Use of enhanced computerized tomography to evaluate osmotic blood-brain barrier disruption.

Enhanced computerized tomography (CT) is a noninvasive means of monitoring blood-brain barrier (BBB) disruption. In the present study this technique was used to monitor the degree, distribution, extent, and reversibility of osmotic BBB disruption. With a canine model, the timing of administration of iodinated contrast agent was shown to be crucial to optimize enhancement by CT of the disrupted BBB.

Malignant pineal region tumors. A clinico-pathological study.

Eight patients with primary malignant pineal tumors have been seen at this institution over the past 6 years; six of them underwent definitive surgical exploration. Complete gross microsurgical excision of well encapsulated tumors was possible in four of these patients. In two cases of pineal germinomas, a biopsy and a subtotal resection were carried out because of the known radiosensitivity of this tumor.

An immunologic approach for the detection of tumor cells in the peripheral blood of patients with malignant lymphoma; implications for the diagnosis of minimal disease.

Lymphocytes were isolated from infiltrated lymph nodes and blood of eight patients with malignant lymphocytic lymphoma. All patients had normal numbers of circulating lymphocytes with normal morphology. None of the patients had serum paraproteins.

Osmotic blood-brain barrier disruption. Computerized tomographic monitoring of chemotherapeutic agent delivery.

The present study describes a canine model of transient reversible blood-brain barrier disruption with hyperosmolar mannitol infusion into the internal carotid artery. Studies in this model show that osmotic blood-brain barrier disruption before intracarotid infusion of methotrexate results in markedly elevated (therapeutic) levels of drug in the ipsilateral cerebral hemisphere. Levels in the cerebrospinal fluid correlate poorly and inconsistently with brain levels.

High-performance liquid chromatographic separation of cobalamins.

Physiological cobalamins were separated by means of high-performance liquid chromatography (HPLC). Optimal conditions for elution of methylcobalamin, adenosylcobalamin, hydroxycobalamin and cyanocobalamin were determined. Excellent separation and resolution of these physiological cobalamins by HPLC were achieved.

Nodular regenerative hyperplasia of the liver in a case of myelofibrosis with extramedullary hematopoiesis and secondary portal venous hypertension.

Nodular regenerative hyperplasia of the liver was identified at autopsy in a patient with myelofibrosis with extramedulary hematopoiesis, an association not previously reported. Portal venous hypertension, documented during the patient's terminal hospitalization, was ascribed, in part, to a high rate of blood flow through the enlarged spleen. Possible mechanisms accounting for the development of nodular regenerative hyperplasia of the liver, and evidence provided by this case pertinent to these mechanisms, are discussed.

Lack of effect of riboflavin deficiency on vitamin B12-related metabolic pathways and fatty acid synthesis.

The neurological sequelae of riboflavin deficiency posed the possibility that this tissue injury was mediated by defective vitamin B12 function due to the requirement for riboflavin-dependent oxidoreductase systems in B12 coenzyme synthesis and function. Studies of the B12-dependent enzymatic reactions (5-methyltetrahydrofolic-homocysteine methyltransferase and methylmalonyl coenzyme A mutase) in a fiboflavin-deficient rat model documented normal B12 activity in liver and neural tissue. In addition, examination of neural lipids and separation and analysis of neural fatty acids failed to reveal the increased odd chain fatty acids characteristically seen in the B12-deficient state.

Evaluation of a packaged kit assay of serum ferritin and application to clinical diagnosis of selected anemias.

The reliability of a radioimmunometric assay of serum ferritin concentration by a packaged kit was evaluated. In addition, application of the serum ferritin assay to the clinical evaluation of selected anemias was assessed. When appropriate serum dilutions were utilized, this method was sufficiently reproducible and reliable for application to the clinical laboratory.

Probable myeloblastic leukemoid reaction with disseminated sarcoidosis.

A 55-year-old woman had progressive weakness, weight loss, night sweats, fever, right-sided facial weakness, and hepatomegaly. Reticulonodular infiltrates were seen on chest x-ray film and a central filling defect was noted on liver scan. Study of the peripheral blood was noted on liver scan.

