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Biomedical subjects

A Dicker

Publications and source records attributed to A Dicker.

At least 19 recordsLinked to original sources
PubMed2005

Differential function of the alpha2A-adrenoceptor and Phosphodiesterase-3B in human adipocytes of different origin.

OBJECTIVE: Human adipocytes can be obtained in vitro by differentiation of human preadipocytes or mesenchymal stem cells (hMSC). Although functionally similar to freshly isolated cells, no detailed comparison of the different cell types has been performed. The antilipolytic alpha2A-adrenoceptor (AR) and the cAMP-degrading enzyme Phosphodiesterase-3B (PDE3B) have been implicated in the fine-tuning of lipolysis but little is known regarding their role in human adipocytes nor whether their expression and/or function differs in fat cells from different precursors. METHODS: The effects of alpha2A-AR and PDE3B inhibition in mature adipocytes was determined and compared to that in differentiated preadipocytes and hMSC-derived fat cells. Gene expression was determined by real-time PCR and protein expression by Western blot. RESULTS: Noradrenaline (NA) stimulated lipolysis in preadipocytes and mature adipocytes but markedly reduced lipolysis in differentiated hMSC derived-adipocytes. This was due to a potent stimulation of alpha2A-AR since co-incubation with NA and the alpha2-AR-inhibitor yohimbine restored NA-induced lipolysis. The order of Yohimbine response was hMSC>preadipocytes>mature adipocytes. Although alpha2-AR mRNA expression was highest in mature adipocytes there was no difference in alpha2A-AR protein levels between the cell types. In contrast, Galphai2 mRNA and protein expression was significantly higher in MSC-derived adipocytes, suggesting that differences in the response to alpha2A-AR inhibition reside at the postreceptor level. Incubation with the cAMP-analog 8-bromo(8b) cAMP increased lipolysis in hMSC-derived fat cells while co-incubation with the PDE3-specific inhibitor OPC3911 did not alter the lipolytic effect. In contrast, OPC3911 increased 8bcAMP-induced lipolysis significantly in preadipocytes and mature adipocytes. The response to PDE3B inhibition was; mature adipocytes>preadipocytes>hMSC a finding that correlated significantly with both PDE3B mRNA expression and enzymatic activity. CONCLUSION: Although differentiated adipocytes of different origins display similar functional characteristics there are important differences in the regulation of lipolysis with a marked alpha2A-AR and less pronounced PDE3B effect in fat cells from MSCs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots.

AIM/HYPOTHESIS: Regional differences in lipolysis, with higher lipolytic activity in visceral than subcutaneous fat, are important for the development of insulin resistance and might be influenced by testosterone. METHODS: We studied testosterone-regulated lipolysis and protein expression (by western blot) in fully differentiated pre-adipocytes from visceral (omental) and abdominal subcutaneous adipose tissue from 52 human subjects. These cells were isolated and cultured in a serum-free medium. RESULTS: Testosterone caused a specific, time- and concentration-dependent 50% reduction of catecholamine-stimulated lipolysis in the subcutaneous depot. Half of the maximum effect occurred at 10 nmol/l. The inhibitory effect was due to the inability of beta-adrenoceptors and cyclic AMP to stimulate the protein kinase A, hormone-sensitive lipase complex. Testosterone caused a depot-specific 50% reduction of the protein expression of hormone-sensitive lipase and beta(2)-adrenoceptors in differentiated subcutaneous pre-adipocytes, but no change in beta(1)-adrenoceptors, protein kinase A subunits or perilipin expression. In contrast, testosterone had no effect on lipolysis or protein expression in the visceral depot. However, testosterone receptors were present in both depots, and the hormone inhibited adipocyte leptin secretion. Similar effects on lipolysis were observed with dihydrotestosterone. CONCLUSIONS/INTERPRETATION: Testosterone in physiological concentrations causes a depot-specific reduction of catecholamine-stimulated lipolysis in subcutaneous fat cells, probably due to reduced protein expression of beta(2)-adrenoceptors and hormone-sensitive lipase. This could be an important pathogenic factor underlying regional differences in lipolysis and development of insulin resistance and hyperandrogenic polycystic ovary syndrome.

Adipocytes↗
PubMed2002

Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet.

AIM/HYPOTHESIS: We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women. METHODS: Glucose transport and insulin signalling were investigated in isolated adipocytes from six obese women (BMI 36-43 kg/m(2)) (before and after 11 days of very low calorie diet) and from six lean women (BMI 22-26 kg/m(2)). RESULTS: Insulin sensitivity of glucose transport was reduced in adipocytes from obese women (p<0.05), with further reductions in basal and maximal insulin-stimulated glucose transport after a very low calorie diet (p<0.05). In obese women, IRS-1 associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2 associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3-kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus lean subjects (p<0.05), and decreased further after a very low calorie diet (from 19+/-4 to 14+/-4 arbitrary units; p<0.05). CONCLUSION/INTERPRETATION: IRS-1 signalling to PI 3-kinase is a site of insulin resistance in adipocytes from obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2 undergo differential regulation in adipocytes from obese insulin resistant subjects. Finally, a very low calorie diet is associated with a further impairment in glucose transport in adipose tissue. The defect in glucose transport after a very low calorie diet occurs independent of further defects in insulin signalling at the level of the PI 3-kinase.

Adipocytes↗
PubMed2001

Using Bowen Therapy to improve staff health.

Positive results from the administration of Bowen Therapy to staff while at work has prompted an innovative project addressing the lowering of stress levels and preventing burn-out for all staff, in and beyond nursing.

Adult↗
PubMed2000

Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication.

BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs.

Adult↗
PubMed2000

The multidisciplinary clinic approach to prostate cancer counseling and treatment.

The optimum management for an individual patient with prostate cancer is not well defined. Patients with localized disease may be offered options ranging from observation, hormonal therapy, cryotherapy, radiation therapy, or surgery. Each option may have unique aspects to consider when counseling a patient often leading to multiple physician visits over an extended period of time. Since 1996, the Kimmel Cancer Center of Thomas Jefferson University has offered newly diagnosed urologic cancer patients the opportunity to be evaluated in a multidisciplinary clinic. Here, multiple physician consultative visits, including pathologic and radiologic evaluation and protocol evaluation, are provided during the session. Herein we report on our experience with this multidisciplinary approach for patients with prostate cancer.

Cancer Care Facilities↗
PubMed1999

Histone deacetylase inhibitors as potential anti-skin cancer agents.

The regulation of squamous differentiation is a tightly regulated process involving transcriptional repression and activation. Previous studies have established that squamous carcinoma cell lines inappropriately regulate the transcription of genes important to the control of squamous differentiation. Histone deactylase inhibitors such as trichostatin A (TSA) and butyrate disrupt normal chromatin structure and cause alterations in gene expression/regulation. For these reasons, we examined the effects of both butyrate and TSA on the growth and differentiation of human keratinocytes or squamous carcinoma cells in tissue culture. We found that treatment of keratinocytes or squamous carcinoma cells with butyrate induced a reversible growth arrest. TSA, on the other hand, induced an irreversible growth arrest in both keratinocytes and squamous carcinoma cells. The growth arrest of keratinocytes induced by TSA or butyrate was accompanied by a reduction in the mRNA levels for proliferation gene cdk1 and an induction of the mRNA for the differentiation-specific transglutaminase type I gene (TG1). In contrast, the squamous carcinoma cells had decreased cdk1 and TG1 mRNA in response to TSA or butyrate. Both of these agents produced transient increases in the acetylation of histone H4 in keratinocytes and squamous carcinoma cells. These data indicated that TSA may have potential as a topical treatment for epidermal malignancies.

Antineoplastic Agents↗
PubMed1998

GPs and junkies

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells.

To examine the significance of brown adipose tissue for the thermogenic response to glucagon, we injected glucagon intraperitoneally into rats (that have glucagon-sensitive brown fat cells) and into hamsters (that have glucagon-insensitive brown fat cells). Although a thermogenic response to glucagon injection was apparently observed in rats, this response was not augmented by cold acclimation and was not dose dependent. Similar observations were made in hamsters. The thermogenic response could be fully blocked by prior injection of the beta-adrenergic blocker propranolol. Thus no direct thermogenic response to injected glucagon could be demonstrated, and the thermogenic response observed was fully due to vehicle injection. However, glucagon injection was able to unmask mitochondrial [3H]GDP binding. As expected, isolated brown fat cells from rats and mice responded thermogenically to glucagon but brown fat cells from hamsters were unresponsive. The EC50 of the rat brown fat cells was high (5 nM); these cells also responded to secretin, with an EC50 of 22 nM. It was concluded that, in contrast to earlier observations, no thermogenic response to injected glucagon could be observed; this may be related to differences in glucagon preparations. Brown fat cells from certain species are, however, glucagon sensitive. It is uncertain whether glucagon is the endogenous agonist for these receptors, but the presence of the glucagon-responsive receptor indicates alternative means to norepinephrine for stimulation of brown adipose tissue thermogenesis and, probably, of recruitment.

Adipose Tissue, Brown↗
PubMed1997

Effect of edema on the post-implant dosimetry of an I-125 prostate implant: a case study.

