Biomedical subjects

Z Williams

Publications and source records attributed to Z Williams.

16 recordsLinked to original sources

PubMed2006

Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge.

BACKGROUND: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma. OBJECTIVES: This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge. METHODS: In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) <or=9 h after allergen challenge. AHR to histamine provocation was measured before and repeated 24 h after allergen provocation. Patients inhaled histamine in doubling concentrations until attaining a decrease in FEV(1) of <or=20% (PC(20)FEV(1)). RESULTS: Roflumilast had no detectable bronchodilator activity 60 min after administration. Roflumilast significantly attenuated AHR compared with placebo, with a mean change in pre- to postallergen challenge PC(20)FEV(1) ratio of 1.23 +/- 2.75 and 2.51 +/- 2.95 for roflumilast and placebo, respectively (p = 0.002). During the late asthmatic response, roflumilast reduced the mean maximum decrease in FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV(1) at 9 h after challenge was significantly higher in patients treated with roflumilast (p = 0.03). Early asthmatic responses to allergen challenge were not significantly reduced by the single dose of roflumilast. CONCLUSIONS: Roflumilast attenuated allergen-induced AHR in patients with mild asthma. These results support further investigation of roflumilast as an anti-inflammatory treatment of asthma.

Administration, Oral↗

PubMed2006

Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis. OBJECTIVE: The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here. METHODS: Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). RESULTS: There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025). CONCLUSION: There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.

Anti-Inflammatory Agents↗

PubMed2005

Persistence of rhinovirus RNA after asthma exacerbation in children.

BACKGROUND: Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. OBJECTIVE: We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). METHODS: Patients aged 4-12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. RESULTS: Fifty children with acute asthma (mean age+/-SD, 7.4+/-2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4+/-16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. CONCLUSION: RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.

Acute Disease↗

PubMed2001

Secretion of mouse ZP3, the sperm receptor, requires cleavage of its polypeptide at a consensus furin cleavage-site.

The mouse egg extracellular coat, or zona pellucida, consists of three glycoproteins, called mZP1-3. Each glycoprotein possesses a consensus sequence recognized by the furin family of proprotein convertases. Previously, it was reported that mZP2 and mZP3 are cleaved at their consensus furin cleavage-sites located near the C-terminus of the polypeptides [Litscher, E. S., Qi, H., and Wassarman, P. M. (1999) Biochemistry 38, 12280-12287]. Here, use of site-directed mutagenesis of the mZP3 gene and a specific inhibitor of furin-like enzymes revealed that secretion of nascent mZP3 from transfected cells is dependent on cleavage of mZP3 at its consensus furin cleavage-site. The dependence of secretion on cleavage represents a novel function for furin family enzymes.

Amidohydrolases↗

PubMed2001

Reduced activation of peripheral blood neutrophils after late-phase asthmatic responses but not in mild stable asthma.

BACKGROUND: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations. OBJECTIVE: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations. METHODS: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined. RESULTS: No differences were detected in adhesion molecule expression and ROS production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations were found between decreases in CD11b and the severity of the LAR (r = 0.9; p < 0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p < 0.05). Again, this measurement was significantly associated with reductions in PEF (r = 0.5, p < 0.03). CONCLUSIONS: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung.

Adolescent↗

PubMed2001

Therapeutic equivalence study of two formulations (innovator v. generic) of beclomethasone dipropionate in adult asthmatic patients.

OBJECTIVE: To study the therapeutic equivalence of two formulations (innovator v. generic) of beclomethasone dipropionate (BDP) 400 micrograms twice daily administered per metered dose inhaler (MDI), in adults with moderate to severe asthma. METHODS: A double-blind randomised parallel-group trial was performed with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult asthmatics on a mean daily dose of 750 micrograms inhaled corticosteroids during run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted normal and a mean histamine concentration provoking a 20% reduction in FEV1 (histamine PC20) of 0.11 mg/l were randomised to one of the two treatment groups. Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine PC20. Secondary variables were beta 2-agonist use, symptom score and nocturnal awakening. The Schuirmann two one-sided tests procedure was used for the statistical analysis. Ninety-five per cent confidence intervals (CIs) were calculated for the differences in means. RESULTS: The mean differences end of treatment to baseline for the two formulations (Becotide and Beclate) respectively were: mPEF 5.6 l/min (CI - 16.4-27.6) and -22.3 l/min (CI -35.6(-)-9); FEV1 -2.9% (CI -11-5.2) and 0.2% (CI -4.8-5.2); Histamine PC20 -0.04 mg/ml (CI -0.15-0.06) and 0.02 mg/ml (CI -0.37-0.4). Changes in clinical variables were not conclusive. The mean differences with CIs for primary variables were contained within the limits set for equivalence. The sample size was sufficient to differentiate the groups for mPEF, but this was not of clinical significance. CONCLUSION: After 8 weeks of treatment the two formulations of BDP, delivered by MDI through a large-volume spacer, were therapeutically equivalent in moderate-to-severe asthmatic adults.

