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Biomedical subjects

T Greene

Publications and source records attributed to T Greene.

At least 55 records · Page 3Linked to original sources

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group.

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.

Antibodies, Bacterial↗

Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study.

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.

Adolescent↗

Cerebrospinal fluid drainage and distal aortic perfusion: reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II.

PURPOSE: This study was conducted to evaluate the role of cerebrospinal fluid (CSF) drainage and distal aortic perfusion (DAP) in the prevention of postoperative neurologic complications for high-risk patients who had undergone type I and type II thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: CSF drainage and DAP were used as an adjunct in the treatment of 94 patients with TAAA (31 type I, 63 type II) between September 1992 and December 1994; 67 were men and 27 were women. The median age was 64 years (range, 28 to 88 years). Aortic dissection occurred in 35 of 94 patients (37%). Thirty-six of 94 patients (38%) had previously undergone proximal aortic surgery. All patients underwent intraoperative DAP and perioperative CSF drainage. Median aortic cross-clamp time was 67 minutes (range, 20 to 131 minutes). RESULTS: The 30-day survival rate was 90% (85 of 94 patients). Early neurologic complications occurred in 5 of 94 patients (5%), and late neurologic complications occurred in 3 of 94 patients (3%). We compared the neurologic complications of our current group of 94 patients with the data from 42 patients (control group) who also underwent repair of TAAA type I and type II with only simple cross-clamp and without CSF drainage or DAP. Both groups were treated by the senior author (HJS) at the same institution. Total neurologic complications for the current group occurred in 8 of 94 patients (9%) versus 8 of 42 patients (19%) for the control group (p=0.090). Neurologic complications for patients with type II TAAA occurred in 8 of 63 patients (13%) versus 17 of 42 patients (41%) (p=0.014). For all patients with aortic clamp times >or=45 minutes, neurologic complications occurred in 7 of 55 (13%) versus 7 of 18 (39%) (p=0.033). CONCLUSION: The period of risk during aortic cross-clamp time is reduced with the adjuncts of CSF drainage and DAP, which significantly lower the incidence of neurologic complications after repair of TAAA types I and II.

Adult↗

Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with malignancy.

A phase I trial of simultaneously administered recombinant interleukin-2 (rIL-2) and recombinant human IL-4 (rHuIL-4) was conducted to evaluate the toxicity and the clinical and immunologic effects of this cytokine combination. Thirty-nine eligible patients with refractory malignancy were treated at eight different dose levels (1A to 3B): 1-3 of rIL-2 [3.0, 12.0, and 48.0 x 10(6) IU/m(2) i.v. three times weekly (TIW)] and A-C of rHuIL-4 (40, 120, and 400 mu g/m(2) s.c. TIW). The toxicity of these two cytokines was moderate and was comparable with that seen with rIL-2 alone. The maximal tolerated dose (MTD) of the combination was not reached because of lack of sufficient rHuIL-4 but is at least 48.0 x 10(6) IU/m(2) of rIL-2 and 120 mu g/m(2) of rHuIL-4. Two patients with melanoma had partial responses. The immunologic effects included increases in absolute lymphocyte numbers, and the CD3- /CD56+/ CD2+, total CD56+, CD8+, and CD16c+ lymphocyte subsets with increasing rIL-2 dose levels, but not with rHuIL-4. This increase in natural killer (NK) cells in the peripheral blood was accompanied by an increase over baseline in NK lytic activity against K562 targets; however, concomitant increases in lymphokine-activated killer (LAK) activity (Daudi targets) were not seen. The CD3+, CD4+, and CD3+/CD25+/HLA-Dr+ T-cell subsets also increased, and these increases were related to both increasing rIL-2 and rRuIL-4 doses. Finally, in four of six patients, serial tumor biopsies demonstrated increases in major histocompatibility complex (MHC) class I or II antigen expression on tumor cells or increasing T-cell infiltrates during cytokine therapy or both. This trial demonstrated that rIL-2 and rHuIL-4 can be administered simultaneously with acceptable toxicity. The immunologic findings demonstrated the expected rIL-2-associated increases of CD56+ and CD16c+ lymphocytes and NK activity, and interestingly, no development of LAK activity. These findings suggest regulatory effects of rHuIL-4 on rIL-2-related effects in vivo.

Adjuvants, Immunologic↗

Comparative safety and immunogenicity of two recombinant hepatitis B vaccines given to infants at two, four and six months of age.

OBJECTIVES: To evaluate the relative safety and immunogenicity of the two recombinant hepatitis B vaccines licensed in the United States with doses recommended for routine immunization of low risk infants and a schedule that corresponds with routine pediatric visits. METHODS: Healthy infants were immunized at 2, 4 and 6 months of age with hepatitis B vaccine manufactured by either SmithKline Beecham (Engerix-B, 10 micrograms/dose, n = 228) or Merck and Co. (Recombivax HB, 2.5 micrograms/dose, n = 200). Adverse reactions were ascertained by parental reports and interviews and by review of medical records. Antibody concentrations to hepatitis B surface antigen (anti-HBs) were measured in sequential serum specimens by enzyme immunoassay. RESULTS: Adverse reactions were mild and the rates were not significantly different between the two groups. After the first and second doses the rates of seropositivity (> or = 10 mIU/ml) and seroprotection (> or = 10 mIU/ml) were significantly higher in infants given SmithKline Beecham vaccine (P < 0.01). After the second and third doses infants given SmithKline Beecham vaccine also had significantly higher geometric mean anti-HBs concentrations compared with those given Merck vaccine (348.0 mIU/ml vs. 66.9 and 1914.8 mIU/ml vs. 514.8 mIU/ml, respectively, P < 0.001). Nevertheless after the third dose 99% of infants in both vaccine groups achieved seroprotective antibody concentrations. CONCLUSIONS: Both recombinant hepatitis B vaccines were safe and immunogenic when administered concurrently with other pediatric vaccines at 2, 4 and 6 months of age, but earlier protective responses were observed with the SmithKline Beecham vaccine than with the Merck vaccine.

Consumer Product Safety↗

A foot risk classification system to predict diabetic amputation in Pima Indians.

OBJECTIVE: To quantify the contribution of various risk factors to the risk of amputation in diabetic patients and to develop a foot risk scoring system based on clinical data. RESEARCH DESIGN AND METHODS: A population case-control study was undertaken. Eligible subjects were 1) 25-85 years of age, 2) diabetic, 3) 50% or more Pima or Tohono O'odham Indian, 4) lived in the Gila River Indian Community, and 5) had had at least one National Institutes of Health research examination. Case patients had had an incident lower extremity amputation between 1983 and 1992; control subjects had no amputation by 1992. Medical records were reviewed to determine risk conditions and health status before the pivotal event that led to the amputation. RESULTS: Sixty-one people with amputations were identified and compared with 183 control subjects. Men were more likely to suffer amputation than women (odds ratio [OR] 6.5, 95% CI 2.6-15), and people with diabetic eye, renal, or cardiovascular disease were more likely to undergo amputation than those without (OR 4.6, 95% CI 1.7-12). The risk of amputation was almost equally associated with these foot risk factors: peripheral neuropathy, peripheral vascular disease, bony deformities, and a history of foot ulcers. After controlling for demographic differences and diabetes severity, the ORs for amputation with one foot risk factor was 2.1 (95% CI 1.4-3.3), with two risk factors, 4.5 (95% CI 2.9-6.9), and with three or four risk factors, 9.7 (95% CI 6.3-14.8). CONCLUSIONS: Male Sex, end-organ complications of eye, heart, and kidney, and poor glucose control were associated with a higher amputation rate. Peripheral neuropathy, peripheral vascular disease, deformity, and a prior ulcer were similarly equally associated with an increased risk of lower extremity amputation.

