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Biomedical subjects

L Goldstein

Publications and source records attributed to L Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Serum cardiolipin antibodies in patients with alcoholic cirrhosis].

OBJECTIVE: Although portal obstruction is a complication in cirrhosis which is usually associated with hepatocellular carcinoma, its precise neoplastic or thrombotic nature is not easy to determine. Serum antiphospholipid antibodies could be involved in thrombosis-related portal obstruction. PATIENTS AND METHODS: The presence of serum anticardiolipid antibodies was investigated by an immunoenzymatic technique in 129 patients with alcoholic cirrhosis, 47 patients with hepatocellular carcinoma with (n = 18) or without (n = 29) portal obstruction, and 82 patients without hepatocellular carcinoma or portal obstruction. Five control groups were included: patients with non alcoholic cirrhosis (n = 21), non cirrhotic alcoholic liver disease (n = 21), chronic viral hepatitis (n = 14), extra-hepatic cholestasis (n = 9), and hypergammaglobulinemia associated with human immunodeficiency virus infection without liver disease (n = 28). RESULTS: The prevalence of serum anticardiolipid antibodies was 57% in patients with alcoholic cirrhosis, which was significantly different from the prevalence in the control groups which ranged from 0 to 32%. Anticardiolipid antibodies were of IgA isotypes in 90.5% of the cases, mainly related to the degree of liver failure but not to hepatocellular carcinoma or portal obstruction. CONCLUSION: In alcoholic cirrhosis, serum anticardiolipid antibodies do not seem to be related to the pathogenesis of portal obstruction in patients with hepatocellular carcinoma. They could rather reflect liver lesions and immunological dysfunctions.

Adult↗
PubMed1995

Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice.

The potential non-additive interactions of polynuclear aromatic hydrocarbon (PAH) mixtures as inducers of Cyp1a-1 and Cyp1a-2 gene expression were investigated in B6C3F1 mice using a reconstituted PAH mixture. The chemical composition (% by weight) of the reconstituted PAH mixture was: 2-ring PAHs--indan (0.22), naphthalene (23.8), 2-methylnaphthalene (23.2) and 1-methylnaphthalene (13.3); 3-ring PAHs--acenaphthylene (7.7), acenaphthene (0.6), dibenzofuran (0.7), fluorene (4.3), phenanthrene (10.5) and anthracene (3.4); > or = 4-ring PAHs--fluoranthene (2.4), pyrene (4.3), benz[a]anthracene (1.4), chrysene (1.5), benzo[b]fluoranthene (0.8), benzo[k]fluoranthene (0.9) and benzo[a]pyrene (0.9). The composition of the 2-, 3- and > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fraction and reconstituted mixture induced hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity and Cyp1a-1 mRNA levels, whereas the 2- and 3-ring PAHs were only weakly active. Direct comparison of the potencies of the reconstituted mixture and > or = 4-ring PAHs showed that the Cyp1a-1 induction activity of the reconstituted mixture was due to the > or = 4-ring PAHs. The reconstituted PAH mixture and > or = 4-ring PAHs also induced Cyp1a-2 hepatic mRNA levels and microsomal methoxyresorufin O-deethylase (MROD) activity; however, their dose-response curves indicated that the reconstituted PAH mixture was more potent as a Cyp1a-2 inducer than the > or = 4 ring PAHs. The differences in potency were due to 3-ring PAHs which were found to be strong inducers of hepatic Cyp1a-2 mRNA levels and microsomal MROD activity at the lowest dose administered (37 mg/kg). The 3-ring mixture caused a maximal 29-fold increase in hepatic MROD activity at a dose of 292 mg/kg, but only 28% of maximal induction of EROD activity. Northern analysis of liver mRNA from mice treated with 3-ring PAHs showed that there was minimal induction of Cyp1a-1 mRNA levels. The 3-ring PAHs did not competitively bind to the mouse hepatic cytosolic aryl hydrocarbon (Ah) receptor suggesting that 3-ring PAHs are a new class of Cyp1a-2 inducers which do not act through the Ah receptor.

Animals↗
PubMed1995

A homogeneous immunofluorescence assay based on dye-sensitized photobleaching.

