Carcinoembryonic antigen and humoral antibody response in patients with thyroid carcinoma.

Carcinoembryonic antigen and antibodies to thyroglobulin and to a microsomal fraction of thyroid were measured. Persons examined were normal volunteers, patients with thyroid cancer, and patients with a history of childhood irradiation to the thymus and/or tonsil who were otherwise normal. Elevated antigen and antibodies were most frequently found in the cancer thyroid group. Thyroid cancer patients with no previous history of childhood irradiation were more frequently positive for antigen and antibodies than all other categories studied. Thyroid cancer patients with a previous history of childhood irradiation showed normal frequencies of antigen and antibodies. The results suggest that the antigenic expression and host response to the tumor in patients with thyroid cancer depend on its pathogenesis. Mention is made of similar findings in animal model systems.

The further heterogeneity of creatine kinase. Presence of isoenzymes of cathodic mobility in rat tissues.

Supernatant fractions from rat tissue homogenates were examined for creatine kinase (EC 2.7.3.2) isoenzymes by agarose gel electrophoresis at pH 8.6. The distribution of the various isoenzymes, and their relative contributions to the total tissue creatine kinase, is stated. A previously unreported isoenzyme associated with brain and kidney preparations is described. It is a minor contributor to brain creatine-kinase activity but is the major isoenzyme for kidney. The presence of an additional isoenzyme for cardiac tissue was confirmed; this isoenzyme exhibits similar levels of activity to that of the MB isoenzyme.

Carcinoembryonic antigen: increased plasma levels in recessive epidermolysis bullosa.

Circulating plasma levels of the oncofetal antigen, carcinoembryonic antigen, were examined in 18 patients with various forms of epidermolysis bullosa. Carcinoembryonic antigen was markedly elevated in the plasma of 4 of 6 patients with recessive dystrophic epidermolysis bullosa and in 1 of 2 patients with recessive epidermolysis bullosa letalis. In contrast, patients with dominantly inherited forms of the disease, dominant epidermolysis bullosa simplex and dominant dystrophic epidermolysis bullosa, had normal levels of antigen. In the recessive patients, the plasma levels of carcinoembryonic antigen appeared to correlate with the severity of cutaneous involvement. Alternatively, it is possible that expression of carcinoembryonic antigen is genetically linked to certain forms of recessive epidermolysis bullosa or is part of a pleiotropic effect of the gene coding for the disease.

Serum albumin and antibodies in the diagnosis of thyroid cancer.

Anti-thyroglobulin antibodies, anti-thyroid microsomal antibodies, serum thyroglobulin, and carcinoembryonic antigen were assayed in sera of patients with a history of thyroid irradiation and in patients with thyroid cancer. In irradiated patients, the frequency of positive results for each test was increased above the frequency found in a control population, with a significant increase at P less than .05 for TGHA and TG levels. However, the tests (with the exception of serum thyroglobulin) did not clearly segregate irradiated patients with benign or malignant lesions from those with no clinically detectable abnormalities. Elevations of serum thyroglobulin above 300 ng/ml were found only in patients with thyroid cancer, but in these patients the diagnosis was usually clinically obvious.

Acute effect of ascorbic acid infusion on carbohydrate tolerance.

Large doses (1 to 2g/3 hr) of ascorbic acid were administered intravenously to normal weight and obese, nondiabetic subjects. Glucose tolerance and fasting plasma glucose levels were unaffected, despite a 3- to 8-fold rise in plasma concentrations of the vitamin. Infusion of ascorbic acid did not alter fasting serum insulin levels in normal subjects, but was associated with lower concentrations of hormone during an intravenous glucose tolerance test. Plasma glucose, serum insulin, growth hormone, and glucagon levels in obese subjects remained unchanged during the ascorbic acid infusion.

The protein-sparing action of protein feeding: absence of relationship to insulin secretion.

The influence of a 2-day fast was compared with that of a modified fast (1.5 g beef protein hydrolysate per kg body wt) on nitrogen metabolism and insulin secretion in three normal young men. During the fast urinary urea excretion indicated a negative nitrogen balance of 10 to 12 g daily in each subjects. With protein feeding nitrogen equilibrium was approached in each instance. Insulin secretion as indicated by the urinary excretion of C-peptide dropped profoundly with fasting to levels which averaged just 13 to 22% of the control base-lines and remained at about these levels during the protein feeding. The fact that this sensitive indicator of insulin secretion disclosed no significant difference during fasting and protein feeding provides strong evidence that the protein-sparing influence of protein feeding cannot be ascribed to the decline in insulin secretion.

