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Biomedical subjects

P Wood

Publications and source records attributed to P Wood.

At least 19 recordsLinked to original sources
PubMed1992

Expression of CD7 on normal human myeloid progenitors.

Existence of biphenotypic leukemias co-expressing CD7 and CD34 has prompted the question of whether a similar population of cells is present in normal human bone marrow. As CD7 is considered to be a T cell-restricted Ag, the co-expression of CD7 with the "human stem cell Ag" CD34 may identify a bipotent stage within hemopoietic differentiation. Cells with this phenotype have previously been isolated from human thymus. In this report we provide evidence that human marrow mononuclear cells also contain a minor subpopulation of cells co-expressing CD7 and CD34. The CD7+/CD34+ cells were found to contain committed myeloid progenitors assayed both as CFU in semi-solid media and by their ability to produce granulocytes in long term marrow cultures. Expression of CD7 on myeloid committed progenitors was further confirmed in a C-mediated cytotoxic assay. We conclude that CD7 expression is not restricted to T cells but is also expressed during early stages of myeloid differentiation.

Antigens, CD↗
PubMed1992

Use of fluorine-19 nuclear magnetic resonance spectroscopy and hydralazine for measuring dynamic changes in blood perfusion volume in tumors in mice.

BACKGROUND: One method of evaluating the mechanism of action of agents which alter tumor oxygenation is to determine their effects on tumor blood flow. PURPOSE: This study tests applicability of a new approach using an emulsion of the inert fluorocarbon perfluorooctylbromide (PFOB) at nontoxic doses as a tracer in fluorine-19 (19F) nuclear magnetic resonance (NMR) spectroscopy to evaluate dynamic changes in vascular perfusion volume in transplanted tumors. METHODS: The PFOB emulsion (100% wt/vol) was injected into the tail vein in tumor-bearing C3H/He or nu/nu mice immobilized in a magnet interfaced to a spectrometer, either as a single bolus injection of 8 mL/kg body weight or in multiple injections to a total dose of 24 mL/kg. A 7-mm external surface coil was placed over the tumor. Signal from the PFOB in the tumor volume seen by the coil rapidly reached equilibrium and was maintained for at least 2 hours, and multiple doses of PFOB emulsion resulted in a linear increase in 19F signal strength. Since the 19F signal strength was directly proportional to the perfusion volume of the tumor vasculature, reduction of signal intensity should correspond directly to any reduction in volume caused by a change in the tumor blood flow. To investigate this hypothesis, the vasoactive agent hydralazine (5 mg/kg) was injected intravenously after administering the PFOB emulsion to induce changes in tumor blood supply. KHT and RIF-1 murine sarcomas, the HT29 human colon carcinoma, and the HX118 human melanoma tumors were studied. In a comparative analysis of changes in blood flow induced by hydralazine, we studied Xe-133 clearance in KHT murine sarcoma and SCCVII/Ha (SCCVII) murine squamous cell carcinoma. RESULTS: Hydralazine significantly reduced the 19F signal intensity in the murine tumors RIF-1 and KHT and in the HT29 human tumor, with little reduction in the SCCVII/Ha murine and HX118 human tumors. Hydralazine induced a statistically significant 64% decrease in mean clearance rate in the KHT tumor, while SCCVII/Ha tumors showed no significant change, indicating that hydralazine restricted blood flow to a greater extent in the tumor type that showed reduced 19F signal from the PFOB emulsion. CONCLUSION: These data demonstrate the potential of PFOB emulsion as a tracer in NMR spectroscopy for studying tumor vasculature.

Animals↗
PubMed1992

Effects of agents which inhibit the regulation of intracellular pH on murine solid tumours.

