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Biomedical subjects

J R Carter

Publications and source records attributed to J R Carter.

At least 91 records · Page 5Linked to original sources

Proposal for a national autopsy data bank: a potential major contribution of pathologists to the health care of the nation.

This report highlights the salient deliberations of the Anatomic Pathology Committee of the College of American Pathologists (CAP) and of its consultants and advisors in formulating a proposal for the establishment of a National Autopsy Data Bank (NADB). It has constituted the major thrust of this Committee for the past five years and is presented in considerable detail in order to familiarize the pathology community and other interested parties with the plan, which, if implemented, would enable pathologists to contribute even further to the health care of the nation while concomitantly realizing benefits both individually and collectively. In order for the proposal to culminate in an optimally functioning NADB, the support and participation of a majority of, if not all, pathologists with autopsy responsibilities would be needed. Goals, objectives, justification, and merits, background, legal considerations, pilot studies, and management plans are discussed and the singular advantages that could accrue with implementation are delineated. If achieved, it would be the first time that any medical discipline or organization would have amassed such kinds of accurate biomedical information potentially so useful to so many for so little.

Autopsy↗

Misdiagnosis of bronchogenic carcinoma: the role of cigarette smoking, surveillance bias, and other factors.

The effects of cigarette smoking and other factors on the accuracy of clinical diagnosis of bronchogenic carcinoma were studied retrospectively in 14,074 autopsies performed over 26 years (1948-1973) at University Hospitals of Cleveland. Within a selected study group of 415 cases diagnosed as bronchogenic carcinoma either clinically, at atuopsy, or both, the disease was diagnosed accurately in 260 cases (63%), overdiagnosed in 38 cases (9%), and underdiagnosed in 117 cases (28%). Misdiagnoses occurred in female patients nearly twice as frequently as in male patients. Elderly men were over- and underdiagnosed more frequently than were young men. An accurate diagnosis of this neoplasm was strongly associated with a histroy of smoking and was also related to the number of hospital admissions, the diagnostic procedures used, and surveillance bias associated with a history of smoking or coughing. In 88% of the misdiagnosed cases, the tumor was either simulated or masked by other diseases. It is estimated from these data that the rate of unavoidable clinical misdiagnosis of the disease is 32% and the true error (overt misjudgment) in clinical diagnosis, 5%. Previous estimates of causal association between smoking and lung cancer would not be affected by the findings of this study.

Adult↗

Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis.

The difficulties encountered in establishing a diagnosis of a malignant peritoneal mesothelioma are emphasized in a patient who developed the lesion 16 years after radiation therapy for a seminoma of the testis. Historically, histologically, electron microscopically, and by microincineration, there was no evidence of asbestos exposure. We believe that present lesion may be a consequence of prior radiation therapy.

Dysgerminoma↗

Angiotensin-converting enzyme in sarcoidosis: a British study.

Serum angiotensin-converting enzyme (ACE) activity was measured in 18 healthy controls, 26 patients with active sarcoidosis, 13 patients with inactive sarcoidosis and seven patients with extensive tuberculosis. The serum ACE activity showed no significant difference between male and female in the control or sarcoidosis groups. There was no correlation between ACE activity and age except in the female active-sarcoid group. ACE activity in the active-sarcoid group was significantly higher than in the control, inactive-sarcoid and tuberculosis groups. The ACE activities at Stages I, II and III of the disease were not significantly different.

Adult↗

Metabolic effects of 2-deoxy-D-glucose in isolated fat cells.

The uptake and phosphorylation of 2-deoxy-D-glucose by isolated adipocytes of the rat was determined by a method of rapid flotation through oil coupled with separation of sugar from sugar phosphate by chromatography on Dowex-1-formate. Uptake of the sugar is rapid and linear over 5 min, with a gradual decline thereafter; by 1 h, no further uptake is observed. Initially only 2-deoxy-glucose phosphate is observed within the cells; by 1 h, however, free 2-deoxy-glucose accumulates to levels approximately those in the medium. Phosphorylation ceases when intracellular levels of 2-deoxyglucose phosphate are about 50 mM regardless of the medium concentration of 2-deoxyglucose; this does not represent feedback inhibition of hexokinase, since the enzyme in fat cell homogenates is not inhibited by 50 mM 2-deoxyglucose 6-phosphate. Accumulation of deoxyglucose 6-phosphate is associated with a marked decline in intracellular ATP levels. Fat cell respiration is also depressed by approximately 50 per cent after a 1 h preincubation with 10 or 20 mM 2-deoxyglucose. Intracellular ATP levels and O2 uptake are only partially corrected by the addition of pyruvate to the incubation medium. Since no glucose was present in the medium, and intracellular concentrations of glycogen are known to be small in adipose tissue, it is proposed that accumulation of 2-deoxyglucose 6-phosphate within fat cells has a direct inhibitory effect on cell respiration unrelated to inhibition of glycolysis. No increase in intracellular free fatty acids was observed to explain this, and under the conditions of the incubations it is unlikely that Pi availability was rate limiting. The exact locus of inhibition is unknown.

