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Biomedical subjects

L Goldstein

Publications and source records attributed to L Goldstein.

At least 19 recordsLinked to original sources

A potentially critical Hpa II site of the X chromosome-linked PGK1 gene is unmethylated prior to the onset of meiosis of human oogenic cells.

Hpa II site H8 is in the CpG-rich 5' untranslated region of the human X chromosome-linked gene for phosphoglycerate kinase 1 (PGK1). It is the only Hpa II site in the CpG "island" whose methylation pattern is perfectly correlated with transcriptional silence of this gene. We measured DNA methylation at site H8 in fetal oogonia and oocytes and found, using a quantitative assay based on the polymerase chain reaction, that purified germ cells isolated by micromanipulation were unmethylated in 47-day to 110-day fetuses, whereas ovaries depleted of germ cells and non-ovary tissues were methylated. We conclude that site H8 is unmethylated in germ cells prior to the onset of meiosis and reactivation of the X chromosome.

Base Sequence

Poisson, compound Poisson and process approximations for testing statistical significance in sequence comparisons.

DNA and protein sequence comparisons are performed by a number of computational algorithms. Most of these algorithms search for the alignment of two sequences that optimizes some alignment score. It is an important problem to assess the statistical significance of a given score. In this paper we use newly developed methods for Poisson approximation to derive estimates of the statistical significance of k-word matches on a diagonal of a sequence comparison. We require at least q of the k letters of the words to match where 0 less than q less than or equal to k. The distribution of the number of matches on a diagonal is approximated as well as the distribution of the order statistics of the sizes of clumps of matches on the diagonal. These methods provide an easily computed approximation of the distribution of the longest exact matching word between sequences. The methods are validated using comparisons of vertebrate and E. coli protein sequences. In addition, we compare two HLA class II transplantation antigens by this method and contrast the results with a dynamic programming approach. Several open problems are outlined in the last section.

Algorithms

Auditory magnetic source localization in twins.

We recorded magnetoencephalographic (MEG) auditory evoked fields (EF) from the L and R hemispheres of 12 paris of twins, 6 monozygotic (MZ), and 6 dizygotic (DZ) and localized the source of the 100 msec latency EF component termed the M100. M100 sources exhibited greater similarity in location in MZ twin pairs, especially in the L hemisphere. These findings support the hypothesis that the functional location of processing of nonmeaningful unattended auditory stimuli may depend more heavily on left hemisphere structures. Furthermore, genetic effects are evident in these left hemisphere structures and their activity, as is a substantial amount of environmental variance.

Acoustic Stimulation

The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation.

Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term.

Adult

Articulatory phonology: an overview.

An overview of the basic ideas of articulatory phonology is presented, along with selected examples of phonological patterning for which the approach seems to provide a particularly insightful account. In articulatory phonology, the basic units of phonological contrast are gestures, which are also abstract characterizations of articulatory events, each with an intrinsic time or duration. Utterances are modeled as organized patterns (constellations) of gestures, in which gestural units may overlap in time. The phonological structures defined in this way provide a set of articulatorily based natural classes. Moreover, the patterns of overlapping organization can be used to specify important aspects of the phonological structure of particular languages, and to account, in a coherent and general way, for a variety of different types of phonological variation. Such variation includes allophonic variation and fluent speech alternations, as well as 'coarticulation' and speech errors. Finally, it is suggested that the gestural approach clarifies our understanding of phonological development, by positing that prelinguistic units of action are harnessed into (gestural) phonological structures through differentiation and coordination.

Female

[A case of direct right pulmonary artery-left atrium fistula].

An unusual case of cyanotic heart disease in a 20-year-old male has been presented. Cyanosis was due to right to left shunt through direct right pulmonary artery--left atrium fistula. After successful operative ligation of the fistula, the patient got rid of cyanosis and is doing well.

Abnormalities, Multiple

[Anatomical correction of transposition of the great arteries in 7 newborn infants].

In the presented article, the course and results of anatomical correction of transposition of great arteries (TGA) in 7 neonates (2 females and 5 males) with mean body mass of 3250 g and 2 to 5 days old (mean 3 days) are reviewed. Surgery was performed in moderate hypothermia. St. Thomas cold cardioplegia was used. Mean aortic clamping time was 70 min (55-115), and the time of extracorporeal circulation was 165 min (117-210). Low cardiac output in all patients in the postoperative period required prolonged mechanical ventilation and positive inotropic drugs. Out of 7 patients operated, two died (29%). The cause of death in both cases was myocardial ischemia of right ventricle. The other 5 patients were discharged after healing of operational wound. In the control echocardiographic examination performed 3 to 12 months postoperatively, apart from one case of moderate pulmonary artery stenosis, no other haemodynamically significant complications were noted.

Coronary Vessel Anomalies

Inhibition by monochloramine of the transport of glutamine and glucose in HeLa cells and lymphocytes.

