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Biomedical subjects

J A Wood

Publications and source records attributed to J A Wood.

At least 19 recordsLinked to original sources
PubMed2004

Gender and procreation among patients with schizophrenia.

OBJECTIVE: Reduced procreation among men with schizophrenia has been reported consistently when compared with female patients, but the cause is unknown. Reports on Caucasian individuals predominate in the published literature. Therefore, analyses were conducted concurrently among independent Indian and US samples in the present study. METHOD: Individuals with schizophrenia or schizoaffective disorder (DSM-IV criteria) were ascertained and interviewed at New Delhi and in the northeastern United States using identical procedures (n=224 and 144, respectively). Selected indices of fertility and fecundity were compared among men and women at each site. RESULTS: In the smaller US sample, male cases were significantly more likely to be single and childless compared with female cases. They also had fewer children. In contrast, there were no significant gender differences in the larger Indian sample with regard to the reproductive indices. Multivariate analyses revealed that the indices of reproduction were associated with different variables in the US and Indian samples. Fertility (the presence or absence of offspring) was associated with gender and age in the US sample while in the Indian sample conjugal status and age were significant predictors. Fecundity (the number of offspring) was associated with gender, conjugal status and educational status in the US sample while in the Indian sample conjugal status and educational status were both significant. CONCLUSIONS: The reproductive deficit observed among US males was not observed among the Indian men. Conjugal status was a significant covariate for reproduction in both samples. The reproductive deficit may be due to difficulties in establishing long-term conjugal relationships among the US men. The differences may also reflect underlying cultural variations related to marital practices in these two countries. Our analyses suggest that the male reproductive deficit in schizophrenia is variable and may be overcome.

Adolescent↗
PubMed2002

Can clinical features of bipolar-I disorder be assessed reliably on the telephone?

BACKGROUND: The reliability of telephone interviews for rating 25 selected individual items of the Diagnostic Interview for Genetic Studies (DIGS) was assessed among persons with remitted bipolar disorder I (BPD I, n = 20). METHODS: The Diagnostic Interview for Genetic Studies (DIGS) was administered directly (with two raters present) and by telephone in random order to 20 adults with bipolar disorder I. RESULTS: Telephone interviews achieved reliability comparable to direct interviews for 16 items (64%), but were considered unsatisfactory for seven others (28%). Two other items, which evaluated the overlap between substance abuse and mood disorder, were considered unreliable for both methods of interview. LIMITATIONS: The presence of two interviewers for the in-person interview may have led to over-estimation of in-person reliability. Investigator bias in favor of phone interviews and a relatively small sample may have confounded the results. CONCLUSIONS: Telephone interviews may be used to evaluate individuals with BPD I in remission, provided the limitations of this method are recognized. They have limited reliability for dissecting overlap between mood abnormalities and psychotic phenomena or substance abuse.

Adolescent↗
PubMed2001

Novel glucocorticoid antedrugs possessing a 17beta-(gamma-lactone) ring.

The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Barton ester decarboxylation and trapping the generated 17-radical with butyrolactone disulfides. The glucocorticoid butyrolactones were hydrolyzed in human plasma by the enzyme paraoxonase to the respective hydroxy acids, which were very weak glucocorticoid agonists. The rate of hydrolysis in plasma was very rapid (t1/2 = 4-5 min) in the case of lactones possessing a sulfur atom in the alpha-position of the butyrolactone group, whereas carbon-linked lactones were stable in plasma. 16alpha,17alpha-Butylidenes were more potent glucocorticoid agonists than the corresponding isopropylidene derivatives. Similarly, 1,4-dien-3-ones were more potent than the corresponding 4-en-3-ones. The butyrolactones linked to the steroidal nucleus via the beta-position were more potent glucocorticoid agonists than those linked through the alpha-position of the lactone. The most potent compounds were also shown to be stable in human lung S9 fraction, showed much lower systemic effects than budesonide in the thymus involution test, and possessed topical antiinflammatory activity in the rat ear edema model.

Administration, Topical↗
PubMed2001

Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and megakaryocytic engraftment in the non-obese diabetic severe combined immunodeficient mouse model.

A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to shorten the period of neutropenia and thrombocytopenia following myeloablative therapy and transplantation. Prolongation of cytokine expansion leads to the production of greater numbers of cells, and should have an impact on neutrophil and platelet recovery. Furthermore, expansion of CD34(+) cells should support the continued production of neutrophils and platelets in the 6-week period following transplantation. We tested these hypotheses by characterization of the kinetics (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19 and CD3) of human engraftment in the non-obese diabetic severe combined immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells and transplantation with increasing numbers of input cells facilitated the production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+) cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo culture of CB will have a beneficial clinical effect.

