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Biomedical subjects

D J Goldstein

Publications and source records attributed to D J Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mutational analysis of the beta-type platelet-derived growth factor receptor defines the site of interaction with the bovine papillomavirus type 1 E5 transforming protein.

The E5 polypeptide of bovine papillomavirus type 1 is a small membrane-bound protein which induces the transformation of immortalized fibroblasts, apparently via the formation of a ternary complex with the platelet-derived growth factor receptor (PDGFR) and the 16-kDa V-ATPase protein. This interaction seems to be mediated, at least in part, by their respective transmembrane domains. E5 also cooperates with transfected beta PDGFR to induce interleukin-3 (IL-3)-independent growth of a mouse myeloid precursor cell line (32D) which normally lacks expression of most known tyrosine kinase growth factor receptors. Cell proliferation induced by beta PDGFR and E5 is also highly specific, since the highly conserved alpha PDGFR and other related receptors did not physically or functionally interact with E5 in these cells. In the current study, analysis of chimeric alpha and beta PDGFRs confirmed that a short region encompassing the beta PDGFR transmembrane domain was sufficient for complex formation with E5, receptor autophosphorylation, and sustained proliferation of 32D cells in the absence of IL-3. Furthermore, a deletion mutant lacking the entire extracellular domain efficiently bound E5 and induced IL-3-independent growth. These data provide direct evidence that the interaction between E5 and the beta PDGFR involves amino acids 531 to 556 of the receptor transmembrane region and that this specific interaction is critical for activation of the PDGFR signaling complex.

Animals↗
PubMed1995

Perfusion technique for treatment of right heart failure.

A simple heparin-bonded circuit to facilitate a femoral vein to femoral artery shunt for the treatment of right-sided circulatory failure is proposed. Desaturated venous blood is shunted to the left-sided circulation to increase systemic blood pressure at the expense of saturation. The circuit comprised 1/4 inch x 3/32 inch tubing with a paediatric Bio-Medicus centrifugal pump head allowing adequate regulation of flow. Paediatric Bio-Medicus cannulae provide flows between 500 and 2000 ml/min. Measurements of pulmonary artery pressure, central venous pressure, arterial pressure, arterial saturation and cardiac output were recorded. In the four case studies presented, the treatment included unloading of the right ventricle with venous to arterial shunting. Likewise, eight Holstein calves underwent shunt utilization after placement of a left ventricular assist device and induction of right ventricular failure. The future use of this device may be instrumental in aiding the cardiothoracic surgical team in the treatment of right-sided circulatory failure.

Adult↗
PubMed1995

Long-term fluoxetine treatment of bulimia nervosa. Fluoxetine Bulimia Nervosa Research Group.

BACKGROUND: A large collaborative 8-week study has shown fluoxetine to be effective and safe in treating patients with bulimia nervosa. The present study evaluated fluoxetine over 16 weeks. METHOD: Fifteen US out-patient psychiatry clinics conducted a double-blind parallel study in men and women with DSM-III-R bulimia nervosa (483 patients entered, 398 randomised [3:1 ratio, fluoxetine 60 mg/day or placebo], 225 completed). Outcome measures included change in vomiting and binge-eating episodes per week. Eating Disorder Inventory, Clinical Global Impressions and Patient's Global Impression. RESULTS: Compared with placebo, fluoxetine treatment resulted in significantly greater reductions in vomiting (F[1,360] = 14.73, P < 0.0001) and binge-eating (F[1,360] = 14.39, P = 0.0002) episodes per week at endpoint and improvement in other outcome measures. Adverse event, vital sign and laboratory analyses indicated that fluoxetine was safe. CONCLUSION: Fluoxetine appeared to be safe and effective in patients with bulimia nervosa for up to 16 weeks.

Adolescent↗
PubMed1995

Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis.