A novel homogeneous immunoassay requiring only one incubation step, and applicable in principle to the determination of low- as well as high-molecular-weight substances, has been developed. The method is based on (a) photooxidation by singlet oxygen (1O2) of a fluorescent substrate (1,3-diphenylisobenzofuran, DPBF) embedded in unilamellar vesicles on the surface of which antibody to the analyte antigen is covalently attached (DPBF-immunoliposomes); (b) generation of singlet oxygen, upon illumination, by a chromophore (erythrosine) covalently attached to an antibody (Ab*) or antigen (Ag*); (c) formation of a "sandwich"- or "competition"-type complex whereupon the singlet oxygen-generating chromophore conjugate (Ab* or Ag*) and immunoliposome-embedded DPBF are brought into close proximity. Competition- and sandwich-type model assay systems for the detection of protein antigens and viruses were investigated. The detection range with protein antigens in competition- and sandwich-type assays was three (10(-10) - 10(-7) M) and two (10(-10) - 10(-8) M) orders of magnitude, respectively. With poliovirus using a sandwich-type assay, the detection range was 10(2) - 10(6) plaque-forming units per milliliter (pfu/ml).

Animals↗
PubMed1995

Transjugular intrahepatic portosystemic shunts: impact on liver transplantation.

This study was designed to evaluate the impact of transjugular intrahepatic portosystemic shunts (TIPS) on liver transplantation. Historically, the complications of portal hypertension have been temporized with sclerotherapy or surgical portosystemic shunts. In patients whose liver disease progressed, liver transplantation has been used as definitive treatment. More recently, TIPS is being used increasingly for the management of the complications of portal hypertension. The impact of this new modality on liver transplantation is evaluated. The records of 135 adult patients undergoing liver transplantation at University of California at Los Angeles between October 1992 and June 1993 were reviewed. Twenty-three patients had received at least one shunt before transplantation. The TIPS procedure complicated the operative course of 5 patients (22%). In 2 patients the TIPS had been placed cephalad, making placement of the suprahepatic vena caval clamp difficult. In 2 other patients, the shunt had been placed caudad, extending in the extrahepatic portal vein. In all 4 of these patients, the intima had been damaged at the area of the subsequent anastomosis. In the fifth patient, the bile duct had been perforated during the placement of the shunt, causing diffuse bile peritonitis, which was sterile, and the transplantation was performed. The average intraoperative blood loss for these 5 patients was 13 U. There was no significant decrease in intraoperative blood loss for all patients with a TIPS when compared with 112 adults who underwent liver transplantation during the same period (11 U v 10.5 U). The TIPS stent did not improve objective intraoperative parameters as compared with liver transplant recipients without TIPS. The indications for TIPS must be carefully weighed against the potential risks of increasing the technical difficulty of the transplantation and jeopardizing the candidacy of some liver transplantation candidates. Liver transplantation is not facilitated by TIPS insertion and therefore should not be used to justify TIPS placement.

Adult↗
PubMed1995

The physiology of coloured hearing. A PET activation study of colour-word synaesthesia.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

Adult↗
PubMed1995

The role of anion channels in osmotically activated taurine release from embryonic skate (Raja eglanteria) heart

Taurine, a major osmolyte of vertebrate hearts, is released from the skate heart at increased rates during hypotonic stress. We tested the hypothesis that this taurine release is mediated by chloride channels activated by swelling. Two inhibitors of the channels, NPPB and DIDS, inhibited the volume-activated release of taurine from embryonic skate hearts. These results support the hypothesis that swelling-activated chloride channels mediate the release of cardiac taurine.

Journal Article↗
PubMed1994

Oligomeric forms of skate erythrocyte band 3. Effect of volume expansion.

Volume expansion of little skate (Raja erinacea) erythrocytes leads to the formation of oligomeric forms of the band 3 protein. The oligomers are formed following incubation in hypotonic media or inclusion of a permeant solute such as ethylene glycol. Oligomers were detected by specifically labeling the skate erythrocyte band 3 homolog with the radiolabeled stilbene [3H]4,4'-diisothiocyano-1,2 diphenylethane-2,2'-disulfonic acid and cross-linking membrane proteins with the homobifunctional agent bis(sulfosuccinimidyl) suberate. Under isoosmotic conditions, the distribution of band 3 in the monomer, dimer, and tetramer forms was 38, 54, and 8%. Medium of 0.5 osmolarity caused the distribution to change to 22% monomer, 31% dimer, and 47% tetramer. Upon return to isoosmotic conditions, cell volume, as well as the distribution of band 3 in the monomer, dimer, and tetrameric forms, returned to control values. Return of hypotonically swollen cells to isoosmotic conditions also returned taurine efflux back to control values. Hyperosmolarity caused a 20% shrinkage of cell volume but did not have any effect on either taurine efflux or the distribution of band 3 in the oligomeric forms. Pyridoxal 5'-phosphate and dinitrostilbene disulfonate, two agents that interact with and cause the formation of the tetrameric form of human band 3, also caused a shift toward to tetrameric peak in skate band 3. To determine whether the cross-linked oligomers had proteins that closely associate with band 3 in the intact cell, Western blots were performed to detect ankyrin and band 4.1. Neither protein appeared with the dimeric or tetrameric forms of band 3, suggesting that the mobility shift was in fact due to association of band 3 monomers. This is the first demonstration that oligomerization of band 3 occurs during a physiologic effect that may be mediated by the band 3 protein.

