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Biomedical subjects

A Malkin

Publications and source records attributed to A Malkin.

At least 55 records · Page 3Linked to original sources

The presence of glycosylated, biologically active chorionic gonadotropin in human liver.

Whole extracts of normal human liver contain hCG-like material as determined by radioimmunoassay using antibodies to the beta subunit of the hormone. However, the extracts are biologically inactive, when analyzed by the in vitro rat Leydig cell assay for steroidogenesis. When subjected to Concanavalin-A-Sepharose chromatography, the radioimmunoassayable material was entirely lectin-bound. After elution with methyl-alpha-D-glucopyranoside, the lectin-bound fractions now displayed biological activity.

Biological Assay↗

Carcinoembryonic antigen: a useful prognostic marker in small-cell lung cancer.

Plasma carcinoembryonic antigen (CEA) was determined in 180 patients with small-cell lung cancer (SCLC) before treatment. An abnormal level (greater than or equal to 6 ng/mL) was found in 34% of patients tested. Patients with extensive disease (39/83) had a significantly higher frequency of abnormal CEA (P = .001) than those with limited disease (22/97). There was a strong correlation between obtaining an objective response--particularly a complete response (P = .00003)--and the absence of an elevated CEA. Patients with an abnormal CEA also had a shorter survival time (P = .0007) and the difference remained statistically significant after logrank adjustment for extent of disease and ECOG (Eastern Cooperative Oncology Group) performance status. There was also a negative correlation between survival time and the quantitative level of CEA. In this series, only the group of patients with normal initial CEA levels included all survivors beyond 2.5 years. We conclude that CEA is a useful prognostic factor in SCLC.

Adult↗

Activation of adrenal adenyl cyclase by anti-thyroid plasma membrane antibodies.

We have previously shown that IgG isolated from rabbit anti-bovine thyroid plasma membrane (anti-BTPM) antiserum exhibits properties similar to thyroid stimulating antibodies (TSAb) in that it activates thyroid adenyl cyclase. In this study, the organ non-specificity of this reaction was investigated. It was observed that anti-BTPM IgG stimulated not only adenyl cyclase of bovine thyroid but also that of the adrenal. The stimulatory activities on the thyroid and adrenal adenyl cyclase were abolished by absorption of the IgG with bovine adrenal plasma membrane (BAPM). These results indicate that anti-BTPM antibodies, similar to TSAb, exert both thyroidal and extra-thyroidal effects. Thus anti-BTPM antibodies may be directed against antigenic determinants that are common to both thyroid and adrenal plasma membranes. Like the anti-BTPM IgG, anti-BAPM IgG also activated both thyroid and adrenal adenyl cyclase. However, when IgG of the anti-BAPM antiserum was absorbed with thyroid plasma membranes, only the thyroid, but not the adrenal stimulating activity was abolished. It was concluded that the anti-BAPM antiserum contained antibodies directed against membrane antigens specific for the adrenal as well as common antigens shared by the thyroid.

Absorption↗

The effect of acute spinal cord compression injury on thyroid function in the rat.

The effect of acute spinal cord injury on thyroid function was studied in rats subjected to severe spinal cord compression at T1. Serum thyroxine (T4), effective thyroxine index (ETI), and thyroid stimulating hormone (TSH) were measured at 1 and 100 minutes at one, three, and seven days after laminectomy and spinal cord injury. Control animals were subjected to laminectomy only. T4 was decreased at 1 minute after laminectomy with or without spinal cord injury, though the animals with cord injury had a much more profound reduction. The effects on TSH at 1 minute were dramatically different: laminectomy alone caused an elevation of TSH, while spinal cord injury produced a marked decline. At the later time intervals both groups showed gradual normalization of T4 and TSH levels, and at seven days there were no significant differences between the groups. Thus, acute spinal cord compression injury produced a major alteration in thyroid function during the acute phase.

Acute Disease↗

Alkali-resistant hemoglobin (HbF) in cancer patients.

