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Biomedical subjects

C Prior

Publications and source records attributed to C Prior.

At least 37 records · Page 2Linked to original sources
PubMed1999

Advanced non-small-cell lung cancer: adjunctive interferon gamma in induction and maintenance therapy.

PURPOSE: To evaluate the feasibility of interferon gamma (IFNgamma) as an adjunct to chemotherapy in advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 32 patients were recruited and received 25 mg/m2 cisplatin and 100 mg/m2 etoposide on days 8, 10 and 12 every 3 weeks for a total of three cycles. A dose of 100 microg IFNgamma was given subcutaneously three times weekly from days 1 to 8 and between days 15 and 29. After induction, all patients except those with progressive disease were offered IFNgamma maintenance therapy: 100 microg three times weekly. RESULTS: The following responses were obtained: partial response, 5 (16%); minor response, 12 (37%); stable disease, 4 (13%); progressive disease, 11 (34%). The survival rates after 1 and 2 years were 47% and 25% respectively. Patients receiving maintenance IFNgamma had a 2-year survival rate of 58%. Toxic side-effects were rare and included grade III/IV fever (7%/1%) and grade III/IV leucopenia (4%/1%). CONCLUSIONS: In patients with advanced NSCLC, an adjunctive dose of 100 microg IFNgamma, given three times weekly in the induction and maintenance phase, is feasible. Survival data seem favourable so this regimen may warrant further investigation in a phase III study.

Adult↗
PubMed1999

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus.

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression. Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.

Cryptogenic Organizing Pneumonia↗
PubMed1999

Systemic sarcoidosis and cutaneous lymphoma: is the association fortuitous?

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.

Anti-Inflammatory Agents↗
PubMed1999

Empty synaptic vesicles recycle and undergo exocytosis at vesamicol-treated motor nerve terminals.

We investigated whether recycled cholinergic synaptic vesicles, which were not refilled with ACh, would join other synaptic vesicles in the readily releasable store near active zones, dock, and continue to undergo exocytosis during prolonged stimulation. Snake nerve-muscle preparations were treated with 5 microM vesamicol to inhibit the vesicular ACh transporter and then were exposed to an elevated potassium solution, 35 mM potassium propionate (35 KP), to release all preformed quanta of ACh. At vesamicol-treated endplates, miniature endplate current (MEPC) frequency increased initially from 0.4 to >300 s-1 in 35 KP but then declined to <1 s-1 by 90 min. The decrease in frequency was not accompanied by a decrease in MEPC average amplitude. Nerve terminals accumulated the activity-dependent dye FM1-43 when exposed to the dye for the final 6 min of a 120-min exposure to 35 KP. Thus synaptic membrane endocytosis continued at a high rate, although MEPCs occurred infrequently. After a 120-min exposure in 35 KP, nerve terminals accumulated FM1-43 and then destained, confirming that exocytosis also still occurred at a high rate. These results demonstrate that recycled cholinergic synaptic vesicles that were not refilled with ACh continued to dock and undergo exocytosis after membrane retrieval. Thus transport of ACh into recycled cholinergic vesicles is not a requirement for repeated cycles of exocytosis and retrieval of synaptic vesicle membrane during prolonged stimulation of motor nerve terminals.

Acetylcholine↗
PubMed1998

Prejunctional effects of the nicotinic ACh receptor agonist dimethylphenylpiperazinium at the rat neuromuscular junction.

1. We have studied the effects of the nicotinic acetylcholine (ACh) receptor agonist dimethylphenylpiperazinium (DMPP) on the evoked release of ACh from motor terminals in the rat isolated hemidiaphragm using an electrophysiological approach. 2. DMPP (1-4 microM) had no effect on the rate of spontaneous quantal ACh release but increased the number of quanta of ACh released per impulse during 50 Hz stimulation. The DMPP-induced increase in evoked ACh release was dependent on the frequency of stimulation, being absent when it was reduced to 0.5 Hz, but was not Ca2+ dependent, being unaffected at 50 Hz by a 4-fold decrease in the extracellular Ca2+ concentration. 3. The facilitation of evoked ACh release at 50 Hz by 2 microM DMPP was abolished by 10 microM of the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide hydrochloride) and, in the presence of W7, 2 microM DMPP depressed evoked ACh release at 0.5 Hz. The ability of the nicotinic ACh receptor antagonist vecuronium (1 microM) to depress evoked ACh release at 50 Hz was also abolished by 10 microM W7. 4. The present findings demonstrate, using an electrophysiological technique, that DMPP can produce changes in the evoked ACh release from rat motor nerve terminals that are consistent with the existence of facilitatory nicotinic ACh receptors on the motor nerve endings. Further, they indicate a role for calmodulin-dependent systems in this facilitatory effect of the compound.

