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Biomedical subjects

J T Anderson

Publications and source records attributed to J T Anderson.

At least 19 recordsLinked to original sources

PUB1 is a major nuclear and cytoplasmic polyadenylated RNA-binding protein in Saccharomyces cerevisiae.

Proteins that directly associate with nuclear polyadenylated RNAs, or heterogeneous nuclear RNA-binding proteins (hnRNPs), and those that associate with cytoplasmic mRNAs, or mRNA-binding proteins (mRNPs), play important roles in regulating gene expression at the posttranscriptional level. Previous work with a variety of eukaryotic cells has demonstrated that hnRNPs are localized predominantly within the nucleus whereas mRNPs are cytoplasmic. While studying proteins associated with polyadenylated RNAs in Saccharomyces cerevisiae, we discovered an abundant polyuridylate-binding protein, PUB1, which appears to be both an hnRNP and an mRNP. PUB1 and PAB1, the polyadenylate tail-binding protein, are the two major proteins cross-linked by UV light to polyadenylated RNAs in vivo. The deduced primary structure of PUB1 indicates that it is a member of the ribonucleoprotein consensus sequence family of RNA-binding proteins and is structurally related to the human hnRNP M proteins. Even though the PUB1 protein is a major cellular polyadenylated RNA-binding protein, it is nonessential for cell growth. Indirect cellular immunofluorescence combined with digital image processing allowed a detailed comparison of the intracellular distributions of PUB1 and PAB1. While PAB1 is predominantly, and relatively uniformly, distributed within the cytoplasm, PUB1 is localized in a nonuniform pattern throughout both the nucleus and the cytoplasm. The cytoplasmic distribution of PUB1 is considerably more discontinuous than that of PAB1. Furthermore, sucrose gradient sedimentation analysis demonstrates that PAB1 cofractionates with polyribosomes whereas PUB1 does not. These results suggest that PUB1 is both an hnRNP and an mRNP and that it may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm.

Animals

Insulin-dependent diabetes in the NOD mouse model. II. Beta cell destruction in autoimmune diabetes is a TH2 and not a TH1 mediated event.

Type I, insulin-dependent diabetes (IDD) in both man and animals results from a specific autoimmune destruction of the pancreatic beta cells involving both humoral and cellular immune mechanisms. The pathognomonic histologic lesion, termed insulitis, is an inflammatory and immune cell infiltrate of the pancreatic islet cells. While recent histological and flow cytometric analyses have identified the cell composition of the infiltrate, the presence of a cell population may not reflect the functional reactivities important for beta cell destruction. In the present study, we have investigated the possible functional reactivities of islet-infiltrating mononuclear cell populations by measuring increased cytokine mRNA usage. Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1 alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. These findings, together with our earlier flow cytometric analyses of the islet-infiltrating cells, have permitted construction of a detailed model for the natural history of autoimmune diabetes. Interestingly, this model, based on a TH2- and not a TH1-mediated scheme, questions the more popular concepts currently thought to form the bases of the autoimmune reactions underlying IDD.

Animals

The effects of exercise and weight loss on plasma lipids in young obese men.

We studied the independent and combined effects of exercise training and weight loss on blood lipids under fixed diet and exercise conditions. Twenty-one obese sedentary men were randomly allocated to one of four treatment groups: (1) inactive and constant weight (control), (2) exercise training and constant weight, (3) inactive and weight loss, and (4) exercise training and weight loss. There were three study periods: a 3 week baseline period inactive and on an isocaloric diet, a 12 week treatment period, and a 3 week weight stabilization period. Exercise consisted of treadmill walking at an energy cost of 3500 kcal/wk for groups 2 and 4 with replacement caloric intake only in group 2. Group 3 reduced caloric intake by 3500 kcal/wk during the treatment period. Weight loss for groups 3 and 4 were 13.4 pounds and 13.7 pounds, respectively. Maximal oxygen uptake (mL/min) increased 6% in both exercise groups (2 and 4), and percent body fat decreased only in these groups. Regression analysis by group assignment on HDL cholesterol (HDL-C) showed that the inactivity-weight loss modality (group 3) and the exercise-constant weight modality (group 2) each significantly increased HDL-C, with an additive effect of exercise and weight loss (group 4). The rate of HDL-C change differed significantly between groups (P = 0.01). HDL-C increased 0.63, 0.61, and 1.89 mg/dL per 3 weeks or 2%, 2.4%, and 5.5% above baseline levels in groups 2, 3, and 4, respectively, while the control group decreased 0.11 mg/dL. Plasma triglycerides and very low-density lipoprotein (VLDL) cholesterol increased with exercise at constant weight (group 2) and decreased with exercise associated with weight loss (group 4). In conclusion, exercise and weight loss separately and independently increase HDL-C, and their effects are additive.

Adult

The effect of alcohol on serum high density lipoprotein (HDL). A controlled experiment.

A cross-over study using 11 male subjects and a closely controlled diet, investigated the effect of alcohol on serum high density lipoprotein (HDL) components. Smoking status and body weight remained essentially constant and exercise changes were adjusted for in the analysis. As compared to sucrose, alcohol consumption was associated with a significant elevation in serum apolipoprotein A-I (0.37 mg/dl/g/day of alcohol) with similar effects for serum HDL cholesterol (0.14 mg/dl/g/day of alcohol) and serum apolipoprotein A-II (0.11 mg/dl/g/day of alcohol) achieving borderline levels of statistical significance.

Adult

Prearterial reversed midgut rotation. A rare congenital anomaly.

