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Biomedical subjects

L M Silverman

Publications and source records attributed to L M Silverman.

At least 73 records · Page 4Linked to original sources
PubMed1985

Skeletal muscle injury and repair in marathon runners after competition.

Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competition may arise from injury to skeletal muscle, myocardium, or a combined tissue source. Normal radionuclide myocardial scintigraphy and the selective increase in skeletal muscle CK-MB reported in such runners strongly suggest a peripheral source. To understand this biochemical finding, the authors examined gastrocnemius muscles by electron microscopy from 40 male marathon runners at intervals after competition and from 12 male nonrunners. Muscle from runners showed post-race ultrastructural changes of focal fiber injury and repair: intra- and extracellular edema with endothelial injury; myofibrillar lysis, dilation and disruption of the T-tubule system, and focal mitochondrial degeneration without inflammatory infiltrate (1-3 days). The mitochondrial and myofibrillar damage showed progressive repair by 3-4 weeks. Late biopsies showed central nuclei and satellite cells characteristic of the regenerative response (8-12 weeks). Muscle from veteran runners showed intercellular collagen deposition suggestive of a fibrotic response to repetitive injury. Control tissue from nonrunners showed none of these findings. The sequential morphologic changes in runners suggest that the increase in skeletal muscle CK-MB is a marker of cellular regeneration.

Athletic Injuries↗
PubMed1984

In vitro characterization of MAT LyLu: a Dunning rat prostate adenocarcinoma tumor subline.

Prostate carcinoma has been a therapeutic challenge. The Dunning tumor, a rat prostate adenocarcinoma tumor model, has been used to evaluate prostate carcinoma treatment protocols. The Dunning tumor subline, MAT LyLu , as described in this report, has been established and characterized as an in vitro continuous cell culture. The cell culture has been stable for greater than 60 passages. The in vitro characteristics of the MAT LyLu cell culture, such as growth rate, loss of contact inhibition, clonogenicity, morphology and tumorigenicity, are consistent with the malignant characteristics of the Dunning tumor subline. The MAT LyLu cell culture has enzyme activities which can be used to characterize the cell line. The establishment of MAT LyLu as a continuous cell culture should provide a controlled approach to evaluate the etiology and treatment of prostate carcinoma.

Adenocarcinoma↗
PubMed1984

A rapid silver-stain procedure for use with routine electrophoresis of cerebrospinal fluid on agarose gels.

Oligoclonal banding patterns, when present in cerebrospinal fluid (CSF) electrophoresed on agarose gels, are important in the diagnosis of multiple sclerosis and other demyelinating diseases. Typically, an 80-fold concentration of 2.5 mL of CSF has been needed before the oligoclonal banding pattern could be detected with Coomassie Brilliant Blue stain. This excessive volume requirement often is a problem, particularly in children. We describe here an improved silver-stain procedure with which we routinely can detect the oligoclonal banding pattern in 1 to 3 microL of unconcentrated CSF. The procedure is inexpensive and takes less than 45 min. Our method is quick, safe, sensitive, and easily performed in the clinical laboratory.

Cerebrospinal Fluid Proteins↗
PubMed1983

Elevated skeletal muscle creatine kinase MB isoenzyme levels in marathon runners.

Mean serum creatine kinase MB isoenzyme (CK-MB) activity in 108 trained marathon runners after competition was 98 +/- 66 (SD) units/L measured by a quantitative electrophoretic technique (normal, less than 5 units/L), or 7.9% of total CK activity. These levels in asymptomatic runners were comparable with peak serum values reported in patients during acute myocardial infarction. Elevated serum levels of CK-MB in runners can arise from skeletal muscle through exertional rhabdomyolysis, from silent injury to myocardium, or from a combined tissue source. To investigate this directly, we analyzed skeletal muscle obtained by needle biopsy for CK isoenzymes from 25 trained male marathon runners and ten sedentary male subjects. The MB isoenzyme accounted for 8.9% +/- 1.3% (SD) of total CK activity per gram of total protein in the skeletal muscle of runners and 3.3% +/- 0.7% (SD) in control tissue, which was significant. Total CK activity was not statistically different between the two groups. Similar relative concentrations of CK-MB in skeletal muscle (8.9%) and serum after competition (7.9%) strongly suggest that elevated serum CK-MB activity in asymptomatic runners arises from a noncardiac or skeletal muscle source.

