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J Bernstein

Publications and source records attributed to J Bernstein.

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

The translational repression mediated by the platelet-derived growth factor 2/c-sis mRNA leader is relieved during megakaryocytic differentiation.

Expression of the platelet-derived growth factor 2/c-sis gene is highly restricted and controlled at multiple levels. Its structured mRNA leader, which is unusually long (1022 nucleotides), serves as a potent translational inhibitor. One of the sites of PDGF2 synthesis is megakaryocytes, implying that PDGF2 translation efficiency is modulated during megakaryocytic differentiation. To study the role of the mRNA leader as a translational cis-modulator, the hybrid T7/vaccinia cytoplasmic expression system was used to disconnect between determinants controlling transcription, alternative splicing, and mRNA stability from those controlling translation. Chimeric transcripts in which the human PDGF2/c-sis mRNA leader positioned in frame upstream of a reporter gene were used to determine whether the mRNA leader can confer variable translational efficiencies during differentiation. It is demonstrated that there is a time window during megakaryocytic differentiation of K562 cells in which the strong translational inhibition by PDGF2/c-sis mRNA leader is relieved. The time course of the translational repression relief is similar to that of PDGF2/c-sis transcriptional induction during the differentiation process. A 179-nucleotides CG-rich fragment immediately upstream of the initiator AUG codon is necessary for coffering stringent modulation of the translational efficiency. In NIH3T3 overexpressing translation initiation factor eIF4E, the inhibitory effect of the mRNA leader of c-sis is not relieved, suggesting that the changes in the translational machinery during megakaryocytic differentiation are beyond eIF4E activity. The possible involvement of a 5'-end-independent translational mechanism is discussed.

Base Sequence↗
PubMed1995

Balance billing under Medicare: protecting beneficiaries and preserving physician participation.

Medicare's experience with balance billing provides valuable lessons for policy making for national or state health care reform. Medicare developed several policies to encourage physicians to become participating providers who accept Medicare-allowed charges as payment in full. Only nonparticipating physicians are permitted to bill for additional amounts beyond that paid by Medicare, and there are limits on the amount of balance billing per claim. As shown by the analysis of claims presented in this article, Medicare has successfully provided financial protection to beneficiaries. In 1986, more than 60 percent of expenditures for physician services were on assigned claims for which there could be no balance billing; by 1990, 80 percent of expenditures were on assigned claims. Balance billing decreased by about 30 percent during the same period. Although these policies have been successful in reducing total expenditures for balance billing, they may not provide financial protection to the most economically vulnerable beneficiaries. Using survey and claims data, we found that the poor have lower balance billing expenditures for services provided by primary care physicians, but that there is no relationship between poverty status and balance billing expenditures for services of nonprimary care physicians. In addition, most low-income beneficiaries are liable for balance bills. Under health care reform, adoption of Medicare's incentive-based approach with mandatory assignment for the poor would allow for some choice based on price and would provide financial protection for all consumers.

Aged↗
PubMed1995

Evaluation of a possible association of urban air toxics and asthma.

The prevalence of asthma, measured either as the frequency of hospital admissions or number of deaths attributed to asthma, has increased over the last 15 to 20 years. Rapid increases in disease prevalence are more likely to be attributable to environmental than genetic factors. Inferring from past associations between air pollution and asthma, it is feasible that changes in the ambient environment could contribute to this increase in morbidity and mortality. Scientific evaluation of the links between air pollution and the exacerbation of asthma is incomplete, however. Currently, criteria pollutants [SOx, NOx, O3, CO, Pb, particulate matter (PM10)] and other risk factors (exposure to environmental tobacco smoke, volatile organic compounds, etc.) are constantly being evaluated as to their possible contributions to this situation. Data from these studies suggest that increases in respiratory disease are associated with exposures to ambient concentrations of particulate and gaseous pollutants. Similarly, exposure to environmental tobacco smoke, also a mixture of particulate and gaseous air toxics, has been associated with an increase in asthma among children. In addition, current associations of adverse health effects with existing pollution measurements are often noted at concentrations below those that produce effects in controlled animal and human exposures to each pollutant alone. These findings imply that adverse responses are augmented when persons are exposed to irritant mixtures of particles and gases and that current measurements of air pollution are, in part, indirect in that the concentrations of criteria pollutants are acting as surrogates of our exposure to a complex mixture. Other irritant air pollutants, including certain urban air toxics, are associated with asthma in occupational settings and may interact with criteria pollutants in ambient air to exacerbate asthma. An evaluation of dose-response information for urban air toxics and biological feasibility as possible contributors to asthma is therefore needed. However, this evaluation is compounded by a lack of information on the concentrations of these compounds in the ambient air and their effects on asthma morbidity and mortality. Through an initial review of the current toxicological literature, we propose a tentative list of 30 compounds that could have the highest impact on asthma and respiratory health. These compounds were selected based on their ability to induce or exacerbate asthma in occupational and nonoccupational settings, their allergic potential and ability to react with biological macromolecules, and lastly, their ability to irritate the respiratory passages. We recommend better documentation of exposure to these compounds through routine air sampling and evaluation of total exposure and further evaluation of biological mechanisms through laboratory and epidemiological studies directed specifically at the role these substances play in the induction and exacerbation of asthma.