Nonalcoholic liver disease. Overlooked causes of liver injury in patients with heavy alcohol consumption.

Alcoholic subjects with abnormal liver chemistry studies are often assumed to have alcoholic liver disease, even though the diagnosis is not established by liver biopsy. To determine the magnitude of nonalcoholic liver disease in patients with heavy alcohol consumption, the data on 145 consecutive patients judged to consume at least 80 g of alcohol daily for prolonged periods, and who underwent liver biopsy at the University of Chicago, were reviewed. Nonalcoholic liver disease was suspected clinically and confirmed by liver biopsy in 40 (28 per cent), whereas alcoholic liver disease was suspected in 105 but confirmed in only 83 (80 per cent). The remaining 22 patients had liver disorders, including cholangitis or pericholangitis, acute hepatitis or some form of chronic hepatitis, for which they required appropriate therapy. Neither clinical features, hepatitis B surface antigen (HBsAg), anti-HBsAg nor serum glutamic oxaloacetic transaminase to serum glutamic pyruvic transaminase (SGOT:SGPT) ratios distinguished these 22 patients from those with alcoholic liver disease. Thus, liver biopsy is necessary for the identification of nonalcoholic liver disease in patients suspected of harboring alcoholic liver disease, since other clinical features do not allow identification of these patients.

Age, sex and gonadal influences on oestrogen receptor content in the rat liver.

Liver cytosol oestrogen receptor (OR) content of intact and gonadectomized male and female rats of defined age (1-18 months) was measured by the controlled pore glass bead assay. The OR content of animals of both sexes aged 3 weeks was low to insignificant (0.12 +/- 0.04 (S.E.M.) pmol/g wet wt liver). In the intact animal, liver OR reached maximum levels at an earlier age in the male (1.35 +/- 0.12 pmol/g at 28-32 weeks) than in the female (4.89 +/- 0.17 pmol/g at 44-52 weeks). In the mature female the OR is thus maintained at a level threefold greater than in males of comparable age. Levels of OR in the gonadectomized male tended to be higher, at all ages, than those in the intact male but this difference was not statistically significant. Ovariectomy was associated with a decreased OR content in rats aged less than 6 months and an increase in the older rats, but these effects (of ovariectomy) were not statistically significant. In the females, regression analysis of pooled data, combining all ages, indicated a significant positive correlation between OR and liver wet weight, independent of gonadal status; no such relationship was found with the males. The results indicate that factors influencing liver cytosol OR content include maturity, age and sex whereas the gonads have little obvious effect. These findings lend further support to the concept that sex differences exist in the liver.

Metabolic control in diabetic patients: assessment by hemoglobin A1 values.

Hemoglobin A1 concentrations were measured in 230 patients with diabetes mellitus. Diabetic patients controlled by diet alone had significantly lower HbA1 levels compared to the insulin or oral hypoglycemic treated groups. Only 13% of insulin-treated patients had HbA1 levels below 10%, while 26% of the oral agent treated group and 70% of the diet treated group fell into this range. The HbA1 levels correlated with fasting and nonfasting plasma glucose concentrations. However, in certain patients, discrepant results between these two variables were found. Hemoglobin A1 was measured on three or more occasions in 60 patients over a 1-yr period. An improvement was noted in 40%, no change in 38%, and a deterioration in 22%. Hemoglobin A1 measurements have proved to be useful in the follow-up and treatment of diabetic patients.

Effects of mild hyperinsulinemia on the metabolic response to exercise.

To assess the effects of mild hyperinsulinemia on the metabolic adaptations to exercise, five normal male subjects were studied during 2 cycles of 30 min rest followed by 60 min mild exercise. During one cycle, insulin was infused at a rate of 0.33 mU/kg/min. During both cycles, plasma glucose concentration was kept constant by a glucose-controlled glucose infusion system. Studies with and without insulin were performed in random order, with 30 min between studies. During the insulin infusion, plasma non-esterified fatty acids fell during rest and failed to rise with exercise, indicating a limited availability of this substrate to working muscle. Insulin infusion also inhibited the expected rise in glycerol and 3-hydroxybutyrate normally observed during exercise. Plasma lactate concentrations at the completion of exercise with insulin infusion were higher than after exercise without insulin infusion. Greater metabolic dependence on carbohydrate metabolism is suggested by an increased respiratory quotient during insulin infusion. Insulin infusion had no significant effect on the amount of glucose which needed to be infused for maintaining a constant plasma glucose during rest, but there was a large and significant difference in the need for infused glucose during exercise with and without insulin infusion. The results indicate that even mild hyperinsulinism interferes with normal metabolic responses to exercise, and suggest that fall in insulin concentration seen with exercise is an important regulatory process, not merely a secondary consequences of a declining plasma glucose level.