Adult↗
PubMed1983

Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction.

Paired serum and cerebrospinal fluid specimens from 19 patients with SLE and central nervous system dysfunction were studied with respect to cerebrospinal fluid IgG index (a measure of intrathecal IgG synthesis), isoelectric focusing using immunoperoxidase staining techniques to detect oligoclonal IgG, and determination of the cerebrospinal fluid/serum albumin quotient (Q albumin) as a measure of blood-brain barrier integrity. Twenty-five patients without neurologic disease and 70 patients with a variety of non-SLE neurologic disorders were also studied for comparison. Of most interest was the observation that 42 percent of the patients with SLE had cerebrospinal fluid oligoclonal IgG, usually in association with elevation of the cerebrospinal fluid IgG index. In addition, two of the cerebrospinal fluid specimens that exhibited oligoclonal IgG also had increased titers of alpha-interferon. Q albumin was normal (under 9.0) in 12 of 13 patients with SLE, who had seizure, psychosis, or cranial neuropathy as principal central nervous system manifestations (mean +/- SD = 5.3 +/- 2.4), but was significantly elevated (mean +/- SD = 27.4 +/- 18.8, p less than 0.001) in five of six patients with diffuse, major central nervous system injury, for example, encephalopathy with coma, transverse myelopathy, paraparesis. Blood-brain barrier impairment was not correlated either with presence of circulating immune complexes or with other clinical or serologic evidence for extra-central nervous system disease activity. Taken together, the data suggest that, within the limitations of the techniques used, impairment of the blood-brain barrier in SLE may be secondary to the central nervous system lesion, rather than a result of systemic immune complex injury. In addition, substantial evidence is provided for an ongoing humoral immune response within the central nervous system in this disorder, which, in certain patients, may be associated with the production of intrathecal alpha-interferon.

Albumins↗
PubMed1983

Serum creatine kinase and CK-MB isoenzyme responses to acute and prolonged swimming in trained athletes.

Six highly-trained male swimmers completed a maximum work capacity tethered swim and a 1-h continuous tethered swim at approximately 70% VO2max in order to evaluate total serum creatine kinase and CK-MB isoenzyme changes. Venous blood obtained before, 5 min post-, 6 h post-, and 24 h post-exercise was analyzed for total serum CK (kinetic UV method, normal = less than 100 U/l) and CK-MB isoenzyme (quantitative electrophoretic technique, normal = less than 5 U/l). VO2max averaged 4.59 +/- 0.28 l/min, with a mean total work time of 24.5 min to achieve maximum capacity. Mean resting total CK was 100.5 +/- 15.8 U/l. Compared to rest, neither swim bout produced a significant (p greater than 0.05) elevation in mean total creatine kinase. No CK-MB isoenzyme was observed in any post-exercise blood sample. Swimming, performed by highly-trained swimmers at high levels of intensity or for prolonged durations, may not impose sufficient degrees of trauma producing muscular stress. Therefore, the structural integrity of the cell membrane is maintained and the loss of intracellular creatine kinase to the bloodstream prevented.

Adolescent↗
PubMed1983

Interpretation of cerebrospinal fluid protein assays in various neurologic diseases.

Albumin and immunoglobulin G (IgG) were determined in cerebrospinal fluid (CSF) and serum, and the CSF/serum albumin Index (CSF X 10(3)/serum albumin concentration ratio) and IgG Index [(CSF/serum IgG)/(CSF/serum albumin)] were calculated. Data for these indices and oligoclonal banding are described in 23 cases of multiple sclerosis (MS), 19 of systemic lupus erythematosus (SLE), eight of sarcoidosis, 48 cases of miscellaneous disease, and 25 control patients with nonspecific complaints. Of the MS, SLE, and sarcoidosis patient groups, 8.5%, 26%, and 12.5% showed an abnormally high CSF/serum albumin Index; 87%, 16%, and 0% an increased IgG Index; and 87.5%, 42% and 0% showed positive oligoclonal banding. IgG Index and oligoclonal banding results for MS patients differed significantly from the sarcoidosis (p less than .001) and SLE (p less than .05) groups. When the CSF/serum albumin Index is considered also, the control and sarcoidosis patient results differ significantly from the MS group (p less than .001 and p less than .01). A strong correlation between the IgG Index and oligoclonal banding is implicated.

