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Biomedical subjects

C R Thomas

Publications and source records attributed to C R Thomas.

At least 19 recordsLinked to original sources

Nocturnal urinary excretion of 6-hydroxymelatonin sulfate in prepubertal major depressive disorder.

Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in overnight urine from 31 prepubertal children with major depressive disorder and 15 normal control children with very low family loading for affective disorder. The two groups did not differ with regard to their nocturnal excretion of this compound, nor was any depressive subgroup identified whose 6-hydroxymelatonin sulfate excretion differed from that of the control group. Previous studies of pineal function in depression are reviewed and discussed in the context of the present investigation.

Adolescent

Racial differences in the anatomical distribution of colon cancer.

The objective of this study was to determine whether racial differences exist with regard to the anatomical distribution of adenocarcinoma of the colon. We conducted a retrospective study of consecutive patients with primary colon cancer seen during a 12-year period (1976 to 1987) identified by the Rush Tumor Registry. The setting was a large, tertiary-care, private medical center, located in the inner city of Chicago, Ill. A chi 2 unpaired Student's t test of association was performed to detect any statistically significant difference in the anatomical sites of distribution between blacks and whites. A statistically significant percentage of black patients had proximally located primary colon lesions compared with white patients. This observation was independent of the actual anatomical definition of right-sided or proximal colon lesions. These findings suggest that a significant percentage of black and white patients are less likely to be diagnosed with colon cancer at a more curable stage, when abiding by the current screening guidelines of the American Cancer Society and the National Cancer Institute. The impact is greater on black patients with adenocarcinoma of the colon.

Adenocarcinoma

Thyroid hormone receptor induction by triiodothyronine in tadpole erythrocytes in vivo and in vitro and the effect of cycloheximide and actinomycin-D.

Tadpole erythrocyte nuclei contain specific T3 binding sites which increase in number during spontaneous or T3-induced metamorphosis. In the present studies the increase in the number of T3 binding sites after a T3 injections appeared to be completely prevented by cycloheximide and actinomycin D, inhibitors of protein synthesis and RNA synthesis, respectively. However, in some experiments the effect was not statistically significant. The increase in sites was prevented only if the inhibitors were administered at 0 or 24 hr after T3 injection, but not at 48 or 72 hr after T3. When tadpole erythrocytes were incubated with T3 in vitro in M199 culture medium, the number of nuclear T3 binding sites increased within 48 hr. This increase was highly sensitive to inhibition by cycloheximide (maximal at 1 x 10(-6) M) or actinomycin D (maximal at 0.02 micrograms/ml). These inhibitor concentrations only slightly reduced the incorporation of labeled precursors. The T3 concentration required to induce a half-maximal increase in binding sites in vitro was about the same as the T3 concentration at which half the binding sites were occupied. The T3 binding sites had a high affinity for thyroid hormone analogs which stimulate metamorphosis. These results support the designation of the T3 binding sites as T3 receptors. They show that the tadpole erythrocytes respond to T3 with an increase in the number of T3 binding sites without the involvement of other tissues. It is proposed that this is a receptor induction involving synthesis of RNA and protein.

Animals

Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats.

Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D-glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat.

Animals

Effect of Pluronic F-68 on the mechanical properties of mammalian cells.

The mechanical properties of TB/C3 hybridoma cells taken from a continuous culture were measured by micromanipulation. The culture conditions were constant except for the presence or absence of Pluronic F-68 in the medium. It was found that the mean bursting membrane tension and the mean elastic area compressibility modulus of the cells were significantly greater (60% and 120%, respectively) in a medium with 0.05% (w/v) Pluronic F-68 compared to that without Pluronic. Pluronic F-68 therefore affected the strength of the membranes when the cells were exposed to it for a long period of time, i.e., in culture. The short-term effect of Pluronic F-68 on cell strength was also tested by its addition at various levels up to 0.2% (w/v) immediately before the mechanical property measurements. The resulting cell strength depended on the Pluronic concentration, but a significant short-term effect could only be detected above a threshold of 0.1% (w/v). Previous reports on the effect of Pluronic F-68 on animal cell culture are evaluated in the light of these observations.