1. Chloramine was previously shown to inhibit glutamine uptake by human lymphoblast tumour cells. In the present study, the effect of monochloramine on the glutamine and glucose transport systems in HeLa cells and rat mesenteric lymphocytes was investigated. 2. Initial exposure to monochloramine slightly inhibited both the glutamine and glucose transport systems in HeLa cells. However, pre-exposing the cells to monochloramine increased its inhibitory action. 3. Similar results were obtained using rat mesenteric lymphocytes, which suggests that monochloramine's effects are not cell specific. 4. Only the Na(+)-independent (system L) component of glutamine transport activity in HeLa cells was inhibited by monochloramine. 5. Dithiothreitol protected both the glucose and glutamine transport carriers in HeLa cells against monochloramine inhibition. 6. Monochloramine did not inhibit HeLa cell metabolism, nor enhance cell lysis, which, in conjunction with other experimental data, suggests that monochloramine inhibits cellular transport activity by binding to thiol groups present on the membrane.

3-O-Methylglucose

Magnetic auditory M100 source location in normal females.

We recorded magnetoencephalographic auditory evoked fields from the left and right hemispheres of six normal adult female subjects, in response to unattended tone pips. Magnetic field data was used to estimate location, orientation, depth, and strength of the 100-ms latency evoked field component (M100). M100 source locations did not significantly differ in left and right hemispheres. Previous studies in six normal males demonstrated M100 sources to be significantly further anterior in the right hemisphere. Compared to the previously reported male subjects, M100 sources in the right hemisphere of these females were significantly further posteriorly, by a mean value of 2.1 cm. These findings, while preliminary, support sex-related functional and/or structural differences in the superior temporal lobe, and would be compatible with the female right temporal planum extending further posteriorly. They suggest MEG recordings may be a useful addition to studies of sex-related difference in brain function and/or structure.

Adult

A microcomputerized task assessment of cognitive change in normal elderly and young adults.

There is need for efficient, acceptable quantitative measures of cognitive differences with senescence which, in addition, have potential to discriminate mild dementia from the performance of normal elderly. A microcomputerized method designed to assess attentional capacity was administered to two elderly age groups, 68-79 and 80-87 years of age. A comparison group of young adults, 25-35 and 35-45 years of age, was similarly studied. The two tasks in the procedure (the tracking task, consisting of following a randomly moving target on a video screen, and the probe task, consisting of visual monitoring of a randomly elongating dot in the video screen) are performed separately and then simultaneously (dual task). The tracking task discriminated between the younger groups. Both the tracking and the probe task discriminated between the two older age groups. On discriminant analysis, the best variables for distinguishing older age groups were the logarithms of the single task scores. The performance scores of both elderly age groups were lower on the dual tasks compared with single tasks, but with significant performance decreases only in the probe scores. Comparing all four age groups, the older groups performed less well on the tasks and particularly poorly on the dual tasks. There were no significant gender effects. These initial data will be useful in application of the method for purposes of discriminating mild dementia from normal senescence, and possibly the effects of drugs used to enhance cognitive function.

Adult

Volume-activated taurine efflux from skate erythrocytes: possible band 3 involvement.

In a previous study (L. Goldstein, S.R. Brill, and E.V. Freund, J. Exp. Zool. 254: 114-118, 1990) it was suggested that volume-activated (VA) taurine efflux from skate (Raja erinacea) erythrocytes might involve the anion exchanger band 3. The aim of the present study was to obtain further evidence for (or against) this possibility. We found that in addition to stilbene disulfonates, two other band 3 inhibitors, N-(azido-2-nitrophenyl)-2-amino sulfonic acid (NAP)-taurine and niflumic acid, also inhibit VA taurine efflux. In addition, there is a close relationship between the dose-response curves for 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibition of VA taurine efflux and sulfate efflux. Furthermore, taurine influx, as well as efflux, is activated by volume expansion, as would be expected with transport facilitated by band 3. However, sulfate (a known band 3 substrate) efflux is not activated by volume expansion, and sulfate influx is only activated minimally, but sulfate does inhibit VA taurine uptake. Thus there is considerable evidence in favor of the involvement of band 3 in VA taurine efflux, but the issue of the sulfate fluxes remains to be resolved.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Taurine secretion in cultured winter flounder renal epithelium.

The mechanism for the secretion of taurine by the marine fish kidney was examined in flounder renal primary cultures and teased tubules. The question addressed was whether the secretion of taurine, but not beta-alanine, a related beta-amino acid, is due to differences in their basolateral uptake, intracellular concentration, or luminal efflux mechanism. Aminooxyacetate (AOA) (10 mM), an inhibitor of beta-alanine oxidation, allowed the basolateral beta-alanine accumulation (measured in teased tubules) and the beta-alanine intracellular concentration (measured in primary cultures) to be similar to that for taurine. However the addition of AOA did not promote the net secretion of beta-alanine (measured as unidirectional fluxes in the cultured epithelium mounted in an Ussing chamber). The organic anions bromcresol green (BCG) (0.1 mM) and probenecid (1 mM) inhibited the net secretion of taurine by affecting the luminal efflux step. This suggests that a BCG- and probenecid-sensitive carrier in the luminal membrane facilitates the cell-to-lumen efflux of taurine and thus achieves net secretion.

