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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site.

Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin.

Animals↗
PubMed1999

Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder.

OBJECTIVES: Psychotherapy and antidepressant medication are helpful to many patients with bulimia nervosa (BN). However, a substantial number of bulimics respond poorly to such treatments. Recent studies suggest that many of the poor responders have cluster B personality disorders. In some ways, the symptomatology of bulimics who have a comorbid cluster B disorder resembles that of patients with attention deficit hyperactivity disorder (ADHD). In particular, individuals in both groups frequently have a high level of impulsivity. Such a resemblance raised the question of whether administration of methylphenidate (MPH), a drug used to treat ADHD, would have therapeutic effects in this subgroup of BN patients. METHODS: In a pilot study, we administered MPH to 2 patients with BN and cluster B traits and found beneficial effects. These patients had not responded to adequate trials of psychotherapy and selective serotonin reuptake inhibitors (SSRIs). RESULTS: MPH treatment was effective. Both Patients had decreased binging and purging. DISCUSSION: MPH may be useful for bulimics with cluster B personality disorder who respond poorly to conventional treatment. Further studies of MPH administration may be worthwhile. Due to the potential risks, however, clinical treatment with this agent is not recommended at this time.

Adult↗
PubMed1999

Thymosin beta4 enhances endothelial cell differentiation and angiogenesis.

When human umbilical vein endothelial cells (HUVEC) differentiate into capillary-like tubes, there is a five-fold upregulation of the mRNA for thymosin beta4 (Tbeta4) (Grant et al. J Cell Sci 1995; 108: 3685-94 [1]) and this endogenous expression plays an important role in endothelial cell attachment to and spreading on matrix components. We now show that exogenous addition of thymosin beta4 (in the ng-microg range) to HUVEC in culture can induce several biological responses. These responses include increased tube formation in vitro. Additionally, exogenous thymosin beta4 enhances vascular sprouting in the coronary artery ring angiogenesis assay. Measurements of these vascular sprouts show a doubling of the vessel area (via increased branching) with as little as 100 ng of synthetic thymosin beta4. These processes appear to involve the binding of thymosin beta4 to an unknown cell surface receptor and internalization of the protein. This cell surface-binding appears not to be mediated through the thymosin beta4-actin binding domain LKTET. An increase in thymosin beta4 cytoplasmic staining in HUVEC exposed 10 microg of the peptide appears to occur without increased mRNA translation. In summary Tbeta4 induces an increase in cell-matrix attachment, proliferation, tube formation, internalization of the peptide and rearrangement of the actin cytoskeleton. The data now defines both an autocrine and paracrine role for thymosin beta4 in vessel formation.

Journal Article↗
PubMed1999

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer.

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.

Adult↗
PubMed1999

Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.

PURPOSE: The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. METHODS: Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. RESULTS: Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). CONCLUSION: We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.

Adult↗
PubMed1999

Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator.

Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (Emu) are the targets of the negative regulator, NF-muNR, found in non-B and early pre-B cells. Expression library screening with NF-muNR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-muNR identity. It is expressed in non-B and early pre-B cells but not mature B cells. It binds to NF-muNR binding sites within Emu with appropriate differential affinities. Antiserum specific for Cux/CDP recognizes a polypeptide of the predicted size in affinity-purified NF-muNR preparations and binds NF-muNR complexed with DNA. Cotransfection with Cux/CDP represses the activity of Emu via the MAR sequences in both B and non-B cells. Cux/CDP antagonizes the effects of the Bright transcription activator at both the DNA binding and functional levels. We propose that Cux/CDP regulates cell-type-restricted, differentiation stage-specific Emu enhancer activity by interfering with the function of nuclear matrix-bound transcription activators.

Animals↗
PubMed1999

The incidence, prevalence, and severity of sarcoidosis in New York City firefighters.

OBJECTIVE: The etiology of sarcoidosis is unknown, but epidemiology suggests that environmental agents are a factor. Because firefighters are exposed to numerous toxins, we questioned whether sarcoidosis was increased in this cohort. SETTING: The New York City Fire Department (FDNY), employing > 11,000 firefighters and nearly 3,000 emergency medical services (EMS) health-care workers (HCWs). DESIGN: In 1985, FDNY initiated a surveillance program to determine the incidence, prevalence, and severity of biopsy-proven sarcoidosis in firefighters. In 1995, EMS HCWs were added as control subjects. RESULTS: Between 1985 and 1998, 4 prior cases and 21 new cases of sarcoidosis were found in FDNY firefighters. Annual incidence proportions ranged from 0 to 43.6/100,000, and averaged 12.9/100,000. On July 1, 1998, the point prevalence was 222/100,000. For EMS HCWs, annual incidence proportions were zero. Radiographic stage 0 or stage 1 sarcoidosis was found in 19 firefighters (76%), and stage 3 was found in 1 firefighter (4%). Pulmonary function (FVC, FEV(1), and diffusing capacity for carbon monoxide) was normal in 17 firefighters (68%), and reduced to </= 65% predicted in 2 firefighters (8%). Maximum oxygen consumption (MVO(2)) was normal in 10 of 17 firefighters (59%), and reduced to 65% predicted in 3 firefighters (12%). Five of seven firefighters (71%) with abnormal MVO(2) had gas exchange abnormalities, and none had O(2) desaturation. All returned to fire fighting. CONCLUSIONS: Annual incidence proportions and point prevalence were increased in FDNY firefighters as compared to EMS HCWs and historical controls. Radiographs and physiologic measurements demonstrated only minimal impairment.

