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1.
Cancer Res ; 60(17): 4830-7, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10987294

RESUMO

Lung cancer is the most commonly occurring malignancy worldwide and one of the few that continues to show an increasing incidence. To understand the molecular basis of host immunity against lung cancer, we investigated tumor antigens recognized by HLA-A24-restricted CTLs established from T cells infiltrating into lung adenocarcinoma and report a new gene coding for antigens recognized by the CTLs. The mRNA of this gene was expressed at different levels in all of the malignant cells tested (high in adenocarcinomas and gliomas and low in esophageal cancers and malignant hematological disease). It was also expressed at the different levels in each of a panel of normal tissues (high in the thymus, low in peripheral blood mononuclear cells, and lowest in the stomach, small intestine, and skeletal muscle). This gene encodes a Mr 60,000 nuclear protein with 414 deduced amino acids. The three peptides at positions 158-165, 170-179, and 188-196 were recognized by the CTLs. One peptide at position 188-196 had the ability to induce HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of lung cancer patients. These CTLs, however, did not lyse HLA-A24+ PHA-activated T cells in which the mRNA of this gene was highly expressed, even in the presence of excess amounts of a corresponding peptide in culture. These results suggest that this gene product and peptide could be applicable to specific immunotherapy of lung cancer patients.


Assuntos
Adenocarcinoma/imunologia , Antígenos de Neoplasias/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Adenocarcinoma/genética , Sequência de Aminoácidos , Animais , Antígenos de Neoplasias/genética , Células COS , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Mapeamento de Epitopos , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HLA-A/imunologia , Antígeno HLA-A24 , Humanos , Neoplasias Pulmonares/genética , Ativação Linfocitária/imunologia , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção
2.
J Bone Miner Res ; 15(12): 2487-94, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11127214

RESUMO

Significant decreases in bone mineral density (BMD) occur on the hemiplegic side in chronic stroke patients, which correlate with the degree of paralysis and hypovitaminosis D. In this double-blind, randomized, and prospective study of 98 patients with hemiplegia involving both an upper and lower extremity (55 males and 53 females; mean age, 71.4 +/- 0.6 years) after an acute stroke, 49 were given etidronate for 56 weeks and 49 received a placebo. The BMD was measured by computed X-ray densitometry (CXD) of the second metacarpal bone bilaterally. Forty age-matched control subjects were followed for 56 weeks. At baseline, both groups had 25-hydroxyvitamin D [25(OH)D] insufficiency, increased serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and low serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D], suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1,25(OH)2D. The BMD on the hemiplegic side decreased by 2.3% and 4.8% in the etidronate and placebo groups, respectively (p = 0.0003). After treatment, the serum 1,25(OH)2D concentration increased by 62.2% in the etidronate group and decreased by 12.4% in the placebo group. The etidronate group had significant decreases in the serum ionized calcium and ICTP and increases in PTH and bone Gla protein (BGP), whereas the placebo group had higher serum calcium and ICTP concentrations but stable PTH. These results suggest that etidronate can prevent decreases in the BMD in hemiplegic stroke patients because it decreases the serum calcium through inhibition of bone resorption and causes a subsequent increase in the serum 1,25(OH)2D concentration.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Ácido Etidrônico/uso terapêutico , Hemiplegia/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Vitamina D/análogos & derivados , Absorciometria de Fóton , Idoso , Aminoácidos/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/etiologia , Cálcio/sangue , Colágeno/sangue , Colágeno Tipo I , Método Duplo-Cego , Ácido Etidrônico/administração & dosagem , Feminino , Hemiplegia/sangue , Humanos , Masculino , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Vitamina D/sangue
3.
Hypertension ; 13(6 Pt 1): 582-8, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2737707

