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Biomedical subjects

E M Goldberg

Publications and source records attributed to E M Goldberg.

At least 19 recordsLinked to original sources
PubMed1996

Ceramide induces structural defects into phosphatidylcholine bilayers and activates phospholipase A2.

We studied the effects of bovine brain ceramide on the structure of dipalmitoylphosphatidylcholine (DPPC) bilayers and cobra venom phospholipase A2, (PL-A2) activity using 2H NMR and specific enzymatic assays. Addition of ceramide to DPPC at 45 degrees C induces lateral phase separation of the bilayers into regions of gel and liquid crystalline phases. The order parameters of the DPPC acyl chains in the liquid crystalline phase are only slightly affected by the presence of ceramide, indicating that the latter is largely partitioned in the gel phase of DPPC, whereas at 60 degrees C the presence of ceramide induced a large increase of the order parameters of DPPC side chains. The observed structural effects of ceramide correlated with ceramide-induced activation of cobra venom phospholipase A2 (PL-A2). Ceramide activated PL-A2 in a concentration-dependent manner, with a significant effect observed at 5 mol% ceramide, which caused an approximately 3-fold increase in PL-A2 activity. The results showing activation of PL-A2 by ceramide illustrate an additional feature of the biological effects of this second messenger and suggest the possibility of cross-talk between the sphingomyelinase and PL-A2 signal transduction pathways.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Effects of diacylglycerols on conformation of phosphatidylcholine headgroups in phosphatidylcholine/phosphatidylserine bilayers.

The effects of five diacylglycerols (DAGs), diolein, 1-stearoyl,2-arachidonoyl-sn-glycerol, dioctanoylglycerol, 1-oleoyl,2-sn-acetylglycerol, and dipalmitin (DP), on the structure of lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine (4:1 mol/mol) were examined by 2H nuclear magnetic resonance (NMR). Dipalmitoylphosphatidylcholine deuterated at the alpha- and beta-positions of the choline moiety was used to probe the surface region of the membranes. Addition of each DAG except DP caused a continuous decrease in the beta-deuteron quadrupole splittings and a concomitant increase in the alpha-deuteron splittings indicating that DAGs induce a conformational change in the phosphatidylcholine headgroup. Additional evidence of conformational change was found at high DAG concentrations (> or = 20 mol%) where the alpha-deuteron peaks became doublets indicating that the two alpha-deuterons were not equivalent. The changes induced by DP were consistent with the lateral phase separation of the bilayers into gel-like and fluid-like domains with the phosphatidylcholine headgroups in the latter phase being virtually unaffected by DP. The DAG-induced changes in alpha-deuteron splittings were found to correlate with DAG-enhanced protein kinase C (PK-C) activity, suggesting that the DAG-induced conformational changes of the phosphatidylcholine headgroups are either directly or indirectly related to a mechanism of PK-C activation. 2H NMR relaxation measurements showed significant increase of the spin-lattice relaxation times for the region of the phosphatidylcholine headgroups, induced by all DAGs except DP. However, this effect of DAGs did not correlate with the DAG-induced activation of PK-C.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Effects of diacylglycerols and Ca2+ on structure of phosphatidylcholine/phosphatidylserine bilayers.

The combined effects of the diacylglycerols (DAGs) with the various acyl chains and Ca2+ on the structure of phosphatidylcholine/phosphatidylserine (4:1 mole/mole) bilayers were studied using 2H- and 31P NMR. The following DAG- and Ca(2+)-induced bilayer perturbations were identified. 1) Increased tendency to form nonbilayer lipid phases was induced by diolein or stearoylarachidonoylglycerol, and was synergistically enhanced by the addition of Ca2+. 2) "Transverse" bilayer perturbation was induced by dioctanoylglycerol. The addition of this DAG caused increased ordering of the phospholipid acyl side chains in the region adjacent to the headgroup, with the concomitant decrease of the order toward the bilayer interior. 3) Separation of the phosphatidylcholine and phosphatidylserine bilayer components was induced by combinations of relatively high (1:5 mole/mole to phosphatidylserine) Ca2+ and 25 mol% (to the phospholipids) of diolein, stearoylarachidonoylglycerol, or oleoylacetylglycerol. 4) Lateral phase separation of the bilayers on the regions of different fluidities was induced by dipalmitin. These physicochemical effects were correlated with the effects of these DAGs and Ca2+ on the activity of protein kinase C. The increased tendency to form nonbilayer lipid phases and the transverse bilayer perturbations correlated with the increased protein kinase C activity, whereas the actual presence of the nonbilayer lipid phases, as well as the separation of the phosphatidylcholine and phosphatidylserine components, was associated with the decrease in the protein kinase C activity. The lateral phase separation of the bilayer on gel-like and liquid crystalline regions did not have an effect on the activity of the enzyme. These results demonstrate the importance of the physicochemical properties of the membranes in the process of activation of protein kinase C.

Biophysical Phenomena↗
PubMed1991

The thoracic vent. Clinical experience with a new device for treating simple pneumothorax.

