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B Goldberg

Publications and source records attributed to B Goldberg.

At least 19 recordsLinked to original sources

In situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (P2) of the African Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense.

African trypanosomes are parasitic flagellates that live in the connective tissues of the host. Trypanosomes must obtain from their host adenine/adenosine and other nucleosides that can be salvaged through enzymatic cleavage. Methylthioadenosine (MTA) is a byproduct of polyamine metabolism, formed from the donation of an aminopropyl moiety by decarboxylated S-adenosylmethionine (dcAdoMet) to form spermidine. MTA is then cleaved phosphorolytically by MTA phosphorylase to methylthioribose-1-phosphate (MTR-1-P) and adenine. The uptake of MTA was compared with that of adenosine in two strains: Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. The K(m) values for MTA and adenosine (with 5 mM inosine) transport by T. b. brucei were 1.4 and 0.175 mM, and the V(max) values were 70 and 7.8 micromol/L/min, respectively. The K(m) values for T. b. rhodesiense MTA and adenosine (with 5 mM inosine) transport were 1.2 and 0.11 mM, and the V(max) values were 52.6 and 2.9 micromol/L/min, respectively. Since MTA was not competitive with either AdoMet (100 microM), inosine (100 microM), or the methionine precursor ketomethylthiobutyrate (100 microM), it appears that MTA enters through the P(2) (adenosine/adenine) transport site. From this study and our previous work, we determined that these organisms transport adenylated intermediates of methionine metabolism found in sera for purine salvage and as an ancillary source of methionine. The significant ability of African trypanosomes to transport MTA and related intermediates is an important consideration in the design and development of selective chemotherapeutic agents.

Adenosine↗

Origin of AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Ulcerative colitis in a renal transplant patient with previous Goodpasture disease.

A renal transplant was performed in a 6-year-old boy who developed end stage renal disease (ESRD) after presenting with antiglomerular basement membrane (anti-GBM) disease. At 10 years of age he developed ulcerative colitis while being immunosuppressed with cyclosporin, prednisone, and azothioprine. He had a pancolectomy, and at 14 years has no symptoms of ulcerative colitis or anti-GBM disease. HLA typing revealed that he was homozygous for HLA DR2. The co-occurrence of anti-GBM disease and ulcerative colitis has not previously been described. Although there is no known common etiology for these two autoimmune diseases, we propose that the patient's homozygosity at HLA DR2 may have predisposed him to both.

Anti-Glomerular Basement Membrane Disease↗

Trypanocidal activity of dicationic compounds related to pentamidine.

Eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC50 values of 2.3 and 900 nM, respectively. Introduction of polar groups into the linker decreased the effectiveness of the compounds against drug-resistant trypanosomes. In compounds with a 2-butene linker between the cationic groups, trans-isomers were more potent than cis-isomers. The cis- and trans-buteneamidines cured infection caused by Trypanosoma brucei brucei (EATRO Lab 110) and protected mice against infection by Trypanosoma brucei rhodesiense isolates, some of which are resistant to diamidines and melarsoprol.

Animals↗

Patient characteristics and physicians' practice activities for patients with chronic low back pain: a practice-based study of primary care and chiropractic physicians.

BACKGROUND: Chronic low back pain sufferers are among those who account for the greatest usage of health care resources. Primary care medical (MD) physicians and chiropractic (DC) physicians treat most of these patients. OBJECTIVES: To study patient characteristics and physician practice activities for patients with chronic low back pain treated by DC physicians and MD physicians. METHODS: A longitudinal, practice-based observational study was undertaken in 14 general practice and 51 DC community-based clinics. A total of 2945 consecutive patients with ambulatory low back pain of mechanical origin were enrolled; 835 patients were in the chronic subgroup. Patients were followed for 12 months. Data were obtained on all of the following: patient demographics, health status, and psychosocial characteristics; history, duration, and severity of low back pain and disability; physicians' practice activities; and low back complaint status at 1 year. RESULTS: Patients treated by MD physicians were younger and had lower incomes; their care was more often paid for by a third party; their baseline pain and disability were slightly greater. In addition, patients treated by MD physicians had one fourth as many visits as patients treated by DC physicians. Utilization of imaging procedures by enrolling physicians was equivalent for the two provider groups. Medications were prescribed for 80% of the patients enrolled by MD physicians; spinal manipulation was administered to 84% of patients enrolled by DC physicians. Physical modalities, self-care education, exercise, and postural advice characterized low back pain management in both provider groups. Patients' care-seeking was not exclusive to one provider type. Most patients experienced recurrences (patients treated by MD physicians, 59.3%; patients treated by DC physicians, 76.4%); 34.1% of patients treated by MD physicians and 12.7% of patients treated by DC physicians reported 12 months of continuous pain. Only 6.7% of patients treated by MD physicians and 10.9% of patients treated by DC physicians reported 1 resolved episode during the year. CONCLUSIONS: Differences in sociodemographics, present pain intensity, and functional disability may distinguish patients with chronic low back pain seeking care from primary care medical physicians from those seeking care from DC physicians. Although the primary treatment modality differs, the practice activities of MD physicians and DC physicians have much in common. Long-term evaluation suggests that chronic back pain is persistent and difficult to treat for both provider types.

