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Biomedical subjects

D M Larson

Publications and source records attributed to D M Larson.

At least 73 records · Page 4Linked to original sources

Influence of taste on dietary choice of rats fed amino acid imbalanced or deficient diets.

Diets with added quinine as the negative taste cue or saccharin as the positive taste cue were employed to determine the influence of taste on dietary choice of rats offered diets containing different proportions of amino acids (amino acid imbalance) and which differed in acceptability. The quinine was added to the protein-free or the corrected (corrected for amino acid imbalance) diet that animals normally preferred and the saccharine was added to the amino acid imbalanced or deficient diets that animals normally avoided. There appeared to be a balance in acceptance of a diet between the undesirability of the quinine and the degree of metabolic benefit from the diets with favorable metabolic or nutritional characteristics. Although the presence of higher levels of quinine could interfere with the normal dietary preference based on metabolic consequences, the animals invariably selected the metabolically favorable diet if they were forced to experience the metabolic characteristics of the diets by having to consume them exclusively. The presence of the taste cues appeared to enhance the acceptance or avoidance of diets in the choice regimens, possibly by aiding in their identification, especially to animals previously not exposed to the taste cues.

Amino Acids↗

Palliation of small bowel obstruction by percutaneous gastrostomy in patients with progressive ovarian carcinoma.

Percutaneous gastrostomy is a useful palliative technique for treatment of patients with bowel obstructions in advanced ovarian carcinoma. A description of the technique is presented along with a review of ten cases in which the procedure was used at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. In all patients, the procedure was well tolerated and associated with little morbidity. In applicable cases, percutaneous gastrostomy appears to be superior to both nasogastric suction and operative gastrostomy for palliation of small bowel obstruction in terminal ovarian cancer.

Catheterization↗

Central nervous system metastases in epithelial ovarian carcinoma.

With the advent of systemic chemotherapy capable of controlling metastases at most sites, central nervous system metastases are becoming more common in patients with epithelial ovarian carcinoma. A retrospective epidemiologic review at The University of Texas M. D. Anderson Hospital and Tumor Institute revealed central nervous system metastases in 13 of 4456 patients with epithelial ovarian carcinoma (0.29%) registered between 1944 and 1984. No patients were identified as having central nervous system metastases before 1968. The median survival overall was 29 months; following the diagnosis of brain metastases it was five months. Five of eight patients treated for central nervous system metastases lived ten months or longer. Patients with isolated metastases to the central nervous system lived longer than patients with accompanying systemic metastases. Patients treated with surgical resection lived longer than those who did not undergo surgery. With surgical resection, postoperative irradiation, and systemic chemotherapy, significant symptomatic improvement and long-term remission are possible.

Adenocarcinoma↗

Cross-sectional studies of personality in a national sample: 2. Stability in neuroticism, extraversion, and openness.

Data from the National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Followup Study were used to examine age differences in neuroticism, extraversion, and openness to experience. Cross-sectional analyses of data from 10,063 respondents showed that older subjects were slightly lower in neuroticism, extraversion, and openness; that age trends were not curvilinear; and that there were no differences in personality scores that might be attributable to a mild-life crisis or transition. Comparison with data from 654 participants in the Augmented Baltimore Longitudinal Study of Aging (ABLSA) showed that the ABLSA sample was lower in extraversion and higher in openness than the national sample, although the differences were small in magnitude. Results were interpreted to mean that sampling and attrition in this longitudinal sample did not seriously bias results on these personality variables, and that cross-sectional findings from a large probability sample support the conclusion that personality is predominantly stable in adulthood.

Adult↗

Reduced metabolic response of the rat brain to haloperidol after chronic treatment.

Local cerebral glucose utilization (LCGU) was determined, using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique, in 47 brain regions of awake rats, after acute and chronic haloperidol (HAL) administration (1 mg/kg or 1 mg/kg/day). LCGU was reduced in fewer regions after chronic HAL (19%) than after acute HAL (72%); the average reduction for all regions was smaller (8% and 25%, respectively). The reduced metabolic effect of chronic HAL is not due to a lower brain concentration of the drug, since similar effects on LCGU were found in rats which received an acute i.p. injection of HAL (as in the acutely treated animals) after chronic administration of HAL for 3 weeks. Furthermore, continuous infusion of HAL for 3 weeks or 1 day resulted in similar tolerance to the metabolic effect of HAL. Tolerance was not observed in the mesocortical dopamine (DA) system. The present findings show that tolerance develops to the effect of HAL on cerebral metabolism, even after 1 day of HAL treatment. Lack of tolerance in the mesocortical pathway may implicate this system in the neuroleptic effect of chronic HAL.

Animals↗

Junctional transfer in cultured vascular endothelium: II. Dye and nucleotide transfer.