Analysis of Variance↗
PubMed2001

Prior cryopreservation of ex vivo-expanded cord blood cells is not detrimental to engraftment as measured in the NOD-SCID mouse model.

Cytokine-mediated expansion has been proposed and successfully used to facilitate engraftment post transplantation. This study examined whether cryopreservation following expansion has a detrimental effect on the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34(+) cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL), and megakaryocyte growth and development factor (MGDF). Expanded CD34(+) cells were transplanted into NOD-SCID mice either fresh or following cryopreservation and thawing. After thawing, recovery of nucleated cells was 94%, of CD34 cells was 63%, and of day-14 progenitors was 17%. The loss of day-14 progenitor cells among the thawed expanded cells did not influence the kinetics of human engraftment in the mouse. Bone marrow (BM) of mice transplanted with thawed expanded CD34(+) cells (14 +/- 3.9%) showed significantly higher levels of human engraftment than mice transplanted with fresh expanded CD34(+) cells (1.5 +/- 0.5%, p = 0.0064). Thawed expanded CD34(+) cells had significantly higher SCID Engrafting Potential (SEP) than freshly expanded CD34(+) cells (p < 0.001). Results suggest that prior cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.

Animals↗
PubMed2000

Conditions that enable human hematopoietic stem cell engraftment in all NOD-SCID mice.

BACKGROUND: Transplantation of human hematopoietic stem cells is the only true test of their long-term repopulation potential. Models are readily available to evaluate murine hematopoietic stem cells, but few exist that allow reliable quantification of human stem cells. The non-obese diabetic-severe combined immunodeficient (NOD-SCID) mouse model enables quantification of human hematopoietic stem cells, but the conditions that permit human engraftment in all animals have yet to be defined. The aims of the project were, therefore, to describe the variables that allow human engraftment in the NOD-SCID mouse model and the techniques that accurately quantify this engraftment. METHODS: NOD-SCID mice that had or had not received 250, 325, or 400 cGy irradiation received cord blood (CB) mononuclear or CD34+ cells i.v. or i.p. Mice were killed 6 weeks after transplantation, and the bone marrow, spleen, and thymus were harvested. Four-color flow cytometric analysis, semi-quantitative PCR, myeloid and erythroid progenitor, and stem cell assays were used to monitor human engraftment. RESULTS: A 250 or 325 cGy and i.v. injection of CB mononuclear or CD34+ cells is required to detect multilineage human engraftment in the bone marrow, spleen, or thymus of NOD-SCID mice. Four-color flow cytometric analysis and semi-quantitative PCR enable accurate detection of 0.1% human cells. Progenitor and stem cell assays provide functional information about the engrafted cells. CONCLUSIONS: Successful development of the NOD-SCID mouse model and techniques to assess human engraftment now allow it to be used reliably to analyze the effects of short-term cytokine exposure on the long-term repopulating capacity of CB stem cells.

Animals↗
PubMed2000

Role of nitric oxide in a toxin-induced model of haemolytic uraemic syndrome.

The role of nitric oxide in the pathogenesis of glomerular thrombotic microangiopathy was explored using an established rat model in which ricin with or without lipopolysaccharide induced glomerular thrombosis. Ricin alone caused a small rise in the plasma concentration of nitric oxide (control 9.2+/-0.7 microM, ricin 23.3+/-6.3 microM at 7 h). This increase occurred after the development of glomerular thrombosis. Nitric oxide synthase (NOS) activity in the kidney showed no significant change from control values (control 5.66+/-2.7 pmol/min per ml homogenate, ricin 7.52+/-1.8 pmol/min per ml homogenate, total activity). When ricin and lipopolysaccharide were administered together, calcium-independent NOS activity increased whereas calcium-dependent activity decreased (1.22+/-2.6 pmol/min per ml homogenate). The increase in calcium-independent NOS activity correlated with a high plasma concentration of interleukin-1beta in the ricin plus lipopolysaccharide group (4,036.83+/-1,001.5 pg/ml). These data indicate that thrombus formation in a rat model of haemolytic uraemic syndrome is independent of the effects of nitric oxide.

Animals↗
PubMed2000

The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone.