RESUMO

Long-term effects of a novel angiotensin converting enzyme (ACE) inhibitor, CS-622, on Ca2+-dependent tone in aortic smooth muscles of spontaneously hypertensive rats (SHR) were examined. CS-622 (3 or 10 mg/kg/day), when orally administered to SHR for 21 weeks, exhibited a dose-dependent antihypertensive action. In Krebs-Henseleit solution, removal of Ca2+ caused much greater relaxation in aortas excised from control SHR than those from SHR treated with CS-622. Restoration of Ca2+ from zero to 2.5 mM elicited a marked contraction in aortas from control SHR but only a small contraction in aortas from both CS-622-treated SHR and normotensive Wistar-Kyoto rats. These findings suggested that myogenic tone that resulted from increased Ca2+ permeability in aortas of SHR was suppressed by long-term treatment with CS-622. The aortic tone from the individual rats correlated well with systolic blood pressure in both CS-622-treated and control SHR. The exaggerated myogenic tone in aortas of SHR was attenuated in the medium containing nicardipine but was not altered in the presence of CS-622 diacid (active form of CS-622) at a concentration high enough to fully inhibit aortic ACE. The myogenic tone in normal Ca2+ concentration was not decreased in aortas excised from SHR treated with hydralazine (5 mg/kg/day) for 21 weeks. We conclude that after prolonged administration CS-622 reduced the high vascular tension resulting from increased Ca2+ permeability of vascular smooth muscle membrane in SHR and that the restoration of normal Ca2+ permeability of vascular smooth muscles may underlie long-term antihypertensive action of ACE inhibitors.


Assuntos
Aorta/fisiopatologia , Hipertensão/fisiopatologia , Tiazepinas/farmacologia , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Masculino , Nicardipino/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Tiazepinas/administração & dosagem , Fatores de Tempo
4.
Neurology ; 49(5): 1273-8, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9371907

RESUMO

Despite excessive hip fractures in patients with Parkinson's disease (PD), little is known about bone changes in these patients. We measured bone mineral density (BMD; Z scores) in PD patients and analyzed its relation to serum biochemical indices and sunlight exposure. We measured BMD in 71 patients in the second metacarpals and divided the patients into two groups according to functional independence; group 1, Hoehn and Yahr stages 1 and 2; and group 2, stages 3 to 5. In four of 20 patients in group 1 (20%), the Z score was less than -1.0, indicating osteopenia. In 51 patients in group 2, 31 (61%) had a Z score less than -1.0. The group 1 patients showed a normal mean serum level of 25-hydroxyvitamin D (25-OHD; 21.7 ng/ml), while most group 2 patients were in a deficiency range (group mean 8.9 ng/ml). Many group 2 patients were sunlight deprived. Both groups had elevated serum ionized calcium levels correlating positively with Hoehn and Yahr stage and markedly depressed serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations, indicating that immobilization-induced hypercalcemia had inhibited 1,25-[OH]2D production. Z scores correlated positively with 25-OHD levels and negatively with parathyroid hormone concentration and Hoehn and Yahr stage. Vitamin D deficiency due to sunlight deprivation and hypercalcemia induces compensatory hyperparathyroidism, which contributes to reduced BMD in PD patients, particularly those who are functionally dependent. Low BMD increases risk of hip fractures in patients with PD but may be improved by vitamin D supplementation.


Assuntos
Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/epidemiologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/metabolismo , Deficiência de Vitamina D/epidemiologia , Absorciometria de Fóton , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/metabolismo , Cálcio/metabolismo , Feminino , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Masculino , Metacarpo/metabolismo , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Doença de Parkinson/complicações , Prevalência , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/complicações
5.
Bone ; 23(6): 555-7, 1998 12.
Artigo em Inglês | MEDLINE | ID: mdl-9855465