Animals

Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats.

1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries of control and streptozotocin-induced diabetic rats. 2. The diabetic rats demonstrated enhanced vascular sensitivity to noradrenaline compared with age-matched controls (pEC50 5.99 +/- 0.06 for diabetic rats, n = 25, versus 5.82 +/- 0.03 for controls, n = 45, P < 0.05). 3. Significant impairment of acetylcholine-induced relaxation was observed in arteries from the diabetic animals compared with controls (pEC50 6.81 +/- 0.17 for diabetic rats, n = 21, versus 7.54 +/- 0.17 for controls, n = 45, P < 0.001). 4. The difference between acetylcholine-induced relaxation in diabetic and control arteries remained in the presence of 10 microM indomethacin (pEC50 6.41 +/- 0.11 for diabetic rats, n = 16, versus 7.59 +/- 0.08 for controls, n = 20, P < 0.001). 5. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) produced profound inhibition of acetylcholine-induced relaxation in diabetic arteries but partial inhibition in controls. The incomplete inhibition of acetylcholine-induced relaxation by L-NMMA in the control arteries was the result of ineffective inhibition of nitric oxide synthase since an alternative inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), led to similar inhibition to that seen in the diabetic arteries with L-NMMA. The endothelium-derived relaxing factor (EDRF)-mediated component of acetylcholine-induced relaxation determined by use of the nitric oxide synthase inhibitors was, therefore, apparently reduced in diabetic rats compared with control animals.6. In further experiments L-NAME was found to enhance the response to noradrenaline in control rats but not in diabetic animals, suggesting that the abnormal response to noradrenaline in the diabetic animals was also due to reduced EDRF release.7. Nitroprusside-induced relaxation (endothelium-independent) was similar in arteries from control anddiabetic rats (pEC5o 7.61 +/- 0.13 for diabetic arteries, n = 18, versus 7.68 +/- 0.15 in the controls, n = 20, P not significant).8. These results suggest that endothelial function is abnormal in mesenteric resistance arteries of streptozotocin-induced diabetic rats and that this is predominantly due to reduced EDRF release.

Acetylcholine

Culturally relevant smoking prevention for minority youth.

A rap contest methodology for smoking prevention was tested with sixth and seventh grade students in a predominantly minority public school district. Contests were held after initial assemblies in which students heard anti-smoking rap messages from same-age and older peers on audio and video tape. Pretesting and posttesting (N = 268) indicated high preference ratings for most aspects of the intervention. Analyses of variance revealed no differences across races on any of the dependent measures. However, smaller assemblies were more effective than larger ones in enhancing attitudes against smoking and obtaining more positive contest evaluations and predictions about smoking behavior. A rap contest method therefore may be effective against the initiation of smoking by disadvantaged children in sixth and seventh grades because it is highly acceptable and perceived as culturally relevant. This effectiveness may be more demonstrable in single classrooms rather than larger assemblies.

Adolescent

Non-Hodgkin lymphoma of the gastrointestinal tract.

The gastrointestinal tract is the most commonly involved extranodal site of lymphoma. Primary gastrointestinal lymphoma must be recognized, characterized, and staged accurately, since, in some areas of the bowel, prognosis and therapy vary substantially when compared with those for other neoplasms, especially carcinoma. Radiologic studies, particularly barium studies of the bowel and computed tomography, may be crucial and only noninvasive modalities to use for the evaluation of gastrointestinal lymphoma. Symptoms are nonspecific and may be present for years before a diagnosis is established. Histologic appearance consists of a dense accumulation of lymphocytic tumor cells in a uniform pattern. Gastrointestinal lymphoma produces a spectrum of pathologic and radiologic appearances. Management of the condition may be accomplished with surgical resection, tumor debulking, or palliation. The advantages of postoperative radiation therapy and chemotherapy are not clear. Primary gastrointestinal lymphoma is encountered often enough to warrant familiarity with the clinical, radiologic, and therapeutic options.

Gastrointestinal Neoplasms

The metabolism of free fatty acids and triacylglycerols by the fetal liver in a guinea pig model of intrauterine growth retardation.