Rats of the Milan normotensive rat strain (MNS) spontaneously develop severe proteinuria and excessive glomerular thromboxane (Tx)A2 production at a young age. These abnormalities are accompanied by podocyte alterations, progressive focal glomerulosclerosis (FGS), and interstitial fibrosis, resembling human FGS. Since it has been shown that pharmacologic Tx-synthase inhibition protects MNS rats from these changes, it was hypothesized that a fish oil (FO) enriched diet, by enhancing TxA3 production instead of TxA2, might afford similar protection, compared with diets enriched in safflower oil (SO) or lard (LD). Rats were pair-fed 11% fat diets from age of 1 to 11 months. Glomerular TxA2 at 11 months was significantly lower in PO-fed rats than in SO- and LD-fed rats (11 +/- 3.0, 69 +/- 3.0, 59 +/- 19.0 nanograms per min/mg, respectively; P < 0.001). At 3 months, urinary albumin excretion was similar among the groups. Over the course of the study, rats fed FO developed significantly less albuminuria than the SO and LD groups (P < 0.001 by analysis of variance for repeated measures), such that the values at 11 months were 25 +/- 5.8, 49 +/- 8.7, and 68 +/- 13.0 mg/24h, respectively. Serum cholesterol and triglycerides were also significantly lower in FO-fed rats than in SO- and LD-fed rats. The extent of FGS was similar in the three groups, but FO-fed rats had less interstitial injury than the other groups. It was observed that a fish-oil diet substantially alleviated albuminuria, normalized nephrotic hyperlipidemia, and reduced interstitial injury, but did not prevent the development of FGS in the MNS model.

Albuminuria↗
PubMed1995

Startle eyeblink elicitation in attention deficit disordered children using low-intensity acoustic stimuli.

The acoustic startle eyeblink response was measured in 11 pediatric psychiatric inpatients, 7 diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and 4 diagnosed with other conditions (non-ADHD). Startle stimuli were 85 or 95 dB SPL, 50-msec. noise pulses. Startle eyeblink responses were reliably measured for all children. Startle response latency was faster for ADHD children than for clinical control subjects in all stimulus conditions. These data show that the acoustic startle eyeblink response can be reliably elicited in ADHD children at lower intensities (85-95 dB) than those used in previous published research (104 dB). This may increase the use of the startle paradigm, since less intense stimuli may be less disturbing to the children, increasing compliance and allowing longer testing sessions.

Acoustic Stimulation↗
PubMed1995

Abnormalities of esterase and glycogen in developing macrophages in non-Hodgkin's lymphoma: a quantitative cytochemical study.

Integrating microdensitometry has been used to quantitate changes in 4 cytoplasmic enzymes (NADH dehydrogenase, succinate dehydrogenase, acid phosphatase and alpha-naphthyl butyrate esterase), DNA, RNA and glycogen in developing macrophages from 17 patients with non-Hodgkin's lymphoma and 19 normal subjects. Cytochemical measurements were made at intervals over 6 days of suspension culture; over 16 000 individual cells were examined in total and the results subjected to analysis of variance. While the levels of enzymes and RNA of both groups showed increases over the period of culture, the levels of alpha-naphthyl butyrate esterase in the patients' cells were consistently lower than the corresponding values for the normal cells and glycogen levels were higher, these differences satisfying the pre-determined requirements for statistical significance. It is concluded that (a) maturational changes take place in cytochemical constituents of developing macrophages of non-Hodgkin's lymphoma (b) there are disturbances affecting the amounts of the specific enzyme alpha-naphthyl butyrate esterase and glycogen (c) these abnormalities may be part of a compromise of host defense mechanisms by the disease, although a pre-existing defect in esterase increasing the susceptibility to malignancy is another possibility, and (d) the methods used may be of value in future investigations of the cause of the disturbances and their correction.

Acid Phosphatase↗
PubMed1995

Developmental expression of the nephritogenic antigen of monoclonal antibody 5-1-6.