Animals↗
PubMed1994

Membrane proteases as potential diagnostic and therapeutic targets for breast malignancy.

Metastasizing cancer cells can invade the extracellular matrix using plasma membrane protrusions, termed invadopodia, that contact and dissolve the matrix. Various membrane associated proteases localized on the invadopodial membranes are responsible for the extracellular matrix degradation. Work from our laboratory shows that secreted proteases including Gelatinase A, and high molecular weight integral membrane proteases are associated with cell surface invadopodia. Three cell types, including chicken embryonic cells transformed by Rous sarcoma virus, human malignant melanoma cell line LOX, and human breast carcinoma cell line MDA-MB-231, retain the invasive phenotype in vitro, express invadopodia, degrade and enter into a fibronectin-rich collagenous matrix. We suggest that invadopodium-associated proteases are ideal targets for the diagnosis and treatment of cancer as their presence in association with primary tumors may signal increased metastatic potential. An approach toward the development of new prognostic markers for breast malignancy involved production of monoclonal antibodies directed against membrane proteases in a mixture of glycoproteins. Double immunofluorescent technique using a known invadopodium marker is designed to select specific monoclonal antibodies colocalizing at the invasion front, on invadopodia of cancer cells. Membrane protease accessibility at the cell surface can therefore be exploited for therapeutic advances by the development of specific antibodies and inhibitors that block their activities, and by the use of monoclonal antibodies to target cytotoxic molecules to micrometastases. Also, this same accessibility may potentially be used to detect surface proteases on micrometastases or to detect components shed by micrometastases in serum.

Antigens, Neoplasm↗
PubMed1994

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice.

The toxic potential of manufactured gas plant residue (MGP) given in the diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycyclic aromatic hydrocarbon (PAH) metabolites in urine and DNA adduct formation in forestomach and lung tissue. Basal gel diets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) were fed to animals for 94 and 185 d. Mice readily consumed adulterated diets without any evidence of acute toxicity. The total amount of MGP and BaP consumed by mice ranged from 118 to 2604 mg and from 12 to 29 mg, respectively. Male mice fed a control or BaP diet and female mice fed a 0.05% MGP diet had the highest body weight gains. Male and female mice fed a 0.50% MGP diet had the lowest body weight gains. The bioavailability of chemical components of MGP was evaluated by monitoring the urinary excretion of PAH metabolites by male mice fed a 0.25% MGP diet. 1-Hydroxypyrene was determined by high-performance liquid chromatography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chemical-related gross lesions were detected. In addition, no treatment-related microscopic lesions were evident in tissues obtained from animals fed a 0.50% MGP- or BaP-adulterated diet. The 32P-postlabeling assay was used to evaluate MGP- and BaP-induced DNA adduct formation in lung and forestomach tissue. The level of DNA adducts formed from the chemical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than forestomach levels when mice ingested a 0.25% or 0.50% MGP diet. These studies demonstrate that the continuous ingestion of MGP or BaP for 185 d does not result in acute toxicity or chemical-related lesions at doses up to 0.50% MGP or 0.005% BaP.

Administration, Oral↗
PubMed1994

Approximations to profile score distributions.

Profiles, which are summaries of multiple alignments of a sequence family, are used to find new instances of the family in databases. In this paper, we study the maximum score M obtained when the profile is aligned without indels at all possible positions of a random sequence. The main theorem gives an approximation to the distribution function of M with an explicit bound on the error. This theorem implies that M has a limiting extreme value distribution.

Computer Simulation↗
PubMed1994

Laparoscopic local excision of a proximal rectal carcinoid.