A patient with a right-sided descending colon, left-sided ascending colon, and transverse colon in front of the superior mesenteric artery is described. We believe that this is only the second case of "prearterial" reversed midgut rotation existing with normally situated stomach and liver. The best explanation for these relationships seems to be (a) anomalous positioning of the primitive midgut-hindgut junction right of midline; (b) ensuing midgut rotation in a reversed, or clockwise, direction.

Adult

The effect of various vegetable supplements on serum cholesterol.

Several previous studies have indicated that vegetables may lower serum total cholesterol. This study, using a Latin square experimental design, investigates the effect of three vegetable supplements (vegetable roots, vegetable leaves and stalks, whole grains) on serum lipoprotein cholesterol. The results from each vegetable supplement are compared to the results from a sucrose supplement of equal caloric content. Dietary fat, alcohol consumption, cigarette smoking, body weight, and physical activity are all controlled in the experimental design or the analysis. The results show that the effect of vegetables on serum cholesterol is not confined to one vegetable grouping or one type of lipoprotein cholesterol. Vegetable leaves and stalks are associated with lower values of very low-density lipoprotein cholesterol (and possibly low-density lipoprotein cholesterol) and total cholesterol. Whole grains are associated with lower values of low density lipoprotein cholesterol and total cholesterol. In addition to the actual cholesterol lowering effect compared to sucrose, the lack of an increase, suggests some advantage in the use of these vegetable groupings (even roots) as a replacement for fat in the diet, and vegetable leaves and whole grains as a replacement for sucrose.

Adult

Swan-Ganz catheter location and left atrial pressure determine the accuracy of the wedge pressure when positive end-expiratory pressure is used.

In 43 percent of 30 consecutive open heart surgery patients, Swan-Ganz catheter tips lodged within 1 cm of or above the left atrium. When in this position the wedge pressure measured by the catheter was not an accurate estimate of left atrial pressure when positive end-expiratory pressure (PEEP) was used, especially when left atrial pressure was low. Catheters located below the left atrium were accurate at all levels of PEEP tested. The position of Swan-Ganz catheters should be confirmed by a lateral chest roentgenogram when PEEP is used, and catheter tips not below the left atrium should be repositioned.

Atrial Function

Immediate internal fixation in open fractures.

Open fractures require emergency treatment. Adequate debridement and copious irrigation are essential in their management. The parenteral administration of antibiotics should be started immediately. If the wound is closed primarily, the antibiotics are discontinued after three days. If the wound is closed secondarily, the antibiotics are continued for another three days after this procedure. Most open fractures should be treated without the use of internal fixation techniques. However, we believe that there are reasons for employing immediate internal fixation, particularly in polytraumatized patients and others sustaining type III open fractures, to facilitate care of the soft tissue. When immediate internal fixation techniques are used in open fractures, the wound must not be closed primarily.

Adult

Diet and serum cholesterol: do zero correlations negate the relationship?

The confounding that results from the uncontrolled conditions under which most epidemiologic observations are made is sufficient to undermine their validity with respect to investigation of the relationship between diet and serum cholesterol. In this paper, the authors show, using both a mathematical model and referring to empirical data, that if certain variances are sufficiently great, even when there is cause and effect, correlation coefficients close to zero would be expected from the actual data of a cross-sectional study. Cross-sectional designs are therefore not suitable for studying this relationship.

Cholesterol

The routine use of positive end-expiratory pressure after open heart surgery.

Because atelectasis of the left lower lobe is a frequent complication of open heart surgery, we evaluated the efficacy of routine therapy with positive end-expiratory pressure (PEEP) to prevent this complication. Twenty-four patients were randomly assigned to either a group receiving therapy with PEEP (ten patients) or to a group with no PEEP (14 patients). The two groups could not be distinguished by age, weight, the forced expiratory volume in one second (FEV1), the ratio of FEV1 over the forced vital capacity, the time on the pump, the units of blood transfused, the tidal volume, or the hours of mechanical ventilation. There was no significant roentgenographic difference between the two groups in either the degree or frequency of left lower lobe atelectasis. While the arterial-alveolar ratios tended to improve over time in those patients receiving therapy with PEEP, this improvement was not clinically significant. No complications were encountered with the use of PEEP. We conclude that the routine use of PEEP following open heart surgery is safe but offers no advantage over standard ventilatory techniques.

Cardiac Surgical Procedures

Purified duck embryo rabies vaccine. An accelerated schedule for preexposure immunization against rabies.

Seroconversion and adverse reaction rates were studied in 92 persons given four or five doses in a two-week period of duck embryo rabies vaccine (DEV) or duck embryo rabies vaccine purified by ultracentrifugation (P-DEV). Mouse-neutralizing antibodies developed in 78 of 92 (84.8%) persons in these accelerated schedules. There were no significant differences in the frequency of antibody conversion or in geometric mean titers of antibody between persons given either vaccine. However, local and systemic adverse reactions were substantially less common with P-DEV. These data suggest that four of five doses of DEV or P-DEV given in a two-week course can be used for preexposure prophylaxis in situations where the more drawn-out regimens would result in continuation of a high-risk of rabies exposure. The antibody response of persons given this more accelerated regimen must be determined.

Animals

Total hip replacement in disseminated neoplastic disease.

Between 1972 and 1975, 11 total hip replacements were performed on ten patients with advanced neoplastic disease. Eight of ten patients survived more than one year after total hip replacement. Eight of 11 hips were rated as having excellent or good functional results six months postoperatively. We suggest that total hip arthroplasty be considered an appropriate procedure in the operative management of patients with advanced neoplastic disease involving the hip.

Adult