Biomedical subjects
Publications and source records attributed to J R Wright.
Weanling CD-1 mice were fed either a control diet or a diet deficient in niacin/nicotinamide for one month and then injected i.v. with 60, 80, 100, 120, 140, or 160 mg/kg streptozotocin. Mice on the deficient diet developed a higher incidence of diabetes and more severe hyperglycemia than those on the control diet.
Spontaneous hydronephrosis was observed in 15 of 33 necropsied C57BL/KsJ mice. The gross and histological appearances of these lesions are described. Spontaneous hydronephrosis is rare in mice and has not been previously described in this strain. At least four different mutations are reported to cause hydronephrosis in the mouse; each is associated with a high incidence of severe skeletal defects. Because no skeletal malformations were observed in the present study, it is likely that either a multigenic trait which has been present for a long time but is expressed variably, or a mutation other than those previously described may be responsible for hydronephrosis in C57BL/KsJ mice.
Multiple i.p. injections of low-dose streptozotocin (40 mg/kg) produce insulitis, beta cell destruction, and diabetes in male CD-1 mice. Recent data also suggest that macrophages figure in the low-dose streptozotocin model. Because other recent studies have shown that essential fatty acid deficiency prevents autoimmune nephritis in mice, decreases the number of resident Ia-positive glomerular macrophages, and decreases the elicitation of macrophages into the glomerulus in inflammation, we examined the effect of essential fatty acid deficiency on the incidence and severity of insulitis and diabetes in CD-1 mice treated with low-dose streptozotocin. Streptozotocin-treated mice on the control diet uniformly developed diabetes (19/19). Essential fatty acid-deficient mice treated with streptozotocin did not develop diabetes (1/13). Mean plasma glucose levels for the control and essential fatty acid-deficient mice were 384.5 +/- 23.6 and 129.1 +/- 15.5 mg/dl, respectively, at the end of 1 month. To discern whether essential fatty acid deficiency prevented the streptozotocin-induced beta cell injury or the inflammatory response to injured beta cells, mice were repleted with daily injections of 99% pure methyl linoleate beginning 3 days after the last streptozotocin injection. These mice also quickly developed severe (3/4) or mild (1/4) diabetes. Histologic examination of the pancreata of control mice or repleted mice showed marked insulitis and beta cell destruction; in contrast, the pancreata of essential fatty acid-deficient mice showed preservation of beta cells and only focal mild peri-insulitis. Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in low-dose streptozotocin-treated CD-1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.
An elective course focusing on exercise physiology and cardiovascular fitness has been offered since 1984 to a limited number of freshman and sophomore students at Saint Louis University School of Medicine. The course consists of a series of weekly lectures. Following each lecture, the students participate in a self-designed fitness program and agree to follow the program on their own time at least two days per week. Using bicycle ergometry testing, the instructors estimated the maximum oxygen consumption for each student before and after completion of the course, and the results over the four years indicate an average increase of 15 percent. The students' evaluation of the course has been favorable. The potential benefits of such a course are discussed.
Nordic ski-jumping fatalities are rare events. Six jumping fatalities have occurred in the United States during the past 50 years. The fatality rate for nordic ski jumping, estimated to be roughly 12 fatalities/100,000 participants annually, appears to be within the range of fatality rates for other "risky" outdoor sports. Cervical fractures appear to be the most frequent fatal ski-jumping injury.
Three weekly intraperitoneal injections of complete Freund's adjuvant (CFA) and, 1 day later, low-dose streptozocin (STZ; 25 mg/kg i.p.) have been reported to cause immune destruction of beta-cells and a gradual onset of diabetes mellitus. In this study, male Lewis rats were injected intraperitoneally with CFA and 1 day later with low-dose STZ; these were repeated at weekly intervals for 3 wk. The incidence of diabetes mellitus (nonfasted plasma glucose greater than 200 mg/dl) in wk 1, 2, 3, and 4 was 50, 80, 93, and 100%, respectively. Rats receiving either CFA or STZ only did not develop diabetes. Injections of either the components of CFA (incomplete Freund's adjuvant and Mycobacterium butyricum), another granuloma-inducing organism (Listeria monocytogenes), or endotoxin before STZ induced diabetes, but the onset was slower and the diabetes was less severe than with CFA and STZ. Because intraperitoneal CFA injections caused peritoneal irritation, acute weight loss, and hypoglycemia on the day after injection, we examined whether fasting alone potentiated low-dose STZ. Fasting for 24 h before and 24 h after low-dose STZ caused diabetes that was similar in rapidity of onset and severity to that induced with CFA and STZ. Administration of CFA subcutaneously before STZ did not cause hypoglycemia or weight loss but did cause diabetes. Thus, the fasting effect of intraperitoneal CFA was not responsible for the induction of diabetes with CFA and STZ. These data indicate that immunologic adjuvants, endotoxin, and fasting all potentiate the diabetogenic action of low-dose STZ.(ABSTRACT TRUNCATED AT 250 WORDS)
Lactation records of cows first calving between 18 and 35 mo were combined with linear type ratings assigned during the same lactation if before 43 mo. Phenotypic relationships were examined between final score and 13 type appraisal traits and first lactation milk yield from 2935 Ayrshire, 3154 Brown Swiss, 13,110 Guernsey, 50,422 Jersey, and 924 Milking Shorthorn records. Most phenotypic correlations between type and milk yield were low. Linear correlations of final score with first lactation milk yield were .18 to .38. Of the linear functional type traits, correlations with first lactation yield had greatest absolute values for dairy character (.19 to .53), udder depth (-.26 to -.30), and rear udder width (.20 to .31). Multiple correlations of all type appraisal traits with first lactation milk yield ranged from .41 to .59. Herd-year-season components of variance averaged 25% for type traits. Herd-year-season with sire interaction averaged 4%. Heritability estimates for final score from paternal half-sib analysis were from .11 to .21. Heritability estimates for linear traits ranged from .01 to .37. Genetic correlation between milk and final score was positive for Guernseys (.25) and Jerseys (.21). Genetic correlations between yield and most linear type traits were low to moderate except for dairy character (.53 to .77).