Early carcinoids of the distal rectum have been treated effectively by transanal local excision. Unfortunately, small carcinoids of the proximal rectum may be unreachable by transanal approaches, and as a result patients have been subjected to more extensive, transabdominal colorectal resections. The recent introduction of minimally invasive techniques for treatment of colorectal diseases has opened new approaches for the treatment of proximal rectal carcinoids. We describe a patient with a 0.5 cm rectal carcinoid located just above the peritoneal reflection in whom transanal local excision was not feasible. We report the first laparoscopic, full-thickness excision of a proximal rectal carcinoid. Intraoperative colonoscopy was used to localize the lesion. This combined laparoscopic and colonoscopic approach spared the patient from the potential morbidity of a low anterior resection and anastomosis.

Aged↗
PubMed1994

Band 3 modulation and hypotonic-stimulated taurine efflux in skate erythrocytes.

Previous studies have shown that exposure of skate erythrocytes to hypotonic medium or isosmotic medium with permeant solutes such as ethylene glycol or ammonium chloride increases cell volume. Initial swelling is followed by a regulatory volume decrease accomplished by efflux of cell solutes, including the beta-amino acid taurine. Taurine efflux, as well as the cell volume recovery, is inhibited by stilbene disulfonates and other anion exchange inhibitors, suggesting involvement of the erythrocyte anion exchanger band 3. In the present study we show that binding of the stilbene dihydro 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS) to intact cells doubles after exposure to one-half hypotonic medium. Binding also increases after exposure of erythrocytes to medium of one-third hypotonic medium and ethylene glycol medium, but DIDS binding is not significantly elevated in ammonium chloride medium. To investigate possible mechanisms for modulation of band 3, cells were labeled with 32PO4 and levels of protein phosphorylation determined. Phosphorylation of three proteins of molecular masses of 99, 65, and 32 kDa increases with hypotonic stress. Because the anion exchanger migrates with molecular mass near 100 kDa, the anion exchanger was immunoprecipitated. Hypotonic stress induces a rapid and persistent increase in the 32PO4 phosphorylation of the exchanger. This modification may be responsible for the increased DIDS binding and could be related to stimulated taurine efflux.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Taurine, betaine, and inositol share a volume-sensitive transporter in skate erythrocyte cell membrane.

Our previous study [J. K. Haynes and L. Goldstein. Am. J. Physiol. 265 (Regulatory Integrative Comp. Physiol. 34): R173-R179, 1993] showed that skate erythrocytes have a volume-sensitive amino acid transporter that passes amino acids across the cell membrane in a size-related nonstereospecific manner. The aim of the present study was to determine whether representatives of other groups of organic osmolytes (polyols, trimethylamines) could be transported by this same system. Volume-sensitive transport was assayed by measuring Na(+)-independent uptake of osmolytes into erythrocytes. Hypotonic stress stimulated uptake of the polyol myo-inositol and the trimethylamine betaine severalfold. There was little or no competition between osmolytes for transport. However, inhibitor studies indicated that both betaine and inositol are transported by the same pathway as amino acids. Inhibitors of the anion exchanger band 3 and a variety of chloride channel inhibitors blocked the hypotonically stimulated uptake of betaine, inositol, and taurine in a quantitatively similar manner. These results show that different chemical classes of organic osmolytes share a common volume-sensitive transporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Occupational impairment and disability among applicants for Social Security disability benefits in Pennsylvania.

OBJECTIVE: The study goal was to assess the extent of workplace-related disease and injury among Social Security Disability Insurance applicants. METHODS: A convenience sample of 240 consecutive applicants to the Pennsylvania Bureau of Disability Determination was studied to assess the prevalence of work-related disorders. An applicant had a work-related condition if there was a clear statement of a workplace illness or injury associated with the impairment, or if the applicant had worked at an occupation with a high likelihood of exposures known or suspected to contribute to the condition of interest. RESULTS: Of the 240 applicants, 166 (69%) were awarded disability insurance benefits; a total of 27 (11%) had work-related conditions, including 14 of the 166 (8%) who were found to be disabled. Forty percent of the 27 had a disorder that was musculoskeletal in origin. Of 59 applicants with cancer, 10.2% had some work-related etiological component. Of an estimated 71,680 adult disability insurance applicants in Pennsylvania in 1990, 5134 new insurance beneficiaries had a projected occupationally related disability. CONCLUSIONS: A substantial number of applicants for disability insurance benefits suffer from an impairment caused or exacerbated by prior workplace exposures. These individuals may serve as sentinel events for initiating follow-up surveillance and prevention activities.

Accidents, Occupational↗