PURPOSE: To investigate the effect of post-implant edema on the CT-based calculation of the total dose delivered by an I-125 prostate implant. MATERIALS AND METHODS: CT scans of a transperineal I-125 prostate implant were obtained 1 and 39-days post-implant. Changes in the prostate dimensions were determined from changes in the spatial distribution of the I-125 seeds. The total dose delivered to the target volume was computed from each CT scan, and the results compared. RESULTS: The volume of the prostate decreased by approximately 17% during the 38-day interval between the first and second CT scans. As a result, the radiation dose computed from the second CT scan was 13% higher. CONCLUSION: Post-implant edema can cause a significant underestimation of the radiation dose delivered by an I-125 prostate implant. Similar analysis should be carried out among a larger cohort of patients to confirm or refute these observations.

Aged↗
PubMed1996

Cold-induced reduction in Gi alpha proteins in brown adipose tissue. Effects on the cellular hypersensitization to noradrenaline caused by pertussis-toxin treatment.

The significance of Gi proteins for the physiological desensitization phenomena observed in brown-fat cells from cold-acclimated hamsters was investigated. For this purpose, pertussis toxin (the inhibitor of Gi function) was injected into control and cold-acclimated hamsters. After 3 days the thermogenic response to noradrenaline injection was monitored in the intact animals. It was found that the pertussis-toxin pretreatment did not affect the thermogenic response to noradrenaline. Nonetheless, the pertussis toxin pretreatment had a dramatic effect on the noradrenaline-sensitivity of isolated brown-fat cells (measured the following day as the respiratory response): a 250-fold-increased sensitivity to noradrenaline was observed in cells from control animals that had been pertussis-toxin pretreated. However, only a 20-fold increase was observed in cells from cold-acclimated hamsters, implying a lower complement of the Gi system in these cells. Therefore the content of Gi proteins was determined by quantitative immunoblotting of purified plasma-membrane proteins. Cold acclimation resulted in a nearly 50% reduction in the content of Gi 1 alpha and Gi 2 alpha, as well as of the beta-subunit, both when expressed on a protein basis and when related to the content of forskolin-stimulated adenylyl cyclase; when expressed per unit of [3H]ouabain-binding (NA+/K+-ATPase), the reduction was even higher. In view of the magnitude of the pertussis-toxin effect, it was concluded that Gi proteins must play a substantial role in the regulation of the response of brown-fat cells to noradrenaline. As the capacity of the Gi pathway is reduced rather than augmented during cold acclimation, Gi activity cannot be responsible for the desensitization to noradrenaline observed in cells from cold-acclimated animals. However, the reduced Gi content may explain the earlier observed desensitization to adenosine that occurs after acclimation to cold.

Acclimatization↗
PubMed1996

Stimulation of nonshivering thermogenesis in the Syrian hamster by norepinephrine and beta-selective adrenergic agents: a phenomenon of refractoriness.

The ability of different adrenergic agents to stimulate nonshivering thermogenesis in Syrian hamsters was investigated. The hamsters were cold-acclimated to 6 degrees C and their thermogenic response was investigated in an open-circuit system at 24 degrees C. Both norepinephrine and the beta 3-specific adrenergic agonist CGP-12177 induced a high rate of nonshivering thermogenesis. However, neither CGP-12177 nor other beta 3-selective agonists (BRL-37344, ICI-D7114) could induce nonshivering thermogenesis fully to the extent induced by norepinephrine. It was further observed that an apparent "thermogenic refractoriness" was induced by certain adrenergic agents (isoprenaline, CGP-12177) but not by others (norepinephrine, BRL-37344, ICI-D7114). It is discussed whether the refractoriness could be secondary to effects of these agents on the vascular system. It is pointed out that the thermogenic response to adrenergic stimulation observed in the intact animal does not always fully correspond to what would be predicted from corresponding studies with isolated brown-fat cells.

Acclimatization↗
PubMed1995

Patients' views of priority setting in health care: an interview survey in one practice.

OBJECTIVES: To explore the assumptions underlying consumers' responses to questions of resource priorities in the NHS. DESIGN: Qualitative analysis of semi-structured interviews with a heterogeneous sample of 16 patients drawn from a general practice. RESULTS: Interviewees were not persuaded that they had a legitimate role to play in the prioritisation of services. They supported the principle of equity and were reluctant to use their own personal needs as a basis for resource allocation; instead they argued from what they perceived to be the needs of others. CONCLUSIONS: Paradoxically, surveys of consumers' views on health care priorities probably do not elicit the personal ideas of respondents but tap into a more general ideological position closer to an earlier collectivist notion of health care.

Adult↗
PubMed1995

Halothane selectively inhibits nonshivering thermogenesis. Possible implications for thermoregulation during anesthesia of infants.

BACKGROUND: During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. METHODS: The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. RESULTS: Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. CONCLUSIONS: A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

Adipose Tissue, Brown↗