RESUMO

Patients with Alzheimer's disease (AD) are at increased risk for falls and hip fractures. To better understand causes and prevention, we measured bone mineral density (BMD) in the second metacarpals of 46 ambulatory elderly women with AD and analyzed its relation to serum biochemical indices, sunlight exposure, and vitamin D intake. BMD was significantly less than in age-matched controls. In 26% of AD patients, the serum 25-hydroxyvitamin D (25-OHD) concentration was at a deficient level (5-10 ng/mL), and in 54% it was at an osteomalacic level (<5 ng/mL). Concentrations of ionized calcium were significantly lower in patients. Conversely, concentrations of serum bone Gla-protein and urinary hydroxyproline in patients were significantly higher than in controls. BMD correlated positively with 25-OHD concentration (p = 0.0041) and negatively with parathyroid hormone (PTH) concentration (p = 0.0022). PTH was higher in patients than in controls, and correlated negatively with 25-OHD (p < 0.0001). Many AD patients were sunlight-deprived and consumed less than 100 IU of vitamin D per day. We concluded that vitamin D deficiency due to sunlight deprivation and malnutrition, together with compensatory hyperparathyroidism, contributes significantly to reduced BMD in AD patients. Low BMD increases risk of hip fractures in patients with AD, but may be improved by vitamin D supplementation.


Assuntos
Doença de Alzheimer/complicações , Densidade Óssea , Proteínas da Matriz Extracelular , Osteoporose Pós-Menopausa/epidemiologia , Deficiência de Vitamina D/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Cálcio/sangue , Proteínas de Ligação ao Cálcio/sangue , Feminino , Humanos , Hidroxiprolina/urina , Japão/epidemiologia , Metacarpo/diagnóstico por imagem , Metacarpo/fisiologia , Casas de Saúde , Osteoporose Pós-Menopausa/sangue , Hormônio Paratireóideo/sangue , Prevalência , Radiografia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Proteína de Matriz Gla
6.
Bone ; 24(3): 271-5, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10071922

RESUMO

A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related increased serum calcium concentration have been observed in hemiplegic stroke patients. To elucidate the influence of increased serum calcium concentration on bone metabolism, we measured serum biochemical indices and bone mineral density (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured. An increased serum calcium concentration (mean 2.543 mEq/L) was observed in this population and correlated negatively with the Barthel index (mean 66), indicating immobilization-induced bone resorption with consequent increased serum calcium. Decreased serum concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L). Serum levels of BGP were decreased significantly, whereas serum ICTP concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of the second metacarpal in patients was decreased significantly compared with control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D concentrations. Immobilization-related increased serum calcium levels may inhibit PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.


Assuntos
Transtornos Cerebrovasculares/sangue , Imobilização , Vitamina D/análogos & derivados , Absorciometria de Fóton , Idoso , Biomarcadores/sangue , Densidade Óssea , Cálcio/sangue , Pessoas com Deficiência , Feminino , Hemiplegia/sangue , Humanos , Masculino , Metacarpo/diagnóstico por imagem , Análise de Regressão , Vitamina D/sangue
7.
Bone ; 23(3): 291-6, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9737352

RESUMO

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Transtornos Cerebrovasculares/complicações , Hemiplegia/etiologia , Hemostáticos/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina K/complicações , Vitamina K/análogos & derivados , Idoso , Biomarcadores/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/complicações , Feminino , Hemiplegia/sangue , Hemostáticos/administração & dosagem , Humanos , Masculino , Metacarpo/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Vitamina K/administração & dosagem , Vitamina K/sangue , Vitamina K/uso terapêutico , Vitamina K 1/sangue , Vitamina K 2/análogos & derivados
8.
J Med Chem ; 30(11): 1984-91, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3669006

RESUMO

alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/síntese química , Tiazepinas/síntese química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Masculino , Conformação Molecular , Coelhos , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Tiazepinas/farmacologia
9.
J Med Chem ; 31(2): 422-8, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3339612

RESUMO

alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6-position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/síntese química , Azepinas/síntese química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Azepinas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Conformação Molecular , Ratos , Relação Estrutura-Atividade
10.
Invest Ophthalmol Vis Sci ; 36(1): 254-8, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7822155