Some observations concerning the demographic and geographic incidence of carcinoma of the lip and buccal cavity.

The geographic and demographic data obtained during the Third National Cancer Survey have provided a perspective on etiologic factors and incidence trends for cancers of low frequency. The incidence of cancer of the lip, oral cavity and skin from this survey was compared to similar studies in 1947 and intra-regional patterns in one area of the Third National Cancer Survey (Dallas-Fort Worth Metropolitan SMSA) were evaluated. The average age-adjusted annual incidence of cancer of the lip in white men in this latter area was 11.

Purification and properties of acetyl coenzyme A synthetase from bakers' yeast.

Acetyl-CoA synthetase, utilized in a coupled reaction system, has been shown to be applicable to the spectrophotometric determination of propionic and methylmalonic acids in biological fluids. The isolation of acetyl-CoA synthetase from yeast is simpler than the purification from mammalian sources. This study also presents some properties of the yeast enzyme and compares it to the more extensively studied enzyme isolated from ammmalian tissue.

Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states.

A rapid sensitive spectrophotometric assay for the measurement of methylmalonic and propionic acids in urine is described. The assay is based upon the quantitation of propionic acid using acetyl coenzyme A synthetase isolated from baker's yeast. This enzyme is highly specific for acetate and propionate, and acetate interference is eliminated by conversion to citrate.

Radioisotopic assay of vitamin B12 in tissues.

The present study delineates the application of the radioisotopic competitive-inhibition assay for the measurement of vitamin B12 in tissues. The extraction of endogenous B12 from tissues was shown to be simple and complete. Proportional dilution studies suggest that tissue factors do not interfere with the assay.

Studies of the mechanism by which hepatic citrate synthase activity increases in vitamin B12 deprivation.

Hepatic citrate synthase activity has been shown to be increased 2- to 3-fold in vitamin B12 deficiency. Immunochemical titrations of the affinity chromatography-purified enzyme obtained from liver of animals with B12 deprivation demonstrated that this increase in activity was the result of a true increase in enzyme protein content. When fixed ratios of aliquots of normal and B12-deprived rat liver homogenates were mixed, the activity measured showed no change from the expected total citrate synthase activity based on the admixture ratios.

Biochemical and ultrastructural hepatic changes during vitamin B12 deficiency in animals and man.

Vitamin B12 deficiency has been shown to result in an increase in content and activity of the hepatic cytosolic enzymes of fatty acid synthesis. The present study demonstrated that ATP citrate lyase, an enzyme whose activity has been positively correlated with rates of fatty acid biosynthesis, also increased in the livers of B12-deficient animals. Total and specific activity of hepatic citrate synthase, an enzyme whose activity is unaffected by a variety of dietary and hormonal changes, also was found to be increased in the B12-deprived state.

Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient rats.

The intracellular localization of the enzymes in the vitamin B12 dependent pathway which involves the oxidation of propionate was studied in rat liver obtained from normal and vitamin B12 deficient rats as well as from man. The subcellular site of propionyl CoA carboxylase and the vitamin B12 dependent-methylmalonyl CoA mutase were determined. All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.

Effect of vitamin B-12 deficiency on the hepatic tissue concentration of acyl carnitines.

Concentrations of carnitine, acetyl carnitine, propionyl carnitine, and long chain acyl carnitines have been measured in hepatic tissue of normal and vitamin B-12 deficient rats using radiolabelled butyrobetaine to label carnitine pools. Increased levels of propionyl carnitine were seen in the livers of vitamin B-12 deprived animals when compared to those from normal animals. Methylmalonyl carnitine was not detected in the B-12 deprived animals.

A simplified and rapid quantitative assay for propionic and methylmalonic acids in urine.

Propionic and methylmalonic aciduria occur individually in inborn errors of metabolism and together in vitamin B12-deficient states. A method is described for the simultaneous and rapid extraction of these acids from urine and their quantification by a simple gas chromatographic technique. The assay is based upon the spontaneous and quantitative decarboxylation of methylmalonic acid (MMA) at 225 degrees C.