A side-effect of the immunosuppressive drug FK506 (Prograf; tacrolimus) is hypomagnesaemia. We have investigated the effects of short-term (7-day) treatment of rats with FK506, using a protocol designed to indicate whether there are modifications in the renal tubular handling of magnesium and other electrolytes, or in the tissue deposition of magnesium, which may account for the hypomagnesaemia. We have also investigated whether parathyroid hormone has a role in the observed hypomagnesaemia. Two studies have been performed; in the first we administered FK506 (0.5 mg x kg(-1) body weight x day(-1)) or vehicle by intraperitoneal injection for 7 days, and then housed the rats in metabolic cages for the 24 h collection of urine. At the end of the metabolic cage period, the animals were anaesthetized, and blood and tissue samples were taken for analysis. In the second set of experiments the dosage regime was identical, but at the end of the treatment period the animals were anaesthetized for implantation of arterial and venous cannulae, and then received a saline (plus inulin) infusion for 6 h, during which time blood and urine samples were collected. The dose of FK506 employed did not decrease the glomerular filtration rate. FK506 elicited hypomagnesaemia in both sets of experiments, accompanied by inappropriately high fractional excretion of magnesium. There was also evidence of disruption of the normal renal reabsorption of calcium, but this did not result in hypocalcaemia. Plasma parathyroid hormone activity was not significantly different between the two groups, and there was no evidence of altered tissue content of magnesium in kidney, liver, heart, skeletal muscle or bone. The study confirms that hypomagnesaemia is a significant side-effect of FK506, even at a relatively low dose which did not decrease the glomerular filtration rate. The effect is not due to a decrease in parathyroid hormone release, or to translocation of magnesium from plasma to tissues, but does reflect decreased renal tubular magnesium (and calcium) reabsorption.

Animals↗
PubMed1999

A laboratory model of toxin-induced hemolytic uremic syndrome.

BACKGROUND: Verocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli infection is the principal cause of hemolytic uremic syndrome (HUS). The pathogenesis is unclear, and there is a need for animal models. These are impeded by the different distribution of verocytotoxin receptors between species. We have circumvented this restriction using ricin, which gains entry into cells via various galactose receptors. Like verocytotoxin, ricin specifically cleaves a single adenine from ribosomal RNA. METHODS: Rats were given ricin at a dose of 6.7 micrograms/100 g body wt, with or without lipopolysaccharide at 10 micrograms/100 g body wt. Lipopolysaccharide alone or saline were used as controls. Changes in glomerular filtration rate, hematological parameters, histology, and plasma cytokine concentrations were measured. RESULTS: Extensive glomerular thrombosis, pyknotic nuclei, and an infiltration of ED1-positive cells into glomeruli were observed eight hours after an injection of ricin. Other vascular beds were unaffected. Histologic changes were preceded by oliguric renal failure, hemolysis, and thrombocytopenia. Ricin produced a rise in plasma concentrations of monocyte chemotactic protein-1, > tumor necrosis factor-alpha, > interleukin-1 beta, > interleukin-6. Interferon-gamma showed a small increase at the end of the experiment. CONCLUSIONS: Ricin induces glomerular thrombotic microangiopathy, closely resembling that which occurs in verocytotoxin-producing E. coli-induced HUS. As in HUS, high concentrations of proinflammatory cytokines are present, which are probably a result of cytokine superinduction by the toxin.

Animals↗
PubMed1999

Developing an injectable formula containing an oxygen-sensitive drug: a case study of danofloxacin injectable.

The purpose of this study was to assess the impact of impurities in formulation components, antioxidants, formulation pH, and processing/packaging on the extent of color change associated with oxidation of danofloxacin injectable. The methods used in this study include reversed-phase HPLC, UV-VIS spectrophotometry, atomic absorption spectroscopy, visual observation, and iodimetric titration for quantification of the antioxidant. The results from this study revealed that trace impurities from two different excipients significantly contributed to color change associated with oxidation. Polyvinyl pyrrolidone (PVP) introduced trace levels of peroxides into the solution. A second excipient also had a significant impact on stability because it introduced trace metal impurities into the product. The minimization of oxygen levels alone in the solution and headspace was not sufficient to completely eliminate the product instability. The addition of an antioxidant, monothioglycerol (MTG), resulted in a formulation less sensitive to processing variables. The impact of pH on the performance of MTG was also studied. At pH 7.5, MTG resulted in significant improvement in stability; however, at pH 6.0 it was not effective as an antioxidant. Process modifications alone may not be sufficient to prevent oxidation. Chemical approaches, such as pH control, addition of an antioxidant, and control of components should be considered first as means of enhancing stability of oxygen-sensitive solutions.