An example of malignant fibrous histiocytoma (MFH) of the stomach, manifesting initially as a pulmonary metastasis, is described. A review of the world medical literature yielded ten other examples of MFH of the alimentary tract--four in the large intestine, two each in the small intestine and rectum, and one each in the esophagus and stomach. Patients ranged in age from 17 to 74 years, and all but one were males. Histologically, 91% of the tumors were of the pleomorphic type, with or without an associated storiform pattern. Six of the 11 patients died, two postoperatively and four with tumor, while the others were alive from 14 months to eight years after therapy. The distinction between gastric MFH and leiomyosarcoma is discussed.
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Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, hand-picked with a Pasteur pipette, and incubated in tissue culture media supplemented with recombinant murine interferon-gamma (rIFN-gamma), recombinant murine tumor necrosis factor (rTNF), or both. IAk-molecules could be identified on the surface of islets incubated for 5 days with a combination of rIFN-gamma (1, 10, or 100 ng/ml) and rTNF (10 or 50 U/ml) by indirect immunofluorescence. Optimal concentrations of rIFN-gamma and rTNF, 10 ng/ml and 50 U/ml, respectively, were used in all subsequent experiments. Weak Ia-positivity could be identified on the surface of islets cultured with both cytokines for as little as 48 hours; however, the staining appeared most intense after 5 days of culture. Intensely Ia-positive islets were then carefully washed and cultured in media without either cytokine; Ia positivity could be identified on the surface of these islets for up to 1 week. Dispersed islet cells were cultured with rIFN-gamma alone (10 ng/ml), rTNF alone (50 U/ml), or both cytokines for 5 or 10 days. After either 5 or 10 days of culture with both cytokines, intense immunofluorescent staining for Ia could be identified on the surface of greater than 80-90% of the viable islet cells. Culture with IFN alone for 10 days resulted in 15-20% Ia positivity; culture with TNF alone did not cause Ia expression.
The alveolar type II cell which synthesizes and secretes surfactant also plays a major role in the reuptake of surfactant lipids. In a recent in vivo study we found that the subfractions of natural surfactant that contained the surfactant protein with molecular weights of 26,000-36,000 (SP-26-36) were preferentially taken up into lamellar bodies of type II cells to a greater extent than were fractions that did not contain SP-26-36. Because the subfractions of natural surfactant in that study differed in other properties than the presence or absence of SP-26-36, the current study was undertaken to determine whether purified SP-26-36 enhanced the uptake of surfactant-like lipids by freshly isolated type II cells. SP-26-36 increased the uptake of label in radioactive surfactant-like lipids by up to 10-fold, and the effect of SP-26-36 was dependent on time, protein concentration, and temperature. The enhancement was inhibited by heat-treating the protein, by a polyclonal antibody against SP-26-36, and by metabolic inhibitors. The distribution of radioactivity in cell-associated phospholipids differed if cells were incubated with or without SP-26-36. If SP-26-36 was present during the incubation, greater than 96% of the radioactivity remained associated with phosphatidylcholine. In the absence of SP-26-36, only 85% of the radioactivity remained associated with phosphatidylcholine and 7% of the label appeared in phosphatidylglycerol. We hypothesize that SP-26-36 may act as a ligand to direct surfactant lipids to type II cells, perhaps to different metabolic pathways, and to regulate recycling and surfactant homeostasis.
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Two cases of oral amyloidosis are reported. In each case there were unusual oral manifestations. In the first case the patient's only complaints were of recurrent swelling of the submandibular glands and xerostomia. The diagnosis of amyloidosis was determined from a labial salivary gland biopsy. In the second case an enlarged tongue had produced displacement of the teeth, causing malocclusion. The resulting difficulty in chewing stimulated the patient to seek advice. In each case the diagnosis was confirmed by electron microscopy, Congo red staining, and serum and urine electrophoresis.
