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Biomedical subjects

R Pollock

Publications and source records attributed to R Pollock.

14 recordsLinked to original sources

A case-control comparison of durability and cost between implanted reservoir and percutaneous catheters in cancer patients.

A case-control study was performed to compare the durability and cost of implanted reservoir catheter systems with percutaneous central venous catheters. Twenty cancer patients had reservoir systems placed in 1985 for chemotherapy delivery. The control group consisted of 60 cancer patients, matched according to age, sex, and diagnosis who were part of a group of more than 700 patients with percutaneous catheters inserted during the same period. The reservoir catheters were found to function for a significantly (P less than 0.0001) longer time (495 +/- 54 days) compared to the percutaneous catheters (197 +/- 22 days). The total cost for each system was calculated by adding the charges for an average insertion (reservoir = $1738, percutaneous = $562) to the maintenance charges accumulated over the catheters' lifespan. Reservoir catheters were associated with a significantly greater total cost than percutaneous catheters ($2233 +/- 54, $1453 +/- 102, respectively) but, if the total cost was spread out over the lifespan of the catheter by dividing the total cost by duration of use, reservoir catheters can be less expensive on a per diem basis. The break point occurs at approximately 6 months. For use less than 6 months, percutaneous catheters are cheaper primarily because of their lower insertion costs, but, for longer periods, reservoir catheters become cheaper because of lower maintenance costs and because a second percutaneous catheterization would likely be necessary.

Adult

Human SRF-related proteins: DNA-binding properties and potential regulatory targets.

Serum response factor (SRF) is a transcription factor that binds the sequence CC(A/T)6GG found in a number of growth factor-inducible and muscle-specific promoters. We describe the isolation and characterization of cDNA clones encoding a family of three human SRF-related DNA-binding proteins. Each of these RSRF (related to SRF) proteins contains an 86-amino-acid amino-terminal region related to the SRF DNA-binding domain: In RSRFC4 and RSRFC9, this region is identical, whereas that present in RSRFR2 differs by seven conservative amino acid substitutions. The DNA-binding specificity of the RSRF proteins, which recognize the consensus sequence CTA(A/T)4TAG, is distinct from that of SRF. The entire RSRF common region is required for DNA binding, and the differential sequence specificity of the RSRFs and SRF is the result of differences in the basic amino-terminal part of this domain. The RSRF proteins bind DNA as dimers and can dimerize with one another but not with SRF. Although the RSRF mRNAs are expressed in many cell types, RSRFR2 mRNA is expressed at elevated levels in several B-cell lines. Consistent with this, extracts from many cell types form CTA(A/T)4TAG-binding complexes that contain RSRF proteins, and oligonucleotides containing RSRF-binding sites function as promoter elements in transfection assays. Like SRF-binding sites, RSRF-binding sites are found in the regulatory sequences of a number of growth factor-inducible and muscle-specific genes, and we show that RSRF polypeptides are components of previously characterized binding activities that interact with these elements. We discuss the potential role of RSRF proteins in the regulation of these genes.

3T3 Cells

A sensitive method for the determination of protein-DNA binding specificities.

We describe a sensitive and rapid method for determination of the sequence specificity of DNA binding proteins. The method allows recovery of specific sites using the small amounts of protein present in crude cell extracts or produced by cell-free translation reactions. Extract proteins are incubated with a pool of random sequence oligonucleotides, complexes purified by immunoprecipitation, and bound DNA amplified by the Polymerase Chain Reaction (PCR). This DNA is then used in further rounds of binding, immunoprecipitation, and amplification, until specific binding is detectable. With the transcription factor SRF as a model system, we demonstrate that authentic high affinity binding sites are recovered, and show that epitope tagging can be used to allow recovery of sites when specific antibodies are unavailable. We also show that specific sites bound by the Fos protein, which binds DNA with high affinity only when complexed with other polypeptides, are easily recovered by this technique.

Animals

Insulin co-injection suppresses the thermogenic response to glutamate microinjection into the VMH in rats.

Selective stimulation of ventromedial hypothalamic nucleus (VMH) neurons by microinjection of the excitatory amino acid glutamate sharply increased interscapular brown adipose tissue (IBAT) and core temperatures in urethane-anaesthetized rats. This effect was blocked by co-injection of insulin (0.1-1 microgram) though not an inactive insulin analog, TNB3 insulin. Injection of insulin (1 microgram) into the contralateral VMH or systemic administration of insulin (1 microgram) had no effect on the thermogenic response to intra-VMH glutamate. These results complement those showing that intra-VMH insulin suppresses the basal firing rate of sympathetic nerves to IBAT and diminishes cold-induced nonshivering thermogenesis in BAT and add support to the view that insulin functions as an inhibitory signal on VMH neurons controlling thermogenesis in BAT.