The aim of this study was to determine whether intrauterine growth retardation (IUGR) is associated with an alteration in hepatic lipid metabolism. IUGR was induced in 25 guinea pigs by uterine artery ligation on gestational d 30. On d 62, after anesthesia, an infusion of [1-14C]-palmitic acid was given. Fetuses were exposed at 15, 30, and 45 min, and simultaneous maternal and umbilical venous blood samples were taken. Livers were divided into right lobe, right and left sublobes of the quadrate lobe, and left lobe. In control fetuses, plasma radiolipids rose in parallel with, but were about half the value of, maternal levels. In IUGR fetuses, plasma radiolipids were lower than in controls at 15 and 30 min but were comparable at 45 min. Most of the radiolipid in the maternal plasma was FFA, with only 6% incorporated into triglycerides at 45 min. In control and IUGR fetal plasmas, 36-37% of the radiolipid was triglycerides by 45 min. Radiolabel incorporation into the right lobe was less than into the left lobe and left half of the quadrate lobe in control and IUGR fetuses. Compared with controls, radiolabel incorporation in IUGR fetuses was less in some or all liver lobes at each time point. The proportion of label associated with FFA and triglycerides did not vary with time, between lobes, or between control and IUGR fetuses. The difference in uptake between lobes reflects their blood supply, implying that most FFA is extracted during the first passage of the umbilical venous blood. Growth retardation was not associated with compromised hepatic FFA metabolism.

Animals

Intraperitoneal insulin is more potent than subcutaneous insulin at restoring hepatic insulin-like growth factor-I mRNA levels in the diabetic rat: a functional role for the portal vascular link.

There is evidence that the hormonal control of hepatic IGF-I production is mediated by GH and insulin. To elucidate the role of these hormones further we administered s.c. or i.p. insulin (at 2.5 and 5.0 IU/day) and/or GH (0.8 IU/day) to rats made diabetic with streptozotocin 16 days previously. Hepatic IGF-I production was then assessed by quantifying hepatic IGF-I mRNA levels by autoradiography of Northern blots. Diabetes resulted in a fivefold reduction in hepatic IGF-I mRNA levels (optical density (OD) of the 0.7-1.1 kb band: controls, 1.3 +/- 0.09; diabetics, 0.28 +/- 0.08; P < 0.01), which was not significantly changed by treatment with s.c. insulin (OD: low dose, 0.55 +/- 0.05; high dose, 0.58 +/- 0.05) or low dose i.p. insulin (OD: 0.40 +/- 0.03). High dose i.p. insulin enhanced hepatic IGF-I mRNA levels (OD: 0.93 +/- 0.23) compared with diabetic rats (P < 0.01) and those given high dose s.c. insulin (P < 0.04), despite the blood glucose values being similar in the treated groups (i.p., 4.72 +/- 0.29 mmol/l; s.c., 3.32 +/- 0.03 mmol/l). Administration of GH alone partially restored the hepatic IGF-I mRNA level (OD: GH-treated, 1.00 +/- 0.05; diabetic, 0.28 +/- 0.08; P < 0.01), whilst having no effect on blood glucose values (diabetic, 36.35 +/- 0.45 mmol/l; GH-treated, 38.65 +/- 2.39 mmol/l). Additional administration of s.c. insulin completely restored IGF-I mRNA levels to those of controls (OD: low dose, 1.35 +/- 0.14; high dose, 1.27 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Isolation, stabilization, and molecular weight estimation of thyroid hormone receptors of tadpole and chick embryo erythrocytes.