Cell killing can be achieved in an acidic environment in tissue culture (medium pH less than 7.0) by agents (nigericin, carbonylcyanide-3-chlorophenylhydrazone (CCCP)) which transport protons from the extracellular space into the cytoplasm. Cell killing is enhanced when these agents are used in combination with compounds (amiloride, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)) which inhibit the membrane-based exchangers responsible for the regulation of intracellular pH (pHi). We describe experiments which assess the ability of these agents to kill tumour cells in spheroids and in vivo. Both nigericin and CCCP were observed to penetrate tissue based on their ability to kill tumour cells in spheroids. The mean extracellular pH (pHe) of the KHT fibrosarcoma and the EMT-6 sarcoma were observed to be 0.21 and 0.32 pH units more acidic than the mean pHe in muscle tissue. Intraperitoneal (i.p.) administration of the vasodilator hydralazine (10 mg kg-1) caused a reduction of the mean pHe of the KHT but not the EMT-6 tumour. Nigericin (2.5 mg kg-1, i.p.) plus amiloride (10 mg kg-1, i.p.) followed 30 min later by hydralazine (10 mg kg-1, i.p.) reduced the surviving fraction of cells in the KHT and EMT-6 tumours, but had minimal effects on growth delay. When KHT tumours were treated with 15 Gy X-rays followed immediately by nigericin plus amiloride and hydralazine a reduced surviving fraction as well as an increase in tumour growth delay was observed compared to radiation alone. The administration of nigericin (2.5 mg kg-1, i.p.) or the combination of nigericin (2.5 mg kg-1, i.p.) followed by hydralazine (10 mg kg-1, intravenous (i.v.)) resulted in reductions of tumour pHi of 0.27 and 0.29 pH units respectively as determined by 31P magnetic resonance spectroscopy (MRS). Our results show that the combination of nigericin and hydralazine (with or without amiloride) can kill cells in rodent solid tumours and that cell killing is associated with a reduction in the mean pHi of tumour cells.

Amiloride↗
PubMed1992

The association of age with the activity of alcohol dehydrogenase in human liver.

Ethanol is principally oxidized in the liver by the cytosolic enzyme alcohol dehydrogenase (ADH). We have examined the effect of age and sex on alcohol dehydrogenase activities in human liver obtained from 16 healthy subjects, age range 45-88 years. There was no correlation between ADH activity, whether expressed as activity per mg cytosolic protein or per gram wet weight liver, and age. Activities were similar in men and women. These results suggest that, in common with activities of other hepatic drug metabolizing enzymes, age has no effect upon the activity of ADH in human liver.

Aged↗
PubMed1992

The detrimental influence of functional ovarian cysts during in-vitro fertilization cycles.

Reviewing 780 in-vitro fertilization (IVF) cycles, where buserelin was commenced in the preceding luteal phase and human menopausal gonadotrophin on day 4 of the ensuing menses, 53 cycles were identified with sonolucent cysts (30-50 mm diameter). Of the latter 53 cycles, the serum oestradiol was significantly greater on day 4 in 22 cycles abandoned for poor follicular development than in 31 cycles which proceeded to oocyte retrieval (P less than 0.05). Of the 31 cycles proceeding to oocyte retrieval, nine had a day 4 serum oestradiol greater than 200 pmol/l (95th centile for day 4 oestradiol in patients without apparent cysts), and these cycles produced significantly fewer grade 1 embryos than the cycles with day 4 oestradiol levels less than or equal to 200 pmol/l (P less than 0.05). Six of the 53 cycles with cysts resulted in conception, and all of these cycles had a day 4 serum oestradiol less than 200 pmol/l. Among the 53 cycles with ovarian cysts, the serum progesterone on the day of abandonment in four cycles and on the day of human chorionic gonadotrophin administration in one non-abandoned cycle, was above the range established for 104 cycles without cysts. No significant difference was seen in day 4 serum androstenedione levels, and the day 4 serum progesterone was less than 5 nmol/l in all but one patient. Functional activity of ovarian cysts is associated with an adverse influence on IVF cycles.

Androstenedione↗
PubMed1991

MDA-image: an environment of networked desktop computers for teleradiology/pathology.

MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.

Clinical Laboratory Information Systems↗
PubMed1990

Studies of the initiation of myelination by Schwann cells.