We report recent experience with a new device, the thoracic vent, in the management of simple pneumothorax. There were 16 patients aged 19 to 73 years who suffered pneumothorax due to spontaneous (4), traumatic (3), or iatrogenic (9) causes. Ease of insertion, patient tolerance, and the presence of a unique signal diaphragm all contributed to patient and physician acceptance of the device. Average time to pneumothorax resolution was 2.5 days, and time to thoracic vent removal averaged 3.2 days. There were no immediate recurrences or significant complications. We conclude that the thoracic vent is an effective device for initial and definitive therapy of simple pneumothorax.

Adult↗
PubMed1989

Comparison of serum CA 19-9 and CEA levels in a population at high risk for colorectal cancer.

The sera of 563 patients who underwent colonoscopy were assayed for glycolipid antigen CA 19-9 and CEA. These patients represented a broad spectrum of clinical diseases ranging from advanced metastatic cancer of the colon, pancreas, or stomach to those with negative colonoscopic examination. Sensitivity and specificity for CA 19-9 and CEA were calculated using the following clinical definitions. Malignant or pre-malignant disease was defined as colon, pancreatic or stomach carcinoma, stomach dysplasia, atypical adenomatous polyp, atypical villous adenoma, carcinoma in situ and carcinoma in an adenomatous polyp. When the normal group included patients with adenomatous polyp, hyperplastic adenoma, inflammatory disease and patients with no disease apparent, the sensitivity and specificity for CA 19-9 was 23% and 96%, and for CEA, 23% and 95%, respectively. When adenomatous polyp patients were placed in the malignant or pre-malignant disease group, the sensitivity and specificity for CA 19-9 was 8% and 96%, and for CEA, 11% and 95%, respectively. When comparing CA 19-9 and CEA in colorectal carcinoma, the percent positivity of the CEA assay was equal to, or better than, CA 19-9 in all Dukes' stages. In pancreatic carcinomas CA 19-9 showed better diagnostic performance than CEA.

Adenocarcinoma↗
PubMed1984

Detection of a circulating gastrointestinal cancer antigen in sera of patients with gastrointestinal malignancies by a double determinant immunoassay with monoclonal antibodies against human blood group determinants.

Monoclonal antibodies (MoAbs) produced against determinants A and B of the human ABO blood group system and against the Lea and Leb determinants of the Lewis (Le) blood group system detected these determinants on molecules released by cultured cells of human colorectal, gastric and/or pancreatic carcinoma (Ca) but not by a variety of other cells maintained in culture. Circulating Le antigen could be demonstrated in sera of patients by inhibiting the binding of MoAbs to a target preparation. A double determinant radioimmunoassay (DDIA) was then developed to detect the association of blood group determinants with a previously defined gastrointestinal cancer antigen (GICA). The DDIA with the anti-blood group and anti-GICA antibody was in some cases more sensitive in detecting GICA in sera than using the anti-GICA MoAb alone. Of 55 sera from patients with primary and early recurrent colorectal carcinoma (CRC), 10 (18%) were scored positive in the DDIA using only anti-GICA MoAb. When MoAb binding to a determinant on Leb and on H, type I, was used as first antibody in DDIA followed by anti-GICA MoAb 11 additional sera were reactive, increasing the percentage of positive sera to 38. Using the same combinations of MoAbs, the sensitivity of detection of GICA was only slightly improved from 63 to 66% in sera of patients with advanced CRC. The number of false positive sera from patients with non-malignant gastrointestinal diseases or from healthy donors remained at low levels when anti-blood group determinant antibodies were used together with anti-GICA MoAb. The results indicate that DDIAs with MoAbs against different blood group determinants and tumour associated antigens can improve the detection of circulating antigens in patients with early stage cancer.

ABO Blood-Group System↗
PubMed1981

A gas chromatographic--mass spectrometric study of profiles of volatile metabolites in hepatic encephalopathy.

Volatile organic substances present in blood plasma and cerebrospinal fluids of certain control groups of human subjects and cirrhotic patients some of whom were suffering from hepatic encephalopathy were quantitatively analysed and identified. A rapid, reproducible, direct injection capillary column gas chromatographic method was developed for the concentration and detection of such volatiles at mg/l and lower concentrations. Of at least forty volatiles detected, twenty-one were identified. The mean concentration of one of these, 3-methylbutanal, was found to be significantly elevated (p less than 0.01) in chronic encephalopathics (2.37 +/- 0.79 mg/l, n = 18), when compared to the controls (0.30 +/- 0.08 mg/l, n = 20). Furthermore, the concentration of this component increased with the clinically diagnosed severity of the encephalopathic state. The presence of 3-methylbutanal is related to leucine, a branched-chain amino acid linked with hepatic encephalopathy.

Aldehydes↗
PubMed1980

The arteriovenous fistula. Its construction in the management of hemophilia.

Arteriovenous fistulae using expanded polytetrafluorethylene (E-PTFE [Gore-Tex]) grafts were constructed in six patients with hemophilia for long-term vascular access where veins had been obliterated. The range of patency was four to 28 months, with a mean of 20 months. All patients had less than 8% level of factor VIII, which may have contributed to fistula patency. This approach was helpful in the management of these patients' conditions.

Adolescent↗