The biogenesis of p51, the target of nephritogenic monoclonal antibody 5-1-6, was studied in the developing glomerulus by immunolocalization and metabolic labeling. The localization of p51 was compared with that of ZO-1, a component of the cytoplasmic face of the epithelial slit diaphragm, and with that of podocalyxin, and apical marker of the podocyte. p51 first became faintly, but clearly, detectable on the basal and lateral sides of the developing podocytes at the S-shaped body stage. Staining intensity increased with further maturation and was restricted to the visceral epithelial cells. On immunoelectron microscopy, the antigen was seen along the basal and lateral surfaces below occluding junction at the early capillary loop stage and later, with the interdigitation of foot processes, became concentrated in the slit pores. At no stage was p51 seen on the apical surface. p51 and ZO-1 were closely localized in the mature glomerulus but arrived at their final positions from opposite directions. p51 was on basal and podocalyxin was on apical sides of the glomerular epithelium from the S-shaped body stage onwards. Metabolic labeling studies showed that p51 is actively synthesized during initial glomerular development and that the rate of synthesis declines substantially with maturation. We conclude that p51 is primarily synthesized during the initial glomerular development, becomes concentrated in the slit pores of mature podocytes, and serves as a basal differentiation marker for podocytes.

Aging↗
PubMed1994

Familial crossed polysyndactyly.

We have observed a distinct form of "crossed" polysyndactyly in 6 generations of a family with 5 affected persons, all males. The polydactyly is postaxial in the hands and preaxial in the feet. Syndactyly in the hands is observed in some relatives, while syndactyly in the feet is present bilaterally in all affected relatives. This seems to be an autosomal dominant trait with male to male transmission over 3 generations by examination and an additional 3 generations by history. This form of polysyndactyly could not be readily categorized by the existing classification by Temtamy and McKusick [1978: BD OAS XIV 6:363-392]. We review and expand the present classification of polydactyly and syndactyly syndromes.

Abnormalities, Multiple↗
PubMed1994

Baseline predictors of success when comparing two treatments.

Since few medications are equally effective in all patients, physicians can maximize the risk/benefit ratio of therapy for their patients by limiting exposure based on baseline predictors of success. Traditional procedures typically evaluate the response of patients receiving the same treatment regimen without evaluating a comparator. However, when treatments are compared, such as in clinical trials, traditional procedures of identifying predictors must be modified to analyze the treatment effect on the primary outcome variable. We focus on clinical and statistical considerations that arise when developing baseline predictors through models which consider treatment differences. To illustrate an application of this method, we used data from 1,026 patients completing at least 6 months of double-blind therapy in clinical trials comparing fluoxetine (N=522) with placebo (N=504) for weight loss. Stepwise regression procedures were used to identify baseline variables which were predictive of a beneficial fluoxetine treatment effect on last-visit-carried-forward (LVCF) weight change. In this example, age, smoking activity, and uric acid concentration were the best baseline predictors of long-term treatment effect relative to LVCF weight change. Patients were more likely to achieve long-term benefit with fluoxetine if they were older, and/or were nonsmokers, and/or had high concentrations of uric acid at baseline. These predictors, developed through models keying on treatment effect, can be used to identify patients who are more likely to accrue benefits with active therapy beyond those expected with placebo therapy, thus enriching the treatment population so that a higher proportion of treated patients are successful.

Anti-Obesity Agents↗
PubMed1994

1987: Adjustable annuloplasty for tricuspid insufficiency. Updated in 1994.

De Vega described a technique for tricuspid annuloplasty using synthetic suture to reduce the size of the dilated annulus. We present our experience with an adjustable modification of de Vega's suture annuloplasty technique. The records of 12 patients followed for 15 to 30 months were reviewed. All 10 survivors had a significant drop in right-sided filling pressure (average, 39% decrease) and an associated improvement in clinical status. The 2 deaths in the series were not related to persistent tricuspid insufficiency. This technique represents a reliable, rapid, and readily teachable method for the surgical management of tricuspid insufficiency.