The rapid morphologic changes in Schwann cells and in their relationships to axons during the transition from the premyelinating to the myelinating state have been known for more than 15 years. The sorting of axons by dividing Schwann cells, the establishment of a 1:1 relationship between a postmitotic Schwann cell, and the onset of myelin sheath formation have all been described in detail. However, the chain of molecular events and mechanisms by which these morphologic changes are regulated has not been elucidated. In this chapter we have reviewed results that strongly suggest that the adhesion molecule L1 is one of the important determinants that mediate the elongation of the Schwann cell along the axon, and the extension of Schwann processes to engulf axons. Thus, L1 functions to promote the spreading of the Schwann cell process over the surface of the axon. L1 does not appear to be exclusively involved in the adhesion of Schwann cells to axons, in the activation of Schwann cell proliferation by axons, or in the induction of synthesis of extracellular matrix proteins. The results from the anti-L1 blocking experiments further provided clues for an understanding of how the expression of GalC and MAG, which are both likely to be involved in the initiation of myelination, are regulated. These results imply that the overall regulation of expression of these early myelin components could require controls other than a single signaling mechanism derived from contact with axons. We propose that the deposition of basal lamina or one of its components could also be involved. Finally, the results from anti-GalC-blocking experiments indicated that GalC is involved in the mechanism of early growth of the myelin spiral.

Animals↗
PubMed1990

Effects of social support from various sources on depression in elderly persons.

Although global measures of social support demonstrate significant effects on psychological and physical well-being, the differential significance of various support sources is largely unknown. The present study examines differences in the effects of functional expressive support by source on depressive symptoms. This approach is contrasted with network interaction studies of elderly persons, which do not measure functional support but do suggest that friends are distinctly significant. Spouse, friends, and adult children were found to rank in descending order of importance; relatives show no effect. Low support may have stronger effects than unavailability of sources. Effects of supports and stressors are not conditioned by age, sex, or widowhood. Implications of findings and further research needs are discussed.

Aged↗
PubMed1990

Defining successful performance among pediatric residents.

The pediatric literature has documented a growing attention to defining the nature and quality of residency training. The critical incident technique, a method widely accepted in industrial settings, was used in this study to determine attitudes and behaviors deemed critical for successful performance of residents in a pediatric training program. Structured interviews with 17 senior teaching faculty produced descriptions of resident behavior that were classified into the following mutually exclusive categories: commitment to learning, clinical judgment, communicating medical information, recognition of limits, professional behavior, interpersonal skills with patients, and dealing with emergency situations. Only 30% of the critical incidents obtained from the faculty were related to criteria traditionally used to select and evaluate residents, such as knowledge and technical skills, while the remaining incidents were noncognitive in nature. The results of this study have implications for the evaluation and selection of residents and suggest that pediatric program directors and faculty must give attention to the means by which noncognitive skills are fostered in residents.

Attitude of Health Personnel↗
PubMed1989

IgM secreted by human T lymphoma virus-I-infected and transformed human B cell clones recognize a 66-kilodalton host-encoded protein.

It has previously been determined that transformed human B cells may be infected by and retain integrated human T cell lymphotropic virus, type I (HTLV-I). Although HTLV-I is primarily associated with transformation of human T lymphocytes, immortalized B cell populations have arisen after cocultivation of normal B cells and irradiated HTLV-I-infected T cells. To test whether HTLV-I infection might be involved in this B cell transformation process, we characterized five independent HTLV-I-infected and -immortalized human B cell clones. All five clones contained clonal HTLV-I integrations, expressed cell surface IgM, and secreted IgM in quantities varying from 0.1 to 4.0 micrograms/ml. Immunoblotting and immunoprecipitation of metabolically labeled cell lysates failed to detect synthesis of HTLV-I gag, env, or tat gene products, and cellular RNA dot blot analysis detected varying levels of HTLV-I gene transcripts in only three of the five clones. The secreted IgM from culture supernatants were affinity purified, and were found to selectively immunoprecipitate an acidic protein (isoelectric point = 5.0) of 66,000 m.w. (p66) from purified radioiodinated HTLV-I virions. This p66 copurified with metabolically labelled HTLV-I-infected B cell IgM from HKA-3 cells. Although HTLV-I RNA transcripts were present at low levels, the absence of HTLV-I proteins in HKA-3 cells made it unlikely that p66 was related to the major HTLV-I envelope glycoprotein, gp62. Anti-idiotypic mAb directed against the IgM produced by one B cell clone (HKA-3), as well as purified HTLV-I virions (containing p66), stimulated HKA-3 cell proliferation. Preincubating the anti-Id antibody or HTLV-I with excess HKA-3 IgM abolished the binding of either to HKA-3 cells. These data suggest that HTLV-I infected cells produce a cellular protein (p66), which is incorporated into and copurifies with HTLV-I virions, and which in at least one case (HKA-3) may act as a mitogenic stimulus, potentially contributing to the HTLV-I mediated transformation process.