RESUMO

PURPOSE: To understand better the immunopathology of HTLV-I uveitis by investigating the clonality of HTLV-I-infected T-cell clones. METHODS: Eleven T-cell clones were established from the aqueous humor (six clones) and the peripheral blood (five clones) of a patient with HTLV-I uveitis, and the clonality of the HTLV-I-infected T cells was investigated by sequencing the T-cell receptor (TCR) alpha gene after the amplification of TCR alpha cDNA using an adaptor-ligation method and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: TCR alpha use was different for each of 11 T-cell clones, encompassing eight different HTLV-I-infected T-cell clones (four from the aqueous humor and four from peripheral blood) and three HTLV-I-negative T-cell clones. CONCLUSIONS: This study demonstrated polyclonal use of TCR alpha for HTLV-I-infected T cells in the ocular lesion and the peripheral blood. Results suggested that these T cells are not precursors of the leukemic cells associated with malignant transformation. Instead, they might be randomly infected with HTLV-I in the process of HTLV-I uveitis.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/virologia , Sequência de Aminoácidos , Sequência de Bases , Células Clonais , DNA/análise , Infecções por HTLV-I/imunologia , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Uveíte/imunologia , Uveíte/virologia
11.
Viral Immunol ; 14(4): 369-77, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11792066

RESUMO

Among cytomegalovirus (CMV) tegument proteins, phosphoprotein 65 (pp65) has been identified as the important target antigen of the cytotoxic T lymphocyte (CTL) response against the virus. We synthesized seven CMV-pp65-derived peptides carrying an HLA-A24-binding motif, and investigated the ability of these peptides to induce CMV-specific CTL. We identified one nonamer peptide (pp65113-121; VYALPLKML) able to bind HLA-A24 and induce CTL responses in vitro in peripheral blood mononuclear cells (PBMC) from CMV-seropositive individuals. The peptide-specific CTLs generated were capable of recognizing pp65 expressed on CMV-infected fibroblasts as well as pp65113-121 peptide bound to the surface of C1R-A*2402 cells in an HLA-A24-restricted manner. The pp65113-121 peptide thus might be considered a synthetic peptide vaccine in HLA-A24-positive individuals.


Assuntos
Citomegalovirus/imunologia , Epitopos de Linfócito T/imunologia , Antígenos HLA-A/análise , Fosfoproteínas/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas da Matriz Viral/imunologia , Antígenos Virais/imunologia , Células Cultivadas , Antígenos HLA-A/imunologia , Antígeno HLA-A24 , Humanos , Peptídeos/síntese química , Peptídeos/imunologia , Fosfoproteínas/síntese química , Proteínas da Matriz Viral/síntese química
12.
Drugs ; 35 Suppl 2: 57-61, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3135170

RESUMO

Antibacterial activities of cefotaxime and its major metabolite, desacetylcefotaxime, against 178 strains (of 10 species) were assessed in terms of minimum inhibitory concentrations (MIC50 and MIC80), and were compared with those of cefoperazone and ceftazidime. The activity of desacetylcefotaxime was several times less than that of cefotaxime against almost all of the species tested. Against Staphylococcus aureus, Morganella morganii, Enterobacter cloacae and Pseudomonas aeruginosa, the MIC80 values of desacetylcefotaxime were higher than those of cefoperazone and ceftazidime. The antibacterial potency of desacetylcefotaxime against Klebsiella pneumoniae and Pseudomonas cepacia was superior to that of cefoperazone and ceftazidime, and comparable with the activities of the latter compounds against the other 4 Gram-negative species. Partial synergy was demonstrated in the activity of cefotaxime and desacetylcefotaxime against most of the strains examined. Antagonism was observed in activity against 2 of 18 strains of M. morganii. In general, desacetylcefotaxime enhances the potency of its parent compound, cefotaxime, when they coexist. Intravenous infusion of cefotaxime 1 g over a period of 1 hour resulted in mean peak serum concentrations of 48.5 mg/L of cefotaxime and 6.5 mg/L of desacetylcefotaxime at the end of the infusion. The mean elimination half-life in beta-phase of cefotaxime was 0.8 hour and that of desacetylcefotaxime was 2 hours.