Air Pollutants↗
PubMed1994

Variations in hypertension control in indigent rural primary care clinics in North Carolina.

OBJECTIVE: To examine blood pressure control and prescribing practices in the treatment of hypertension, including the use of sample medications, in rural populations. DESIGN: Retrospective chart review of 296 hypertensive patients and surveys of primary care providers serving these patients. SETTING: Twenty-seven rural, primary care clinics in North Carolina. OUTCOME MEASURE: Blood pressure control, with the practice site as the unit of analysis. RESULTS: An average of 29% of patients per clinic had blood pressures that were inadequately controlled. Wide variations existed between clinics in blood pressure control and medication costs. Thirty-two percent of all blood pressure medications used were either angiotensin converting enzyme inhibitors or calcium channel blockers compared with 26% use of diuretics. Virtually all clinics used sample antihypertensive agents and reported that sample medications were an important source of free medications for their indigent patients. Reported sample use by practice was positively correlated with the mean daily hypertensive medication costs. Variations in blood pressure control were not explained by any measured variables, although the sample size was small. CONCLUSIONS: Large variations exist within rural North Carolina primary care clinics in blood pressure control and medication costs. We need to study further the relationships of new antihypertensive agents, medication costs, and sample use with blood pressure control, health care costs, and other patient outcomes.

Adult↗
PubMed1994

Renal failure in the neonate associated with in utero exposure to non-steroidal anti-inflammatory agents.

In utero exposure to non-steroidal anti-inflammatory agents (NSAIAs) can produce combinations of oligohydramnios, a bleeding diathesis, ileal perforation, premature closure of the ductus, and acute or chronic renal injury. NSAIAs induce renal dysgenesis in fetal monkeys and renal structural abnormalities in the developing human fetus. We report oligohydramnios and renal failure associated with in utero exposure to early, prolonged, high-dose indomethacin in four neonates, and to ibuprofen in one neonate. Four of the affected neonates were one of twins. In each set of twins, only one of the pair was affected. One set of twins was proven to be identical, whereas the other three sets seemed to be identical. It is possible that the histopathological findings of uncertain or incomplete tubular differentiation may be the result of a direct effect of NSAIAs on developing or "immature" tubules. Therefore, the advantages of NSAIAs as tocolytics need to be weighed against the complication of severe renal injury.

Acute Kidney Injury↗
PubMed1994

Why renal cysts grow.

The growth of renal cysts leads to morbidity, contributes to mortality, and is a lesson in applied physiology. The fact that chemical, electrical, osmotic, and hydrostatic driving forces determine cyst volumes is inferred from observations that cyst fluids vary in their concentrations of osmotically active substances. Most have concentrations of sodium-based salts that are lower and nonsodium-based salts that are higher than those present in normal plasma. Nonsodium solutes include osmolytes that normally are present in higher concentrations inside of cells, including potassium, amino acids, and so-called idiogenic osmoles. The basic process of cyst growth therefore involves 1) the osmotic equilibration of water across cysts walls that have variable permeability characteristics and 2) the replacement of sodium salts with other osmotically active solutes in cyst fluids. Cyst volume is governed by the amounts and kinds of osmolytes that enter and become entrapped in lumina. Proliferation and necrosis of mural cells are events that are fundamental to the growth of renal cysts.

Animals↗
PubMed1994

Renal tubular dysgenesis: evidence of abnormality in the renin-angiotensin system.

Renal tubular dysgenesis is an autosomal recessive condition characterized by short, abnormally developed cortical tubules that lack proximal differentiation. Despite the lack of normal proximal tubules, the major site of water resorption in the kidney, the principal clinical manifestations are caused by fetal and neonatal oliguria. The kidneys in three cases of neonatal renal tubular dysgenesis were found to contain large amounts of immunohistochemically reactive renin in preglomerular arterioles, glomerular hilums, and glomerular mesangial areas, far exceeding the intensity of staining and the numbers of sites stained in control kidneys. The increased accumulation of renin may reflect strong local vasoconstriction, which is responsible for reduced glomerular perfusion. This accumulation suggests faulty feedback control of renin secretion, the basis of which is still to be identified.