Antibodies, Anti-Idiotypic↗
PubMed1989

High-level expression, purification, and characterization of recombinant human tumor necrosis factor synthesized in the methylotrophic yeast Pichia pastoris.

Human tumor necrosis factor (TNF) alpha/cachectin was expressed in the methylotrophic yeast Pichia pastoris at high levels (greater than 30% of the soluble protein) by placing the TNF cDNA under the control of regulatory sequences derived from the alcohol oxidase gene. Batch fermentor cultures at cell densities of 50 and 85 g dry cell weight/L contained approximately 6 X 10(10) and 10(11) units/L TNF bioactivity (6 and 10 g/L TNF), respectively. TNF productivity of 0.108 g L-1 h-1 was obtained in the continuous mode on glycerol- and methanol-mixed feed at 25 g dry cell weight/L cell density. TNF contained in the yeast cell lysate was soluble, displayed full cytotoxic activity, and was recognized by antibodies prepared against TNF derived from Escherichia coli. TNF was purified to greater than 95% purity with greater than 75% recovery by using three sequential chromatographic steps with a coordinated effluent-affluent buffer scheme which allowed one eluate to also serve as the loading buffer for the succeeding column. The amino acid composition, NH2-terminal amino acid sequence, isoelectric point, and minimal molecular weight determined for TNF corroborated those properties predicted from the nucleotide sequence. Sedimentation data indicated that TNF in the native form is a compact trimer held by noncovalent interactions. Circular dichroic spectra of TNF resemble those of proteins with high beta structure. TNF exhibited cachectic activity on mouse 3T3-L1 cells at about the same equivalence as the cytotoxic activity toward mouse L929 cells. In the criteria examined, TNF derived from P. pastoris closely resembles TNF derived from recombinant E. coli and human HL-60 cells.

Animals↗
PubMed1989

Mechanisms of cyclosporine protection against spontaneous diabetes mellitus in the BB/W or rat.

Anti-islet cell-mediated immunity in the Bio-Breeding/Worcester (BB/Wor) rat was studied by measuring the cytotoxic activity of splenic lymphoid cells from diabetes-prone (DP) rats receiving either oral cyclosporine (Cy-A, 10 mg/kg/d) or olive oil vehicle (DP control) from age 40 to 105 d. Splenic cells were incubated with concanavalin A (Con-A) for 16 h, then used as effector cells in cytotoxicity assays with 51Cr labeled cells from a rat islet cell line (RIN) as targets. Lysis of RIN cells (% 51Cr release) by Con-A-activated splenic cells from control DP rats increased from age 40 d (5.4 +/- 1.6%) to 105 d (32.7 +/- 1.8%). This increase was significantly less in Cy-A-treated DP rats (14.5 +/- 3.2%) and remained low at 15 d after stopping Cy-A (14.8 +/- 2.5%). Diabetes developed in control DP rats between 74 and 120 days of age, and in none of the Cy-A-treated DP rats by age 105 d, nor for 15 d after stopping Cy-A. The Con-A-activated splenic cells responsible for lysis of RIN cells also lysed normal rat islet cells and had the functional and phenotypic properties of natural killer (NK) cells. In contrast to the lower Con-A-inducible NK cell cytotoxic activity in Cy-A-treated DP rats, basal NK cell activity and monoclonal antibody-defined NK cell subsets were increased in the Cy-A-treated DP rats. Therefore, Cy-A had inhibited the ability of NK cells to respond to cytotoxic activation despite their increased numbers. To investigate the mechanism(s) of the protective effect of Cy-A, we examined the direct effects of Cy-A in vitro. Cy-A (100 ng/ml) inhibited completely Con-A activation of DP splenic cells cytotoxic to islet cells, and this was accompanied by a similar inhibition of interleukin-2 (IL-2) production. Also Cy-A (300 ng/ml) inhibited partially (approximately 65%) IL-2 activation of DP splenic cells cytotoxic to islet cells. In addition, Cy-A inhibited the cytotoxic effects of DP cells previously activated by Con-A, and 300 ng/ml Cy-A produced a maximum inhibition of 47 +/- 5%.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1989

Measuring the communication of social support from adult children.