Assuntos
Bactérias/efeitos dos fármacos , Cefotaxima/análogos & derivados , Cefotaxima/farmacologia , Cefoperazona/farmacologia , Cefotaxima/farmacocinética , Ceftazidima/farmacologia , Antagonismo de Drogas , Sinergismo Farmacológico , Enterobacter/efeitos dos fármacos , Escherichia coli , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
13.
Chest ; 105(1): 318-9, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8275768

RESUMO

We established an endoscopic classification of tracheobronchial tuberculosis with healing processes. According to this classification, the period of time needed for healing was found to be shorter in patients who were treated by aerosolized streptomycin than in those treated with the conventional triple-drug oral regimen.


Assuntos
Broncopatias/classificação , Broncopatias/patologia , Broncoscopia , Doenças da Traqueia/classificação , Doenças da Traqueia/patologia , Tuberculose Pulmonar/classificação , Tuberculose Pulmonar/patologia , Tuberculose/classificação , Tuberculose/patologia , Aerossóis , Humanos , Masculino , Pessoa de Meia-Idade , Estreptomicina/administração & dosagem , Estreptomicina/uso terapêutico , Cicatrização
14.
Chest ; 107(1): 120-5, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7813262

RESUMO

The clinical effectiveness of erythromycin for patients with diffuse panbronchiolitis (DPB) was previously recognized. However, it remains unknown what kind of airway lesions change with the clinical effectiveness induced by erythromycin. We performed the present study to clarify this unknown. We devised a method for scoring findings on high-resolution computed tomography (HRCT) to aid in the objective evaluation of the airway lesions in patients with DPB. The 18 patients with DPB were treated with oral erythromycin, 600 mg/d. All patients were evaluated by pulmonary function tests and HRCT before and after 3 months of therapy. Characteristic HRCT findings in patients with DPB pretherapy were small nodules, airway ectasia, periairway thickening, and mucus plugging. After erythromycin therapy, there was significant reduction in scores for the extent of small nodular opacities, the severity of periairway thickening, and the extent of mucus plugging with a corresponding significant improvement in results of the pulmonary function test parameters. The present study demonstrated reversible airway lesions in patients with DPB in response to erythromycin therapy.


Assuntos
Bronquiolite/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Bronquiolite/tratamento farmacológico , Bronquiolite/fisiopatologia , Eritromicina/uso terapêutico , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Capacidade Vital
15.
Chest ; 106(3): 690-2, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8082340

RESUMO

We studied eight patients with miliary tuberculosis (TB). In all instances, tuberculomatous lesions were demonstrated in the aspirated bone marrow. We conclude that the bone marrow aspiration has great value in diagnosing miliary TB because it provides sufficient material to permit examination of serial sections as needed to confirm the diagnosis. The bone marrow aspiration also is safer than the alternative procedures of lung or liver biopsies.


Assuntos
Medula Óssea/patologia , Tuberculose Miliar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Medula Óssea/microbiologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Esterno , Tuberculose Miliar/microbiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
16.
Chest ; 104(1): 309-11, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7686837

RESUMO

Behçet's disease (BD) affects the lung as well as the intestine, central nervous system, kidney, and other organs. Pulmonary vasculitis is one of the most severe complications in BD because it can cause fatal bleeding. Corticosteroids and other immunosuppressive drugs have been used to treat pulmonary vasculitis, but the efficacy of these agents has not yet been established. We administered FK506, a novel immunosuppressive agent, as a treatment for BD. A 21-year-old woman presented definitive symptoms of BD, ie, repeated oral and genital ulcers, folliculitis, and panuveitis. The patient showed localized pulmonary infiltrates on her chest x-ray film that were histologically proved to be venulitis consistent with BD. These pulmonary infiltrates evanesced after the oral administration of FK506 for 8 weeks; in addition, the skin lesions and uveitis improved. This clinical observation indicates that FK506 is an effective agent in the treatment of pulmonary vasculitis associated with BD.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Tacrolimo/uso terapêutico , Vasculite/tratamento farmacológico , Adulto , Síndrome de Behçet/patologia , Feminino , Humanos , Pulmão/irrigação sanguínea , Pneumopatias/patologia , Vasculite/patologia , Vênulas/patologia
17.
Lung Cancer ; 29(1): 49-56, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10880847

