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Biomedical subjects

E Alpert

Publications and source records attributed to E Alpert.

At least 37 records · Page 2Linked to original sources

Congenital deficiency of alpha-fetoprotein.

Although alpha-fetoprotein may play a role in fetal immune function or in maintenance of osmotic pressure, its exact function is unknown. We report two infants documented to have congenital deficiency of alpha-fetoprotein. One infant had cord blood levels less than 0.5 ng/ml. The second infant had a neonatal level of 120 ng/ml, which is about 2% of the usual concentration for a term newborn. These infants document the existence of congenital deficiency of serum alpha-fetoprotein. Because it is homologous to albumin, congenital deficiency of alpha-fetoprotein may be analogous to analbuminemia, a benign genetic trait.

Adult↗

Alpha-fetoprotein levels in normal adults.

Alpha-fetoprotein (AFP) is a fetal specific glycoprotein normally produced primarily by the fetal liver. Normally, AFP levels decline rapidly after birth, reaching undetectable levels (less than 10 ng/ml) within several months after birth. The authors have developed a more sensitive radioimmunoassay, which has allowed them to study low levels of AFP in normal adults and to determine factors which may affect its normal level. Two hundred and seventy normal Houston blood donors were screened for the absence of hepatitis B and normal ALT levels. The mean AFP level was 3.04 ng/ml +/- 1.9 SD. There was a statistically significant higher level in men compared to women (p less than .004). Regression analysis demonstrated a statistically significant increase of AFP levels with age both in men (p less than .05) and in women (p less than .01). These data delineate the normal level of serum AFP in normal adults in the United States. With the normal level now defined, it becomes possible to compare levels in different populations including those exposed to hepatotoxins or hepatocarcinogens in the environment.

Adolescent↗

Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes.

Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor for AFP on the immune recognition cell, the monocyte/macrophage. Microscopic autoradiography exhibited an obvious binding of AFP almost exclusively on human peripheral monocytes but not on lymphocytes. In a human monocyte cell line (U937) Scatchard plot analysis indicated the presence of two distinct AFP-specific binding sites with a Kd of 5 x 10(-11) M, 49 binding sites per cell, and 2.5 x 10(-7) M, 7,800 binding sites per cell. 125I-ASD-AFP, AFP-radiolabeled bifunctional photoactivatable thio-cleavable cross-linker, was used to isolate the AFP binding protein from U937 cells. After ultraviolet photoactivation, 125I-sulfosuccinimidyl 2-(p-azido-salicylamido)ethyl-1,3'-dithiopropionate was covalently linked to the putative receptor. Autoradiography of SDS gradient PAGE under reducing conditions showed a major radiolabeled band at between 62 and 65 kD. To confirm the specificity of the finding, recombination of AFP with the isolated receptor was examined in artificially reconstituted membrane vesicles, which also resulted in a single band at approximately 62-65 kD by SDS-PAGE autoradiography. From the data above, we concluded that human monocytes possess a specific AFP binding protein on the membrane, a putative receptor, which may be involved with the physiological regulation of the immune response.

Cell Line↗

A double-blinded, randomized trial of hydrocortisone in acute hepatic failure. The Acute Hepatic Failure Study Group.

The Acute Hepatic Failure Study Group (AHFSG) has conducted a double-blinded, randomized evaluation of hydrocortisone in patients with acute hepatic failure. From July 1975 through August 1978, a 38-month period, 18 medical centers in the United States and one in Canada participated in this trial. A total of 64 patients were accessed and found eligible to participate in the study; two of them were subsequently eliminated from our analysis. Eighteen patients received placebo; 23 received 400 mg hydrocortisone per day, and 21 patients were administered 800 mg hydrocortisone per day. We did not observe any therapeutic effect of hydrocortisone, and the survival rates for placebo versus 400 mg and versus 800 mg hydrocortisone per day were 22%, 9%, and 24%, respectively. Fulminant hepatitis associated with drug hepatotoxicity or non-A, non-B hepatitis seemed to have a worse prognosis than fulminant B, although these differences were not significant. Serum alpha-fetoprotein had a modest prognostic value of survival and seemed to be limited to fulminant B. The AHFSG recommends, therefore, that corticosteroid use in acute hepatic failure with hepatic encephalopathy be discontinued.

Adult↗

The effect of gestational age on the detection rate of Down's syndrome by maternal serum alpha-fetoprotein screening.

Low levels of maternal serum alpha-fetoprotein are currently being used to screen for Down's syndrome in midpregnancy. Because of the possibility that gestational age may affect the detection rate of Down's syndrome, we analyzed maternal serum AFP levels and gestational age in 51 Down's syndrome pregnancies that had been confirmed by amniocentesis or at birth, and we compared these pregnancies with 3239 screened singleton pregnancies with known normal outcomes. The highest yield of a low risk for Down's syndrome associated with maternal serum alpha-fetoprotein occurred at 16.5 to 17.5 weeks' gestation. Our data suggest that maternal serum alpha-fetoprotein screening for Down's syndrome should be done between 16 and 18 weeks' gestation, which is the gestational age currently recommended for neural tube defect screening.