Animals↗
PubMed1998

Effects of the enantiomers of R,S-salbutamol on incompletely fused tetanic contractions of slow- and fast-twitch skeletal muscles of the guinea-pig.

1. The effects of racemic R,S-salbutamol, and its individual enantiomers have been studied on incompletely fused (sub-tetanic) contractile responses of fast- and slow-contracting isolated skeletal muscles of the guinea-pig. 2. R,S-salbutamol (2-4 microM) decreased the peak force of sub-tetani in the slow-contracting soleus muscle and increased the peak force of sub-tetani in the fast-contracting peroneus longus muscle. It also increased the force of the first twitch of sub-tetani in both muscles. The decrease in the peak force of sub-tetani in the soleus muscle was due to defusion of the individual twitches caused by a shortening of their time course. 3. The effects of 4 microM of the racemate on both fast- and slow-contracting muscles were mimicked by 2 microM R-salbutamol (levalbuterol). However, 2 microM S-salbutamol was devoid of activity in both muscles. 4. We concluded that all the effects of R,S-salbutamol on guinea-pig skeletal muscles are due to the activity of the R-enantiomer. Thus there is a common enantiomeric profile for the skeletal muscle and bronchorelaxant activity of the compound.

Albuterol↗
PubMed1997

Modulation by presynaptic adenosine A1 receptors of nicotinic receptor antagonist-induced neuromuscular block in the mouse.

We have investigated how altering the activation of adenosine A1 receptors modifies nicotinic receptor antagonist-induced fade of tetanic contractions in the mouse isolated hemi-diaphragm. Vecuronium-induced tetanic fade was attenuated by an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, DPCPX, 10(-7) M) and by an inhibitor of the synthesis of extracellular adenosine from ATP (alpha,beta-methylene ADP, MeADP, 5 x 10(-5) M). Conversely, vecuronium-induced tetanic fade was potentiated by an adenosine A1 receptor agonist (N6-cyclohexyladenosine, CHA, 10(-7) M) and an inhibitor of the extracellular destruction of adenosine (erythro-9-[2-hydroxy-3-nonyl]adenine, EHNA, 10(-4) M). The ability of an adenosine A1 receptor antagonist to attenuate vecuronium-induced tetanic fade indicates that a component of this fade is due to endogenous adenosine. Further, the ability of the inhibitor of adenosine synthesis to attenuate vecuronium-induced tetanic fade indicates that this endogenous adenosine is derived from ATP. Hexamethonium-induced tetanic fade was also potentiated by increasing adenosine A1 receptor activation, albeit with a higher concentration of CHA (10(-4) M). However, unlike for vecuronium, hexamethonium-induced tetanic fade was not attenuated by reducing adenosine A receptor activation. This latter observation suggests that the tetanic fade produced by hexamethonium and vecuronium does not share a common mechanism of action.

Adenine↗
PubMed1997

Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals.

1. The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/ hemidiaphragm preparations. 2. Hexamethonium (200 microM), but not MLA (0.4-2.0 microM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. 3. At low frequencies of stimulation (0.5-2 Hz), hexamethonium (200 microM) and MLA (2.0 microM) increased e.p.c. quantal content by 30-40%. At high frequencies (50-150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. 4. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. 5. At the concentrations studied, MLA and hexamethonium produced a small (10-20%) decrease in the peak amplitude of m.e.p.cs. 6. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca(2+)-activated K(+)-channels. 7. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the alpha-bungarotoxin-insensitive neuronal type.

Acetylcholine↗
PubMed1997

Adjunctive interferon-alpha-2c in stage IIIB/IV small-cell lung cancer: a phase III trial.

