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Biomedical subjects

M J Franz

Publications and source records attributed to M J Franz.

At least 19 recordsLinked to original sources

Transcriptional activation of the granulocyte-macrophage colony-stimulating factor receptor gene in cell mutants.

Retroviral insertional mutagenesis has proven to be a powerful in vivo approach for identifying genetic mutations involved in tumorigenesis or developmental abnormalities. Applying this approach to an in vitro system, where experimental design can be readily manipulated, would greatly increase its efficacy. In this study, we sought to determine whether retroviral insertional mutagenesis could be used to isolate cell mutants, in which the transcriptional activation of a receptor gene has occurred. Cells of the myeloid progenitor cell line FDC-P1(M), which do not express the alpha receptor subunit (GMRalpha) for granulocyte-macrophage colony-stimulating factor (GM-CSF), were infected and selected for growth in GM-CSF. Over 100 mutants were isolated at a frequency up to ninefold higher than that of uninfected controls. Expression of GMRalpha in these mutants was confirmed by blocking proliferation with GM-CSF antibodies, detection of high-affinity receptors, and Northern blot analysis. Significantly, in 7/18 mutants analyzed, gross DNA rearrangements had occurred in the GMRalpha locus. These rearrangements were demonstrated to be due to intergenic rearrangements, juxtaposing an active enhancer/promoter upstream of the GMRalpha gene. In one mutant it could be demonstrated that the wild-type allele was also expressed, providing evidence that secondary mutations had occurred. The implications of these results for retroviral insertional mutagenesis are discussed.

Animals↗

Managing obesity in patients with comorbidities.

Type 2 diabetes, cardiovascular disease, and hypertension are comorbities associated with obesity. Treatment and prevention strategies for these comorbidities of obesity are often assumed to be the same-weight loss. Although many persons may lose weight initially, recidivism is a major concern. Therefore, medical nutrition therapy for obese persons with comorbidities should be refocused from weight loss to attaining and maintaining metabolic parameters--normal blood glucose levels, optimal lipid levels, and blood pressure levels within normal limits. Moderate weight loss is only one lifestyle strategy that can be recommended. Research has also supported other lifestyle strategies, including becoming more physically fit. In type 2 diabetes, a restricted energy diet even without weight loss, spacing of meals throughout the day, and fat intake modifications have been shown to improve glycemia. Dyslipidemia can be improved by reducing or changing the fat content of the diet. Blood pressure levels can be reduced by a diet high in fruits and vegetables and low in fat. Research is underway to determine if weight loss can prevent chronic disease; however, once comorbidities are present, lifestyle strategies should be directed toward the improvement of metabolic parameters associated with the comorbidity.

Cardiovascular Diseases↗

Lifestyle modifications for diabetes management.

Nutrition therapy and physical activity can assist persons with diabetes to achieve metabolic goals. Several lifestyle strategies can be used. Monitoring metabolic parameters, including blood glucose, glycated hemoglobin, lipids, blood pressure, and body weight, as well as assessing for quality of life are essential to determine whether treatment goals are being achieved by lifestyle changes. If not, adjustments in the overall management plan need to be made.

Diabetes Mellitus, Type 1↗

Practice guidelines for medical nutrition therapy provided by dietitians for persons with non-insulin-dependent diabetes mellitus. International Diabetes Center.

Nutrition practice guidelines define a systematic approach for medical nutrition therapy (MNT) provided by dietitians and are derived from scientific evidence and expert opinion. Nutrition practice guidelines for persons with non-insulin-dependent diabetes mellitus (NIDDM) can be implemented for those with newly diagnosed or previously diagnosed NIDDM at the first visit to a dietitian for initial or ongoing MNT. The guidelines apply to patients treated with MNT alone, MNT and oral glucose-lowering agents, or MNT and insulin. They provide a framework to assist the dietitian in the assessment, intervention (nutrition prescription, education, goal setting), and evaluation of outcomes for MNT. Minimum referral data for clinical decision making and outcome criteria are defined. Basic nutrition care is defined as one visit with the dietitian. Nutrition practice guidelines care consists of a series of visits with the dietitian. At the second follow-up visit, the dietitian assesses what has been accomplished with the nutrition interventions. If the patient has implemented the nutrition recommendations to the best of his or her ability and has not achieved the treatment goals, the dietitian should notify the physician and recommend that changes in medical management are needed. Ongoing nutrition care is recommended at 6-month to 1-year intervals for both basic and practice guidelines care.