Anti-Infective Agents↗
PubMed1998

Experimental rationale for treatment of high-risk human melanoma with zinc chloride fixative paste. Increased resistance to tumor challenge in murine melanoma model.

BACKGROUND: Fixed-tissue micrographic surgery (Mohs) of melanoma has been shown by retrospective analysis to improve 5-year survival. OBJECTIVES: To determine whether zinc chloride fixative paste acts as an immune adjuvant to increase host resistance to melanoma. METHODS: We performed a murine study using the poorly immunogenic B16 melanoma of C57Bl6J mice, and the more immunogenic K1735p melanoma of C3H/HeN mice. Tumors were treated with zinc chloride paste and excised 24 hours later (Group 1), or simply excised (Group 2). Mice were challenged 7 days later with injection of melanoma cells at a distant site, and tumor growth in this second site was followed. RESULTS: K1735p melanomas developed at the challenge site in 69% of mice treated with excision versus 32% of mice treated with zinc chloride fixation (P < 0.025). Development of B16 melanoma was not altered by zinc chloride fixation. CONCLUSION: Zinc chloride fixation of the more immunogenic K1735p melanoma increased resistance to subsequent tumor challenge, suggesting that zinc chloride fixative paste acts as an immune adjuvant.

Animals↗
PubMed1997

Reduction in costs, blood products, and operating time in patients undergoing open heart surgery.

OBJECTIVE: To test the hypothesis that use of aprotinin at hall dose would be more cost-effective or as efficacious as full-dose aprotinin or no aprotinin during open heart surgery. DESIGN: Cost-effective analysis, unmasked prospective comparison. SETTING: Community hospital. PATIENTS: One hundred thirty-three patients undergoing open heart surgery. INTERVENTIONS: Patients in 3 consecutive groups undergoing open heart surgery were allocated to receive no aprotinin, full-dose aprotinin, or half-dose aprotinin. MAIN OUTCOME MEASURES: Total cost (in dollars) of blood products administered plus cost of aprotinin at various dosages, comparison of total blood products administered during hospitalization, and closure time required in the operating room. RESULTS: Full-dose and half-dose aprotinin significantly (P < .05) reduced the total blood products administered during hospitalization and the operating room closure time. However, use of half-dose aprotinin resulted in a significant cost savings (P < .05) when compared with either the cost of blood products required in the nodose aprotinin group or the cost of blood products plus aprotinin in the full-dose aprotinin group. CONCLUSION: Use of aprotinin at half dose in a community hospital resulted in a significant reduction in costs, blood product use, and operating room closure time in patients undergoing open heart surgery.

Aged↗
PubMed1997

Comparing the difficulty of letter, semantic, and name fluency tasks for normal elderly and patients with Parkinson's disease.

Research on the effect of Parkinson's disease (PD) on verbal fluency has produced conflicting results. In this study, 88 PD patients with no dementia, 11 PD patients with questionable mental status, 15 PD patients with dementia, and 46 elders free from mental disorder were administered a variety of semantic, letter, and name fluency tasks. The results revealed that, contrary to popular assumption, semantic fluency was not always superior to letter fluency. Rather, verbal fluency was influenced by the nature of the individual categories. Interestingly, the relative difficulty of many categories was fairly stable across groups. The results also indicated that the individual fluency tasks were differentially sensitive to the mental status of the PD patients. Overall, the findings suggest that closer attention to the nature of the tested categories may help clarify the inconsistent effects of PD on verbal fluency.

Aged↗
PubMed1997

Induction of hapten-specific tolerance of human CD8+ urushiol (poison ivy)-reactive T lymphocytes.

The interaction of CD28 with B7 molecules (CD80 or CD86) is an essential second signal for both the activation of CD4+ T cells through the T-cell receptor and the prevention of anergy. We studied the requirement of hapten-specific human CD8+ cells for CD28 co-stimulation in recognition of hapten, and anergy induction. Urushiol, the immunogenic hapten of poison ivy (Toxicodendron radicans), elicits a predominantly CD8+ T-cell response. Autologous PBMC were pre-incubated with urushiol prior to fixation by paraformaldehyde. Fixed antigen-presenting cells were unable to present urushiol to human CD8+ urushiol-specific T cells. Addition of anti-CD28, however, overcame this antigen-presenting defect, enabling CD8+ cells to proliferate. Fixation of antigen-presenting cells prevents upregulation of B7, and addition of anti-CD28 substitutes for this signal. Proliferation of CD8+ T cells in response to urushiol was blocked by CTLA4Ig, a recombinant fusion protein that blocks CD28/B7 interactions. Preincubation of urushiol-specific CD8+ cells with fixed PBMC + urushiol for 7 d induced anergy. Anergic CD8+ cells were viable and able to proliferate in response to IL-2, but not in response to urushiol. Induction of anergy required the presence of urushiol, and pre-incubation with irradiated PBMC + urushiol did not have this effect. It is proposed that anergy was induced by presentation of urushiol by fixed PBMC, in the absence of adequate co-stimulation signals. Induction of anergy by blocking of co-stimulation could potentially induce clinical hyposensitization to haptens.