Vascular endothelial cultures, derived from large vessels, retain many of the characteristics of their in vivo counterparts. However, the observed reduction in size and complexity of intercellular gap and tight junctions in these cultured cells (Larson, D.M., and Sheridan, J.D., 1982, J. Cell Biol. 92:183) suggests that important functions, thought to be mediated by these structures, may be altered in vitro. In our continuing studies on intercellular communication in vessel wall cells, we have quantitated the extent of junctional transfer of small molecular tracers (the fluorescent dye Lucifer Yellow CH and tritiated uridine nucleotides) in confluent cultures of calf aortic (BAEC) and umbilical vein (BVEC) endothelium. Both BAEC and BVEC show extensive (and quantitatively equivalent) dye and nucleotide transfer. As an analogue of intimal endothelium, we have also tested dye transfer in freshly isolated sheets of endothelium. Transfer in BAEC and BVEC sheets was more rapid, extensive and homogeneous than in the cultured cells, implying a reduction in molecular coupling as endothelium adapts to culture conditions. In addition, we have documented heterocellular nucleotide transfer between cultured endothelium and vascular smooth muscle cells, of particular interest considering the prevalence of "myo-endothelial" junctions in vivo. These data yield further information on junctional transfer in cultured vascular endothelium and have broad implications for the functional integration of the vessel wall in the physiology and pathophysiology of the vasculature.

Animals↗

Selective changes in local cerebral glucose utilization induced by phenobarbital in the rat.

Alterations in cerebral metabolic activity were measured after different doses of phenobarbital. Local cerebral glucose utilization was determined in 58 brain regions with the use of the [14C]deoxyglucose technique in 3-month-old Fischer 344 rats, at 1 h after the ip administration of saline or of phenobarbital. Whole brain glucose utilization declined in a dose-related manner by 4%, 13%, 33%, 35%, and 56% after phenobarbital 18, 60, 180, 300, and 600 mg/kg, respectively. The number of regions significantly affected (P less than 0.05) increased from 7 to 95% of the regions examined between doses of 18 to 600 mg/kg. Metabolism decreased in all significantly affected regions except the interpeduncular nucleus, where it was increased. In a separate group of rats, the number of falls per 5 min from a constantly rotating cylinder was measured at subanesthetic doses of phenobarbital. Doses of drug that affected performance on the rotating cylinder (18 and 60 mg/kg) reduced glucose utilization in brain regions involved with motor performance, including the red nucleus, vestibular nucleus, substantia nigra, and deep layers of the superior colliculus, whereas cerebral cortical regions were not altered significantly. The results demonstrate that phenobarbital reduces cerebral glucose utilization, in a dose-dependent manner, in most brain regions and affects subcortical regions of the motor system significantly before reducing metabolism in the cerebral cortex.

Anesthesia, General↗

Renin expression by vascular endothelial cells in culture.

Cultured bovine aortic endothelial cells were examined for renin activity by biochemical, immunological, and immunohistochemical techniques. When cell sonicates were incubated with renin substrate, linear generation of angiotensin I was observed (1.12 +/- 0.2 ng angiotensin I/10(6) cells per hr). The effect of pH on this activity was similar to that of bovine renal renin, and renin antibodies inhibited a large portion of the enzymatic activity. Furthermore, immunofluorescence microscopy with antirenin antisera confirmed the presence of renin within these cells. Biosynthetic radiolabeling, followed by immunoprecipitation, demonstrated de novo synthesis of a renin precursor in the endothelial cells, which was processed to a more mature protein. Thus, bovine aortic endothelial cells in culture contain and biosynthesize renin, a key component of the renin-angiotensin system. The expression of renin activity by endothelium may contribute to the local regulation of vascular tone.

Angiotensin I↗

Traumatic neuroma of the bile ducts with intrahepatic extension causing obstructive jaundice.

Most traumatic neuromas of the biliary tract occur in the cystic duct stump after cholecystectomy and produce no symptoms. The authors report the rare occurrence of traumatic neuroma of the bile ducts that arose from injury to the duct occurring during cholecystectomy. The neuroma blocked the common hepatic duct and extended into the left hepatic duct, causing obstructive jaundice. The pseudotumor was removed from the common hepatic duct, but intrahepatic extension prevented complete removal. The patient remains well ten years after the surgical procedure.

Adult↗

Myosin in cultured vascular smooth muscle cells: immunofluorescence and immunochemical studies of alterations in antigenic expression.

Vascular smooth muscle cells (VSMC) in the rat mesenteric artery show specific immunofluorescent staining with antisera against purified human uterine myosin (ASMM) but not human platelet myosin (APM). However, in primary cultures produced by enzymatic dissociation of this vessel, VSMC stain specifically with both ASMM and APM within 5 h after plating and throughout growth to confluence (4-10 d). In confluent cultures, APM staining remains bright while ASMM staining is reduced in intensity in most cells. In contrast, cellular myosin content, determined by quantitative SDS PAGE, is comparable in confluent and growing cultures. Immunoprecipitation of high salt extracts of cultured VSMC with ASMM and APM yields myosins with the same mobilities on SDS PAGE. When serial, exhaustive precipitations are performed with one antiserum, followed by reprecipitation with the other, myosin in subconfluent and confluent VSMC cultures is exhaustively precipitated by either antiserum, thus indicating complete immunological cross-reactivity. These results might be explained by synthesis of a new myosin isoform reactive with both ASMM and APM. However, the development of APM staining in cultured VSMC did not require protein synthesis. Therefore, it is more likely that the changes in immunofluorescent staining observed in vitro reflect conformational alterations, perhaps related to cytoskeletal rearrangements. These changes in myosin antigenic expression may be relevant to the problem of VSMC phenotypic modulation both in vitro and in vivo.