Pulmonary surfactant is synthesized and secreted by alveolar type II cells. Radioactive phosphatidylcholine has been used as a marker for surfactant secretion. We report findings that suggest that surfactant inhibits secretion of 3H-labeled phosphatidylcholine by cultured rat type II cells. The lipid components and the surfactant protein group of Mr 26,000-36,000 (SP 26-36) inhibit secretion to different extents. Surfactant lipids do not completely inhibit release; in concentrations of 100 micrograms/ml, lipids inhibit stimulated secretion by 40%. SP 26-36 inhibits release with an EC50 of 0.1 microgram/ml. At concentrations of 1.0 microgram/ml, SP 26-36 inhibits basal secretion and reduces to basal levels secretion stimulated by terbutaline, phorbol 12-myristate 13-acetate, and the ionophore A23187. The inhibitory effect of SP 26-36 can be blocked by washing type II cells after adding SP 26-36, by heating the proteins to 100 degrees C for 10 min, by adding antiserum specific to SP 26-36, or by incubating cells in the presence of 0.2 mM EGTA. SP 26-36 isolated from canine and human sources also inhibits phosphatidylcholine release from rat type II cells. Neither type I collagen nor serum apolipoprotein A-1 inhibits secretion. These findings are compatible with the hypothesis that surfactant secretion is under feedback regulatory control.
We hypothesized that when the lung makes the transition from the fluid- to the air-filled state at birth, there are changes in physical and functional properties of the alveolar surfactant. To test this hypothesis, newborn rabbits were killed at different times in the first 24 h of life, their lungs lavaged with ice-cold saline, and the lavage fluid subfractionated by differential centrifugation. The phospholipid and protein content and composition and the kinetics of surface tension lowering of the subfractions were examined. We found that with the onset of breathing, shifts occur in the distribution of surfactant subfractions as a surfactant apoprotein-free phospholipid fraction is generated. The ratio of rapidly sedimentable apoprotein-rich to slowly sedimentable, apoprotein-free fractions decreases from 31 at birth to 4 at 24 h of life. Concurrently, rates of surface tension lowering by the subfractions increase with time. The results suggest that the adult pattern of pool sizes and surface activity of alveolar surfactant is not present at birth but evolves slowly over the 1st day of life.
Despite the grave difficulties that beset researchers who are trying to isolate and characterize the various intracellular and extracellular forms of lung surfactant; despite the serious ambiguities of interpretation of experimental data caused by the multicomponent nature of the surfactant; despite the inaccessibility for diagnostic purposes of this material, which functions deep in the lungs; despite the fact that incisive methods of protein chemistry and molecular biology have only recently been brought to bear on lung surfactant; despite all these problems, our knowledge and understanding of lung surfactant are rapidly increasing. We know now that it is a dynamic system with many parts, and that the reserves of these are normally not large and are recycled. We believe that tight metabolic control must exist to maintain these reserves, and we already have experimental techniques to raise or lower the reserves. Heroic methods of surfactant substitution are now being tested in patients whose deficiency or risk thereof is sufficiently desperate, and the results of these clinical trials, if they are carefully documented with lung function data, will add a new dimension to our knowledge of surfactant dynamics. We may expect in the future that more subtle alterations in surfactant function will become detectable and more sophisticated methods to manipulate the system will be invented. Essential to these will be a deeper understanding of surfactant forms, pathways, kinetics, and controls. Fortunately, research on surfactant structure, metabolism, and turnover intrigues many investigators. They, we may hope, will soon provide the necessary information.
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Effect of nonrandomness of bulls' mates on daughter milk yield was examined from first lactation records of cows with birth dates in 1965 and later. Results were based on 67,081 Ayrshire, 77,633 Brown Swiss, 241,486 Guernsey, 1,433,761 Holstein, 291,201 Jersey, and 10,465 Milking Shorthorn records. Extent of assortative mating was examined. Correlations between sire Predicted Difference and dam (mate) Cow Index for individual years ranged from -.08 to .20. Correlations for all records within herd-year (.00 to .02) indicated essentially no assortative mating for milk yield for any breed except Ayrshire. For Ayrshires, negative assortative mating was indicated by a correlation of -.07. Within-sire regressions of daughter milk yield deviated from contemporary average (which had been adjusted for average Predicted Difference of contemporaries' sires) on dam Cow Index (merit of mates) by breed were .84 to 1.08. Expected regression was 1.00. Effect of merit of mates on sire evaluation was determined by comparing evaluations from standardized yield with those from standardized yield minus dam Cow Index. Correlations between evaluations for 4233 Ayrshire, 5275 Brown Swiss, 13,742 Guernsey, 32,572 Holstein, 13,688 Jersey, and 1240 Milking Shorthorn bulls rounded to 1.00 except for Milking Shorthorns (.99); average absolute differences in evaluations were 9 to 16 kg, and maximum differences were 49 to 118 kg. Adding an adjustment to Sire Summaries to account for nonrandomness of mates would do little to increase accuracy.