Case-Control Studies↗

Liver transplantation for cholesteryl ester storage disease.

This case describes a patient with cholesteryl ester storage disease who underwent liver transplantation for progressive cirrhosis, portal hypertension, ascites, and uncontrollable gastrointestinal bleeding. Four and one-half years posttransplant, her growth improved, cholesterol levels have returned to normal, and she is clinically well except for mild hypersplenism and an elevated blood urea nitrogen (BUN) and creatinine. Serum triglycerides remain elevated, but there have been no signs of progressive renal, intestinal, vascular, or pulmonary disease.

Adolescent↗

Polyethylene glycol significantly enhances the transfer of membrane immunoblotting.

Poly(ethylene glycol)n is a group of water-soluble, hydrophobic, optically transparent and biomacromolecule-nondenaturing polymers. These properties have caused it be widely used for various purposes in the biological sciences. In this study, the effects of poly(ethylene glycol)n on protein preservation, electrotransferring, and immunoblotting from sodium dodecyl sulfate (SDS)-polyacrylamide gel onto polyvinylidene difluoride (PVDF) membrane have been systematically evaluated. After SDS-polyacrylamide gel electrophoresis, 30% poly(ethylene glycol)n may be applied to reversibly fix proteins within the gel more completely, differing from irreversible fixation produced by solutions such as trichloroacetic acid-sulfosalicylic acid or acetic acid-methanol systems. The intragel proteins, fixed by poly(ethylene glycol)n, can be electroblotted directly onto PVDF membranes in the presence of 30% poly(ethylene glycol)n. We have shown that treatment with poly(ethylene glycol)n may reduce background, raise signal-to-noise ratio, sharpen protein bands, and increase resolution, resulting in enhancement of the immunoblotting transfer. It is possible to visualize a few picograms of a single protein band, increasing the sensitivity of the method by 10- to 100-fold, as compared with standard immunoblotting techniques.

Animals↗

Hereditary persistence of alpha-fetoprotein.

Persistently elevated alpha-fetoprotein levels were found in a 43-yr-old man in the absence of any specific pathology. Elevated serum alpha-fetoprotein levels were subsequently found in three first-degree relatives, two siblings, and one daughter. This represents the third documented family with hereditary persistence of alpha-fetoprotein. The pedigree is consistent with an autosomal dominant inheritance. Such elevated alpha-fetoprotein levels may be difficult to interpret in patients being screened for malignancy or in maternal serum alpha-fetoprotein screening programs. This rare genetic condition seems benign, with no discernable disease or functional abnormality noted in follow-up over a 6-mo period.

Adult↗

Serum aldolase isozyme levels in patients with cerebrovascular diseases.

A subunit specific radioimmunoassay was developed for the quantification of human aldolase A, B, and C. The method used was a double antibody radioimmunoassay using radioiodinated purified aldolase A, B, or C subunits as the ligand, specific chicken antibodies to aldolase isozymes and rabbit antibodies to chicken IgG. The Iodogen method was used for iodination of the purified isozyme subunits in this study. Human brain tissue contained similar concentrations of aldolase A and aldolase C, and a smaller amount of aldolase B, which was the main isozyme of liver tissue. Levels of serum aldolase A were greater than 203 ng/ml, the upper limit of normal, in six of 24 patients with cerebral infarction and in 11 of 31 patients with cerebral hemorrhage. Nine of 24 patients with cerebral infarction and 16 of 31 patients with cerebral hemorrhage had serum aldolase C levels greater than 4.1 ng/ml, the upper limit in normal sera. These data suggest that serum aldolase C may be a more specific and sensitive marker of cerebrovascular diseases than aldolase A. We also demonstrated that serial measurement of serum aldolase C in patients with cerebrovascular diseases might be useful in estimating prognosis, since serially increasing serum aldolase C levels during the course of these diseases were correlated with a high mortality rate.

Adult↗

Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid.

A breath test to assess hepatic mitochondrial function in vivo was evaluated in rats. Following the i.p. administration of [1-14C]-alpha-ketoisocaproic acid, 14CO2 exhalation reached a peak within 10 to 20 min and then declined exponentially, with a half-life of 14.3 min. Control animals exhaled 38.6% of the administered radioactivity within 1 hr. In functionally anhepatic animals, 14CO2 in breath amounted to 23% of that in control animals, indicating that alpha-ketoisocaproic acid decarboxylation reflects mainly hepatic mitochondrial function in vivo. Ethanol (3 gm per kg) significantly decreased alpha-ketoisocaproic acid decarboxylation (21.8% of the dose appearing in breath in 1 hr), probably due to the ethanol-induced shift in the NAD+:NADH ratio. In contrast, an uncoupler of mitochondrial respiration, sodium salicylate (375 mg per kg), increased the decarboxylation of alpha-ketoisocaproic acid (56.3% of the dose recovered as 14CO2 in 1 hr). Mitochondrial damage induced by 4-pentenoic acid decreased the decarboxylation of alpha-ketoisocaproic acid but did not affect the microsomal metabolism of antipyrine. The present data indicate that the alpha-ketoisocaproic acid breath test provides a noninvasive estimate of hepatic mitochondrial function in vivo which, when applied to man, might yield clinically useful information.