Adult↗
PubMed1999

[Pulmonary infection from Rhodococcus equi after renal transplantation. Review of the literature].

Rhodococcus Equi, a strictly aerobic Gram positive coco-bacillus, is a pathogen for horses and foals. It may induce opportunistic infections and is described in AIDS infected patients. We report the case of a 47-year old man, breeder of horses, with kidney transplant who has presented, 8 years after his graft, an impairment of health, a fever and evidence of pulmonary disease. The pulmonary biopsy under scanner guidance and microbiology study, has displayed the diagnosis of Rhodococcus equi infection. The evolution has been favorable with double antibiotherapy (follow-up 27 months). Ten comparable observations have been published after organ transplantation: (kidney: 8; heart: 1; liver: 1). Pulmonary locations are widely predominant. The animal contact is found only in 30% of cases. The presentation of the sickness has been compared to pulmonary tuberculosis or to nocardiosis, pathologies often observed in this context of immunosuppression. The antibiotic treatment is difficult and should required two bactericidal antibiotics. A surgical lobectomy can be envisaged in case of relapse. The mortality is 30%.

Actinomycetales Infections↗
PubMed1998

The two-dimensional histogram as a constraint for protein phase improvement.

The joint distribution of electron density and its gradient in a protein electron-density map was examined. This joint distribution was represented by a two-dimensional histogram (2D histogram) of electron-density values and the modulus of the gradient. 16 structures representing distinct protein-fold families were selected to study the dependence of the 2D histogram on resolution, overall temperature factor, structural conformation and phase error. The similarity between the histograms for a pair of structures was measured by correlation coefficient, and the residual provided a measure of the difference. The 2D histogram was found to vary with resolution and overall temperature factor, but was found to be insensitive to structure conformation. The average correlation coefficient between pairs of 2D histograms at three different resolutions examined was 0.90 with a standard deviation of 0.04. The average residual for the same condition was 0.13 with a standard deviation of 0.03. The 2D histogram was also found to be sensitive to phase error. The average correlation coefficient and residual between 2D histograms with 10 degrees phase difference are 0.71 and 0.18, respectively. The variation of the 2D histogram resulting from structure-conformation changes was estimated to be equivalent to that of a 4 degrees phase error. This establishes the minimal phase error that a 2D histogram-matching method could achieve. The conservation of the 2D histogram with respect to structure conformation enables the prediction of the ideal 2D histogram for unknown structures. The sensitivity of the 2D histogram to phase error suggests that it could be used as a target for the density-modification method and also could be used as a figure of merit for phase selection in ab initio phasing.

Electrons↗
PubMed1998

Correlation of color Doppler flow in the prostate with tissue microvascularity.

BACKGROUND: The pathophysiology of increased color Doppler (CD) flow has not previously been addressed in histologic evaluations of microvascular parameters. In this study, the authors attempted to define the differences between benign and malignant biopsy cores found in regions of the prostate with normal and high CD flow. METHODS: Forty patients were retrospectively chosen for CD histologic comparison, each of whom had a core from a sextant biopsy with the following characteristics: malignant tissue with distinct increased CD flow (n=11), malignant tissue with normal CD flow (n=10), benign tissue with distinctly increased CD flow (n=9), or benign tissue with normal CD flow (n=10). All biopsy cores were stained with factor VIII-related antigen to identify microvasculature and to determine the number of microvessels per square millimeter (mm2) in an average cross-sectional area of microvessels, the percentage of tissue occupied by microvasculature, and the Gleason score. RESULTS: In biopsies of benign tissue, high CD flow was associated with greater numbers (P < 0.025) of vessels of similar size than in normal flow benign biopsies. Biopsies of malignant tissue contained significantly greater numbers (P < 0.01) of much smaller vessels (P < 0.0005) than biopsies of benign tissue. In biopsies of malignant tissue, no significant differences in microvasculature parameters were noted between high and normal CD flow, yet biopsies with high CD flow had average Gleason score of 6.7 compared with only 5.9 for biopsies with normal CD flow (P < 0.025). CONCLUSIONS: Increased CD flow in biopsies of benign tissue was correlated with a greater number of vessels/mm2, yet all biopsies of malignant tissue had more vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of malignant tissue cannot be explained by standard microvasculature analysis but significantly guides biopsies to regions with a greater Gleason score.