Abatacept↗
PubMed1996

Change in cognitive function in idiopathic Parkinson disease.

OBJECTIVE: To study the effects of Parkinson disease (PD) on cognitive function by determining the frequency and amount of change in Mini-Mental State Examination (MMSE) performance. DESIGN: During a 4-year period, 77 patients with idiopathic PD and 43 normal elders were administered a neuropsychological test battery twice at 2 years apart. RESULTS: A 4-point score difference on the MMSE was the amount that was statistically calculated to be a significant difference at the .05 probability level. Using this metric, 17 (22%) patients with PD had a change in their MMSE performance during a 2-year period. Fifteen individuals performed poorer, and 2 individuals improved. Using the same metric, no normal subjects changed in their MMSE performance. The groups of patients with PD who had a change and did not have a change in their MMSE performance were not characterized by significant differences in their years of education, duration of illness, age at onset, age at test time 1, estimated premorbid intelligence, Hamilton Psychiatric Rating Scale for Depression score at test time I, or Unified Parkinson's Disease Rating Scale score. The singular difference was the higher frequency of change that was found in subjects who were taking dopamine agonists at the second test time. CONCLUSION: A change in cognitive function in patients with PD, as measured by a change of 4 points or more in their MMSE performance, was observed in only 22% of a sample of 77 patients with idiopathic PD during a 2-year period.

Aged↗
PubMed1996

A mutation at glycine residue 31 of toxic shock syndrome toxin-1 defines a functional site critical for major histocompatibility complex class II binding and superantigenic activity.

Random mutagenesis with hydroxylamine was done on toxic shock syndrome toxin-1 (TSST-1) to identify the amino acid residues critical for binding to major histocompatibility complex (MHC) class II molecules of human monocytes. A double mutant with amino acid substitutions of glycine 31-->arginine and aspartic acid 184-->asparagine (G31R.D184N) demonstrated markedly reduced binding to human monocytes and induction of mitogenesis or cytokine secretion. Site-directed mutagenesis revealed that G31R, but not D184N, was at least 4 orders of magnitude less active than wild type recombinant (r) TSST-1 in these biologic activities and did not induce lethal shock in mice. The global structure of G31R remained highly similar to wild type rTSST-1 as evidenced by circular dichroism spectroscopy and binding to anti-TSST-1 polyclonal and monoclonal antibodies. These studies identified TSST-1 residue 31 as critical for binding to MHC class II molecules and for the consequent superantigenic and lethal properties of TSST-1.

Animals↗
PubMed1996

Sensitization of mice to topically applied drugs: albuterol, chlorpheniramine, clonidine and nadolol.

Allergic contact dermatitis from drugs is a significant obstacle to the development of transdermal drug delivery systems. Protocols for the sensitization of mice to drugs are needed to test methods for the prevention of allergic contact dermatitis. CBA/J female mice were sensitized to the drugs albuterol, chlorpheniramine, clonidine and nadolol by topical application. Sensitization was achieved by application of drug at 5% (w/v) to shaven dorsal skin for 5 days in a hydroxyethylcellulose vehicle. Contact sensitization was determined by measuring the ear swelling response to application of 1% drug in vehicle. Control mice treated by application of vehicle alone did not exhibit an ear swelling response to drug. Supplementation of the mice with vitamin A boosted the ear swelling response, as did application of drug to dorsal versus abdominal skin. Although plasma amounts of retinol were higher in vitamin A supplemented versus control mice, the rate of drug (albuterol and nadolol) permeation was not significantly different between vitamin A supplemented and control mice. Permeability of dorsal skin for nadolol was twice that of ventral skin, which may explain the differences in sensitization at these sites. This sensitization protocol should be useful in the development of hypoallergenic transdermal drug delivery systems.

Administration, Cutaneous↗