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Biomedical subjects

R Booth

Publications and source records attributed to R Booth.

At least 19 recordsLinked to original sources

Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia.

BACKGROUND: The membrane-associated folate receptor (FR) type beta is elevated in the spleen in patients with chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). In this study, the authors investigated possible cell type and differentiation stage specificity of expression of FR-beta in normal and leukemic hematopoietic cells. METHODS: An affinity-purified rabbit polyclonal antibody specific for FR-beta was employed for immunostaining representative bone marrow smears and peripheral blood smears from normal individuals and from a limited number of patients with various leukemias. Multiple samples of normal bone marrow and peripheral blood were analyzed for the expression of FR-beta and selected CD antigens by two- or three-color flow cytometry. RESULTS: Of the morphologically identifiable cells, only neutrophils were positive for FR-beta. The leukemic blasts in CML patients showed expression of FR-beta with no apparent relation to the occurrence of the Philadelphia chromosome. Among acute nonlymphocytic leukemias, FR-beta was expressed in promyelocytic leukemia, in the myeloblast populations of myelomonocytic and erythroleukemias, and variably in M1/M2 AML. Neither the blasts of acute lymphocytic leukemia nor the more mature cells of chronic lymphocytic and hairy cell leukemias expressed FR-beta. The less differentiated FR-beta positive AML samples also were positive for CD34 and HLA-DR. Flow cytometric analysis of normal bone marrow and peripheral blood revealed low or insignificant coexpression of FR-beta with CD34, CD19, and CD3, whereas significant coexpression was observed with high levels of CD33, CD13, and CD11b; coexpression of FR-beta with CD14 was high in the immature bone marrow cells, comparable to that in myeloid cells, but relatively low in peripheral blood. CONCLUSIONS: The results of this study suggest a narrow expression pattern of FR-beta marking the neutrophilic lineage and the possibility of defining a subtype or subtypes of myeloid leukemia based on FR-beta expression. The identification of FR-beta positive leukemias and the absence of the receptor in normal CD34 positive cells may enable selective receptor-mediated targeting of leukemic cells.

Animals↗

RHO-associated protein kinase alpha potentiates insulin-induced MAP kinase activation in Xenopus oocytes.

We recently identified Xenopus Rho-associated protein kinase alpha (xROKalpha) as a Xenopus insulin receptor substrate-1 binding protein and demonstrated that the non-catalytic carboxyl terminus of xROKalpha binds Xenopus insulin receptor substrate-1 and blocks insulin-induced MAP kinase activation and germinal vesicle breakdown in Xenopus oocytes. In the current study we further examined the role of xROKalpha in insulin signal transduction in Xenopus oocytes. We demonstrate that injection of mRNA encoding the xROKalpha kinase domain or full length xROKalpha enhanced insulin-induced MAP kinase activation and germinal vesicle breakdown. In contrast, injection of a kinase-dead mutant of xROKalpha or pre-incubation of oocytes with an xROKalpha inhibitor significantly reduced insulin-induced MAP kinase activation. To further dissect the mechanism by which xROKalpha may participate in insulin signalling, we explored a potential function of xROKalpha in regulating cellular Ras function, since insulin-induced MAP kinase activation and germinal vesicle breakdown is known to be a Ras-dependent process. We demonstrate that whereas injection of mRNA encoding c-H-Ras alone induced xMAP kinase activation and GVBD in a very low percentage (about 10%) of injected oocytes, co-injection of mRNA encoding xROKalpha and c-H-Ras induced xMAP kinase activation and germinal vesicle breakdown in a significantly higher percentage (50-60%) of injected oocytes. These results suggest a novel function for xROKalpha in insulin signal transduction upstream of cellular Ras function.

Animals↗

Sex partners of Native American drug users.

This study describes patterns of sexual behavior and condom use in a sample of Native American drug-using men and women (N = 114). Data are self-reports of sexual behavior in the last 30 days, including descriptions of the most recent sex partners up to five. These data provided information on 157 sex partner pairs, of which at least one partner was a drug user. Native American women (55%) were more likely than Native American men (23%) to report never using condoms for vaginal and anal sex in the last 30 days. Compared with other ethnic pair combinations, sex partner pairs composed of Native American women and white men (n = 18) were the least likely to use condoms (6% of pairs) and the most likely to report an injection drug user (IDU) sex partner (33% of pairs). These results suggest a potential vector of HIV and other sexually transmitted disease (STD) transmission between white male IDUs and Native American women and highlight the need for further qualitative and quantitative research to examine the factors underlying this pattern of sexual risk behavior.