Hemodynamics↗
PubMed1994

Long-term weight loss: the effect of pharmacologic agents.

We reviewed 20 English-language weight-reduction studies, reported between 1967 and March 1993, of the effect of > or = 6 mo of pharmacologic therapy on weight loss and its maintenance to determine the clinical benefits of extended treatment, propose treatment guidelines, and identify future research needs. Pharmacologic agents included phentermine, mazindol, fenfluramine, dexfenfluramine, and fluoxetine. Study designs varied with respect to blinding, use of a single agent vs a combination, dosing, length of therapy, patient selection, adjunctive therapy, and visit frequency. At endpoint, weight loss varied from study to study but a plateauing of weight loss or weight regain was observed after approximately 6 mo. The benefits of extended treatment appear to outweigh the risks for those patients who are unable to lose sufficient weight without pharmacologic therapy but who maintain adequate weight loss with long-term pharmacologic therapy. Future studies should define and evaluate pharmacologically responsive and unresponsive subgroups.

Appetite Depressants↗
PubMed1994

The bovine papillomavirus type 1 E5 transforming protein specifically binds and activates the beta-type receptor for the platelet-derived growth factor but not other related tyrosine kinase-containing receptors to induce cellular transformation.

The 44-amino-acid E5 protein of bovine papillomavirus type 1 is a highly hydrophobic protein which appears to transform cells through the activation of growth factor receptors. To investigate the specificity of E5-growth factor receptor interactions required for mitogenic signaling, we utilized a nontumorigenic, murine myeloid cell line (32D) which is strictly dependent on interleukin-3 (IL-3) for sustained proliferation in culture. This IL-3 dependence can be functionally substituted by the expression of a variety of surrogate growth factor receptors and the addition of the corresponding ligand. Several receptor cDNAs for the alpha- and beta-type platelet-derived growth factor receptors [alpha PDGFR and beta PDGFR], the epidermal growth factor receptor, and the colony-stimulating factor 1 receptor) were transfected into 32D cells constitutively expressing the E5 protein to test for IL-3-independent growth. Only beta PDGFR was capable of abrogating the IL-3 dependence of 32D cells. The proliferative signal induced by the coexpression of beta PDGFR and E5 was accompanied by stable complex formation between these proteins, constitutive tyrosine phosphorylation of the receptor, and tumorigenicity in nude mice. The lack of cooperative interaction between E5 and the epidermal growth factor receptor, the colony-stimulating factor 1 receptor, and the highly related alpha PDGFR was paralleled by the inability of E5 to bind to these receptors and failure to increase receptor tyrosine phosphorylation. Thus, these data indicate that the ability of E5 to induce sustained proliferation and transformation of 32D cells is a direct consequence of specific interaction between the E5 protein and the beta PDGFR signaling complex and the subsequent stimulation of receptor tyrosine phosphorylation.

Animals↗
PubMed1994

Visual-motor coordination and intelligence as predictors of reading, mathematics, and written language ability.

Previous research on the relationship between visual-motor coordination and academic achievement has been equivocal and has frequently not included controls for the effect of intelligence on achievement. In the present study, scores on three tests of children's visual-motor coordination correlated moderately to highly with scores on a test of reading, mathematics, and written language for a sample of 44 elementary school children referred for learning difficulties. Multiple regression analyses indicated that visual-motor coordination scores accounted for little unique achievement test score variance when IQs were included in the equations.

Child↗
PubMed1994

Evaluating success of weight loss programs, with an application to fluoxetine weight reduction clinical trial data.

We modified criteria for judging successful obesity treatment proposed by Atkinson to provide objective criteria for successful benefit from weight reduction programs with respect to data from a clinical trial. The criteria include assessments of changes in both weight-related factors (e.g. excess weight, excess body fat) and obesity-related risk factors (e.g. hypertension, hyperglycemia, hyperlipemia). To demonstrate the use of this methodology, we applied the criteria in an analysis of eight randomized, double-blind controlled trials comparing fluoxetine (n = 522) with placebo (n = 504) for weight loss. The results suggest these criteria can be useful for evaluating a treatment program or for comparing treatments from clinical trials.