Animals↗

A novel approach to experimentally estimating the number of reactive epitopes on multivalent antigens.

Various coefficients in radioimmunoassays are expressed in a series of equations. These equations provide an approach to estimating the number of epitopes on a multivalent antigen as well as a macromolecular topogram. In this paper, pig insulin (Ins), horse myoglobin (Mb), human serum albumin (HSA), human alpha-fetoprotein (AFP) and adr-hepatitis B type virus surface antigen (HBsAg) were chosen as objects of study. The number of epitopes was calculated to be Ins = 2, Mb = 5, HSA = 16, AFP = 6, HBsAg = 146. These epitope numbers, calculated by equations, were very similar to those previously identified experimentally. This suggests that our theoretical approach may be useful in predicting the number of epitopes on other macromolecules of biological and clinical interest.

Animals↗

Decreased serum aldolase B levels in patients with malignant tumors.

Serum aldolase B levels were determined in patients with malignant tumors using a radioimmunoassay method. Thirty-one of 52 patients with malignant tumors had decreased serum aldolase B levels of less than 20 ng/ml, whereas almost all of the normal subjects and the patients with liver diseases and other benign diseases showed serum aldolase B levels of more than 20 ng/ml. The decreased aldolase B levels observed in cancer patients were unrelated to the clinical stage of their disease. The decrease of aldolase B correlated well with the decrease of fructose-1-phosphate (F1P)-aldolase activity, but not with fructose-1,6-diphosphate (FDP)-aldolase activity in the sera of cancer patients. Mixing experiments did not identify an inhibitor of aldolase B in sera of cancer patients. Furthermore, recovery of serum aldolase B levels after successful surgical resection in cancer patients suggested that the low levels of aldolase B in sera of cancer patients was not of genetic origin. The mechanism responsible for the decrease of aldolase B in sera of cancer patients is unclear.

Adult↗

Factors affecting the prognosis of primary liver carcinoma.

Analysis of the clinical records of 163 patients with primary liver carcinoma was performed to identify factors affecting prognosis. The overall 3-year survival rate was 10%, and the median survival was 7.8 months. Survival was similar for patients with single or multiple tumor nodules. There was no significant association between nodule size of 3 cm or larger and survival. Patients who underwent resection had a longer survival. For patients without cirrhosis, location of the tumor in the left lobe regardless of whether it is resected appears to be a prognostic factor associated with prolonged survival. Female sex and the absence of cirrhosis were also associated with longer survival.

Age Factors↗

Clinical impact of stool cultures for Campylobacter in adults with acute or chronic diarrhea.

Campylobacter jejuni has emerged as a frequent cause of diarrhea. During a 12-month period at the Houston Veterans Administration Medical Center, we isolated C jejuni from 3.4% of the 290 stool cultures from patients with diarrhea. This compared to an isolation rate of 4.1% for Salmonella and 3.1% for Shigella. During the same period, 17 additional cases of Campylobacter-associated diarrhea were identified in adults at the two other Baylor College of Medicine teaching hospitals. We correlated the clinical history, treatment, and outcome of these 27 cases of Campylobacter-associated diarrhea (22 cases of acute diarrhea and five of chronic diarrhea). In most patients with acute disease, the diarrhea was resolving by the time the results of the cultures were available. The duration of illness was the same whether treated with antibiotics to which Campylobacter was susceptible (effective therapy) or antibiotics to which it was not susceptible (ineffective therapy); the mean duration of diarrhea after submitting the culture was 5.2 days for those with ineffective therapy versus 5.6 days for those receiving effective therapy. Thus, antibiotic therapy did not appear to shorten the duration of acute diarrhea due to Campylobacter. Five patients had chronic diarrhea; all had an unrelated underlying disease, and antibiotic treatment did not change the clinical course despite bacteriologic cure. This study raises questions as to the value of antibiotic therapy for campylobacteriosis, and in this light, we discuss the value of routine culturing for Campylobacter.

Acute Disease↗

Captopril-induced liver dysfunction.

We have described a patient with captopril-induced cholestatic jaundice. Captopril was confirmed as the causative agent, because jaundice occurred after administration of captopril and resolved quickly after administration was stopped.

Captopril↗