Adult↗

The mutational specificity of 1-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair.

We have examined the mutational specificity of 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene, in the lacI gene of Escherichia coli strains which are deficient in nucleotide excision repair (strain NR6113, delta uvrB; strain CM6114, delta uvrB, plasmid pKM101). Separate collections of lacI- mutations and dominant lacI-d mutations, which contain DNA sequence alterations in the region of the lacI gene that encodes the DNA binding domain of the lacI repressor, were made following 1,6-NONP treatment. The DNA sequence of 418 mutations was determined, of which 228 were lacI- mutations and 190 were lacI-d mutations. Ninety three percent of the induced point mutations occurred at G:C residues.0 -(G:C) frameshifts were the dominant mutational class in the lacI- collections of both NR6113 and CM6114, and in the lacI-d collection of NR6113. The frameshift mutations occurred preferentially in runs of guanine residues and their frequency increased markedly with the length of the reiterated sequence. In strain CM6114, which contained the plasmid pKM101, there was a marked stimulation in the frequency of G:C-->T:A transversions that was particularly apparent in the lacI-d collection. We discuss models which might account for the apparent differences in mutational specificity resulting from the presence of the UmuD/C and MucA/B proteins. The results suggest that major classes of mutation are recovered in both the lacI- and lacI-d collections. However, the proportions of the major classes of mutations within the two collections can differ significantly. Depending on the genetic background of the host strain, the relative ratios of base substitutions to frameshift mutations in the lacI-d target can differ by almost an order of magnitude as compared with the lacI- target. This is primarily a function of the relative mutational target size of the different classes of mutation.

Bacterial Proteins↗

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Aged↗

Bilateral tibial marrow ablation in rats induces a rapid hypercalcemia arising from extratibial bone resorption inhibitable by methylprednisolone or deflazacort.

The goals of this study were to quantitate biochemical markers of bone metabolism on days 1-15 after bilateral tibial marrow ablation surgery in young adult rats and to determine the effect of a single dose of methylprednisolone (2 mg/kg) or deflazacort (2.5 mg/kg) given at the time of ablation. Unexpectedly, serum calcium levels rose to a maximum of 15.9 mg/dl on day 7 after marrow ablation and remained above normal through day 15. This increase was blocked by a single intramedullary injection of methylprednisolone or deflazacort immediately following ablation; however, the fact that both drugs produced a characteristic rapid 3- to 10-fold increase in the serum alpha 2-macroglobulin level demonstrates that the drugs rapidly reached the circulation. Both methylprednisolone and deflazacort also inhibited intramedullary deposition of collagen by 40-60% on day 7, a time near which operated control animals achieved maximal accumulation of new bone in this model. Histological comparisons among the three experimental groups were largely consistent with biochemical results. The urinary hydroxyproline/creatine ratio for the operated control group doubled on day 3 and then returned to presurgical levels on day 7 and later. The timing and size of the hydroxyproline/creatinine peak, as well as the fact that the intratibial osteoclastic response peaks on days 8-10 after ablation, suggests it results from extratibial bone resorption induced by marrow ablation. Consistent with this rationale, urinary calcium excretion in operated controls rose 9-fold from day 0 to day 3 and appeared to plateau over the period from day 3 to day 9, before returning to a near presurgical level on day 15. Elevated excretion of calcium noted on days 9-15 in deflazacort-treated animals, which occurs in the absence of a detectable increase in resorption marker hydroxyproline, may however be due to the known action of glucocorticoids in increasing kidney filtration of calcium. In summary, this is the first report to show that bilateral tibial marrow ablation in rats causes a rapid hypercalcemia and calciuria which is accompanied initially by a peak of bone resorption marker urinary hydroxyproline. We speculate that the source of calcium and hydroxyproline is extratibial osteoclastic bone resorption induced by circulating cytokines whose release from ablated tibias or osteoclastogenic action is inhibitable by methylprednisolone and deflazacort.

