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Biomedical subjects

B Lowell

Publications and source records attributed to B Lowell.

15 recordsLinked to original sources
PubMed2001

Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance.

Several lines of investigation suggest that the hypothalamic neuropeptide melanin-concentrating hormone (MCH) regulates body weight in mammals. Obese mice lacking functional leptin overexpress the MCH message in the fed or fasted state. Acute intracerebroventricular injection of MCH increases energy intake in rats. Mice lacking the MCH gene are lean. To test the hypothesis that chronic overexpression of MCH in mice causes obesity, we produced transgenic mice that overexpress MCH (MCH-OE) in the lateral hypothalamus at approximately twofold higher levels than normal mice. On the FVB genetic background, homozygous transgenic animals fed a high-fat diet ate 10% more and were 12% heavier at 13 weeks of age than wild-type animals, and they had higher systemic leptin levels. Blood glucose levels were higher both preprandially and after an intraperitoneal glucose injection. MCH-OE animals were insulin-resistant, as demonstrated by markedly higher plasma insulin levels and a blunted response to insulin; MCH-OE animals had only a 5% decrease in blood glucose after insulin administration, compared with a 31% decrease in wild-type animals. MCH-OE animals also exhibited a twofold increase in islet size. To evaluate the contribution of genetic background to the predisposition to obesity seen in MCH-OE mice, the transgene was bred onto the C57BL/6J background. Heterozygote C57BL/6J mice expressing the transgene showed increased body weight on a standard diet, confirming that MCH overexpression can lead to obesity.

Adipose Tissue↗
PubMed2000

A mini-fellowship in clinical nutrition for primary care physicians.

When the Regional Nutrition Center's (RNC's) mini-fellowship was being developed, physicians teaching in medical schools and residency programs had little formal training in nutrition, so it was difficult to identify faculty to serve as role models and clinical preceptors. Using funds provided by an NIH/NCI R-25 grant, the mini-fellowship in clinical nutrition was developed as a model to meet the nutrition education needs of senior residents and junior faculty in primary care disciplines. It provided a brief but broad exposure to clinical nutrition topics, with a focus on issues relevant to the practice of primary care and teaching skills. In four weeks, fellows completed didactic course work, a clinical preceptorship, and a teaching project. Tracking of the 55 physicians who completed the program by questionnaires has shown significant improvement in their nutrition-related patient care activities.

Fellowships and Scholarships↗
PubMed1999

Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.

Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs). PGC-1 stimulates a powerful induction of NRF-1 and NRF-2 gene expression; in addition, PGC-1 binds to and coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription factor A (mtTFA), a direct regulator of mitochondrial DNA replication/transcription. These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function.

3T3 Cells↗
PubMed1999

Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system.

Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TR alpha and TR beta isoforms are products of 2 distinct genes, and the beta 1 and beta 2 isoforms are splice variants of the same gene. Whereas TR alpha 1 and TR beta 1 are widely expressed, expression of the TR beta 2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TR beta 2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TR beta 2 isoform. TR beta 2-null mice have preserved expression of the TR alpha and TR beta 1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TR beta-null mice, indicating the important role of TR beta 2 in the regulation of the hypothalamic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TR beta 2-null mice exhibit no evidence of hearing impairment, indicating that TR beta 1 and TR beta 2 subserve divergent roles in the regulation of auditory function.

Animals↗
PubMed1996

Role of leptin in the neuroendocrine response to fasting.

A total deficiency in or resistance to the protein leptin causes severe obesity. As leptin levels rise with increasing adiposity in rodents and man, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance. Starvation is also a threat to homeostasis that triggers adaptive responses, but whether leptin plays a role in the physiology of starvation is unknown. Leptin concentration falls during starvation and totally leptin-deficient ob/ob mice have neuroendocrine abnormalities similar to those of starvation, suggesting that this may be the case. Here we show that preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starvation-induced delay in ovulation in female mice. In contrast, leptin repletion during this period of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin.

Adrenal Glands↗
PubMed1996

Bereavement services development in a rural setting.