Administration, Inhalation↗

PubMed2000

Sonic hedgehog promotes proliferation and tyrosine hydroxylase induction of postnatal sympathetic cells in vitro.

The role of Sonic hedgehog (shh) in neural crest development was initially suggested by its involvement in patterning of the neural tube. While largely implicated in cell fate determination during development, its recently discovered role in the development of neurons postnatally prompted the possibility that neural crest derivatives of the sympathoadrenal lineage may respond to Shh postnatally. In the present study, we show that Shh promotes proliferation of postnatal sympathetic cells in culture. While it has been previously found to induce tyrosine hydroxylase (TH) production in the developing midbrain, we also demonstrated that Shh is capable of promoting TH induction of mature sympathetic neurons in vitro. This duality in Shh can be inhibited by activation of protein kinase A. These findings suggest that cell response to Shh is conserved in sympathetic ganglia derived from the neural crest, and further supports the notion that Shh can function postnatally in a dose-dependent manner to mediate neuronal cell fate.

Animals↗

PubMed1999

Structure and function of the mammalian egg zona pellucida.

The zona pellucida is a thick extracellular coat that surrounds all mammalian eggs and preimplantation embryos. The zona pellucida supports communication between oocytes and follicle cells during oogenesis; protects oocytes, eggs, and embryos during development, and regulates interactions between ovulated eggs and free-swimming sperm during and following fertilization. Mutant females that produce eggs that lack a zona pellucida are infertile. The functions of the zona pellucida during fertilization now can be ascribed to certain of its glycoproteins. Here we describe some aspects of zona pellucida structure and function as they relate to mammalian fertilization. J. Exp. Zool. (Mol. Dev. Evol.) 285:251-258, 1999.

Animals↗

PubMed1998

Cavernous sinus syndrome caused by a primary paranasal sinus non-Hodgkin's lymphoma.

Although uncommon, non-Hodgkin's lymphomas occasionally arise from the nose and paranasal sinuses. Rarely, they may invade into the cavernous sinus and produce signs and symptoms that characteristically include unilateral ophthalmoplegia, sensation loss in the distribution of the ophthalmic and other divisions of the trigeminal nerve, sympathetic nerve paralysis and proptosis. In this report, we present a case of cavernous sinus syndrome (CSS) caused by infiltration of non-Hodgkin's lymphoma from the adjacent paranasal sinuses and address issues regarding its diagnosis and treatment.

Aged↗

PubMed1990

Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer.

Twenty-five human bladder tumors were examined for loss of heterozygosity of markers on chromosomes 6p, 9q, 11p, 14q, and 17p. These studies show that all of the markers were reduced to homozygosity in at least some of the tumors. They also confirmed earlier studies by Fearon et al. [Nature (Lond.), 318: 377-380, 1985] that approximately 40% of bladder tumors were reduced to homozygosity for markers on chromosome 11p. However, the greatest frequency of allelic loss was seen for chromosomes 9q (67% of informative cases) and 17p (63% of informative cases) with both chromosomes being lost concordantly in 10 out of 20 informative tumors. Allelic loss of chromosome 9q has not been previously observed with other human cancers; however, deletions of 17p have been reported in breast, lung, and colorectal carcinomas. The data raise the interesting possibility that allelic losses of specific chromosomes might be a feature of cancer in a particular differentiated cell type whereas loss of other chromosomes harboring more generally acting tumor suppressor genes might be a common feature of human cancers.

Alleles↗

PubMed1988

The effect of deoxycoformycin on bone marrow cells treated with adenosine and deoxyadenosine and hemopoietic growth factors.