Animals↗

Hepatitis C.

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Cross Infection↗

In vivo 1H MRS choline: correlation with in vitro chemistry/histology.

We correlated the in vivo 1H Magnetic Resonance Spectroscopy (MRS) concentration of the choline peak (CHO) with in vitro chemical measures of choline-containing compounds and a histological grade of cellularity in 18 patients with neoplastic and infectious brain lesions. Gas-chromatography-mass-spectrometry (GCMS) was used to measure the concentrations of free choline (Cho), glycerophosphocholine (GPCho), phosphocholine (PCho) and phosphatidylcholine (PtdCho) from biopsies in the same area where MRS was performed. Cellular density, free Cho, PCho and GPCho were the strongest determinants of 1H MRS CHO while PtdCho was not. Just as the 1H MRS 2.0 peak reflects both the concentration of n-acetyl-l-aspartate and neuronal density, the 1H MRS 3.2 peak reflects the concentration of water-soluble choline-containing compounds and cellular density.

Brain↗

Eastern barred bandicoot recovery: the role of the veterinarian in the management of endangered species.

The eastern barred bandicoot, Perameles gunnii, formerly widespread on the volcanic plains of western Victoria, has been reduced to a single, rapidly-declining, remnant population at Hamilton. Recovery of this critically endangered species has included local management, in an attempt to stabilise the wild population, captive breeding and reintroduction to selected sites. Veterinary advice and assistance have been an integral part of the investigation, planning and implementation phases of the program. The development of appropriate, standardised techniques has enabled successful treatment of problems in the captive colony. Husbandry, including the hand-rearing of pouch young has been refined. Parasitism, identified as a contributor to poor health or death, has been investigated. Experimental development of techniques for the attachment of radio-transmitters to bandicoots has enabled improved field research to take place. Fox predation, a major limiting factor in the recovery program, has been studied in detail, in order to refine control protocols.

Animal Husbandry↗

Phospholipids in meibomian gland secretion.

The bulk of the lipid layer overlying the aqueous portion of the precorneal tear film is composed of polar and nonpolar components. The nonpolar lipids have been the subject of numerous studies; however, the polar lipids have remained relatively uncharacterized. The polar lipids are thought to contain surfactant phospholipids that are critical to the spreading of a lipid film over the aqueous layer, by providing an interface between this layer and the nonpolar lipids. The purpose of the present study is to identify and quantitate the phospholipid complement of meibomian gland secretion which provides the tear film with phospholipids. Meibomian gland secretion was collected from rabbits and phospholipids identified and quantitated by 31P nuclear magnetic resonance spectroscopy. Ten phospholipids were detected from meibomian gland secretion: diphosphatidylglycerol, dihydrosphingomyelin, ethanolamine plasmalogen, phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysophosphatidylcholine, phosphatidylinositol, alkylacylphosphatidylcholine, and phosphatidylcholine (PC). The two major phospholipids were PC and PE, together comprising nearly 60% of the total phospholipid profile. The nature and relative concentrations of the meibomian gland secretion phospholipids are congruous with a surfactant role at the aqueous-lipid interface and, considering the physical chemistry of the tear film, suggest that the phospholipids should be organized in a very flat or planar configuration.

Animals↗

Assessing reading level of drug users for HIV and AIDS prevention purposes.

Using the short form of the Woodcock Reading Mastery Test-Revised and the reading subtest of the Wide Range Achievement Test-Revised, the reading abilities of 284 male and 128 female drug users from five sites across the United States were evaluated. All subjects were participants in a National Institute on Drug Abuse HIV/AIDS prevention project aimed at intravenous drug users and cocaine smokers. Results revealed differences in reading abilities among ethnic groups with Native and white subjects having significantly higher reading levels than Hispanic and black subjects. Significant site differences were revealed, with mean grade equivalent scores ranging from 2.7 to 10.1 grades. Across all subjects, the average grade equivalent reading level was 5.8 to 7.7, indicating that the subjects read below the level of 81.5% to 93% of the general population. We provide implications for development of educational materials that are accessible for this population.

Adult↗

Autologous lymphocyte therapy for experimental canine lymphoedema: a pilot study.