Adenosine Triphosphate↗

Cell surface changes in diabetic rats. Studies of lectin binding to liver cell plasma membranes.

We have previously reported changes in the chemical composition of cell surface membranes in diabetic rats (Chandramoulis, V. and Carter, Jr., J. R. (1975) Diabetes 24, 257-262 [1]). To examine the possible implications of these changes for cell surface structures, we have measured the binding of labeled lectins and desialylated glycoproteins to plasma membranes prepared from the livers of streptozotocin--diabetic and control rats. Lectins were chosen which have affinities for different carbohydrate moieties. The binding of ricin and concanavalin A to liver cell membranes from the diabetic rats was significantly reduced, but no change in the binding of wheat germ agglutinin was noted. Binding of desialylated thyrozine--binding globulin, previously shown to be dependent on membrane sialic acid residues, ws strongly suggest that insulin deficiency leads to generalized changes in cell surfaced glycoproteins, at least in this animal model of diabetes.

Animals↗

Renal tubular site of action of fluoride in Fischer 344 rats.

Methoxyflurane is capable of producing high-output renal failure in some patients and animal models, probably through metabolic liberation of free fluoride. The tubular site of action of fluoride was examined in Fischer 344 rats using clearance techniques. Free water reabsorption (TCH2O) and free water excretion (CH2O) were measured during mannitol or water diuresis in control rats and in rats given methoxyflurane or pretreated with sodium fluoride. Pretreatment produced statistically significant increases in urinary flow (from 10.5 +/- 1.4 to 20.1 +/- 1.9 mul/min/100 g b. wt.), in glomerular filtration rate (from 814 +/- 31 to 1,039 +/- 53 mul/min/100 g b. wt.), in per cent sodium excretion (from 0.107 +/- 0.008 to 0.155 +/- 0.015 per cent), and in per cent water excretion (from 1.27 +/- 0.15 to 2.00 +/- 0.20 per cent). Free water excretion remained relatively unaltered in rats pretreated with fluoride, perhaps due to elevated glomerular filtration rate and/or reduced proximal tubular reabsorption combined with inhibition of reabsorption in the ascending loop. Percentage free water reabsorption, on the other hand, was markedly reduced by the pretreatment, from 2.66 +/- 0.21 to 0.66 +/- 0.09 per cent. The observations are consistent with the hypothesis that fluoride inhibits tubular reabsorption primarily in the medullary portion of the ascending limb of Henle's loop, perhaps by inhibition of an active chloride pump located in this nephron segment.

Animals↗

Regulation of lipolysis in adipose tissue.

The normal human or animal has a series of finely coordinated and overlapping control mechanisms that regulate the storage or release of fat according to the overall energy requirements of the body. We have examined only one side of this system, the part responsible for the release of fatty acids from adipose tissue. Considerable information is available on the extracellular factors that control lipolysis on a minute-to-minute or day-to-day basis, but less is known about long-term regulation or about the precise role of intracellular factors that almost surely condition the response of the fat cell to external stimuli. When one poses the question of what determines the overall fat mass or adiposity of an individual, even less is known. Psychogenic factors regulating food intake, circulating hormonal signals, and local regulators of metabolism in the adipose tissue may all play a role. This remains an intriguing but elusive problem to be answered by future research.

Adenosine↗

Storage and retrieval of SNOP-coded pathologic diagnoses using offsite computing and optical character recognizing systems.