Adult↗

Pain, disability, and satisfaction outcomes and predictors of outcomes: a practice-based study of chronic low back pain patients attending primary care and chiropractic physicians.

BACKGROUND: Few studies exist on the prognostic value of demographic, clinical, or psychosocial factors on long-term outcomes for patients with chronic low back pain. OBJECTIVE: This study reports on long-term pain and disability outcomes for patients with chronic low back pain, evaluates predictors of long-term outcomes, and assesses the influence of doctor type on clinical outcome. METHODS: Sixty chiropractic (DC) and 111 general practice (MD) physicians participated in data collection for a prospective, longitudinal, practice-based, observational study of ambulatory low back pain of mechanical origin. The primary outcomes, measured at 6 months and 12 months, were pain (by using the Visual Analog Scale), and functional disability (by using the Revised Oswestry Disability Questionnaire). Satisfaction was a secondary outcome. RESULTS: Overall, long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians. Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee. However, an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts (adjusted differences = 8.0 to 15.2; P <.002). A greater proportion of chiropractic patients were satisfied with all aspects of their care (P =.0000). The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes. Income, smoking, comorbidity, and chronic depression were also identified as predictors of outcomes in this study. CONCLUSION: Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes. Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction. Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians' practice activities that better serve these patients' needs.

Adult↗

The SNOMED RT Procedure Model.

BACKGROUND: SNOMED RT represents a fundamental change from prior versions of SNOMED. The logic-based structure of SNOMED RT enables concepts to be defined more explicitly, providing an opportunity to address inconsistencies and ambiguities present in prior SNOMED concept definitions. OBJECTIVES: Create a unifying organizational strategy for all SNOMED RT procedures, and remove ambiguities in procedure concept definitions. METHODS: A comprehensive model of procedures was developed, based on a set of guiding principles and a review of known existing models. RESULTS: All SNOMED RT procedures are categorized by a common set of "root procedures" (high level atomic actions), and are more explicitly defined by a shared set of defining relationships. CONCLUSIONS: While the objectives have largely been met, open issues continue to be addressed. The similarity between procedure models of SNOMED RT and the U.K. s Clinical Terms Version 3 is proving to greatly facilitate the full integration of the two terminologies into a merged vocabulary to be known as SNOMED Clinical Terms (SNOMED CT), slated to be released in the near future.

Clinical Medicine↗

Beyond danger: unmethylated CpG dinucleotides and the immunopathogenesis of disease.

Oligonucleotide sequences containing unmethylated cytidine phosphate guanosine (CpG) motifs are known to have significant immunostimulatory properties. Because of these immunostimulatory effects, unmethylated CpG oligonucleotides are thought to act as 'danger signals' that produce a favorable immune response by alerting the host to the presence of invading organisms or abnormal cells. In contrast to this concept, we review the evidence that unmethylated CpG sequences derived either from microbial agents or from endogenous CpG-rich Alu motifs promote disease progression by inducing an aberrant or autoreactive immune response. Recognition of the negative effect of unmethylated CpG dinucleotides should lead to more effective immune strategies to combat infectious, inflammatory, autoimmune and malignant diseases.

Alu Elements↗

Bridging the gap: human diploid cell strains and the origin of AIDS.

Recent descriptions of the first human and chimpanzee cases of human immunodeficiency virus type 1 (HIV-1)-related retroviral infections dating from 1959 have stirred interest in the origin of AIDS. Although the theory of a chimpanzee origin of HIV-1 with cross-species transfer to man has now gained popularity, a more likely scenario is that chimps and humans were infected by an HIV-1 precursor virus derived from a contaminated poliovaccine. The reason for the rapidity and ease of cross-species transfer of this precursor virus has not been elucidated. We hypothesize that the poliovaccine was passaged in a human diploid cell strain. This simple manipulation allowed the retrovirus to adapt to human tissues and may have spawned the AIDS pandemic.

Acquired Immunodeficiency Syndrome↗

Kinetics of methionine transport and metabolism by Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense.