Animals↗

Heterogeneity of myosin antigenic expression in vascular smooth muscle in vivo.

Rabbit antisera elicited against purified human nonmuscle (platelet) and smooth muscle (uterine myometrium) myosins identified distinct species of myosin when frozen sections of a variety of mammalian tissues were examined by immunofluorescence microscopy. Antiplatelet myosin antiserum specifically stained several nonmuscle cell types including epithelial, some connective tissue, and all vascular endothelial (arterial, venous, capillary) cells. Antismooth muscle myosin antiserum stained only smooth muscle and no other cell types. Neither antiserum reacted with rat cardiac (ventricular) or skeletal muscle cells. Antismooth muscle myosin antiserum staining was detectable in medial vascular smooth muscle in all vessels examined from rat, bovine, human, and guinea pig sources (including elastic and muscular arteries, arterioles, venules, and veins). Although antiplatelet myosin antiserum did not stain nonvascular smooth muscle or vascular smooth muscle in muscular arteries, arterioles, venules, or veins, it did uniformly and specifically stain medial vascular smooth muscle in elastic arteries. This staining of elastic arteries was abolished by absorption of antiplatelet myosin antiserum with purified platelet myosin but not uterine myosin. Similarly, the reactivity of antismooth muscle myosin antiserum was abolished by incubation with uterine but not platelet myosin. The differences in staining patterns observed with antiplatelet myosin antiserum and antismooth muscle myosin antiserum in elastic arteries versus other blood vessels suggests a heterogeneity of antigenic expression in vascular smooth muscle myosin. The most likely explanations for this heterogeneity are the presence of different gene products (myosin isozymes) or a posttranslational alteration (possibly conformational) of a single myosin species. Heterogeneity in this important component of the contractile apparatus of vascular smooth muscle may have significant implications for the physiology and pathophysiology of the vessel wall.

Animals↗

Junctional transfer in cultured vascular endothelium: I. Electrical coupling.

Vascular endothelial cultures are composed of flat, polygonal monolayer cells which retain many of the growth, metabolic and physiological characteristics of the intimal endothelium. However, intercellular gap and tight junctions, which are thought to perform important roles in normal intimal physiology, are reduced in complexity and extent in culture. We have used electrophysiological techniques to test confluent (3- to 5-day) primary cultures of calf aortic (BAEC) and umbilical cord vein (BVEC) endothelium for junctional transfer of small ions. Both cell types are extensively electrically coupled. The passive electrical properties of the cultured cells were calculated from the decrease in induced membrane potential deflections with distance from an intracellular, hyperpolarizing electrode. Data analyses were based on a thin-sheet model for current flow (Bessel function). The generalized space constants (lambda) were 208.6 microns (BAEC) and 288.9 microns (BVEC). The nonjunctional (6.14 and 8.72 X 10(8) omega) and junctional (3.67 and 3.60 X 10(6) omega) resistances were similar for the BAEC and BVEC, respectively. We detected no statistically significant differences in the resistance estimates for the two cell types. In vivo ultrastructural studies have suggested that aortic endothelium has more extensive gap junctions than venous endothelium. We have found that these ultrastructural differences are reduced in culture. The lack of any significant difference in electrical coupling capability suggests that cultured BAEC and BVEC have functionally similar junctional characteristics.

Animals↗

Intercellular junctions and transfer of small molecules in primary vascular endothelial cultures.

The ultrastructure of gap and tight junctions and the cell-to-cell transfer of small molecules were studied in primary cultures and freshly isolated sheets of endothelial cells from calf aortae and umbilical veins. In thin sections and in freeze-fracture replicas, the gap and tight junctions in the freshly isolated cells from both sources appeared similar to those found in the intimal endothelium. Most of the interfaces in replicas had complex arrays of multiple gap junctions either intercalated within tight junction networks or interconnected by linear particle strands. The particle density in the center of most gap junctions was noticeably reduced. In confluent monolayers, after 3-5 days in culture, gap and tight junctions were present, although reduced in complexity and apparent extent. Despite the relative simplicity of the junctions, the cell-to-cell transfer of potential changes, dye (Lucifer Yellow CH), and nucleotides was readily detectable in cultures of both endothelial cell types. The extent and rapidity of dye transfer in culture was only slightly less than that in sheets of freshly isolated cells, perhaps reflecting a reduced gap junctional area combined with an increase in cell size in vitro.

Animals↗