Adult↗

Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study.

OBJECTIVE: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study. DESIGN: 2 randomized trials in patients with chronic renal diseases of diverse cause. SETTING: 15 outpatient nephrology practices at university hospitals. PATIENTS: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded. INTERVENTIONS: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age) or a low blood pressure goal (target mean arterial pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age). MAIN OUTCOME MEASURES: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up. RESULTS: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20; P < 0.001) and study B (r = -0.34; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate. CONCLUSIONS: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.

Adolescent↗

Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1.

During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.

Animals↗

Heregulin-stimulated signaling in rat pheochromocytoma cells. Evidence for ErbB3 interactions with Neu/ErbB2 and p85.

We have reported that overexpression of Neu leads to heregulin-stimulated neurite outgrowth and the tyrosine-phosphorylation of Neu and other cellular proteins in PC12 cells. Considering that Neu/ErbB2 alone is not able to functionally couple to heregulin, we looked for the possible involvement of ErbB3 in these neurite outgrowth and tyrosine phosphorylation responses. We found that heregulin stimulates the tyrosine phosphorylation of endogenous ErbB3 protein in PC12 cells and that this phosphorylation, like that of Neu, is greatly enhanced in cells that overexpress Neu. Furthermore, overexpression of ErbB3 in PC12 cells led to heregulin-stimulated neurite extension. In addition to becoming tyrosine-phosphorylated, Neu/ErbB2 and ErbB3 associate with each other, and each associates with the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase in a heregulin-dependent manner. Thus, Neu/ErbB2 and ErbB3 appear to cooperate to mediate the heregulin signal in PC12 cells. Like heregulin, epidermal growth factor (EGF) also stimulate the tyrosine phosphorylation of both Neu and ErbB3. However, there are clear differences between the EGF- and heregulin-stimulated phosphorylations of ErbB3. In the heregulin response, two tyrosine-phosphorylated forms of ErbB3 are detected. Of these, only the more quickly migrating form (on SDS-polyacrylamide gel electrophoresis) is found to be associated with Neu, whereas the other, more slowly migrating form is uniquely capable of forming stable complexes with p85. In the EGF response, at least two tyrosine-phosphorylated forms of ErbB3 are detected, but these phosphoproteins have distinctly lower apparent molecular weights compared with the heregulin-stimulated ErbB3 phosphoproteins and do not complex with p85. Thus the formation of a stable ErbB3-p85 complex in PC12 cells is a unique outcome of heregulin signaling that correlates with the differences in cell morphology induced by the activated EGF receptor and the Neu tyrosine kinase.

Animals↗

Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease.

We investigated the histological effects of ciliary neurotrophic factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human ciliary neurotrophic factor (or a vehicle solution), 1-mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene-related peptide was higher in mice receiving rat ciliary neurotrophic factor (p < 0.03), although the number of choline acetyltransferase-reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human ciliary neurotrophic factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In ciliary neurotrophic factor-treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end-plates were also higher in the ciliary neurotrophic factor-treated mice (p < 0.001 and p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease.

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of developing motor neurons in vitro and to rescue motor neurons from axotomy-induced cell death in vivo. In this study, we examined the effects of exogenous BDNF on the progression of wobbler mouse motor neuron disease (MND). After clinical diagnosis at age 3 to 4 weeks, 20 affected mice received subcutaneous injections of recombinant human BDNF (5 mg/kg, n = 10) or vehicle (n = 10), three times a week for 4 weeks. In a separate experiment done to conduct a histometric analysis of the C-5 and C-6 ventral roots and to determine the number of myelinated nerve fibers, 7 wobbler mice received identical BDNF treatment. In the 10 BDNF-treated wobbler mice, grip strength declined at a slower rate (p < 0.03) and was twice as great as that of vehicle-treated animals at the end of treatment (p < 0.01). In vivo biceps (p < 0.01) and in vitro muscle twitch tensions (p < 0.02) were also greater than those of vehicle-treated mice. The biceps muscle weight was 20% greater (p < 0.05) and the mean muscle fiber diameter was significantly larger in BDNF-treated mice (p < 0.001) because the number of small (denervated) muscle fibers was markedly reduced. The number of myelinated motor axons at the cervical ventral roots studied in the additional 7 affected mice was 25% greater with BDNF treatment (p < 0.0001). This study establishes that exogenous BDNF administration can retard motor dysfunction in a natural MND and diminish denervation muscle atrophy and motor axon loss.

