research suggests that negative psychological responses to traumatic events can be prevented or mitigated by a supportive and empowering posttrauma environment. The implications of trauma theory for improving the psychosocial conditions of homeless people are discussed.

Adaptation, Psychological

Neuroleptic-induced vacuous chewing movements as an animal model of tardive dyskinesia: a study in three rat strains.

Vacuous chewing movements (VCMs) in three different rat strains developed at considerably different rates after 19 weeks of continual haloperidol treatment at an average daily dose of 1.5 mg/kg. Sprague Dawley (SD) rats displayed relatively high rates of VCMs with low variability, compared to Wistar (W) and Long Evan (LE) rats. Atropine decreased but did not abolish VCMs in two of the three strains (LE greater than SD). After haloperidol withdrawal, VCMs remitted gradually in all strains, but least rapidly in the SD rats. In a separate group of SD rats. VCMs were rated weekly from the start of haloperidol treatment and showed considerable interindividual variability. Even after 24 weeks of continuous haloperidol, 12 out of 32 treated rats showed no VCMs at all, while 13 out of 32 had intense movements, analogous to the clinical situation in which only some patients treated with neuroleptics develop tardive dyskinesia. These results indicate that there are individual and strain differences in the development of VCMs, and suggest that there may also be genetically determined differences in the development of tardive dyskinesia.

Animals

Prescription of aerobic exercise during pregnancy.

Available evidence supports the existence of both risks and benefits of aerobic conditioning during human pregnancy. During intensive exertion, maternal skeletal muscle and the fetus may compete for blood flow, oxygen delivery and essential fuel substrates. Hence, the most important hypothetical risks include acute fetal hypoxia, hyperthermia and malnutrition. If exercise is repeated on a chronic basis, teratogenic effects, fetal growth retardation or altered fetal development may result if maternal/fetal adaptive reserve is exceeded. A dose-response relationship for such effects has been demonstrated in laboratory animals, but specific findings may have limited applicability to voluntary exercise in pregnant women. Although further investigation is needed, the majority of published studies suggest that fitness-type conditioning does not jeopardise fetal well-being in healthy well-nourished women. Benefits of such exercise appear to include increases in maximal aerobic power (VO2max, L/min) and enhanced cardiopulmonary reserve. It has also been proposed that exercise prevents accumulation of excess body fat, promotes psychological well-being, helps to prevent gestational diabetes and low back pain and may facilitate labour. However, these benefits remain to be confirmed by objective scientific study. Due primarily to a lack of scientific data, existing medical guidelines for exercise during pregnancy are conservative and follow a common sense approach. Good agreement exists on the need for preparticipation medical screening and continuing surveillance to verify the existence of maternal/fetal adaptive reserve. Women are advised to select safe, non-ballistic exercise modalities and to avoid thermal or hyperbaric environmental stress during exercise. Exercise in the supine position is also prudent to avoid, particularly in late gestation. The usefulness of heart rate in prescribing and monitoring exercise intensity has been questioned, with use of conventional perception of exertion scales being the most logical alternative. Prediction of maximal aerobic power (VO2max) from submaximal work rate/heart rate relationships is also problematic during pregnancy. Other areas of debate include the advisability of initiating a new exercise programme during pregnancy, methods for prevention of fetal hyperthermia, the safety of weight-training/isometric exercise and optimal methods for training of pre/postnatal fitness instructors.

Exercise Therapy

Comparative in vitro activity of A-56268 (TE-031) against gram-positive and gram-negative bacteria and Chlamydia trachomatis.

The in vitro activity of A-56268 (TE-031) was determined and compared with that of 13 antibiotics against 401 gram-positive and gram-negative bacteria and 11 strains of Chlamydia trachomatis. A-56268 was very active against methicillin-susceptible Staphylococcus aureus and Neisseria gonorrhoeae, and was among the most active of the agents tested against Listeria monocytogenes, streptococci and Chlamydia trachomatis. It was moderately active against Haemophilus spp., Vibrio spp., Campylobacter jejuni and Campylobacter fetus subsp. fetus. It was inactive against enterococci, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Campylobacter coli, Salmonella spp., Shigella spp. and Yersinia enterocolitica. A-56268 was not consistently bactericidal or more active than erythromycin for any organism except Chlamydia trachomatis.

Animals