Blood Glucose↗

Effectiveness of medical nutrition therapy provided by dietitians in the management of non-insulin-dependent diabetes mellitus: a randomized, controlled clinical trial.

OBJECTIVE: To assess the effect of medical nutrition therapy (MNT) provided by dietitians on medical and clinical outcomes for adults with non-insulin-dependent diabetes mellitus (NIDDM), and to compare MNT administered according to practice guidelines nutrition care (PGC) to MNT administered with basic nutrition care (BC). DESIGN: A prospective, randomized, controlled clinical trial of two levels of MNT on metabolic control in persons newly diagnosed with or currently under treatment for NIDDM was conducted at diabetes centers in three states (Minnesota, Florida, and Colorado). BC consisted of a single visit with a dietitian; PGC involved an initial visit with a dietitian followed by two visits during the first 6 weeks of the study period. Data were collected at entry to the study and at 3 and 6 months. SUBJECTS: Results are reported for 179 men and women aged 38 to 76 years: 85 assigned randomly to BC and 94 to PGC. This represents 72% of the 247 subjects enrolled. An additional 62 adults with NIDDM at one site who had no contact with a dietitian were identified as a nonrandom comparison group. OUTCOMES: Medical outcome measures included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and serum lipid levels. Clinical outcomes included weight, body mass index, waist-to-hip ratio, and changes in medical therapy. STATISTICAL ANALYSES: Initial analysis of the discrete variables was done using the chi 2 statistic with Yates' correction. Initial analysis of continuous variables was done by analysis of variance. The changes in variables between time periods were analyzed by paired t test, and comparisons between groups were analyzed using a t test for independent groups. RESULTS: At 6 months, PGC resulted in significant improvements in blood glucose control as indicated by FPG and HbA1c levels and BC resulted in significant improvements in HbA1c level. Participants assigned to the PGC group had a mean FPG level at 6 months that was 10.5% lower than the level at entry, and those in the BC group had a 5.3% lower value. Among subjects who had diabetes for longer than 6 months, those who received PGC had a significantly better HbA1c level at 3 months compared with those receiving BC. The comparison group showed no improvement in glycemic control over a comparable 6 months. PGC subjects had significant improvements in cholesterol values at 6 months, and subjects in both the PGC and the BC groups had significant weight loss. CONCLUSIONS: MNT provided by dietitians resulted in significant improvements in medical and clinical outcomes in both the BC and PGC groups and is beneficial to persons with NIDDM. Persons with a duration of diabetes longer than 6 months tended to do better with PGC than with BC. Because of the upward trend in glucose levels after 3 months, ongoing MNT by dietitians is important for long-term metabolic control.

Adult↗

Cost-effectiveness of medical nutrition therapy provided by dietitians for persons with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To conduct a cost analysis and cost-effectiveness study based on a randomized clinical trial of basic nutrition care (BC) and practice guidelines nutrition care (PGC) provided by dietitians in outpatient clinics. DESIGN: Subjects with non-insulin-dependent diabetes mellitus (NIDDM) from three states (Minnesota, Florida, Colorado) were randomly assigned to a group receiving BC or a group receiving PGC for a 6-month clinical trial. Along with data about medical and clinical outcomes, data about cost resources were collected. The cost-effectiveness of PGC compared with BC was calculated using per-patient costs and glycemic outcomes for the 6 months of the study. A net cost-effectiveness ratio comparing BC and PGC, including the cost savings resulting from changes in medical therapy, was also calculated. SUBJECTS: The study reports on a sample of 179 subjects with NIDDM between the ages of 38 and 76 years who completed the clinical trial. RESULTS: Patients in the PGC group experienced a mean 1.1 +/- 2.8 mmol/L decrease in fasting plasma glucose level 6 months after entry to the study, for a total per-patient cost of $112. PGC costs included one glycated hemoglobin assay used by the dietitian to evaluate nutrition outcomes. Patients in the BC group experienced a mean 0.4 +/- 2.7 mmol/L decrease, for a total per-patient cost of $42. In the PGC group, 17 persons had changes in therapy, which yielded an average 12-month cost savings prorated for all patients of $31.49. In contrast, in the BC group, 9 persons had changes in therapy, for an average 12-month prorated cost savings of $3.13. Each unit of change in fasting plasma glucose level from entry to the 6-month follow-up can be achieved with an investment of $5.75 by implementing BC or of $5.84 by implementing PGC. If net costs are considered (per-patient costs--cost savings due to therapy changes), the cost-effectiveness ratios become $5.32 for BC and $4.20 for PGC, assuming the medical changes in therapy were maintained for 12 months. APPLICATIONS: These findings suggest that individualized nutrition interventions can be delivered by experienced dietitians with a reasonable investment of resources. Cost-effectiveness is enhanced when dietitians are engaged in active decision making about intervention alternatives based on the patient's needs.