Functioning as a hospital-based hospice program of a large medical center, bereavement services are not limited to hospice families in one location. Bereavement services are offered to those who died within the medical center and to the residents of the three county area the hospice serves. This paper identifies ways to offer bereavement follow-up to hospice and non-hospice families. This will include discussion of mixing together survivors of different types of death in a support group atmosphere. Due to the smaller population of a rural setting, the need to be creative to offer bereavement services to the community is imperative. This paper will discuss how our Bereavement Services have expanded in response to the needs of the communities in the three county area we serve. We will discuss survey results, meeting and support group data used to generate supporting information to allow our services to grow. Learning objectives for this article consist of readers being able to identify ways to develop and expand bereavement services; incorporating various types of death in a support group setting; and ways to better serve non-hospice families in need of bereavement follow-up. Topics include a description of Bereavement Services; Pre-Death Bereavement Intervention; Open and Closed Support groups; Routine Bereavement Follow-up of Hospice families; Quarterly Nursing Home Staff Support groups; Widow/Widower Brunch Social; opportunities to educate the community about Death/Dying; and data collection for Bereavement Needs.

Aftercare↗
PubMed1989

Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice.

Adipsin expression at the protein and mRNA levels is greatly reduced in several distinct syndromes of obesity in the mouse: genetic obesity due to the db/db and ob/ob genes, and a chemically induced model secondary to neonatal exposure to monosodium glutamate. We considered first the possibility that the adipsin gene might be identical to the db or ob locus and the lowered expression of this protein might result from a mutation in this gene. We show here that the adipsin structural gene is located on chromosome 10 and hence is physically distinct from any obesity genes so far identified in the mouse. A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments. Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls. Exogenous administration of corticosterone completely blocks the effects of adrenalectomy on adipsin, suggesting that the effect of this endocrine ablation is through reduction of adrenal glucocorticoids. Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice. The effect of exogenous corticosterone in lean mice occurs within 2 days and hence is not secondary to the obesity which these hormones eventually elicit. These results indicate that glucocorticoids can regulate adipsin expression in vivo and strongly suggest that the hyperglucocorticoid state seen in certain obese models plays a significant role in lowering adipsin mRNA and protein levels. Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity.

Adipose Tissue↗
PubMed1984

Sites of protein conservation and loss during starvation: influence of adiposity.

Previous studies have established that older (16 wk) and more obese rats conserve body protein during prolonged starvation. This adaptation is due in part to a curtailment of muscle proteolysis. To determine whether this response occurs also in younger rats and whether protein is conserved at sites other than muscle, studies were conducted in young 6-wk-old rats previously fed either a chow or a high-fat diet before starvation. Fat feeding caused a marked increase in adipose mass and prolonged survival. Whereas chow-fed rats survived the fast for approximately 5 days, fat-fed rats lived for 10 days and diminished their excretion of nitrogen for at least 6 days, indicative of protein conservation. Despite the ability of fat-fed rats to survive the fast longer, protein was conserved in only a few organs. The timing and magnitude of protein loss from liver, kidney, intestine, and lung was similar to that in chow-fed rats, and little protein was lost during the fast from brain, stomach, skin, and soleus muscle in either group. In fat-fed rats, cardiac and skeletal muscle were the principle tissues in which protein was conserved, and this adaptation was lost when body fat stores were nearing exhaustion. In both groups nitrogen excreted in the urine early in the fast was derived mainly from protein lost from muscle, liver, and to a lesser extent intestine. Later in the fast, the principal source was muscle. These findings indicate that during starvation in the rat the conservation of protein occurs principally in skeletal and cardiac muscle. They also suggest that the ability of the rat to conserve protein is dependent on the size of its lipid stores.

Adipose Tissue↗
PubMedDate not supplied

Popliteal artery thrombosis in a young woman, secondary to bony exostosis.

Idiopathic thrombosis of the popliteal artery in young people is exceedingly uncommon. Previously suggested etiologies are cystic adventitial disease, popliteal entrapment syndrome, Buerger's Disease, juvenile arteriosclerosis and synovial cysts. An instance of popliteal artery thrombosis secondary to compression by a bony exostosis is recorded to call attention to this unusual etiological mechanism in a 21 year old woman. Restoration of arterial continuity was achieved by endarterectomy and a venous patch graft following excision of the bony exostosis.

Adult↗