Blood-Brain Barrier↗
PubMed1982

Synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells.

Malignant and uninvolved human breast tissues were maintained in organ culture for 3 to 6 days. Under these conditions, the three-dimensional glandular architecture is maintained with the least disruption of tissue integrity. The biosynthesis and release of glycoproteins were studied by using the incorporation of [14C]glucosamine and [14C]leucine by the breast surgical specimens. Five major families of labeled glycoproteins were identified from culture supernatants using two-dimensional gel electrophoresis. Quantitative immunoprecipitation established that 16 to 30% of the total of labeled glycoproteins were recognized as normal serum components. Two of these glycoproteins were antigenically related to normal human serum components as demonstrated with crossed immunoelectrophoresis. Evidence was obtained for the active synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells. alpha 1-Antichymotrypsin accounted for 0.9 to 7.8% of the biosynthetically labeled glycoproteins from organ culture supernatants. This component was 11.9% of the glycoproteins released by a monolayer culture of the established breast carcinoma cell line, MCF-7. alpha 1-Acid glycoprotein made up 0.7 to 3.1% of the labeled glycoproteins. alpha 1-Antichymotrypsin is a known neutral serine proteinase inhibitor with a particularly strong affinity for cathepsin G. alpha 1-Acid glycoprotein may function primarily as a potent immunomodulator by suppressing lymphoblastogenesis. These glycoproteins may thus have regulatory roles in the proteolytic modification of breast tissue and represent the tissue's own protecting shield against invading leukocytes.

Breast↗
PubMed1982

Enhancement techniques for detecting trace and fluid-specific components in two-dimensional electrophoresis patterns.

Albumin and other serum-derived proteins were removed from several types of body fluids by affinity chromatography, to facilitate detection of trace or non-serum-derived proteins in two-dimensional electrophoresis patterns. Albumin was removed by the dye Cibacron Blue F3G-A coupled to Sepharose. Two-dimensional patterns of albumin-depleted serum lack the large albumin spot, and several families of spots become visible that ordinarily are partly or totally hidden by it. However, other proteins also bind to Cibacron Blue. Most serum proteins, including albumin, were effectively removed by anti-human serum antibodies coupled to Sepharose. Two-dimensional patterns of serum-depleted cerebrospinal fluid exhibit five clusters of probable nervous-system protein families not detected in serum. One additional family, probably antigenically related to transferrin, was removed by the affinity step. Two-dimensional patterns of serum-depleted prostatic fluid exhibit five major non-serum families, two of which may be creatine kinase B subunits and prostatic acid phosphatase. Two-dimensional patterns of serum-depleted malignant effusions exhibit one or more of three proteins that possibly are tumor products. Pattern matching suggests the presence of one non-serum-derived protein family common to cerebrospinal fluid, prostatic fluid, and malignant effusions. Prostatic fluid and malignant effusions have in common as many as three non-serum families of proteins.

Blood Proteins↗
PubMed1981

Elevated creatine kinase MB isoenzyme levels in marathon runners. Normal myocardial scintigrams suggest noncardiac source.

Elevated serum creatine kinase MB isoenzyme (CK-MB) levels are regarded as a sensitive and specific marker for myocardial injury. Serum CK-MB was measured in male marathon runners during training and after competition. Mean serum CK-MB measured by a quantitative electrophoretic technique (normal, less than 5 IU/L) showed borderline elevation during training with peaks 24 hours after competition. Mean CK-MB in 64 serum samples from 35 runners after competition was 130 IU/L or 8.3% of total CK activity. Levels of CK-MB averaging 26 times the upper limits of normal would usually be considered indicative of massive myocardial necrosis. Myocardial scintigraphy with technetium Tc 99m pyrophosphate was performed after competition in 12 randomly selected runners with a mean postrace serum CK-MB level of 160 IU/L or 13%. Infarct-avid ("hot-spot") scintigraphy, appropriately timed to detect underlying myocardial abnormalities, was within normal limits in all subjects. Normal results of infarct-avid scintigraphy coincident with marked serum CK-MB elevations strongly suggests that CK-MB arises from a noncardiac or skeletal muscle source in these runners.