Adipose Tissue, Brown

Apparent biliary pseudolithiasis during ceftriaxone therapy.

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of change. A total of 6 of 28 (21.4%) ceftriaxone-treated patients and 1 of 8 (12.5%) patients who received the placebo demonstrated abnormal gallbladder sonograms on day 14 (P = 0.491). Four of the six ceftriaxone-treated patients demonstrating abnormal sonograms were clinically asymptomatic, while two patients reported vomiting. The abnormal sonograms of gallbladders of patients treated with ceftriaxone returned to normal between 9 and 26 days posttherapy. These data suggest an association between ceftriaxone treatment and the development of gallbladder abnormalities on ultrasound examination which resolve spontaneously on discontinuation of ceftriaxone therapy.

Adult

A novel fluorescence-based system for assaying and separating live cells according to VDJ recombinase activity.

We describe two retroviral vector-based recombination substrate systems designed to assay for lymphoid VDJ recombinase activity in cultured cells. Both substrates incorporate a constitutive dominant marker gene (the simian virus promoter-driven neo gene) to allow selection of cells that stably integrate the substrate. Both substrates also include a second marker gene that becomes transcriptionally active only when inverted by a site-specific recombination event between flanking immunoglobulin variable-region gene segments. The first vector, similar in structure to previous retrovirus-based recombination substrates, utilizes the bacterial guanine-xanthine phosphoribosyltransferase gene (gpt) as its activatable marker; detection of inversion (VDJ recombinase activity) involves drug selection and Southern blotting analyses. We have used this vector to make a more extensive and quantitative survey of VDJ recombinase activity in B-lineage cell lines than has previously been performed with stable substrates, and we have compared our results with those of other studies that use transient recombination substrates. In the second vector, the activatable gene is the bacterial beta-galactosidase gene (lacZ). Detection for inversional activation of this gene is achieved by a fluorogenic assay, termed FACS-Gal, that detects beta-galactosidase activity in viable cells. The latter assay has the unique advantage of rapidly detecting cells that undergo recombination and also allows viable sorting of cells on the basis of the presence or absence of VDJ recombinase activity. We have used the lacZ vector to rapidly quantitate VDJ recombinase activity in B-lineage cell lines and compared the results with those obtained with the gpt vector. We have also used the lacZ vector to isolate variant pre-B-cell lines with low and high levels of VDJ recombinase activity.

Animals

Intra-ventromedial hypothalamic injection of insulin suppresses brown fat thermogenesis in the anaesthetized rat.

Insulin can affect metabolic functions such as glucose production and fat mobilization through action in the ventromedial nucleus of the hypothalamus (VMH), and the VMH has been implicated in the regulation of heat generation in brown adipose tissue (BAT) in the rat. To study the role of insulin in modulating VMH mechanisms concerned with BAT thermogenic activity we evaluated the effect of intra-VMH microinjection of insulin on BAT (T(bat)) and core (T(core)) temperatures and BAT thermogenic activity (T(bat)-T(core)) in anaesthetized rats. Intra-VMH insulin (10 ng, 100 ng and 1 microgram) enhanced the decreases in T(bat) and T(core) resulting from exposure of the anaesthetized rats to mild cold, as well as diminished BAT thermogenic activity in a dose-dependent manner. This effect could be partially reversed by systemic treatment with norepinephrine (400 micrograms/kg). Intra-VMH injection of insulin analogs having reduced binding affinity to insulin receptors and diminished biological activity--i.e., acetyl3 insulin, succinyl3 insulin and TNB3 insulin--was much less effective at enhancing the decrease in T(bat) and T(core) or at inhibiting BAT thermogenic activity. These results demonstrate that insulin can modulate BAT thermogenesis in a specific manner through action in the VMH.

Adipose Tissue, Brown

Intra-hypothalamic injection of thyrotropin-releasing hormone suppresses brown fat thermogenesis in the anaesthetized rat.