Typical procedures for the isolation of triiodothyronine (T3) receptors from mammalian nuclei involve extraction of nuclei with buffers containing divalent cations and 0.40M KCl. However, when applied to tadpole erythrocyte (RBC) nuclei, this method gave low yields of relatively unstable T3 receptors. The use of EDTA (10 mM) and 0.4M KCl in a sucrose-Tris buffer resulted in the extraction of 90% of the specifically bound [125I]-T3 from RBC nuclei. It was also found that 5 mM thiol reagent (DTT, GSH, or beta-mercaptoethanol) was required for maximal stability of the receptor. Fractionation of labeled RBC nuclear extracts on a Sephadex G-100 column yielded only one peak of specific T3 binding activity. The T3 receptor peak eluted at the same position as bovine serum albumin (BSA), with an estimated mol wt of 68 kDa. Specific T3 binding activity was destroyed by protease digestion but not by DNAse or RNAse. Scatchard analysis of the fractions from the receptor peak supported the existence of one class of T3 binding sites, with an estimated Kd (about 7 pM) comparable to the Kd reported for the intact RBC. Using the same methods, T3 receptors from the nuclei of chick embryo RBCs were also isolated, again with a Kd (7 pM) similar to that for the intact RBC. The chick receptor also eluted from the Sephadex G-100 column at the same position as BSA. The estimated mol wt of the T3 receptors from both sources is comparable to those reported for T3 receptors from other sources. The results show that T3 receptors derived from both tadpole and chick RBC nuclei could be isolated in a soluble and stable form with no apparent change in Kd.

Animals

Gastrointestinal lymphoma.

Primary GI lymphoma is a rare clinical entity. A primary nodal tumor should be ruled out. Symptoms may not be localizing and B symptoms are less common. A tissue diagnosis, preferably by transmural biopsy for small intestinal involvement, often reveals a high-grade morphology. The staging work-up should include a bone marrow examination, although formal staging laparatomy is not always required. Patients with Mushoff stage IE or IIE1 disease do better than those with extraregional nodal disease or distant metastatic involvement. Surgical resection with clear margins is required in order to maximize the changes for cure. Chemotherapy or radiotherapy may give a survival advantage when used as adjuvant treatment for selected stage IE and IIE disease. Chemotherapy should be used after surgical debulking in more advanced disease in order to minimize the chance for bleeding or performation. Future randomized, multi-institutional trials will give more direction as to the best modes of management.

Aged

A novel micromanipulation technique for measuring the bursting strength of single mammalian cells.

Information about the bursting strength of animal cells is essential if the mechanisms of cell damage in bioreactors are to be understood, and if cell mechanical properties are ever to be related to cell structure and physiology. We have developed a novel cell compression technique that makes it possible to directly measure the bursting strength of single mammalian cells, and to infer information about cell mechanical properties.

Animals

Mediastinal tumors.

Of the many types of tumors located in the mediastinal compartments, most are metastatic. The most common adult tumor in the anterior compartment is thymoma. A number of important cytogenetic, immunohistochemical, and molecular analytical observations have been reported over the past year regarding this tumor. In addition, reports on the multimodality management of thymoma have raised important issues regarding the prognostic significance of selected pretreatment parameters. Of special interest are reports which may clarify differences which may exist between thymic carcinoma, a separate pathologic entity, and thymoma. Finally, important observations regarding the association of hematologic malignancies with germ cell tumors of the mediastinum have been made in the past year. The following review summarizes pertinent progress in the above-mentioned areas and cites interesting reports pertaining to less common mediastinal tumors of the posterior and middle mediastinum.

Humans

The effects of diabetes on placental lipase activity in the rat and human.

Lipase activities were measured at pH 4 and pH 8 in the placentas of rats made diabetic by streptozotocin treatment and also in the placentas of women classified as having 1) impaired glucose tolerance or type 2 diabetes, 2) type 1 diabetes with no associated vascular complication, and 3) type 1 diabetes with associated vascular disease. In both sets of experiments, the placentas were compared with normal control groups. The placental lipase activity measured at pH 8 was not significantly different in either streptozotocin-treated rats or impaired glucose tolerance/diabetic women as compared with controls, whereas the lipase activity measured at pH 4 increased significantly as compared with controls in both species. Furthermore, in the women there was a significant correlation between placental lipase activity at pH 4 and birth weight in impaired glucose tolerance/type 2 diabetes. It is suggested that the increased placental lipase activity may contribute to the increased fetal weight in human diabetic pregnancy, by contributing to the increased fat transfer across the placenta from mother to fetus.

Animals