Meyer Friedman: type A behavior cardiovascular research continues. Interview by Nancy Yanes Hoffman.
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Biomedical subjects
Publications and source records attributed to M Friedman.
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Our experience with germ cell tumours of the ovary is reviewed. Over the last 10 years, 15 cases, representing 6,4% of all our referred patients with malignant ovarian tumours, have been analysed. The type of tumour, histological appearances, stage, treatment and results of treatment are presented. The tumour most commonly seen was the dysgerminoma, comprising 60% of all cases (9 patients). Multimodal treatment generally consisted of surgery and radiotherapy for dysgerminoma with the addition of chemotherapy for the non-dysgerminomas. Survival depends on the stage and histological appearances of the tumour. Patients in whom the disease is at advanced stages have a poor prognosis, irrespective of histological features. A general review of this subject is also given.
In cases of ovarian carcinoma distant metastases are rarely discovered before local spread has become evident. This article reports an unusual case in which renal metastases appeared 9 years after the initial diagnosis of epithelial ovarian carcinoma. A discussion of the histological features of the tumour and the spread of ovarian carcinoma is included.
Computed tomographic (CT) scanning has been used in the preoperative examination of patients with head and neck cancer. Although early reports on the use of CT scanning for cervical lymphadenopathy were encouraging, the accuracy of CT in detecting nodal metastases has not been well established. Fifty consecutive patients underwent radical neck dissection and preoperative CT scanning. The clinical staging of the neck, CT diagnoses, and pathologic findings were correlated; CT accuracy was then compared with clinical accuracy. Our findings show the overall accuracy of CT diagnoses to be 90%. Comparison with clinical accuracy shows the CT scan to be superior to the clinical examination, particularly in detecting occult metastases.
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A gas chromatographic (GC) method for monitoring valproic acid and valpromide in plasma was developed. The procedure involved a single solvent extraction of drugs from acidified plasma samples, followed by a GC injection of the organic phase. This rapid, sensitive, specific, and reproducible method is a key factor in pharmacokinetic and stability studies of valpromide. Pharmacokinetic application of the new GC method is presented by a simultaneous plasma monitoring of valpromide and valproic acid levels obtained after intravenous administration of valpromide to a dog.
Heat and alkali treatment of proteins catalyzes formation of crosslinked amino-acid side chains such as lysinoalanine, ornithino-alanine and lanthionine, and concurrent racemization of L-isomers of all amino acid residues to D-analogues. Factors that favor these transformations include high pH and temperature, long exposure, and certain inductive or steric properties of the various amino acid side chains. Factors that minimize crosslink formation include the presence of certain additives, such as cysteine or sulfite ions, and acylation of epsilon-NH2 groups of lysine side chains. Free and protein-bound lysinoalanine and D-serine induce nephrocytomegaly in rat kidney tissues. The presence of lysinoalanine and D-amino acid residues along a protein chain decreases its digestibility and nutritional quality. Understanding the factors that govern the formation of potentially harmful unnatural amino acid residues in food proteins and the toxic and nutritionally antagonistic action of these compounds in animals should lead to better and safer foods.
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Oxygen, oxidizing enzymes such as polyphenol oxidase (tyrosinase) and alkaline pH, irreversibly inactivate the mutagenicity of quercetin in the Ames test. The loss of mutagenic activity correlates with decreases in the ultraviolet absorption maximum of quercetin near 370 nm. The extent of inactivation increases with time but apparently not significantly with temperature of exposure, and decreases with quercetin concentration. Metal salts such as ferrous and copper sulfates also facilitate inactivation, but these effects may be reversible. Understanding the factors which minimize the mutagenic potential of food ingredients should lead to safer foods.
A simple and rapid method of isolating plasma membranes from human peripheral lung tissue is described. The method involves homogenization of tissue in 0.25 M sucrose-buffered medium followed by differential and sucrose density gradient centrifugation. Enzymatic and morphological characterization of the plasma membrane fraction revealed minimal contamination by nonplasma membrane fragments. The isolated plasma membranes showed an 18-fold purification of 5'-nucleotidase activity compared to the original homogenate. Electron-microscopic studies of the plasma membrane fraction revealed the presence of small membrane vesicles having a trilaminar membrane structure. To further examine the purity of the plasma membrane preparation, the binding of the H1 receptor antagonist, 3H pyrilamine, to the plasma membrane-enriched fraction was compared to the binding to crude membrane preparations. Both the plasma membrane-enriched fraction and the crude membrane preparation had similar Kd's for the histamine antagonist, but the plasma membrane-enriched fraction had a threefold greater binding capacity, reflecting the relative enrichment of plasma membranes of the preparation. Thus, a method has been developed for the isolation of plasma membranes from human peripheral lung which should provide material for a variety of biochemical and pharmacological studies.