Preliminary studies have shown bioactivity of interferons (IFNs) in the treatment of small-cell lung cancer (SCLC). The aim of the present study was to determine whether, in patients with advanced SCLC, a combination of recombinant IFN-alpha-2c and standard induction chemotherapy would improve response rates and survival at acceptable toxicity. Of the 85 patients recruited by 11 centres in Austria, 77 were evaluable for response after induction therapy; of these, 43 were randomized to receive the combined treatment (three cycles each of cyclophosphamide/vincristine/doxorubicin and cisplatin/etoposide plus subcutaneous IFN-alpha-2c), and 34 received chemotherapy alone. After the induction phase, patients in the IFN arm had higher rates of complete (30 vs 15%) and partial remission (42 vs 29%) than those who received chemotherapy alone. Accordingly, there was a lower rate of progressive disease in the interferon arm (21 vs 44%; p < 0.05). Whilst there were no significant differences in time to progression (7.6 vs 5.4 months) patients in the IFN arm survived longer than those in the chemotherapy arm (p < 0.02). Six of the patients treated with IFN (14%) survived for more than 2 yrs, whereas none in the chemotherapy arm did. We conclude that the addition of interferon-alpha-2c to induction chemotherapy may improve response rates and survival in advanced small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Characterization of the NHA1 gene encoding a Na+/H+-antiporter of the yeast Saccharomyces cerevisiae.

The NHA1 gene (2958 nt) encoding a putative Na(+)/H(+) antiporter (986 aa) in Saccharomyces cerevisiae was cloned by selection based on increased NaCl tolerance. The putative protein is highly similar to sodium/proton antiporters from Schizosaccharomyces pombe (gene sod2), and Zygosaccharomyces rouxii (gene Z-SOD2). Overexpression of the NHA1 gene results in higher and partially pH-dependent tolerance to sodium and lithium; its disruption leads to an increased sensitivity towards these ions.

Amino Acid Sequence↗
PubMed1996

RAG3 gene and transcriptional regulation of the pyruvate decarboxylase gene in Kluyveromyces lactis.

The RAG3 gene has been cloned from a Kluyveromyces lactis genomic library by complementation of the rag3 mutation, which shows impaired fermentative growth on glucose in the presence of respiratory inhibitors. From the nucleotide sequence of the cloned DNA, which contained an open reading frame of 765 codons, the predicted protein is 49.5% identical to the Pdc2 protein of Saccharomyces cerevisiae, a regulator of pyruvate decarboxylase in this yeast. Measurement of the pyruvate decarboxylase activity in the original rag3-1 mutant and in the null mutant confirmed that the RAG3 gene is involved in pyruvate decarboxylase synthesis in K. lactis. The effect is exerted at the mRNA level of the pyruvate decarboxylase structural gene KIPDCA. Despite analogies between the RAG3 gene of K. lactis and the PDC2 gene of S. cerevisiae, these genes were unable to reciprocally complement.

Amino Acid Sequence↗
PubMed1996

Early sensitization to farming-related antigens among young farmers: analysis of risk factors.

It was the aim of this study to investigate the prevalence of and risk factors for IgE- and IgG-mediated allergy in young farmers. We investigated 147 young men attending a farming college in the Austrian Tyrol and 57 age-matched pupils at a grammar school. All individuals completed a questionnaire and had spirometry, skin prick tests, total and specific IgE analysis, and testing for precipitins against thermophilic actinomycetes and true fungi. In the farming group, a family history of atopy or asthma was reported less frequently than in the control group (p < 0.001) but there were no differences in the frequencies of actual respiratory symptoms. Forced expiratory volume in the first second (FEV1) was slightly lower in the farmers than in the pupils (p < 0.05). There was no difference in the prevalence of IgE-mediated allergy. Nine of the farmers but none of the pupils had precipitating antibodies against Faeni rectivirgula (p < 0.05). Overall reactivity (as defined by at least one positive finding with the skin prick test, specific IgE, or precipitins) was associated with larger farming estates, lack of a haydrying device, use of mouldy hay, and positive family history of asthma (p < 0.05). We conclude that in farmers, precipitin formation may occur at an early age and that even in younger age groups there is a clear relationship between allergic sensitization and occupational allergen exposure.

Adolescent↗
PubMed1996

Pulmonary sarcoidosis: patterns of cytokine release in vitro.

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n = 8; stage II/III n = 9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1 beta (IL-1 beta), IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and neopterin. Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-alpha, IL-6, IFN-gamma and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1 beta and GM-CSF. In the sarcoid group, the levels of IL-1 beta, IL-6, TNF-alpha and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-gamma or neopterin. Sarcoid patients whose BALC released more TNF-alpha or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1 beta, TNF-alpha, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1 beta, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity. We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-gamma and IL-2, are not the primary triggers.

Adult↗
PubMed1996

Early visual recovery after excimer laser surgery for myopia: the Melbourne OmniMed results.

BACKGROUND AND OBJECTIVE: Although the refractive outcome can change for months after photorefractive keratectomy (PRK), early visual results are of particular importance during pre-operative counseling of prospective PRK candidates. The expected vision in the first week post-operatively, following 6.0 mm or larger zone photoablation for myopia with the Summit OmniMed (Apex) laser, has not been analyzed in the literature to date. This study is intended to provide an indication of the early visual acuity that may be experienced by a patient undergoing PRK for myopia. PATIENTS AND METHODS: The visual acuity recorded for 123 consecutive patients, (79 low myopes [-1.00 to -5.90 diopters (D)], 44 high extreme myopes [-6.00 to -19.00 D]), one week after they had undergone PRK, was analyzed. All patients included in the study had undergone PRK with the Summit OmniMed (Apex) excimer laser, leaving small degrees of astigmatism uncorrected. RESULTS: One week after PRK, uncorrected visual acuity was better for low myopes than high myopes. Of the low myopes, 83.0% were 20/40 or better compared with high myopes of whom 61.4% were 20/40 or better. CONCLUSION: Patients can be counseled that functional vision will be present in the period immediately after re-epithelialization.

Adult↗
PubMed1996

Automated cell differentiation of bronchoalveolar lavage samples with two-step image analysis.

OBJECTIVE: To establish an easy method for performing an automated differential cell count on bronchoalveolar lavage (BAL) cytocentrifuge samples using morphometric parameters acquired by a digital image analyzer. STUDY DESIGN: The study population comprised 20 satisfactory cytocentrifuge preparations routinely processed in our laboratory. Images of at least 40 fields of interest were digitized and stored. The images were analyzed to assess the planimetric parameters. These were used for cell identification. Basic morphometric parameters were acquired by an automated image analysis procedure. The results obtained by this method are compared to those of the manual counting procedure. RESULTS: Following sequential analysis, computerized identification corresponded, in > 97% of the cells, to the results of manual cell typing. After data analysis, < 1% of cells remained unidentifiable. CONCLUSION: Although the number of specimens evaluated is not yet large enough to allow a definitive statement, the use of image analysis systems seems a promising approach in automated differential cell counting in BAL preparations.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Effect of veratridine on miniature endplate current amplitudes at the rat neuromuscular junction and acetylcholine uptake by Torpedo synaptic vesicles.

Veratridine produces a marked elevation in spontaneous quantal release from nerve endings through its ability to enhance sodium-channel activity, leading to sustained membrane depolarization. In the course of an electrophysiological investigation into the effects of vesamicol, an inhibitor of the synaptic vesicle acetylcholine transporter, on veratridine-induced acetylcholine release from rat motor nerve terminals we observed that veratridine itself has an effect on miniature endplate current amplitude distributions suggestive of an effect of the compound on the filling of cholinergic synaptic vesicles with acetylcholine. This effect of veratridine is release-dependent, being inhibited by either removal of extracellular calcium ions or by the addition of the sodium channel blocking toxin, tetrodotoxin. Biochemical studies using synaptic vesicles isolated from Torpedo electroplaque confirmed the ability of veratridine to directly inhibit the vesicular transport of acetylcholine. This appears to be a consequence of its ability to dissipate the trans-vesicular membrane proton gradient, which normally drives the active transport of acetylcholine into synaptic vesicles. We discuss how such an action of veratridine could lead to the observed release-dependent effects of the compound on electrophysiologically monitored spontaneous quantal acetylcholine release. The action of veratridine on cholinergic synaptic vesicles could be of considerable import when using this agent to elicit neurotransmitter release from either peripheral or central nerve endings.

Acetylcholine↗