Animals↗

A twin study of age-related macular degeneration.

PURPOSE: To determine the importance of genetic factors in age-related macular degeneration by using a twin study to compare the concordance of age-related macular degeneration in monozygotic and dizygotic twin pairs. METHODS: We prospectively examined 134 consecutive twin pairs and two triplet sets for age-related macular degeneration. The zygosity was determined by genetic laboratory tests. RESULTS: The concordance of age-related macular degeneration was 100% (25 of 25) in monozygotic and 42% (five of 12) in dizygotic twin pairs. The other twins or triplets had no macular changes of age-related macular degeneration. CONCLUSIONS: The statistically significant higher concordance of age-related macular degeneration in monozygotic than in dizygotic twin pairs and the clinical heterogeneity of age-related macular degeneration strongly suggest the importance of genetic and nongenetic factors, respectively, in age-related macular degeneration.

Adult↗

Neonatal diagnosis of fetal alcohol syndrome: not necessarily a hopeless prognosis.

A neonatal examination for fetal alcohol syndrome (FAS) should promote the guidance of parents, the planning of remediation for affected children, and the collection of prevalence data. A blinded examination of FAS characteristics conducted as part of a large prospective study of disadvantaged alcohol-exposed infants identified eight neonates who met the published criteria for FAS. These children were followed through the preschool years with a blinded assessment protocol. Seven of these children were found to have no impairment in cognitive and language development, when compared with their peers, and to be of average size. The one child who was mentally and growth retarded at follow-up who had been diagnosed as FAS might not have been diagnosed FAS using clinical criteria (as opposed to blinded research criteria), because his mother provided in-pregnancy reports of only low alcohol intake; she later acknowledged drinking an average of over 21 drinks/week during the pregnancy. The findings are positive in that they provide hope for children who present FAS at birth, although concern with adverse outcomes is certainly not dispelled. In particular, the possibility of later-emerging impairment in more complex tasks is not ruled out.

Adult↗

The effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease.

Ciliary neurotrophic factor is the first neurotrophic factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human ciliary neurotrophic factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat ciliary neurotrophic factor (n = 6) resulted in delayed weight gain (p < 0.001), grip strength normalized to body weight in the factor-treated mice was significantly greater (p < 0.02) and declined at a slower rate (p < 0.05) compared to that in vehicle-treated animals. Human ciliary neurotrophic factor (n = 27) produced no change in body weight and reduced paw position and walking pattern abnormalities (p < 0.001 and p < 0.02, respectively). After 4 weeks of treatment, the mean grip strength of human ciliary neurotrophic factor-treated animals was twice as great (p < 0.001) and declined at a much slower rate (p < 0.005) than that of control mice. The time required to run 2.5 ft was less (p < 0.005) and muscle twitch tension was greater (p < 0.002) in ciliary neurotrophic factor-treated animals. Thus, ciliary neurotrophic factor retarded the disease progression and improved muscle strength in this motor neuron disease model.

Animals↗

Serum lipid changes associated with modified protein diets: results from the feasibility phase of the Modification of Diet in Renal Disease Study.