Hemoglobin A1c and diabetes mellitus.

HbA1 is the result of the non-enzymatic glycosylation of HbA. HbA1 reflects the integrated blood glucose level that prevailed over a period of weeks; it thus has clinical application in the assessment of the long-term blood glucose control. This ability to determine easily the long-term blood glucose should enable the clinical investigator to gain insights into the relationship of glycemia and the complications resulting from long-standing diabetes mellitus.

Post-mortem glycosylated hemoglobin (HbA1c): evidence for a history of diabetes mellitus.

Glycosylated hemoglobin (HbA1c) levels on blood obtained from 28 cadavers were compared with that of healthy volunteers and patients with diabetes mellitus. Levels of HbA1c did not correlate with post-mortem intervals of four to 36 hours, suggesting that HbA1c is stable under these conditions. All deceased with a history of diabetes mellitus, five cases, had an elevated post-mortem blood HbA1c. Twenty-three deceased had a negative history for diabetes mellitus and seven of this group had an elevated HbA1c. These seven cases had diagnosis of malignancies and a history of prolonged exposure to steroids in excess compared to the remaining 16 cases.

Age and incidence of estrogen receptor positive breast tumors.

Estrogen receptors of primary breast cancer tumors were determined by sedimentation analysis. Positive tumors from pre- and post-menopausal patients were those that contained estrogen receptor content greater than 250 and greater than 750 fmoles per g wet weight tissue, respectively. A positive correlation of patients' age with increasing incidence of estrogen receptor positive tumors was found; test for linear trend significance z = 5.38 (P less than 0.001). One-sixth of those less than 29 years had positive tumors, 27 percent in the age group 40 to 49 years, 46 percent in those 70 to 79 years, and 62 percent in those 80 years or older.

Folate binding protein and the estrogen receptor in breast cancer.

Folate binding protein (FBP) and estrogen receptor (ER) content were determined in primary breast cancers of 48 patients. The mean FBP level was significantly higher in ER-negative tumors than in ER-positive tumors and largely independent of the degree of tumor involvement or menopausal status. FBP correlated negatively with ER and this was most marked for tumors from postmenopausal women. Since FBP may decrease available intracellular folate the present data support clinical findings that chemotherapeutic agents may be more effective for ER negative tumors.

Separation of estrogen receptors from nonspecific binding employing receptor antibodies.

Sedimentation analysis in the presence of monoclonal antibodies to the estrogen receptor results in a well-marked separation of the estrogen receptor peak from that containing significant amounts of nonspecific binding. This method has been applied to the study of liver and breast cancer cytosols. These findings are of importance in the study of breast cancer metastases and of endocrine-responsive organs such as the liver, that previously could not be readily analyzed because of the presence of significant amounts of nonspecific binding.

The effect of temperature and anoxia of kidney on the subsequent oxidative phosphorylation of mitochondria.

1. Kidneys were kept anoxic at 4 degrees , 20 degrees and 38 degrees . Mitochondria were then isolated and their oxidative phosphorylation and respiration were determined. 2. Under all conditions the rate of phosphate esterification was affected to a greater extent, or earlier, than oxygen consumption. 3. Glutamate and succinate were used as substrates. The depression of P/O ratio was greater for glutamate at 4 degrees , and for succinate at 20 degrees . 4. Anoxia abolished the inhibiting effect of fluoride on respiration. 5. Phosphate esterification, after anoxia, was higher in the presence of fluoride than its absence, whereas in control preparations they were the same. 6. The decrease in P/O ratio did not appear to be due to activation of adenosine triphosphatase, as activities of both Mg(2+)-and dinitrophenol-activated adenosine triphosphatases were decreased after anoxia.

Haemoglobin A1: An indicator of the metabolic control of diabetic patients.

The level of the minor glycosylated haemoglobins (HbA1) in ambulatory diabetic patients correlated closely with their physicians' ratings of the degree of control and their fasting plasma-glucose levels. In patients admitted to hospital for more detailed study, HbA1 correlated significantly with the mean fasting glucose, mean daily glucose, and highest daily glucose values. HbA1 measurement is a simple, rapid, and objective procedure to assess diabetic control and may serve both as a screening test for uncontrolled diabetes and as an indicator of the efficacy of various therapeutic regimens.