Case-Control Studies↗
PubMed1994

The impact of health care financing on family budgets.

Although businesses, federal and state governments, and insurance companies are major funding sources for health care, they are just intermediate sources. Ultimately, individuals and families pay all health care costs through out-of-pocket spending, insurance premiums, or federal, state, and local taxes. Using a microsimulation model with data from the 1987 National Medical Expenditure Survey, the Internal Revenue Service's Individual Tax Model, and the Consumer Expenditure Survey, the authors examine the distribution of health care spending, by decile, among families and individuals. They find that the distribution of health expenditures is very regressive, with low-income families paying twice the share of income paid by high-income families. The distribution of out-of-pocket expenditures, which comprise 24 percent of total spending, is the most regressive, with low-income families paying 8.5 times the share of income paid by high-income families. Spending on premiums is also regressive, and the regressivity would increase if everyone had private insurance. Expenditures through the public sector are progressive. Regressivity is greater among the elderly than the nonelderly. Out-of-pocket expenditures account for 41 percent of all health care spending by the elderly. A more equitably financed health care system would increase the share of funding raised through progressive taxes, and decrease reliance on expenditures made out of pocket and on premiums.

Adolescent↗
PubMed1993

Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Connecticut.

In order to investigate etiologic distinctions among the anatomic sub-sites of the large bowel by sex, the relationship between large-bowel-cancer incidence and age at diagnosis, time period at diagnosis, and birth cohort was analyzed by anatomic sub-site and by sex, using data from the Connecticut Tumor Registry. Included in the study were all incident large-bowel-cancer cases occurring between 1950 and 1984 among Connecticut residents aged 40 to 79. Cancers of the large bowel were classified into 5 anatomic sub-sites: ascending colon (including cecum), transverse colon (including flexures), descending colon, sigmoid colon, and rectum (including rectosigmoid junction, anal canal, and anus). The data were fitted to log-linear age-period-cohort models. For each of the sub-sites, the age-period-cohort patterns for males and females differed. Within each sex, sub-site groupings with common patterns were indicated. Among males, the age-period-cohort patterns for the colon sub-sites were fairly similar; but the pattern for the rectum differed markedly from that for the colon sub-sites. There were secondary differences among the colon sub-sites that pointed to a secondary distinction between the right and the left colons. Among females, the age-period-cohort patterns for the left colon sub-sites and the rectum were fairly similar. The pattern for the transverse colon differed moderately from that of the left colon, and differed substantially from that of the rectum and the ascending colon. The ascending colon differed markedly from each of the other sub-sites. It is possible that these differences in age-period-cohort patterns reflect etiologic distinctions among sub-site groupings and between the sexes.

Adult↗
PubMed1993

Hyperechoic kidneys in the newborn and young infant.

Increased echogenicity of the kidney in the newborn has many causes, some of which reflect serious renal disease. The major abnormal imaging pattern is the large, diffusely hyperechoic kidney with abnormal architecture. Its differential diagnosis includes recessive and dominant polycystic kidney disease (PKD), glomerulocystic kidney disease, and diffuse cystic dysplasia. The family history and ultrasonic screening of the parents and siblings are essential in the evaluation. The identification of associated nonrenal abnormalities is important to the recognition of syndromal cystic disease. Glomerulocystic kidney disease, which comprises sporadic and syndromal forms, appears similar to dominant PKD. While renal biopsy almost always differentiates recessive from dominant PKD, renal biopsy cannot differentiate among the forms of glomerulocystic kidney disease, except in the case of tuberous sclerosis, which has unique histopathological characteristics. Other causes of the enlarged hyperechoic kidneys with abnormal architecture include renal vein thrombosis and congenital nephrotic syndrome. A second pattern is the hyperechoic small kidney with abnormal architecture. Many of these kidneys are dysplastic and associated with urinary tract obstruction. The combination of hyperechoic parenchyma and pyelocaliceal dilatation suggests obstructive cystic dysplasia. Cortical and medullary necrosis in the newborn also causes hyperechogenicity in small kidneys. A third pattern contains those kidneys with medullary hyperechogenicity, the most common cause of which in the newborn is nephrocalcinosis associated with furosemide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗
PubMed1993

Glomerulocystic kidney disease--nosological considerations.