The use of low-protein diets for the management of progressive renal insufficiency may require increases in dietary fats to maintain caloric balance. This raises the concern that such diets might exacerbate the lipid problems already prevalent in chronic renal insufficiency. We present a study in which protein-restricted diets were followed by a group of patients with renal insufficiency without a compensatory increase in fat calories and without adverse effects on serum lipids. Ninety-six patients with renal insufficiency were enrolled in the feasibility phase of the Modification of Diet in Renal Disease Study and were assigned to dietary protein intakes of 1.3, 0.575, or 0.28 g/kg body weight/d. The last diet was supplemented with amino acids or their keto analogs. Of this group, 25 participants were excluded from the present study of lipids because of changes in their intake of medications with known effects on serum lipids, three were excluded because of proteinuria increasing by more than 2 g/d, and seven were excluded because of incomplete measurements. For the remaining 61 participants, median serum total cholesterol at baseline was 215 mg/dL. In 72% of participants it exceeded the age- and sex-adjusted median of the Lipid Research Clinics Prevalence Study. Glomerular filtration rates varied from 8 to 56 mL/min/1.73 m2. The patients' serum lipid levels were stable by 6 months on assigned diets. Serum total and low-density lipoprotein cholesterol levels tended to decrease with reduced protein intake. The baseline to follow-up change in protein intake calculated from urinary urea measurements was significantly correlated with the change in serum total cholesterol (Spearman r = 0.31, P < 0.05) and also with change in low-density lipoprotein cholesterol (r = 0.34, P < 0.01). Surprisingly, correlations between change in serum cholesterol and intake of fats were small in magnitude and did not approach statistical significance. Protein intake did correlate, however, with intake of cholesterol. We conclude that the use of low-protein diets for patients with renal insufficiency did not adversely affect serum lipids.

Adolescent↗

CATCH: process evaluation of environmental factors and programs.

The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a multicenter trial designed to test the effectiveness of school and family-based cardiovascular health promotion for preadolescents. CATCH interventions target multiple cardiovascular health behaviors such as dietary intake of fat and sodium, physical activity, and tobacco use. Evaluation includes physiological, psychosocial, behavioral, and process measures. An important aspect of the process evaluation is the assessment of environmental factors and "secular events" in both intervention and control schools that may affect outcomes independently of the CATCH interventions. With such information, CATCH investigators are able to isolate the impact of the CATCH intervention from competing (non-CATCH) factors as well as "track" proximal (i.e., immediate and short term) changes related to the intervention that may in turn lead to "distal" (long-term) behavior change. The School Health Questionnaire, the major process evaluation tool for monitoring secular and environmental changes in the schools, is described in detail, and data describing tobacco-related environmental factors and secular events are presented.

Adolescent↗

Expression of the potato tuber ADP-glucose pyrophosphorylase in Escherichia coli.

cDNA clones encoding the putative mature forms of the large and small subunits of the potato tuber ADP-glucose pyrophosphorylase have been expressed separately and together in an Escherichia coli B mutant deficient in ADP-glucose pyrophosphorylase activity. Expression of both subunits from compatible vectors resulted in restoration of ADP-glucose pyrophosphorylase activity. Maximal enzyme activity required both subunits. The expressed ADP-glucose pyrophosphorylase was purified and characterized. The recombinant enzyme exhibited catalytic and allosteric kinetic properties very similar to the enzyme purified from potato tuber. The expressed enzyme activity was neutralized by incubation with antibodies raised against potato tuber and spinach leaf ADP-glucose pyrophosphorylases but not with anti-Escherichia coli enzyme serum. 3-Phosphoglycerate was the most efficient activator and its effect was increased by dithiothreitol. In the ADP-glucose synthesis direction, 3-phosphoglycerate activated the recombinant enzyme nearly 100-fold in the presence of dithiothreitol, with an A0.5 value of 57 microM. The recombinant ADP-glucose pyrophosphorylase was less sensitive to P(i) inhibition and more sensitive to heat denaturation than the potato tuber enzyme. Results suggest that bacterial expression of potato tuber cDNAs could be used to study the role and interaction of the subunits of the native ADP-glucose pyrophosphorylase.

Allosteric Regulation↗