Obstructive lymphoedema, an accumulation of protein-rich fluid in interstitial spaces, was created in five dogs by a combination of the irradiation of one groin and subsequent surgical ablation of any remaining lymphatics. The lymphoedema was stable for up to 2 years. The aim was to test the efficacy of intra-arterial injection of autologous lymphocytes as a therapy for lymphoedema. The hypothesis was that cytokines produced by lymphocytes mediate proteolysis by macrophage proteinases in the lymphoedematous limb to remove the excess protein and relieve the oedema. A concentrated lymphocyte-rich preparation was isolated from blood by the Ficoll-Paque method. These preparations were injected into the femoral artery four times at approximately 4 weekly intervals. Three months after the first injection of lymphocytes, lymphoedematous limbs showed a marked 69% reduction in the mean excess circumferences compared with opposite control limbs. After treatment, skin thickness and hydroxyproline content (both measures of fibrosis) as well as water content (a measure of oedema) had reduced significantly. In specimens of interstitial fluid and in skin homogenates acidic proteinase activity increased and the protein concentration decreased significantly compared with controls. It is concluded that increased proteolysis, possibly due to activated macrophages recruited to the lymphoedematous limb, may partly explain these results.

Animals↗

The reduction of claustrophobia--II: Cognitive analyses.

A clinical experiment comparing methods of fear reduction in claustrophobia was used as the basis for analysing the relationships between a number of cognitive variables and the reduction of claustrophobia. Both the number and believability of negative cognitions present were associated with fear reduction and return of fear; this was also found when considering the number of body sensations experienced. High fear and panic were always accompanied by these phenomena whilst zero fear was never reported in the presence of believable cognitions and body sensations. An absence of believable cognitions post-test was accompanied by an absence of claustrophobia in 10/13 subjects. Specifically, removal of belief in any of the cognitions "I will be trapped", "I will suffocate" and/or "I will lose control" was associated with removal of belief in all the other cognitions and a dramatic reduction in claustrophobia. Belief in one of these central cognitions was associated with the maintenance of fear. We conclude that it is possible to conceptualize claustrophobia as comprising a number of cognitions centred on key thoughts of trappedness, suffocation and loss of control.

Adaptation, Psychological↗

The reduction of claustrophobia--I.

The purpose of this study was to investigate the process of change during three interventions for claustrophobia, with particular reference to cognitive changes. Forty-eight participants, recruited from the community through the local media, were randomly assigned to one of four groups: pure exposure, exposure to the sensations of anxiety (interoceptive exposure), modification of negative cognitions, or a control group. All interventions were given over three sessions. The exposure group proved superior to the control on a wide range of measures. In the cognitive group, scores of reported fear and panic, declined significantly. The interoceptive group made some modest gains. An analysis of the timing of fear reduction and of treatment generalization, provides some indications of the mechanism of change.

Adult↗

Intravenous drug users and AIDS: risk behaviors.

Risk-taking behaviors were studied in this assessment of 345 intravenous drug users from Baltimore, El Paso, and Denver. Over 50% reported injecting drugs daily and 70% shared needles with others, averaging 6.3 partners. In addition, 86% had shared a "cooker" and nearly 50% injected in a "shooting gallery." More than half of the males sampled had two or more sex partners, including 18% with five or more. Females averaged 19 sex partners in the preceding 6 months, with 22% reporting sex with five or more. Two-thirds of the total sample never used a condom, while only 6% always used this form of protection. On the other end of this risk continuum were those subjects who did not share needles or always cleaned their needles with an effective agent, had no sexual relations or always used a condom. Subjects following such practices could be considered low risk if they adopted safe behaviors in other associated areas of their lives. However, in an analysis of total risk, it was found that only 14 subjects (4%) practiced safe needle use and safe sex. Despite these findings, some encouraging results were seen. In an analysis of risk according to location, Baltimore subjects were significantly less at risk according to number of needle-sharing partners, borrowing needles, sharing a "cooker," injection in a "shooting gallery," cleaning needles, use of disinfectants, number of sexual partners, and use of condoms than either their cohorts in El Paso or Denver. Street outreach to modity risk behaviors among IVDUs began in Baltimore approximately 2 years prior to funding in El Paso and Denver. These results suggest that there may be a potential to moderate risk through intervention.

Acquired Immunodeficiency Syndrome↗