Glomerulocystic kidneys can be categorized into three major groups: (1) glomerulocystic kidney disease, comprising nonsyndromal heritable and sporadic forms of severely cystic kidneys in children and adults, (2) glomerulocystic kidneys in heritable malformation syndromes, and (3) glomerular cysts in dysplastic kidneys. The first category includes diffusely glomerulocystic kidneys in newborns and young children, many of whom have family histories positive for classical polycystic kidney disease. No differences between familial and sporadic cases have been identified, apart from the family histories. The sporadic cases are conceivably new mutations of the same disease. The first category also includes sporadic and familial disease in older children and adults. The inheritance in adult familial disease, as in childhood familial disease, has been dominant. An apparently distinct entity is hypoplastic glomerulocystic kidney disease, a dominant reported in only a few families. These kidneys, apart from being glomerulocystic, are small, and imaging studies show abnormal pyelocaliceal anatomy. The second category includes glomerulocystic kidneys as major components of heritable syndromes such as tuberous sclerosis, orofaciodigital syndrome, brachymesomelia-renal syndrome, trisomy 13, and the short rib-polydactyly syndromes. The category also includes glomerular cysts in several syndromes, namely Jeune syndrome and familial juvenile nephronophthisis, better known for chronic progressive tubulointerstitial disease. Glomerular cysts occur as a minor component, i.e., scattered cortical cysts, in several other syndromes, among them Zellweger's, in which the cysts are typically present and are usually inconsequential, only occasionally serious enough to affect renal function. In all of these syndromes, the cysts are inconsistently expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Renal cystic disease in the tuberous sclerosis complex.

Renal cysts are relatively common in tuberous sclerosis, occasionally causing severe cystic disease with renal failure. Although the imaging features and gross appearances resemble dominant polycystic kidney disease, the histopathological appearances are distinctive, perhaps unique, differing from appearances in other forms of renal cystic disease. The cysts are lined with hypertrophic and hyperplastic cells that probably cause the cysts by obstructing lumina. The renal abnormality may be inherent in tuberous sclerosis, although inconstantly expressed. Renal enlargement is sometimes the first recognized expression of tuberous sclerosis, and the occurrence of renal cysts in a child with seizures and developmental retardation leads to a strong suspicion of the diagnosis.

Adolescent↗
PubMed1993

Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group.

Histological indices of renal pathology in lupus nephritis have been proposed as prognostic signs and as a method to quantitate therapeutic response. We tested the reproducibility of the activity (AI) and chronicity indices (CI) in the renal biopsies from 83 patients with lupus nephritis, enrolled in a controlled therapeutic trial. The AI/CI were calculated separately by four renal pathologists using published criteria. Pair-wise Spearman's rank correlation coefficient was used to examine the relationship among the scores of the four raters, and their degree of reproducibility was evaluated using the coefficient of reliability. The mean CI scores ranged from 2.84 to 4.61, and the mean AI ranged from 9.64 to 12.89. The correlation among the different pathologist's scores ranged from 0.44 to 0.63 for the AI and 0.60 to 0.76 for the CI. One pathologist (M.M.S.) rated the biopsies twice, and the correlation between the two ratings was 0.58 for the AI and 0.74 for the CI. Thus, the AI and CI calculated by different pathologists and the temporally separate observations of a single observer were only moderately correlated. The reproducibility of a single rating was low, showing a reliability coefficient of 0.48 for the AI and 0.57 for the CI. The low reliability coefficient suggests that the variability among pathologists was the result of interpretative differences. We conclude that the AI/CI are too subjective to be used as therapeutic guides or as prognosticators.

Atrophy↗
PubMed1993

Laparoscopy explosion hazards with nitrous oxide.

BACKGROUND: During laparoscopic surgery utilizing carbon dioxide as the insufflating agent, nitrous oxide will diffuse into the peritoneal cavity if it is used as part of the anesthetic. Bowel perforation and the subsequent release of volatile bowel gas could create a explosion hazard. METHODS: Two related studies were undertaken. The first quantified the transfer of nitrous oxide, over time, in 19 female patients undergoing laparoscopy. The second established the lower limits of flammability of a range of concentrations of methane and hydrogen diluted with nitrogen (simulated bowel gas) in a range of concentrations of nitrous oxide diluted with carbon dioxide (simulated peritoneal gas). RESULTS: The mean concentrations of N2O at 10, 20, and 30 min from the time of insufflation were 19.9 +/- 4.8%, 30.3 +/- 6.8%, and 36.1 +/- 6.9%, respectively. The maximum reported concentrations of methane and hydrogen in bowel gas are 56% and 69%, respectively. The concentration of nitrous oxide necessary to support combustion of 56% methane is approximately 47%. By contrast, the concentration of nitrous oxide needed to support combustion of 69% hydrogen is approximately 29%. CONCLUSIONS: The authors have shown that it is possible for nitrous oxide to reach concentrations in the peritoneal cavity that can support combustion of bowel gas.

Adult↗