A computerized cross-reference system for retrieving autopsy and surgical pathology cases on the basis of case number or diagnosis has been implemented. The system achieves economy and flexibility by using offsite computer service bureaus for job production, eliminating the need for expensive onsite equipment. Coded diagnoses may be typed using the OCR (Optical Character Recognition) font simultaneously with or separately from the clinical documentation. The flexibility of new OCR equipment permits production of machine-readable code sheets with an ordinary pencil and completely eliminates the need for typing. The system produces year-to-date books that list all diagnoses, on an accumulating basis, in alphabetic order by SNOP* topology, morphology, etiology and function, and will be compatible with SNOMed. Because all data are stored on magnetic tape, they may be manipulated and retrieved as desired through user programming. The initial setup cost was dollar 1,000 for programming and testing, and production runs and all report printing cost about dollar 1,000 per year (autopsies and surgical pathology cases), which is about 1.1 cents per diagnosis.

Computer Systems↗

Community screening for diabetes by blood glucose measurement. Results of a five-year experience.

The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of the positives were retested, and 65 per cent of these again had two-hour levels greater than 139 mg. per cent. Seventy-one per cent of the original screening values were between 104 and 199 mg. per cent. The rate of positivity on retesting increased with the original screening bracket reaching 90 per cent at an original screening level of 240 mg. per cent or higher. The frequency of positive retests also increased with age irrespective of whether the original screening level was less than or greater than 200 mg. per cent. The implications of this large detection experience for conducting future mass surveys for diabetes are discussed.

Age Factors↗

Biogenesis of erythrocyte membrane proteins. In vivo studies in anemic rabbits.

To study the process of red cell membrane protein synthesis we have followed the time course of [3-H]leucine appearance in total protein and individual peptides of the erythrocyte membrane following injection of the amino acid into phenylhydrazine-anemic rabbits. Multiple peripheral blood samples were taken from single animals over a 5-week period. Erythrocyte membrane proteins were separated by polyacrylamide gel electrophoresis in sodium dodecylsulfate and dithiothreitol; incorporation of radioactivity was determined by gel slicing and liquid scintillation spectrometry. Appearance of [3-H]leucine in circulating erythrocytes reached a peak at 1-3 days, with a steady decline thereafter. The radioactive amino acid appeared first in the lowest molecular weight peptides and last in the largest peptides; at the earliest time point (8 h), little radioactivity was observed in any of the four largest peptides present in the membranes (bands A, 1, 2 and 3). Certain smaller peptides (bands 4, 5 and 9) were the predominant species labeled at this time. By 24 h all peptides showed significant incorporation. With maturation of the red cells, label largely disappeared from bands A, 9 and several smaller peptides; this was confirmed by finding that the peptides are virtually absent from mature circulating erythrocytes. These data are interpreted as showing that red cell membrane proteins are synthesized asynchronously during the life cycle of the erythrocyte; the largest peptides are made predominantly in the earlier marrow stages of development, while certain of the smaller peptides are still being synthesized in the reticulocyte stage. Several membrane proteins appear to be specific to the reticulocyte and are lost during the process of cell maturation in the circulation.

Anemia↗

Biogenesis of erythrocyte membrane proteins. In vitro studies with rabbit reticulocytes.

The capability of rabbit reticulocytes to synthesize red cell membrane proteins has been tested in vitro. Reticulocyte-rich blood from phenylhydrazine-treated rabbits was incubated in vitro in a complete amino acid medium containing ferrous salts, glucose, rabbit plasma and [3-H]leucine. Red cell ghost membranes were prepared by hypotonic lysis and leucine incorporation into hemoglobin and total membrane proteins determined. The pattern of incorporation into individual peptides was determined by polyacrylamide gel electrophoresis of labeled membranes on large (19 mm) gels which were then sliced into 1 mm sections; radioactivity was compared with densitometric tracings of Coomassie blue stained analytical (6 mm) gels. Incorporation of [3-H]leucine into both hemoglobin and membrane protein was linear over 1 h. Gel analysis of labeled membranes revealed that the amino acid was primarily incorporated into peptides with molecular weights of 90 000 or less; three peptides of molecular weights 90 000, 60 000 and 33 000 showed the highest specific activity. Synthesis of the four largest peptide species was negligible. Removable of ferrous salts inhibited synthesis of both globin and membrane protein equally (approx. 50%). However, puromycin and cycloheximide preferentially inhibited the synthesis of globin as compared to membrane proteins. Reticulocytes remain capable of synthesizing a number of membrane proteins; these results are consistent with studies of red cell membrane synthesis in anemic rabbits in vivo.

Anemia↗