Methionine is an essential amino acid for both prokaryotic and eukaryotic organisms; however, little is known concerning its utilization in African trypanosomes, protozoa of the Trypanosoma brucei group. This study explored the Michaelis-Menten kinetic constants for transport and pool formation as well as metabolic utilization of methionine by two divergent strains of African trypanosomes, Trypanosoma brucei brucei (a veterinary pathogen), highly sensitive to trypanocidal agents, and Trypanosoma brucei rhodesiense (a human pathogenic isolate), highly refractory to trypanocidal arsenicals. The Michaelis-Menten constants derived by Hanes-Woolf analysis for transport of methionine for T. b. brucei and T. b. rhodesiense, respectively, were as follows: K(M) values, 1. 15 and 1.75 mM; V(max) values, 3.97 x 10(-5) and 4.86 x 10(-5) mol/L/min. Very similar values were obtained by Lineweaver-Burk analysis (K(M), 0.25 and 1.0 mM; V(max), 1 x 10(-5) and 2.0 x 10(-5) mol/L/min, T. b. brucei and T. b. rhodesiense, respectively). Cooperativity analyses by Hill (log-log) plot gave Hill coefficients (n) of 6 and 2 for T. b. brucei and T. b. rhodesiense, respectively. Cytosolic accumulation of methionine after 10-min incubation with 25 mM exogenous methionine was 1.8-fold greater in T. b. rhodesiense than T. b. brucei (2.1 vs 1.1 mM, respectively). In African trypanosomes as in their mammalian host, S-adenosylmethionine (AdoMet) is the major product of methionine metabolism. Accumulation of AdoMet was measured by HPLC analysis of cytosolic extracts incubated in the presence of increasing cytosolic methionine. In trypanosomes incubated for 10 min with saturating methionine, both organisms accumulated similar amounts of AdoMet (approximately 23 microM), but the level of trans-sulfuration products (cystathionine and cysteine) in T. b. rhodesiense was double that of T. b. brucei. Methionine incorporation during protein synthesis in T. b. brucei was 2.5 times that of T. b. rhodesiense. These results further confirm our belief that the major pathways of methionine utilization, for polyamine synthesis, protein transmethylation and the trans-sulfuration pathway, are excellent targets for chemotherapeutic intervention against African trypanosomes.

Allosteric Regulation↗

Sonography of palpable breast cancer.

PURPOSE: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting. METHODS: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded. RESULTS: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma. CONCLUSIONS: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting.

Adolescent↗

Changes in body composition after a 12-wk aerobic exercise program in obese boys.

UNLABELLED: Previous studies have shown that vigorous aerobic training programs for obese children result in minimal weight changes, and concluded that they may not be beneficial. Weight change alone may not detect important beneficial changes in body composition associated with vigorous training in these children. Fifteen obese boys (aged 9-12 yr, body mass index (BMI) 31.8+/-6.5, average percent body fat (%BF) 41+/-4.2) underwent a supervised aerobic and resistance training program (12 wk, 2 days/wk for 30 min/session), to investigate the effects on weight and body composition. After the 3-month training period, weight loss averaged only 1.5+/-1.0 kg (not significant), but total body fat decreased by 4.1+/-1.8 kg (p<0.05) and fat-free mass (FFM) increased by 2.6+/-1.1 kg (p<0.05) based on hydrostatic weighing. As a result, %BF fell by 10% (p<0.01). There was a 5.8+/-2.8 mL/kg/min (p<0.05) increase in peak volume of oxygen uptake (VO(2)), along with a 248+/-120 kcal/d (p<0.05) increase in resting energy expenditure (REE). Activity questionnaires showed a significant increase in high intensity recreational activities (6.5+/-1.5 vs 3.5+/-0.5 h physical activity/wk; p<0.01) in the home and a significant decrease in low intensity activities (7+/-2.0 vs 12+/-3.5 h TV viewing/wk; p<0.01). CONCLUSIONS: Vigorous supervised aerobic training in obese boys has beneficial effects on body composition, fitness and leisure time activities that are not apparent by measurement of changes in body weight alone.

Journal Article↗

Three-dimensional multiplanar transvaginal ultrasound of the cervix in pregnancy.

OBJECTIVES: To develop a standard technique for using three-dimensional ultrasound (3D US) to study and evaluate the cervix in pregnant women at high risk for premature delivery, comparing the findings on 3D US with those on conventional two-dimensional ultrasound (2D US). STUDY DESIGN: Twenty-one pregnant women at high risk for premature delivery had a total of 37 transvaginal 2D and 3D US examinations of the cervix between 11 and 32 weeks' gestation. A 3D US vaginal probe (5.0-8.0 MHz, Voluson 530D, Medison, Pleasanton, CA, USA) was used. Measurements made from the 2D and 3D US were compared. RESULTS: Of the 37 cervical length measurements in 3D US sagittal plane, seven were shorter and three were longer than on 2D US (varying by 5-15 mm) indicating that the true mid-sagittal plane was not obtained in ten (27%) of the 37 2D US examinations. Of 21 examinations showing funneling, funneling was seen on both 2D and 3D US in 15, but was seen only on 3D US in six. There was a significant (P < 0.05) difference between funnel width as measured in the coronal 3D plane versus 2D US, as well as between funnel width in the coronal 3D US plane versus sagittal 3D US plane (P < 0.05). The cerclage was seen in its entirety in nine of 10 examinations; the 3D US axial plane was most valuable for imaging the cerclage. CONCLUSIONS: 3D US appears to offer a more complete assessment of the cervix than 2D US. Multiplanar correlation shows that the standard 2D US sagittal view may under- or over-estimate cervical length. Our preliminary data suggest that 3D US has the potential to improve our understanding of cervical morphology.

Adult↗