Humans↗
PubMed1998

A comparison of forensic and nonforensic malingerers: a prototypical analysis of explanatory models.

Explanatory models of malingering strive to understand the primary motivation underlying attempts to feign. Rogers, Sewell, and Goldstein (1994) provided empirical support for the conceptualization of pathogenic, criminological, and adaptational models. In the current study, a prototypical analysis of 221 forensic experts results in a slightly refined formulation: the adaptational models was decomposed into its two broad dimensions (cost-benefit analysis and adversarial setting). An important findings is that the factor structure for the explanatory models remained stable when applied to both forensic and nonforensic cases. As a first investigation, significant differences were observed in prototypical cases of malingering by the category of referral (forensic or nonforensic) and by type of feigning (mental disorders, cognitive impairment, and medical syndromes). Surprisingly, the feigning of medical syndromes appeared to play a relatively prominent role in both forensic and nonforensic cases and to be influenced by the apparent adversarial context of the assessment. Finally, important gender differences were observed, especially with nonforensic prototypical cases of malingering.

Adaptation, Psychological↗
PubMed1998

Panoramic radiology quality assessment.

A procedure is proposed for performing noninvasive x-ray quality assessment tests on panoramic radiology equipment. A simple cardboard tube jig eliminates relative motion between the measurement system and the narrow, collimated x-ray beam. Accurate measurements of beam HVL, x-ray exposure coefficient of variation and mA linearity may be obtained. Use of the tube jig permits easy and routine monitoring of these important x-ray parameters as well as consistency checks of tube output. Film/screen contact also should be routinely checked in the clinic.

Biophysical Phenomena↗
PubMed1998

Exposure and dose in panoramic radiology.

Panoramic radiology entrance skin exposure (ESE) was measured for a Siemens Orthopantomograph 10 E using a thimble chamber and TLDs. Thimble chamber measurements are shown to be inaccurate for the moving, narrow beam panoramic scan geometry due to partial volume and partial charged-particle equilibrium effects. For 75 KVp, 8 mA panoramic scans the TLD measured beam central ray ESE on the scan central plane (patient midsagittal plane) was an approximately constant 20 mR for the first 7.5 cm from the entrance slit. A theoretical model of central plane ESE for a fixed rotation center agrees very well with the TLD measurements and is consistent with all of the known ESE (and dose) properties near rotation centers. Head phantom skin dose measurements demonstrate the dependence of skin dose on exact equipment mode of use and patient anatomy. Central plane, beam central ray ESE is judged to be a convenient, universal measure of panoramic radiology radiation output.

Biophysical Phenomena↗
PubMed1997

A peptide derived from an extracellular domain selectively inhibits receptor internalization: target sequences on insulin and insulin-like growth factor 1 receptors.

Certain peptides derived from the alpha1 domain of the major histocompatibility class I antigen complex (MHC-I) inhibit receptor internalization, increasing the steady-state number of active receptors on the cell surface and thereby enhancing the sensitivity to hormones and other agonists. These peptides self-assemble, and they also bind to MHC-I at the same site from which they are derived, suggesting that they could bind to receptor sites with significant sequence similarity. Receptors affected by MHC-I peptides do, indeed, have such sequence similarity, as illustrated here by insulin receptor (IR) and insulin-like growth factor-1 receptor. A synthetic peptide with sequence identical to a certain extracellular receptor domain binds to that receptor in a ligand-dependent manner and inhibits receptor internalization. Moreover, each such peptide is selective for its cognate receptor. An antibody to the IR peptide not only binds to IR and competes with the peptide but also inhibits insulin-dependent internalization of IR. These observations, and binding studies with deletion mutants of IR, indicate that the sequence QILKELEESSF encoded by exon 10 plays a key role in IR internalization. Our results illustrate a principle for identifying receptor-specific sites of importance for receptor internalization, and for enhancing sensitivity to hormones and other agonists.

Adipocytes↗
PubMed1997

Lack of phospholipase A2 mutations in neuroblastoma, melanoma and colon-cancer cell lines.

A candidate murine tumor-suppressor gene, Mom1, has been identified as the secretory phospholipase A2 (GDB nomenclature: PLA2G2A) gene. Evidence suggests that PLA2G2A functions as a tumor-suppressor because mice lacking PLA2G2A expression demonstrate increased colonic polyposis. The human homologue of PLA2G2A has been mapped to chromosome 1p36, a region frequently implicated in the pathogenesis of neuroblastoma, colon cancer and melanoma. We identified 2 alterations in the PLA2G2A gene in a single neuroblastoma cell line out of 20 examined; however, we found no mutations in 24 melanoma cell lines, 12 lymphoblastoid cell lines from patients having chromosome 1-linked familial melanoma and 10 colon cancer cell lines. Secretory phospholipase A2 is unlikely to play a significant role in the pathogenesis of these tumors.

Animals↗