Thyrotropin-releasing hormone (TRH) has diverse effects on body temperature in rodents, but the effector mechanisms that mediate its thermoregulatory actions are not well defined. In the present study, microinjection of 10 ng to 5 micrograms of TRH into the anterior hypothalamus (AHy) dose-dependently suppressed heat production in interscapular brown adipose tissue (BAT) in chloral hydrate-anaesthetized rats tested at a room temperature of 23 +/- 2 degrees C. This effect of TRH was mimicked by the structurally related peptides acid-TRH and luteinizing hormone releasing hormone (LH-RH), and by the TRH analog CG 3509, but not by the TRH fragments pGlu-His and His-Pro. The AHy plays a role in the regulation of BAT thermogenic activity, and the present results suggest that some of the effects of TRH on body temperature involve an AHy-mediated inhibitory action on BAT thermogenesis.

Adipose Tissue, Brown

Transpelvic rectus abdominis flap reconstruction of defects following abdominal-perineal resection.

Abdominal-perineal resection for advanced rectal carcinoma may leave a large defect for which complete secondary healing can be slow. In such cases, the inferiorly based rectus abdominis myocutaneous flap, passed through the pelvis into the perineum, can provide a large amount of well-vascularized tissue that may be placed in the defect to facilitate primary healing and allow a quicker recovery. Additional advantages include displacement of the bowel out of the pelvis to facilitate postoperative radiotherapy, and the ability to reconstruct vaginal wall defects. We report a series of seven patients for whom the transpelvic rectus abdominis myocutaneous flap was used to cover perineal defects following abdominal-perineal resection. Although one flap failed, all patients healed rapidly and the only lasting complication was a possibly related small upper-abdominal hernia found one year after surgery.

Abdominal Muscles

Mitogen- and IL-4-regulated expression of germ-line Ig gamma 2b transcripts: evidence for directed heavy chain class switching.

Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line gamma 2b locus and gamma 2b class switching. In both cell types, LPS induces transcription specifically through the germ-line gamma 2b locus before gamma 2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line gamma 2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.

Animals

Protracted severe immune dysregulation induced by cardiopulmonary bypass: a predisposing etiologic factor in blood transfusion-related AIDS?

A large percentage of patients with blood transfusion related AIDS received their transfusion during cardiac surgery requiring cardiopulmonary bypass. We hypothesized that the procedure of cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery might be associated with severe immune dysregulation and hence predispose this group in particular to the acquisition of blood transfusion transmitted AIDS. T-cell subset enumeration and their ratio (T4/T8) and T-cell function (local GVH reaction) were serially studied before, during, and 1 and 6 days after surgery in 15 patients undergoing cardiac surgery requiring CPB, in 10 patients undergoing cancer resections (CA), and 11 patients without cancer undergoing elective, non-cardiac general surgical procedures (GEN). Compared to the preoperative values, a significant decline (p less than 0.002) in T4/T8 ratios occurred during CPB (1.63 +/- 0.80 vs 2.55 +/- 0.95), during CA (1.26 +/- 0.71 vs 1.81 +/- 0.72), and during GEN procedures (1.18 +/- 0.59 vs 1.64 +/- 0.68). T4, T8, and T4/T8 ratios returned to preoperative values in both the CA and GEN groups by the first postoperative day; in contrast, T4/T8 ratios remained significantly depressed (p less than 0.05) in CPB patients on the first and also on the sixth postoperative days when compared to preoperative values. This sustained depression in T4/T8 ratios is attributable to a significant increase in the proportion of T8 (suppressor cell) subset in the CPB patients which persisted through the sixth postoperative day. In contrast, in CA and GEN, the proportion of T8 subset returned to the preoperative level by the sixth postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Bovine saccocystosis: patholgic features of naturally occurring infection with Sarcocystis cruzi.

Naturally occurring bovine sarcocystosis caused death and illness in eight dairy heifers. Clinical disease was characterized by cachexia, peripheral lymph node enlargement, and anemia. Increased amounts of serum enzymes and anti-Sarcocystis antibody titers were present in affected animal. Macroscopic findings in two heifers at necropsy included emaciation and serous atrophy. Necropsied heifers (No. 1 and 2) contained different developmental stages of Sarcocystis cruzi; each stage was characterized by specific histopathologic findings. Heifer 1 had vascular endothelial schizonts in various soft tissues, with mild mononuclear cell infiltration, alveolar capillary fibrinous thrombi, and multifocal splenic necrosis. Heifer 2 had developing young S cruzi cysts, in myofibrils of cardiac and skeletal muscles, with a concurrent multifocal degenerative myositis. Marked lymphoid hyperplasia occurred in both heifers.

Animals

A solid state delayed auditory feedback system for speech therapy.

A delayed auditory feedback system has been constructed using solid state integrated circuit components. The construction of the instrument is described and the advantages of such an electronic device over conventional electro-mechanical systems are discussed.

Analog-Digital Conversion