Adult↗

Practice guidelines for nutrition care by dietetics practitioners for outpatients with non-insulin-dependent diabetes mellitus: consensus statement.

In summary, nutrition practice guidelines for dietitians who provide outpatient care for persons with NIDDM provide a roadmap for nutrition care that allows for consistency in individualized care. A field test that compares care according to practice guidelines with usual or basic care can provide evidence, based on medical, education/behavior, and cost outcomes, that practice guidelines are not only reasonable and realistic but also effective.

Ambulatory Care↗

Diabetes and nutrition recommendations: a practical perspective.

Nutritional management is a major therapeutic tool in the care of persons with diabetes. Goals for insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM and NIDDM) differ due to the underlying pathophysiology of the conditions. This article discusses the nutrition management goals for IDDM and NIDDM and provides practical recommendations to achieve them. The authors supply a sample meal plan, a list of high-fiber and low-fat foods, a sample diet history, and a food record to facilitate assessment and patient behavior changes. NPs can use this information in practice when nutrition consultation is not available.

Diabetes Mellitus↗

Retrotransposons as mutagens in the induction of growth autonomy in hematopoietic cells.

Factor-independent mutants of hematopoietic cells, especially of multipotent cells, are valuable tools to identify genes that regulate stem cell proliferation and differentiation and thus may be important in leukemogenesis. Factor-independent mutants from both myeloid precursor and hematopoietic stem cell lines were isolated. The frequency of such mutants in a given cell population was one to two orders of magnitude lower for the multipotent cell line FDC-Pmix (3.6 x 10(-9)) than for the myeloid precursors, FDC-P1-M (1.7 x 10(-8)) and D35 (2.2 x 10(-7)). Analysis of these mutants revealed several mechanisms by which growth autonomy was obtained, either with or without direct contribution of growth factor gene activation. The molecular basis of spontaneous activation of the Multi-CSF (Interleukin3) gene was determined and compared to activation of the GM-CSF gene in a previous study. Multi-CSF gene activation in both precursor and stem cells was caused by the insertion of an intracisternal A particle (IAP) provirus. In two independent mutants of the D35 cell line, activation of the Multi-CSF or the GM-CSF gene was caused by almost identical IAPs with a 99% homology in the U3 and R region of the long terminal repeat. This result demonstrates that only one class of IAPs, or perhaps a single provirus, is involved in transposition and gene activation in a particular cell line. A unique example of anti-sense promotion from an IAP provirus in one Multi-CSF mutant underlines the versatility of these elements as natural insertional mutagens.

Amino Acid Sequence↗

Aberrant expression of the multi-CSF gene in hematopoietic precursor and stem cell lines initiates leukemogenic progression.