Medium conditioned by pokeweed-mitogen-activated human spleen cells enhances the survival of human multipotent stem cells (CFU-mix), erythroid progenitors (BFU-E), and myeloid progenitors (CFU-C) in liquid culture. The effect of adenosine on bone marrow cell survival in liquid culture in the presence of 2'deoxycoformycin and pokeweed-mitogen spleen-conditioned medium was studied. The combination of 2'deoxycoformycin and adenosine was found to have opposite effects on T lymphocytes and hemopoietic progenitors, i.e., the latter were preserved whereas the growth of T lymphocytes was inhibited following prolonged (4-7 days) incubation in suspension culture. The combination of 2'deoxycoformycin and adenosine removed not only all antigenically detectable T cells, but also functionally detectable cells, as judged by response to mitogens. The results suggest that in vitro culture of bone marrow cells in the presence of 2'deoxycoformycin and adenosine might be considered as an alternative way for the removal of T lymphocytes for allogeneic bone marrow transplantation.

Adenosine↗

PubMed1988

Role of pokeweed mitogen spleen conditioned medium in regulating haematopoiesis in long-term human marrow cultures.

The modulatory effect of pokeweed mitogen spleen conditioned medium (PWM-SCM) on the growth of myeloid progenitors (CFU-C) and on the composition of the stromal layer in human bone marrow long-term cultures was studied. In the presence of PWM-SCM there was enhanced CFU-C growth in the adherent layer throughout 6 weeks of incubation, with 2-fold, 2-fold and 3.4-fold increases during wk 2, 4 and 6 respectively (p less than 0.05). In the non-adherent layer of control cultures, however, there was a rapid decline in haematopoiesis which could not be offset by PWM-SCM. The differentiation pattern of CFU-C (entailing monocyte - macrophage progenitors CFU-M, granulocytic progenitors CFU-G or monocyte - granulocyte progenitors CFU-GM) was not altered by PWM-SCM. Fewer lipid-containing cells developed in the adherent layer of cultures treated with PWM-SCM than in control cultures, but the distribution pattern of monocytes - macrophages or granulocytes was not affected. These results suggest that in long-term cultures of human marrow cells there may be extensive haematopoiesis in the presence of PWM-SCM. Whether this is a direct effect on progenitor cells of stimulating factors, or rather of accessory cells in the adherent layer, remains to be clarified.

Bone Marrow Cells↗

PubMed1986

Alteration of antigenic expression of human myeloid precursor cells (CFU-GM) in long-term cultures.

Comparison of myelopoiesis in continuous human bone marrow and cord blood cultures was performed. The presence of major histocompatibility complex (MHC) antigens on myeloid precursors (CFU-GM) from cord blood was confirmed using monoclonal antibodies (MoAb) defining class I (i.e., anti-beta 2-microglobulin (B2, MG1) anti-HLA-A,B heavy chain (W6/32), and anti-HLA locus B(4E), and class II (HLA-DR (7,2] antigens. The effect of long-term culture on the expression of these antigens was investigated. Our studies indicate that following prolonged in vitro culture there is a decrease in the expression of MHC antigens on CFU-GM. Our observations provide a rationale for considering the use of cord blood leukocytes subjected to long-term culture as an alternative to allogeneic hematopoietic cell transplantation.

Aging↗

PubMed1983

Use of mice tolerant to lipopolysaccharide to demonstrate requirement of cooperation between macrophages and lymphocytes to generate lipopolysaccharide-induced colony-stimulating factor in vivo.

Injection of lipopolysaccharide (LPS) into mice was followed by a rapid elevation of colony-stimulating factor (CSF) in the serum. A second, challenging injection of LPS given 3 to 4 days later failed to induce elevated levels of CSF in the serum. Such mice tolerant to LPS were used as an experimental tool to identify the CSF-producing cells which respond to LPS. We observed that generation of LPS-induced CSF in mice tolerant to LPS could be restored by an intraperitoneal injection of spleen cells 24 h before the challenging injection of LPS. Depletion of the adherent cells from the spleen cells reduced the ability of the splenic lymphocytes to restore the capacity of the mice tolerant to LPS to generate serum CSF. Reconstitution of the splenic lymphocytes with 5% thioglycolate-elicited peritoneal macrophages, however, reestablished the restorative capacity of these cells, whereas almost no restoration was observed after direct injection of elicited peritoneal macrophages. These data suggest that the spleen cells are active in generating CSF, provided that macrophages are present and can interact with the splenic lymphocytes to generate LPS-induced CSF in the serum.

Animals↗

PubMed1976

A hall of health.

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California↗

PubMedDate not supplied

Ependyma-lined cysts.

Ependyma-lined cystic lesions of the subarachnoid space are uncommon. They form a histologically heterogeneous group and have been referred to as epithelial, ependymal, glioependymal and neuroepithelial cysts depending on their respective histological characteristics. In this report, we describe two cases of ependyma-lined cysts in the posterior fossa that support a common pathogenesis for this diverse group of lesions.

Adult↗