ECONOMIC GROWTH OF THE SOUTH VERSUS OTHER REGIONS: PAST TRENDS AND FUTURE PROSPECTS

Community/Rural/Urban Development,

Black Farmers and the Economic and Social Conditions Where They Live: Some Policy Implications

Black farmers tend to live in southern counties where nonfarm employment opportunities are limited. These counties have grown slowly, much more slowly than southern metropolitan areas. In counties with concentrations of black farmers, blacks face severe economic and social conditions. They have a higher incidence of poverty, less education, and higher unemployment than other blacks in the South. In addition, blacks in these counties lag far behind whites in socioeconomic status. Economic growth and socioeconomic conditions in counties with black farmers vary considerably by region. Strategies to address the black farm crisis must consider both the characteristics of black farmers, such as their advanced age, and the economic and social conditions of areas where they live

Hyperuricemia and hypertriglyceridemia: Metabolic basis for the association

Hypertriglyceridemia has been reported frequently in patients with hyperuricemia and gout. The current studies have evaluated this relationship. To examine whether hypertriglyceridemia leads to hyperuricemia, IV Intralipid was given to three gouty patients. Triglycerides increased from 169 to 700 mg/dl for three hours but caused no change in serum urate level or urine uric acid and oxypurine excretion. We next examined whether high carbohydrate intake increases serum urate and triglyceride levels. Four obese patients were placed on a 2000 kcal/d sucrose diet for seven days. The serum urate increased from 6.3 +/- 1.7 to 7.9 +/- 2.0 mg/dL. The percent uric acid clearance to creatinine clearance decreased from 5.9 +/- 1.3 to the lowest mean value of 3.7 +/- 1.2, while serum triglycerides increased from 106 +/- 33 to 252 +/- 57 mg/dL and blood lactate from 607 +/- 227 to 1167 +/- 381 [mu]mol/L. A 3000 kcal/d glucose diet in four other obese subjects produced no change in serum urate levels but increased lactate and triglyceride levels. During an isocaloric sucrose diet in two normal men, the serum urate level increased from 5.3 and 4.0 to peak values of 9.5 and 7.4 mg/dL. The percent uric acid to creatinine clearance decreased from 5.6 and 6.6 to 2.9 and 3.3. The uric acid turnover did not increase. In three gouty patients the mean serum urate increased from 8.5 +/- 1.5 to 10.6 +/- 1.4 mg/dL following an isocaloric sucrose diet. The urine uric acid excretion increased from 0.30 and 0.25 to 0.37 and 0.38 mg/mg creatinine in two patients. The percent uric acid clearance to creatinine clearance decreased from 3.8 to 2.5 in one patient. The serum triglycerides were substantially elevated during the sucrose diet in the normal subjects and the gouty patients. Our studies show that a pure sucrose diet increases both the serum urate and triglyceride levels. The mechanism of the hyperuricemia is decreased renal clearance of uric acid in the obese normal controls and the normal subjects. Increased urate production and decreased uric acid clearance accounted for the hyperuricemia in the gouty patients. The contribution of excessive sucrose ingestion to clinically associated hyperuricemia and hypertriglyceridemia remains to be elucidated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25613/1/0000161.pd

Immunology and genetics of type 1 diabetes

Type 1 diabetes is one of the most well-characterized autoimmune diseases. Type 1 diabetes compromises an individual's insulin production through the autoimmune destruction of pancreatic Β-cells. Although much is understood about the mechanisms of this disease, multiple potential contributing factors are thought to play distinct parts in triggering type 1 diabetes. The immunological diagnosis of type 1 diabetes relies primarily on the detection of autoantibodies against islet antigens in the serum of type 1 diabetes mellitus patients. Genetic analyses of type 1 diabetes have linked human leukocyte antigen, specifically class II alleles, to susceptibility to disease onset. Environmental catalysts include various possible factors, such as viral infections, although the evidence linking infections with type 1 diabetes remains inconclusive. Imbalances within the immune system's system of checks and balances may promote immune activation, while undermining immune regulation. A lack of proper regulation and overactive pathogenic responses provide a framework for the development of autoimmune abnormalities. Type 1 diabetes is a predictable and potentially treatable disease that still requires much research to fully understand and pinpoint the exact triggering events leading to autoimmune activation. In silico research can aid the comprehension of the etiology of complex disease pathways, including Type I diabetes, in order to and help predict the outcome of therapeutic strategies aimed at preserving Β-cell function. Mt Sinai J Med 75:314–327, 2008. © 2008 Mount Sinai School of MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60987/1/20052_ftp.pd

Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis

Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development

Key Role of the GITR/GITRLigand Pathway in the Development of Murine Autoimmune Diabetes: A Potential Therapeutic Target

BACKGROUND: The cross-talk between pathogenic T lymphocytes and regulatory T cells (Tregs) plays a major role in the progression of autoimmune diseases. Our objective is to identify molecules and/or pathways involved in this interaction and representing potential targets for innovative therapies. Glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand are key players in the T effector/Treg interaction. GITR is expressed at low levels on resting T cells and is significantly up-regulated upon activation. Constitutive high expression of GITR is detected only on Tregs. GITR interacts with its ligand mainly expressed on antigen presenting cells and endothelial cells. It has been suggested that GITR triggering activates effector T lymphocytes while inhibiting Tregs thus contributing to the amplification of immune responses. In this study, we examined the role of GITR/GITRLigand interaction in the progression of autoimmune diabetes. METHODS AND FINDINGS: Treatment of 10-day-old non-obese diabetic (NOD) mice, which spontaneously develop diabetes, with an agonistic GITR-specific antibody induced a significant acceleration of disease onset (80% at 12 weeks of age). This activity was not due to a decline in the numbers or functional capacity of CD4(+)CD25(+)Foxp3(+) Tregs but rather to a major activation of 'diabetogenic' T cells. This conclusion was supported by results showing that anti-GITR antibody exacerbates diabetes also in CD28(-/-) NOD mice, which lack Tregs. In addition, treatment of NOD mice, infused with the diabetogenic CD4(+)BDC2.5 T cell clone, with GITR-specific antibody substantially increased their migration, proliferation and activation within the pancreatic islets and draining lymph nodes. As a mirror image, blockade of the GITR/GITRLigand pathway using a neutralizing GITRLigand-specific antibody significantly protected from diabetes even at late stages of disease progression. Experiments using the BDC2.5 T cell transfer model suggested that the GITRLigand antibody acted by limiting the homing and proliferation of pathogenic T cells in pancreatic lymph nodes. CONCLUSION: GITR triggering plays an important costimulatory role on diabetogenic T cells contributing to the development of autoimmune responses. Therefore, blockade of the GITR/GITRLigand pathway appears as a novel promising clinically oriented strategy as GITRLigand-specific antibody applied at an advanced stage of disease progression can prevent overt diabetes

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

Regional Changes in Egg Production

Excerpts from the report: Over the last decade or so, egg production has not kept pace with population growth mainly because the demand for eggs has been declining. At the same time, egg production has been limited because of relatively more attractive economic opportunities for people in other lines of agriculture and in nonfarm pursuits. The 24 percent increase in population between 1947-49 and 1961 has been accompanied by only an 11 percent rise in farm egg output, despite declining prices for eggs and rising per capita incomes. All regions did not share equally in the larger egg production. Output expanded at several times the national rate in the South Atlantic and Western regions and declined significantly in the North Central Region. These changes brought about a substantial shift in the regional distribution of egg production in the United States

Income Growth in Nonmetro America, 1968-75

Total personal income grew 25 percent faster in nonmetro counties than in metro counties between 1968 and 1975, narrowing the inflation-adjusted gap in income per person between metro and nonmetro areas by a tenth, to $1,403. Nonmetro earnings increased by the largest percentage in mining, agriculture, transportation, communications, and public utilities. In addition, net transfer payments more than tripled. Growth in total personal income in nonmetro areas exceeded metro growth in all four U.S. regions (South, West, North Central, Northeast). Nonmetro growth was greatest in the West, although combined metro-nonmetro growth was greatest in the South

Rural Income Growing and Changing

Rural development policy since the 1960's has sought to arrest economic decline in rural areas and reduce the disparity between rural and urban incomes. And between 1968 and 1975, some progress was made. During this period, personal income in nonmetro counties grew 25 percent faster than in metro counties, reversing a trend during the fifties and sixties. Nonmetro income grew substantially faster than metro income in all regions except the South, but even there, nonmetro counties had a slight growth advantag