Elevated levels of alkali-resistant (fetal) hemoglobin were found in patients with cancer, in the absence of any overt hematologic disorders. This phenomenon was observed most frequently in patients with gonadal tumors and appears to reflect tumor burden and activity of disease.

Female↗

Aldolase isoenzyme patterns during human ontogeny and in lung, kidney and breast cancer.

Enzyme patterns characteristic of fetal tissue have been noted in some experimental tumor models, particularly in hepatomas. In this study we undertook to determine whether biochemical evidence of a similar reversion could be detected in tumors of other human organs. As marker, we chose to use the aldolase isoenzymes A, B and C, for which distinct adult and fetal tissue patterns have been described. Using monospecific antibodies, we determined the aldolase isoenzyme pattern in a variety of human organs ranging in age from 14 to 40 weeks of gestation, in the 2- to 3-month postnatal period and in adults. In addition, 19 breast cancers, 19 primary lung cancers and 8 kidney cancers were examined. Our studies on breast cancer revealed three apparently distinct groups -- one showing primarily the A isoenzyme type (6 cases), a second containing mainly A with considerable quantities of B and C isoenzymes (9 cases) and a third group (4 cases) which may contain a different isoenzyme altogether since the combined activity of the three known forms was less than 100% in each case. In lung cancer, fetal characteristics could be substantiated since in fetal and adult lung tissue, the isoenzyme pattern is almost identical; 3 out of 19 cases showed substantial quantities of the B isoenzyme. In kidney tumors, a reversion to the A form with an appreciable fraction of the C form was found, which is similar to the fetal pattern.

Adenocarcinoma↗

Dynamic changes of serum gamma-glutamyl transferase in chronic alcoholism.

Elevated serum gamma-glutamyl transferase (GGT) levels were found in 29% of 155 chronic alcoholics undergoing detoxification treatment. Alkaline phosphatase (AP) was increased in 16%, alanine aminotransferase--SGPT (ALT) in 12% of the patients, while 23% had elevations of either AP or ALT or both. Of the foregoing parameters, GGT was the best single indicator of liver involvement. In course of the follow-ups GGT/ALT correlation improved, but GGT/AP correlation deteriorated. In 9 patients, abstinence during follow-up was associated with progressive decrease in previously elevated serum GGT. Because of its unique sensitivity, GGT may be useful as a screening and/or monitoring aid in alcoholism.

Alanine Transaminase↗

Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer.

Combinations of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (GGT), pregnancy-associated macroglobulin (PAM) and placenta-like alkaline phosphatase (PLAP) were studied in groups of patients with ovarian and cervical cancer. In ovarian cancer, only CEA and PLAP levels appeared to reflect tumor burden and were complementary in detecting active disease. In cervical cancer, CEA and GGT reflected tumor burden, while PLAP showed just the reverse--the highest degree of positivity being present in minimal disease. PLAP positivity was even more pronounced in patients with cervical dysplasia and carcinoma in situ while CEA and GGT were negative. The data indicate that the use of marker combinations can improve our capacity to detect minimal disease and provide information regarding tumor biology that may not be available by studying individual markers or by other means. It remains to be determined whether the use of tumor markers can influence existing therapy sufficiently to alter the outcome in cancers which are notoriously difficult to treat.

Alkaline Phosphatase↗

Carcinoembryonic antigen in breast cancer.

Carcinoembryonic antigen (CEA) levels were determined in 742 postoperative patients with breast cancer. Within this group the percentage of elevated (greater than or equal to 4.0 ng/ml) assays increased with UICC clinical stage and was 14.8% (12/81), 23.7% (27/114), 73.1% (190/260) and 20.0% (49/245) for stages I, II, III, IV and X (unstagable due to insufficient data) patients. We have now followed the above 482 stages I, II, III and X patients in whom CEA was performed less than or equal to 3 months after initial surgery at a time when there was no evidence of residual disease, for an average interval of 255 days from date of diagnosis. At present 16.2% (17/105) of patients with elevated CEA values compared to only 4.8% (18/377) of patients with normal values have developed recurrent disease (p less than .0005). There is an association of elevation of CEA postoperatively with different clinical stages of breast cancer. Elevated CEA levels postoperatively are associated with an increased risk of development of recurrent disease in breast cancer patients.