Eight hundred sixty-two postmyocardial infarction patients volunteered to be randomly selected and enrolled into: (1) a control section of 270 patients, who received group cardiologic counseling; and (2) an experimental section of 592 patients, who received group type A behavior counseling in addition to group cardiologic counseling. Reduction in type A behavior at the end of 3 years was observed in 43.8% of the 592 participants, who initially were enrolled to receive group cardiologic and type A behavioral counseling. This degree of behavioral reduction was significantly greater than that observed in participants who initially were enrolled to receive only group cardiologic counseling. The 3-year cumulative cardiac recurrence rate was 7.2% in participants who initially were enrolled to receive group cardiologic and type A behavioral counseling. This was significantly less (p less than 0.005) than that (13%) observed in participants who initially were enrolled to receive only cardiologic counseling. This difference in recurrence rates was due to a lesser incidence of nonfatal infarctions in the patients who had been enrolled in the section receiving type A behavioral as well as cardiologic counseling. These data suggest that type A behavior can be altered in a sizable fraction of postinfarction patients and that such alteration is associated with a significantly reduced rate of nonfatal myocardial infarctions.
The cholesterol granuloma, a rare entity in the oral cavity, has been given little attention in the dental literature. As a result, there is a lack of accurate data regarding its nomenclature, pathogenesis, and histologic appearance. A new case of cholesterol granuloma in the oral cavity embedded in an odontoma is presented. The literature is reviewed and the nomenclature is clarified.
Combinations of oxygen and alkaline pH were found to inactivate irreversibly the mutagenicity of quercetin towards Salmonella typhimurium strain TA98. Exposure time, quercetin concentration and polyphenol oxidase were also important variables determining the extent of quercetin inactivation. Temperature had a relatively weak influence on the extent of inactivation. The metal salts, ferrous, ferric and copper sulphates also brought about inactivation but this effect was partially reversed when the pH of the incubation medium was reduced from 7 to 2. Ferric sulphate had a much smaller effect than did the ferrous salt except in the presence of tyrosinase and oxygen at pH 7. Zinc sulphate impaired quercetin mutagenicity only very slightly in the presence of tyrosinase and oxygen. When an oxygen-saturated solution of quercetin was exposed to tyrosinase at various pH values, the ultraviolet absorption maximum of quercetin near 370 nm decreased to an extent that correlated with the mutagenicity of quercetin under those conditions.
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Growth studies in mice fed synthetic amino acid diets showed that: 1) the biological utilization of D-phenylalanine relative to its L-isomer ranged from 28-81%, depending on the respective concentrations of these amino acids in the diet; 2) L-tyrosine can replace about one-half of the L-phenylalanine needed to achieve maximum weight gain and 3) D-tyrosine has no similar sparing effect on L-phenylalanine. In fact, addition of D-tyrosine to amino acid or casein diets depressed weight gain to 10% that of the control. This inhibition was significantly reduced by increasing the L-phenylalanine content of the amino acid diets and the protein content of the casein diets. Growth inhibition, therefore, appears to be related to the ratio of D-tyrosine to L-phenylalanine and possibly other amino acids in the diet, rather than to the absolute levels of D-tyrosine. Mechanistic rationalizations are offered to account for the toxic or antinutritional manifestation of D-tyrosine.
Heating soy flour at 45 degrees C in pH 8.5 Tris buffer for 1 hour in the presence of cysteine or N-acetylcysteine followed by dialysis to remove unreacted thiols resulted in the introduction of new half-cystine residues and lowered trypsin inhibitor content from 37.5 to 6.8 or 4.8 mg/g, respectively, compared to only 14.8 mg/g in the absence of sulfhydryl compounds. Presence of cysteine or N-acetylcysteine during treatment increased protein efficiency ratio (PER) from 0.95 to 2.01 or 2.20, respectively. Corresponding values at 65 degrees C are 1.61, 2.43 and 2.02; and at 75 degrees C, 2.14, 2.53 and 3.19, respectively. Proteins are modified through formation of mixed disulfide bonds, which leads to loss of inhibitory activity and increased protein digestibility and nutritive value.
Growth assays on a synthetic amino acid diet fed to mice showed that substituting D-methionine for the L-isomer resulted in a dose-dependent relative weight gain reaching approximately 76% when D-methionine was fed at a level equivalent to that optimal for the L-form. L-Cysteine and L-cystine stimulated growth in the presence of suboptimal levels of L-methionine, but D-cystine was growth depressing. L-Cystine is at least equally efficient in stimulating growth in the presence of D-methionine as in the presence of the L-isomer. Compared to a suboptimal (25% of maximum) level of L-methionine alone, supplements to this level L-methionine by N-acetyl-L-cysteine produced a weight gain of 214%; L-cysteine, 178%; L-cysteic acid, 154%; DL- + meso-lanthionine, 127%; L-cysteine sulfinic acid, 113%; D-cysteine, 76%; and S-methyl-L-cysteine, 13%. The observed growth-depressing effect of D-cysteine, D-cystine and S-methyl-L-cysteine at a concentration no greater than that optimal for methionine implies that these three sulfur-containing amino acids may be toxic. The results are discussed in terms of known and postulated transamination and transsulfuration pathways that govern the biological utilization of isomeric sulfur-containing amino acids and derivatives.
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