Adolescent↗
PubMed1994

Pattern analysis method for assessing successful weight reduction.

Researchers reporting on clinical weight loss programmes have been challenged to provide information about long-term follow-up. To evaluate long-term weight reduction, a methodology was developed for analysis of longitudinal data. Under this method, a pattern of interest is defined a priori, and the proportions of patients attaining the pattern are compared between treatments. The methodology permits objective summarization and statistical analysis of the data. Applications of the method and corresponding results demonstrate its utility for assessing the treatment effect on weight reduction and systolic blood pressure. To show that the method may be further generalized, suggestions for alternative types of patterns are presented.

Adult↗
PubMed1994

Fluoxetine: a randomized clinical trial in the treatment of obesity.

Fluoxetine hydrochloride (Lovan, Eli Lilly and Company, Indianapolis, Indiana, USA), a specific serotonin uptake inhibitor, was compared with placebo in 458 obese outpatients in a 52-week double-blind randomized ten-site trial to study its effect on weight reduction. Patients in the fluoxetine and placebo groups were predominantly Caucasian (81% and 85%, respectively) and female (81% and 79%, respectively), with a mean body mass index (BMI) of 36.2 and 35.8 kg/m2, respectively, and a mean age of 43 years (both groups). Fluoxetine therapy (60 mg/day) resulted in statistically significantly (P < or = 0.05) greater mean weight loss than placebo to week 28. Although some patients continued to lose weight throughout the 52-week therapy period, maximum mean weight loss occurred at week 20. There was no treatment difference at 52 weeks. The change in visit frequency (biweekly to week 8, monthly to week 20, then bimonthly to week 52) may have affected results. Patients with higher baseline BMIs (> 40 kg/m2) attained and maintained a greater weight loss than patients with lower baseline BMIs (< 40 kg/m2). Two sites demonstrated greater efficacy than the study as a whole. The use of nutrition counselling at one site and behaviour modification at the other, or other site-to-site differences, may account for the improved efficacy. Fluoxetine was well tolerated and appeared to be safe therapy for the treatment of obesity with efficacy demonstrated for 28 weeks.

Adult↗
PubMed1993

Follow-up of preterm infants treated with dexamethasone for chronic lung disease.

OBJECTIVE: To study the outcome of prolonged treatment with dexamethasone sodium phosphate in preterm infants who depend on assisted ventilation. DESIGN: Longitudinal follow-up using historic controls. SETTING: Regional intensive care nursery. PARTICIPANTS: Sixty-one very-low-birth-weight infants treated with a 42-day course of dexamethasone and 61 historic controls matched for birth weight, gestational age, race, and sex. All 122 subjects required assisted ventilation for at least 15 days. INTERVENTION: Infants were given dexamethasone sodium phosphate at a dose of 0.5 mg/kg per day. The dose was then tapered over 42 days. MEASUREMENTS/MAIN RESULTS: Infants treated with dexamethasone received assisted ventilation for a median of 33 days; controls, a median of 47 days (P < .05). One hundred infants survived; 94 were examined at age 1 year. The two groups were similar with respect to the proportions hospitalized for respiratory infection in the first year of life and the proportions with weight, length, and head circumference below the fifth percentile. Rates of cerebral palsy were also similar between the two groups, as were median Bayley Mental and Psychomotor developmental index scores. CONCLUSIONS: Dexamethasone treatment was associated with fewer days of assisted ventilation, but not with improved outcome at age 1 year. More assessment should be made of dexamethasone's effect on long-term outcome before dexamethasone becomes widely used in preterm infants who depend on assisted ventilation.

Chronic Disease↗