Breast Neoplasms↗

Gamma-glutamyltransferase in putative premalignant liver cell populations during hepatocarcinogenesis.

The activity of gamma-glutamyltransferase, as measured quantitatively and by histochemical staining, was studied in different cell populations during the induction of liver cancer with 2-acetylaminofluorene (2-AAF) or diethylnitrosamine and compared with findings in fetal and in intact and regenerating adult liver. The enzyme activity is 20-fold higher in 12-week nodules than in control livers and 30-fold higher in 20-week nodules than in controls. A similar 30-fold increase in activity relative to control is present in hepatomas, induced by either 2-AAF or diethylnitrosamine, and in fetal hepatocytes. The enzyme shows increases in activity in foci of very early putative preneoplastic hepatocytes induced by a single dose of diethylnitrosamine and selected by low doses of 2-AAF plus partial hepatectomy. By 7 days, the foci show a 4-fold increase in enzyme activity, and by 3 weeks they are 40-fold higher than in the control liver. Histochemically, the foci are strongly positive for gamma-glutamyltransferase, especially in the bile canaliculi. By 21 days, the ductular (oval) cells induced by 2-AAF have disappeared. When stained for the enzyme activity, the foci stand out clearly against the negative background of the liver, allowing easy quantitation. It appears that gamma-glutamyltransferase is a useful marker for preneoplastic hepatocytes.

2-Acetylaminofluorene↗

Radiologic, clinical and biochemical features of non-seminomatous testicular tumors.

Current therapy for metastatic non-seminomatous testis tumors is effective but toxic. Careful investigation is needed to select those who need treatment and yet avoid needless toxicity in patients who have no disease. Current radiographic investigations and measurement of two biochemical tumor markers (AFP & BHCG) provided accurate monitoring in 19 patients. Preoperative urography and lymphography correctly predicted the presence or absence of retroperitoneal metastases in 9 of 12 patients but did not show microsocpic metastases in 3. There was good correlation between the clinical, readiographic and biochemical evidence of disease progression and regression. Serial ultrasonography and tumor marker determinations were particularly useful in following asymptomatic abdominal metastases. Radiography and tumor marker determinations each have specific advantages which make them complementary.

Abdominal Neoplasms↗

Activation of thyroid adenyl cyclase by antisera to thyroid plasma membrane preparations.

Adenyl cyclase was assayed in a series of plasma membrane fractions prepared from bovine thyroids using sucrose density gradient ultracentrifugation. The activity of adenyl cyclase in the plasma membranes was found to be stimulated several-fold by antisera raised in rabbits against the plasma membranes and by purified IgG prepared from these antisera. The data indicate that the antibodies to thyroid plasma membrane manifest properties similar to those of the immunoglobulins long-acting thyroid stimulator (LATS) and human specific thyroid-stimulating immunoglobulin (HTSI) found in patients with Graves' disease. It is suggested that, in these patients, the antigen which leads to the production of LATS and HTSI is most likely situated in the thyroid plasma membrane.

Adenosine Triphosphatases↗

Placenta-like alkaline phosphatase in gynecological cancers.

In 302 patients with tumors of the cervix, corpus uteri, and ovaries, assessment by clinical staging (tumors-nodules-metastasis system) (4) and histopathology has been related to the presence of serum heat-stable, placenta-lide alkaline phosphatase (PLAP) activity. Early stages of cervical tumors show the highest incidence of this isoenzyme. In advanced stages of this disease, a decrease in frequency was observed that might be interpreted as the result of gradual dedifferentiation of the tumor cells to a point where synthesis of PLAP became undetectable. The same observation was made in adenocarcinomas of the corpus uteri, i.e., patients with advanced disease tended to have the lowest incidence of serum PLAP. Only in cancers of the ovaries did we find a positive correlation between this enzyme marker and the extent of the disease. In more than one-third of the patients examined, PLAP levels were an index of the tumor burden.

Adenocarcinoma↗