Aminooxyacetic Acid

Improved methods in long term venous access using the P.A.S. Port.

An over-all lower cost implantable chronic venous access is readily accomplished using the Cath-finder and implantable P.A.S. Port. This system has few complications and is less expensive, time saving and easy to maintain. The Cath-finder system allows the surgeon to access accurately the central venous circulation without the use of a fluoroscope. The implantable P.A.S. Port has wide acceptance with many types of patients, including those with tumors, cystic fibrosis and AIDS.

Catheterization, Central Venous

OSHA bloodborne pathogens standard. Implications for the occupational health nurse.

The Occupational Safety and Health Administration (OSHA) has promulgated a standard, expected to become mandatory in mid 1991, designed to protect employees from all exposure to blood and other potentially infectious materials. Employers should begin now to institute an infection control plan. Methods of compliance of the standard include: universal precautions, engineering and work practice controls, personal protective equipment, and housekeeping. The occupational health nurse should coordinate development, maintenance, and revision of a program to comply with the OSHA regulations. The occupational health nurse should also educate management about the hazards of bloodborne pathogens and assist them in complying with the final standard so that a safe and healthy work environment can be achieved.

Blood

Application of a thermally-reversible polymer-antibody conjugate in a novel membrane-based immunoassay.

We have developed a novel method to immobilize antibodies onto a cellulose acetate membrane using a conjugate of an N-isopropylacrylamide polymer covalently bound to the antibody. When compared with the unconjugated antibody, over 30-fold increase in retention of the antibody on the membrane was observed when it was conjugated to poly (N-isopropylacrylamide). Studies of the polymer-membrane interaction suggest a combination of hydrophobic and ionic forces, especially the former, is responsible for the high retention. We applied this novel immobilization technology in the development of a membrane-based immunoassay.

Antibodies

Mechanisms of mercurial and arsenical inhibition of tyrosine absorption in intestine of the winter flounder Pseudopleuronectus americanus.

Effects of HgCl2 (100 microM) para-chloromercuribenzene sulfonate (PCMBS) (1 mM), and oxophenylarsine (OPA) (250 microM) were determined on (a) the rate of Na pump activity in intact winter flounder intestine; (b) activity of Na-K-ATPase in tissue homogenates; and (c) Na-dependent and Na-independent uptake of tyrosine in brush border membrane vesicles. Initial rate of uptake (influx) of 86Rb from the serosal solution of tissues mounted in Ussing chambers, a measure of Na-K-ATPase activity in the intact cell, was inhibited by all three agents with differing time courses. Rapidly permeating HgCl2 inhibited influx to the same degree as ouabain at 30 min, whereas the effects of PCMBS and OPA required 90 min. Cell potassium was also measured as an indirect indicator of ATPase activity and cell membrane permeability. All three agents decreased cell K, although effects on cell K lagged behind those for inhibition of the ATPase. At the concentrations used in the Ussing chamber (or at one-tenth concentration), all agents completely inhibited Na-K-ATPase activity in enzyme assays performed with tissue homogenates. In contrast, only HgCl2 decreased Na-dependent uptake of tyrosine by brush border membrane vesicles. These results suggest that mercurial and arsenical effects on tyrosine absorption are due to inhibition of the Na-K-ATPase thus decreasing the driving force for the cellular uptake by the Na-tyrosine cotransport system. Direct effects on Na-tyrosine cotransport may play a role in the inhibition observed with HgCl2, but not for PCMBS or OPA.

4-Chloromercuribenzenesulfonate

Cell volume regulation by skate erythrocytes: role of potassium.

The role of K transport during cell volume regulation in response to extracellular osmolality, protein kinase C activation, and cellular Ca was examined in skate (Raja erinacea) red blood cells (RBC). Reduction of medium osmolality from 960 to 660 mosmol/kgH2O had no effect on K uptake or efflux despite a 25% increase in cell volume. Further reduction to 460 mosmol/kgH2O caused K uptake to double and K efflux to triple resulting in net K loss. Net K efflux in 460 mosmol/kgH2O medium was correlated with the presence of a regulatory volume decrease, which was sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and insensitive to chloride replacement. K-K exchange was absent in both isotonic and hypotonic media. Treatment with the Ca ionophore A23187 in the presence of Ca had no effect on either cell volume or K efflux in isotonic medium, indicating the absence of Ca-activated K transport. In contrast, phorbol ester treatment caused cell volume, Na content, and proton and K efflux to increase. Consistent with activation of Na-H exchange, phorbol ester effects were inhibited by dimethylamiloride. This study constitutes the first demonstration of volume-sensitive K transport in RBC from the most primitive vertebrate studied to date.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid