bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Method to Measure Airway Obstruction in Nonanesthetized Allergen-Sensitized and Challenged Mice
Authors: Lin Ching-Chi 
Published: April 2003

<i>Background:</i> Conventional methods used to measure bronchoconstriction are invasive, technically demanding and time consuming. <i>Objectives:</i> Our purpose was to evaluate a noninvasive method, by barometric whole-body plethysmography (WBP), to evaluate bronchoconstriction and bronchial hyperreactivity in mice induced by ovalbumin (OA) inhalation challenge in comparison with an invasive method. Enhanced pause (P<sub>enh</sub>) was used as an index of airway obstruction. <i>Methods:</i> Eight mice were sensitized by OA (group I) and then challenged with OA. Twenty-four hours later, pulmonary function testing (PFT) was measured by WBP at baseline and after a methacholine (MCh) inhalation challenge. Eight weight-matched normal mice served as controls (group II). Four hours after PFT in a nonanesthetized condition, all animals were anesthetized and paralyzed. Baseline PFT was performed by the maximal forced expiratory maneuver (MFEM), and then the animals were given varying doses of acetylcholine (ACh; 25, 50, 75, 100 µg/kg) injected through the jugular vein. Five seconds after ACh injections, pulmonary functions were examined, including MFEM, peak airway pressure and total lung compliance. After completing PFT, bronchoalveolar lavage (BAL) was performed, the animals were sacrificed, and the lungs were examined histologically. <i>Results:</i> Group I had increased P<sub>enh</sub> in response to MCh in the nonanesthetized condition and decreased flow in the anesthetized condition, characterized by greater decreases in MFEM flow rates MFEF 50% and MFEF 25% than the control group. The peak flows, MFEF 75%, MFEF 50% and MFEF 25%, for group I were lower than those for group II at doses of ACh higher than 25 µg/kg. There were concentration-dependent increases in P<sub>enh</sub> in response to aerosolized MCh in both groups, but the P<sub>enh</sub> in response to aerosolized MCh was significantly enhanced in group I when compared with controls. The doses of MCh required for 100% increases in P<sub>enh</sub> were significantly reduced for sensitized and challenged mice. There was a positive correlation between provocative doses PD200 P<sub>enh</sub> MCh, PD20 MFEF 50% ACh and PD20 MFEF 25% ACh. There was a negative correlation between the PD200 P<sub>enh</sub> MCh and the percentage of eosinophils in BAL fluid. There was an increased total cell count and an increased percentage and absolute number of eosinophils and lymphocytes in the BAL fluid of sensitized animals. OA-sensitized mice also had a severe inflammatory reaction of airway and lung tissue, characterized by congestion, edema and inflammatory cell infiltration and desquamation of bronchial epithelial cells. <i>Conclusion:</i> The noninvasive method of WBP can be used to evaluate airway obstruction and hyperreactivity induced in mice by allergen challenge.
Colonization with <i>Schizophyllum commune</i> of Localized Honeycomb Lung with Mucus
Authors: Iizasa Toshihiko , Kamei Katsuhiko , Chiyo Masako , Suzuki Makoto , Baba Masayuki , Toyosaki Tetsuya , Hiroshima Kenzo , Ohwada Hidemi , Kanno Shigeharu , Nishimura Kazuko , Fujisawa Takehiko 
Published: April 2003

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a <i>Schizophyllum commune,</i> which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as <i>S. commune.</i> This is the first report of <i>S. commune</i> leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.
Evidence of a Restrictive Spirometric Pattern in Older Thalassemic Patients
Authors: Filosa A. , Esposito V. , Meoli I. , Stefanelli F. , Cassandro R. 
Published: April 2003

<i>Background:</i> Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. <i>Objectives:</i> The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. <i>Methods:</i> We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 ± 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 ± 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 ± 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (D<sub>CO</sub>), corrected for both Hb values (D<sub>CO*</sub>) and alveolar volume (K<sub>CO</sub>), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. <i>Results:</i> All patients in group A showed normal PFTs, D<sub>CO*</sub> and K<sub>CO</sub> values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced D<sub>CO*</sub> (63 ± 8%), elevated K<sub>CO</sub> values (120 ± 14%), a variable degree of hypoxia (P<sub>O2</sub> 82 ± 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced D<sub>CO*</sub> values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, D<sub>CO*</sub> was negatively correlated with both serum ferritin (r = –0.58; p < 0.05) and age (r = –0.57; p < 0.05). <i>Conclusions:</i> The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.
N-Omega-Nitro-<i>L</i>-Arginine Methyl Ester Increases Airway Responsiveness to Serotonin but Not to Acetylcholine in Cats in vivo
Authors: Aizawa H. , Takata S. , Shigyo M. , Matsumoto K. , Inoue H. , Hara N. 
Published: April 2003

<i>Background:</i> We previously reported that N<sup>ω</sup>-nitro-<i>L</i>-arginine methyl ester (<i>L</i>-NAME) enhances airway responsiveness to inhaled serotonin in cats treated with atropine and propranolol. <i>Objective:</i> To further elucidate the role of nitric oxide (NO) in airway responsiveness, we investigated whether <i>L</i>-NAME induces airway hyperresponsiveness to serotonin and acetylcholine (ACh) in animals with intact innervation. <i>Methods:</i> Cats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.), and mechanically ventilated. To assess airway responsiveness, we measured increase in total pulmonary resistance (R<sub>L</sub>) produced by delivering serotonin or ACh aerosol to the airway, and determined PC<sub>200</sub> (the concentration which caused a 200% increase in R<sub>L</sub>). <i>Results:</i> The following results were obtained: (1) Airway responsiveness to serotonin was significantly enhanced by the administration of <i>L</i>-NAME (100 mg/kg) in animals treated with atropine and propranolol. (2) Airway responsiveness to serotonin was also significantly enhanced by <i>L</i>- NAME in animals with intact innervation. (3) In contrast, airway responsiveness to ACh was not changed by the addition of <i>L</i>-NAME in cats with intact innervation. <i>Conclusion:</i> These results suggest that NO modulates nonspecific airway responsiveness in animals with intact innervation, presumably by a reflex mechanism.
Pulmonary Nocardiosis: Clinical Experience in Ten Cases
Authors: Mari Begoña , Montón Concepción , Mariscal Dolors , Luján Manel , Sala Montserrat , Domingo Christian 
Published: April 2003

<i>Background:</i> Pulmonary nocardiosis is an infrequent infection whose incidence seems to be increasing due to a higher degree of clinical suspicion and the increasing number of immunosuppressive factors. <i>Objective:</i> To study the predisposing factors, clinical characteristics, diagnostic procedures, treatment and progress of pulmonary nocardiosis (PN). <i>Methods:</i> Review of 10 patients (9 male, 1 female, mean age 61) with PN in a 600-bed teaching hospital, diagnosed from 1992 to 1999. <i>Results:</i> Associated diseases observed were chronic obstructive pulmonary disease (COPD) in 6 patients, human immunodeficiency virus (HIV) infection in 3 and polymyalgia rheumatica in 1. Four patients had received oral corticotherapy for COPD for over a year (mean dose 13 mg/day of prednisone or equivalent). The main reason for consultation was an increase in dyspnea in the patients with COPD (6/6) and fever in those with HIV (3/3). Mean time between onset of symptoms and diagnosis was 5 weeks. In 8 patients, the infection occurred outside the hospital setting. The infection was restricted to the lung in 9/10; in the remaining case, the central nervous system (CNS) and subcutaneous tissue were affected. Lobar or multilobar consolidation was the most frequent radiographic pattern found (6/10). Sputum culture was positive when performed (8 cases). Diagnosis was made or confirmed by bronchoscopy (bronchoaspirate or protected specimen brush) in 5 patients. Germs isolated were: <i>Nocardia asteroides</i> (8/10), <i>Nocardia farcinica</i> (1/10), <i>Nocardia otitidiscaviarum</i> (1/10). Cotrimoxazole was the most used empirical treatment (6/10). Resolution was achieved in 5 cases. Four subjects died: 1 HIV patient with disseminated nocardiosis, and 3 COPD patients, 2 of whom had received long-term corticotherapy. Illness recurred in only 1 case, due to failure to comply with treatment. <i>Conclusions:</i> (1) In our geographical setting <i>Nocardia</i> presents as a subacute or chronic pulmonary infection, mainly outside the hospital. (2) It tends to affect only the lung. (3) Diagnosis requires a high clinical suspicion, and can be made on the basis of a sputum culture. (4) <i>Nocardia</i> tends to attack patients with underlying COPD, or immunodepressed patients treated with glucocorticoids, or patients with HIV infection. (5) Mortality is high in both COPD and HIV patients. (6) In our area, cotrimoxazole seems to be the most commonly prescribed treatment.
Serial Pentamidine Levels in Bronchial Epithelial Lining Fluid after Aerosol Administration
Authors: Yamamoto H. , Koizumi T. , Miyahara T. , Kaneki T. , Kubo K. 
Published: April 2003

<i>Background:</i> There is no information on serial pharmacokinetic assessment in the lungs after administration of aerosolized pentamidine. <i>Objective:</i> The present study was performed to evaluate the elimination of aerosolized pentamidine from bronchial airways following inhalation. <i>Methods:</i> We used 4 sheep with tracheotomies in the present study. Pentamidine (300 mg) was administered by inhalation to each animal. Serial bronchial washing to obtain epithelial lining fluid (ELF) was performed 1, 7, 10, 14, 21 and 28 days after administration of aerosolized pentamidine in each animal. The pentamidine concentration in the supernatant of ELF was measured by high-performance liquid chromatography. <i>Results:</i> The maximal pentamidine level on the first day (12 h after inhalation) was 616.5 ± 238.2 ng/ml (mean ± SE) in ELF. The pentamidine levels rapidly decreased within 2 weeks (8.9 ± 1.2 ng/ml at 14 days), followed by slow elimination (8.9 ± 0.8 ng/ml at 28 days). Thus, inhaled pentamidine showed a rapid clearance from the bronchial wall within the first 2 weeks. <i>Conclusions:</i> These findings may be useful in designing and interpreting future studies of aerosolized pentamidine in patients who are receiving inhaled pentamidine, especially for those with failure of prophylaxis for <i>Pneumocystis carinii</i> pneumonia.
Fosinopril as a Possible Pemphigus-Inducing Drug
Authors: Parodi A. , Cozzani E. , Milesi G. , Drosera M. , Rebora A. 
Published: April 2003

Fosinopril has recently been added to the angiotensin-converting enzyme inhibitors inducing pemphigus. The observation of a patient in whom pemphigus vulgaris (PV) worsened after taking fosinopril prompted us to study an experimental way to assess its responsibility. Slices of normal human skin (NHS) were simultaneously incubated for 2, 6, 12 and 24 h at 4°C with progressively diluted fosinopril and captopril solutions and used as indirect immunofluorescence (IIF) substrates for 2 sera containing anti-desmoglein-3 (anti-Dsg3) antibodies at a dilution of 1/160. With captopril, IIF was negative, irrespective of dilution and time of incubation. Only at 1/40,000 dilution was IIF positive. With fosinopril, IIF was negative for the 2- and 6-hour-long incubations but turned positive after 12 h and so remained with all other solutions and incubation times. IIF negativity with captopril suggests that anti-Dsg3 antibodies contained in the PV sera were unable to find molecules in NHS to bind to. Captopril would therefore induce acantholysis by blocking the adhesion molecules. With fosinopril, instead, a partial block of the adhesion molecules was seen only with the very concentrated solution, unlikely to occur in vivo. Fosinopril, therefore, is probably unable to block the adhesion molecules in vivo. Our method might be used to verify the acantholytic properties of a drug.
Intestinal Proliferation and Delayed Intestinal Transit in a Patient with a GLP-1-, GLP-2- and PYY-Producing Neuroendocrine Carcinoma
Authors: Byrne Maria M. , McGregor Gerard P. , Barth Peter , Rothmund Mathias , Göke Burkhard , Arnold Rudolf 
Published: April 2003

Glucagon-like peptides (GLP) 1 and 2 are hormones derived from the post-translational processing of proglucagon in the intestinal L cells that influence intestinal motility and small bowel growth, respectively. We describe a patient with a neuroendocrine tumor of unknown primary origin with peritoneal carcinomatosis and diffuse liver metastases, who presented with constipation and nocturnal itching for over 3 years. Small bowel follow-through showed decreased small intestinal motility and marked intestinal hypertrophy. Biopsies from mesenterial lymph nodes showed, histologically, a well-differentiated neuroendocrine tumor (G1), with positive immunostaining for chromogranin A, GLP-1, GLP-2 and polypeptide YY (PYY). Jejunal biopsy demonstrated marked intestinal mucosal hypertrophy. HPLC analysis combined with RIA of tumor and serum extracts revealed that the tumor was producing and releasing fasting levels of GLP-1 of 738±20.7 pg/ml (normal levels (nl) <100 pg/ml), GLP-2 of 3,150±9 pg/ml (nl <100 pg/ml) as well as PYY 550 pg/ml (nl <100 pg/ml). Octreotide administration decreased levels of GLP-1 and GLP-2 and reduced small intestinal transit time from 150 to 50 min. However, tumor growth was not inhibited by octreotide, interferon or dacarbazine therapy and the patient died 8 months later. This is the first case report demonstrating the overproduction of GLP-1, GLP-2 and PYY from an neuroendocrine tumor, in a patient with intestinal hypertrophy and delayed intestinal transit time.
Delayed Healing of Gastric Ulcers in Adjuvant Arthritis Rats: Role of Acid Secretion and Basic Fibroblast Growth Factor
Authors: Kato Shinichi , Ogawa Yoshihiro , Tanaka Akiko , Kunikata Tomonori , Takeuchi Koji 
Published: April 2003

<i>Background/Aim:</i> We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF). <i>Methods:</i> Arthritis was induced in male dark Agouti rats by a single injection of Freund’s complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70°C for 30 s) 7 days after FCA injection. <i>Results:</i> Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of N<sup>G</sup>-nitro-<i>L</i>-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-α synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats. <i>Conclusion:</i> The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF.
Acute Cerebrovascular Disease in Women
Authors: Arboix Adrià , Oliveres Montserrat , García-Eroles Luis , Maragall Clara , Massons Juan , Targa Cecilia 
Published: April 2003

In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.
Effect of Renin-Angiotensin System Blockade on the Expression of the Angiotensinogen Gene and Induction of Hypertrophy in Rat Kidney Proximal Tubular Cells
Authors: Zhang Shao-Ling , To Catherine , Chen Xing , Filep Janos G. , Tang Shiow-Shih , Ingelfinger Julie R. , Carrière Serge , Chan John S.D. 
Published: April 2003

Studies have shown that high levels of glucose and angiotensin II (Ang II) stimulate hypertrophy and the expression of matrix protein genes in mouse proximal tubular cells in vitro. The present study tested the hypothesis that blockade of the renin-angiotensin system (RAS) inhibits the stimulatory effect of high levels of glucose on the expression of the renal angiotensinogen (ANG) gene and the formation of Ang II and subsequently attenuates the induction of hypertrophy in kidney proximal tubular cells. Immortalized rat proximal tubular cells (IRPTC) were cultured in monolayer. The levels of expression of rat ANG and ANG mRNA in the IRPTC were quantified by specific radioimmunoassays for rat ANG (RIA-rANG) and by a reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. Hypertrophy of IRPTC was analyzed by flow cytometry (FACScan) and cellular protein assay. Our studies showed that losartan (an Ang II (AT<sub>1</sub>)-receptor blocker), perindopril and captopril (inhibitors of angiotensin-converting enzyme) blocked the stimulatory effect of a high level of glucose (i.e. 25 m<i>M</i>) on the expression of the rat ANG gene and hypertrophy in IRPTC but not by the Ang II (AT<sub>2</sub>)-receptor blocker. Our studies indicate that the blockade of RAS is effective in inhibiting the stimulatory effect of hyperglycemia on the expression of the ANG gene and hypertrophy in IRPTC, supporting the notion that the local formation of intrarenal Ang II may play a role in the development of renal hypertrophy during early diabetes.
High Glucose Decreases Matrix Metalloproteinase-2 Activity in Rat Mesangial Cells via Transforming Growth Factor-β<sub>1</sub>
Authors: Singh Rekha , Song Ruo Hua , Alavi Nahid , Pegoraro Alfredo A. , Singh Ashok K. , Leehey David J. 
Published: April 2003

Diabetic nephropathy is characterized by accumulation of mesangial matrix. Glucose-induced inhibition of matrix-degrading enzymes such as collagenases is believed to contribute to matrix accumulation. We have previously demonstrated that 72 kDa type IV collagenase activity is decreased in the rat mesangial cells cultured in high glucose media [<i>Diabetes</i> 1995;44:929–935]. The present studies were designed to investigate if the cytokine transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) mediates this effect of glucose. Type IV collagenases degrade type IV collagen as well as gelatin (denatured collagen) and are thus also called gelatinases. They belong to the family of matrix metalloproteinases (MMPs); MMP activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). The activity of 72 kDa type IV collagenase, also known as matrix metalloproteinase-2 (MMP-2), was assessed using three methods: (1) fluoresceinated gelatin degradation assay to detect free enzyme activity (activity which is present in excess of TIMP-inhibited activity); (2) zymography to measure total (free + TIMP-bound) enzyme activity; (3) ELISA using specific antibodies to measure MMP-2 levels. TGF-β<sub>1</sub> and TIMP-2 levels were also determined by ELISA. Incubation of primary cultures of rat mesangial cells for 5 days in 30 vs. 5 m<i>M</i> glucose resulted in a 3-fold increase in production of total TGF-β<sub>1</sub>, a significant decrease in MMP-2 activity and immunoreactive MMP-2 levels, and an increase in TIMP-2 levels. Addition of exogenous TGF-β<sub>1</sub> to mesangial cells incubated in 5 m<i>M</i> glucose replicated the high glucose effect by producing a significant decrease in MMP-2 levels with a concurrent increase in TIMP-2 levels. Furthermore, glucose-induced inhibition of MMP-2 activity was completely blocked by neutralization of TGF-β<sub>1</sub> with anti-TGF-β<sub>1</sub> antibody. We conclude that the decrease in MMP-2 activity induced by glucose loading is mediated via TGF-β<sub>1</sub>.