Tumorigenesis of hemopoietic cells and acquisition of factor independence as a consequence of aberrant growth factor release are closely correlated. In previous work we were able to dissect two stages leading to growth factor autonomy of cells: the first step requires the secretion of the constitutively expressed CSF gene product and extracellular interaction with its cognate receptor. This requirement for external stimulation is abrogated by a second step. We were interested in characterizing the parameters that influence the conversion from nonautonomous to autonomous growth properties of hematopoietic precursor cells. The frequency with which this alteration occurs varies and correlates with the level of growth factor production. However, a significant increase of CSF production accompanying the progression to autonomy could not be detected. We thus conclude that there is no direct link between level of CSF production and acquisition of true autonomy but an indirect influence enhancing the frequency of genetic alteration(s) that lead to growth autonomy. Lang et al. have suggested that the acquisition of autonomous growth occurs due to internal receptor-ligand interaction. Indeed, Keating and Williams have claimed that PDGF may react with an intracellular PDGF receptor resulting in autocrine stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rates of mutation to growth factor autonomy and tumorigenicity differ in hematopoietic stem and precursor cells expressing the multilineage colony-stimulating factor gene.

At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony-stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lines (FDC-P1 or FDC-P2) than in stem cell lines (FDC-Pmix). Autonomous, but not density-dependent, growth is tightly coupled to tumorigenicity in precursor cells; however, neither growth-factor-independent nor autonomously growing stem cell lines are tumorigenic.

Animals↗

Exercise and the management of diabetes mellitus.

Fuel metabolism in individuals with well-controlled diabetes is similar to that occurring in persons who do not have diabetes. During the initial phase of physical exercise, muscle glycogen is the primary source of fuel. As exercise continues, blood glucose and free fatty acids (FFAs) become increasingly important substrates. FFAs become the major fuel source as glucose utilization decreases. Whereas in individuals who do not have diabetes, blood glucose levels vary little during exercise, the person with insulin-dependent diabetes mellitus (IDDM) may experience an increase in blood glucose, a modest decrease, or a marked decrease, which can result in hypoglycemia. In insulin-treated persons with mild hyperglycemia, exercise is accompanied by a fall in blood glucose. In contrast, in persons with marked hyperglycemia and ketosis, exercise may cause a further rise in both blood glucose and ketone levels. The glycemic response to exercise is dependent on the plasma concentration of insulin. Physical training improves glucose tolerance in individuals with noninsulin-dependent diabetes mellitus (NIDDM); in persons with IDDM, it may diminish insulin requirements. The repletion of muscle and liver glycogen, which takes place for 24 to 48 hours after exercise, requires a minimum amount of insulin in addition to carbohydrate feeding. Persons using insulin may need to increase food intake prior to, during, and after exercise and/or decrease insulin dosage as well. Persons with IDDM can exercise safely, and persons with NIDDM can achieve better control by following the guidelines outlined for exercise prescription.

Blood Glucose↗

Exchange lists: revised 1986.

A committee composed of members of The American Dietetic Association and the American Diabetes Association has revised Exchange List for Meal Planning. Changes were made, as deemed necessary, on the basis of nutritional recommendations for persons with diabetes as understood in 1986. Major changes include rewriting the text to make it more useful in the education of persons with diabetes; changing the order of the exchange lists to emphasize a high-carbohydrate, high-fiber diet, as well as to better reflect the order of foods in menu planning; adding symbols to foods high in fiber and sodium; changing nutritive values for the starch/bread and fruit lists; adding lists of combination foods, free foods, and foods recommended only for occasional use; developing a data base; and initiating a plan for field testing and evaluation. The committee also developed a simplified meal planning tool, Healthy Food Choices, to be used for initial or "survival" level education. In poster format, foods are grouped by calories into six food groups. Approximate portion sizes of commonly used foods are listed. Blank lines are provided for the nutrition counselor to write in a suggested menu or meal plan for the client. Because the booklet does not use the word "diabetes" specifically, it is appropriate as a general teaching tool.

Diabetes Mellitus↗

Practical aspects of implementing increased dietary fiber intake.

Two hundred twenty dietitians participated in a workshop conference on Health Implications of Dietary Fiber. They were given lectures to increase their knowledge base, and then in group sessions answered questions and wrote concensus opinions. The results are the content of this paper. The topics covered and responses are reported in four categories, diabetes and obesity, hyperlipidemia, hypertension and coronary heart disease, gut function and gastrointestinal disease, and cancer. Specific recommendation for implementing high fiber diets are made in each category. However, the dietitians expressed caution on accepting all of the conclusions expressed in the literature on the value of fiber and believed much education and instruction is needed in order to increase dietary fiber intake.

Colonic Neoplasms↗