Further knowledge of the nature and significance of the relationships of elderly persons to their adult children requires the application of social support scales tapping the quality and content of their interactions. Scaling efforts must further address conceptual and operational specification, the differentiation of sources and dimensions of support, the objectification of self-report scales, and construct validity. Respondents to this survey are a community, stratified probability sample of adults aged 50 and older (N = 1,174). Measures employed include 2 items reflecting instrumental support and 17 items designed to tap Cobb's (1976) definition of expressive support as consisting of information that one is loved, esteemed, and embedded in a social relationship characterized by mutual caring and obligation. Factor analyses consistently discern one instrumental and three expressive dimensions of support: Caring and Concern, Social Integration, and Love and Affection. These subscales are differentially correlated with sociodemographic characteristics of the parents and adult children, as well as with depression and disability. Implications of these and other findings are discussed.

Adult↗
PubMed1989

Cross-institutional stability of behavioral criteria desirable for success in radiology residency.

Certain dimensions of job performance are critical to radiology residents, and several of these dimensions are noncognitive in nature (eg, interpersonal skills, conscientiousness, recognition of limits). Our initial study examined these factors in only one residency program, so the general nature of these dimensions must be documented. The current study was a cross institutional analysis involving 31 faculty radiologists at three separate academic institutions (82% of total faculty) who participated in a critical incident interview to obtain data on important resident behaviors and attitudes. The resultant 172 incidents were sorted by two physicians into the six categories (knowledge, technical skills, attitudes toward self and [both recognitions of limits and confidence in abilities], conscientiousness, curiosity, and interpersonal skills); inter-rater reliability was 92%, kappa = .89. A Chi square analysis revealed similar distributions of incidents across categories (x2 12 = 17.22) among the three institutions, supporting the general reliability of these dimensions across the institutions studied. Further, the distributions of these incidents demonstrated that the noncognitive dimensions again were given considerable importance by faculty radiologists. For example, more than 40% of the critical incidents pertained to the conscientiousness dimension. These findings documented the generalization of these behavioral dimensions across several sites and support their importance in selection and evaluation of residents.

Attitude of Health Personnel↗
PubMed1989

Effects of extracellular slime produced by Staphylococcus epidermidis on oxidative responses of rabbit alveolar macrophages.

Bacterial slime produced in mass cultures of the RP 12 strain of Staphylococcus epidermidis was extracted with 4 M guanidine-HCl plus 0.05 M sodium acetate and 0.5% CHAPS, concentrated, dialyzed, and subjected to separation on DEAE sephacel columns. Three fractions, I-2A, I-2B, and I-4, were eluted with linear gradients of NaCl. Fractions I-2A and I-2B were alcian blue positive, whereas I-4 was alcian blue negative but the most electronegative fraction. The crude polysaccharide fraction and the three purified fractions were incubated individually for 2.5 or 20 h with normal rabbit alveolar macrophages (AM) to determine their effect on a subsequent PMA-induced oxidative burst. The crude fraction (50-200 micrograms/mL) and I-2B (50-200 micrograms/mL) primed the AM to give approximately a threefold increase in the PMA-induced burst after 2.5 h incubation. In contrast, a 20-h incubation resulted in a 30-40% inhibition of the PMA-induced burst with AM incubated with the same concentrations of the crude, I-2A, or I-2B fractions. Fraction I-4 had no detectable effect. The fractions also were tested to determine if they could elicit an oxidative burst in BCG-immune AM. None of the fractions (up to 500 micrograms/mL) elicited a significant oxidative burst even though BCG-immune AM yielded a PMA-induced burst 100 times that observed with normal resident AM. These data suggest that slime from S. epidermidis can impair the PMA-induced oxidative burst of normal AM during a 20-h incubation period and could explain in part why host defenses are compromised by slime-producing S. epidermidis.

Animals↗