Clinical Enzyme Tests↗
PubMed1981

Creatine kinase BB and other markers of prostatic carcinoma.

Creatine kinase BB has been described to be elevated in the serum of patients with prostate cancer. The incidence of abnormal serum levels correlates with the degree of differentiation of the tumor; that is, the more poorly differentiated tumors are associated most frequently with elevated CK-BB levels. We have recently described two additional findings which involve CK-BB in prostate cancer: 1) the finding of abnormally migrating CK-BB bands reported to be IgG-CK-BB complexes in several Stage D patients and in 2/3 Stage B patients following 125I implants, and 2) significant differences between CK-BB purified from prostatic fluid from CK-BB of brain origin. In particular, we find two bands of prostatic CK-BB following purification as compared to a single band from brain, when the same purification protocol is used. While further characterization of these differences is proceeding, the two bands of CK-BB are being used to develop a prostate-specific antiserum for use in immunoassays to detect prostate cancer in conjunction with other traditional markers such as prostatic acid phosphatase. If serum detection of tumor markers is to be efficacious, tumor marker panels such as CK-BB and prostatic acid phosphatase may provide a significant advantage over individual markers.

Brain↗
PubMed1980

Incidence of a split alpha 2-glycoprotein band in the electrophoretic pattern for serum of adenocarcinoma patients.

We electrophoresed serum samples on Mylar-backed cellulose acetate membranes and stained for glycoproteins with the periodic acid--Schiff reagent. The samples were from untreated adenocarcinoma patients, adenocarcinoma patients receiving chemotherapy, and patients with other malignancies, and also from patients with benign proliferative diseases, inflammatory diseases, and other non-malignant conditions. Forty-five per cent of the sera from untreated adenocarcinoma patients and 80% of those from adenocarcinoma patients with progressive systemic disease exhibited a splitting of the alpha 2-glycoproteins into a fast and slow band. Such a pattern was seen in only 4% of the non-adenocarcinoma cancer patients and 4% of the control group. Serial studies indicated that electrophoretic patterns of alpha 2-glycoproteins change with clinical status. Non-cancer patients with high concentrations of acute-phase proteins in their serum did not exhibit two alpha 2-glycoprotein bands. Further characterization of serum proteins from the fast alpha 2 region suggest that alpha 1-acid glycoprotein and haptoglobin beta chains are the principal components staining with periodic acid--Schiff reagent. These components are markedly less apparent in, or are absent from, the fast alpha 2 region of normal sera.

Adenoma↗
PubMed1979

Creatine kinase BB: a new tumor-associated marker.

Creatine kinase isoenzyme BB (CK-BB) is found in the serum of patients with various types of cancer. Using both radioimmunoassay and agarose electrophoresis, we found abnormal amounts of this isoenzyme in the serum of 15 of 17 patients with untreated prostatic carcinoma. Among patients with other types of adenocarcinomas and metastatic disease, serum CK-BB was increased in most of those who were unresponsive to therapy. In benign or malignant prostate tissue and in malignant pleural effusions, cytoplasmic CK-BB as determined by immunoperoxidase staining was found in epithelial cells. Prostatic fluid had high concentrations of CK-BB, as did malignant, but not benign, pleural fluid supernates. We conclude that glandular epithelial cells contain CK-BB, which is released in benign and malignant states and may appear in higher concentrations in the circulation in malignant states. These conclusions are consistent with predictions we have made from a model experimental system concerning characteristics of possible tumor markers. The observations indicate a role for CK-BB as a tumor marker, particularly for adenocarcinoma of the prostate.

Adenocarcinoma↗