RESUMO

The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within an acceptable range. Surgery was not indicated for two patients because of distant metastasis; one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Cuidados Pré-Operatórios , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagem
18.
Am J Hypertens ; 7(7 Pt 1): 637-46, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7946166

RESUMO

CS-905 is a dihydropyridine calcium channel antagonist which stands out for its prolonged hypotensive effect, and which is currently under investigation for the treatment of hypertension. The aim of the current series of studies was to investigate the effects of CS-905 on renal function in relation to its effects on arterial pressure. In anesthetized spontaneously hypertensive rats (SHR), intravenous bolus injection of CS-905 reduced mean arterial pressure (MAP) in a dose-dependent fashion. In parallel, there was a dose-related increase in urine flow (V), sodium excretion (UNaV), renal plasma flow (RPF), and glomerular filtration rate (GFR). In chronically cannulated unanesthetized SHR, single-dose CS-905 by gavage produced a sustained reduction in MAP, a significant increase in V and UNaV, no effect on RPF, and an increase in GFR. Continuous intrarenal infusion of CS-905 in anesthetized normotensive Munich Wistar rats at doses that did not affect MAP caused a marked diuresis and natriuresis, without affecting RPF or GFR. To determine whether the diuretic and natriuretic effects of CS-905 were mediated by changes in inner medullary blood flow, the effect of CS-905 on vasa recta blood flow (Qvr) was studied by fluorescent videomicroscopy in anesthetized normotensive Munich Wistar rats during continuous intrarenal infusion. At low infusion rates, CS-905 was diuretic and natriuretic while increasing Qvr. With a high infusion rate, although the diuretic and natriuretic effects of CS-905 were maximal, Qvr decreased. These findings suggest that the diuretic and natriuretic effects of CS-905 are dissociated from and cannot be accounted for by changes in RPF, GRF, or Qvr, and are most likely secondary to a direct action of CS-905 on renal tubule handling of sodium and water.


Assuntos
Ácido Azetidinocarboxílico/análogos & derivados , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Diurese/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Anestesia , Animais , Ácido Azetidinocarboxílico/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Infusões Intravenosas , Injeções , Rim , Medula Renal/irrigação sanguínea , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos
19.
J Neurol ; 245(9): 598-602, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9758298

RESUMO

We have noted two morphologically distinct types of atypical lymphocytes (AL) in the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we designate type-I AL, with multilobulated nuclei resembling those of the abnormal cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by large lymphocytes with basophilic cytoplasm and nuclei containing coarse chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other viruses, but not in meningitis resulting from Cryptococcus neofirmans (n = 14), Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15), or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in meningitis of various aetiologies and in aseptic meningeal reactions, but not in leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to be indicative of enteroviral meningitis with the highest predictive value (69%), while type-II AL had a lower diagnostic positive predictive value in meningitis of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL were stained for CD8. The presence of type-I AL in CSF strongly suggests enteroviral meningitis, which warrants careful follow-up without antifungal, antituberculous or antibacterial agents. However, type-I AL, which are likely to be virally transformed lymphocytes, must be distinguished from ATL cells, which frequently involve the meninges.


Assuntos
Linfócitos/patologia , Meningite Viral/líquido cefalorraquidiano , Adolescente , Adulto , Líquido Cefalorraquidiano/citologia , Feminino , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/patologia , Meningite Viral/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos
20.
J Neurol ; 239(2): 69-70, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1313077

RESUMO

In three of five patients with herpes zoster meningitis, varicella-zoster virus (VZV) DNA was detected by the polymerase chain reaction (PCR) in the initial samples of cerebrospinal fluid. DNA fragments of group A or B, following classification of VZV strains by the size of the variable region IV of VZV genome, were found at the 7th, 10th and 24th illness day in the three positive cases: one of these cases did not have skin lesions. These results suggest that the detection of VZV DNA by PCR is useful for the diagnosis of herpes zoster meningitis, as well as for its molecular epidemiology.


Assuntos
DNA Viral/líquido cefalorraquidiano , Herpesvirus Humano 3/isolamento & purificação , Meningite Viral/microbiologia , Reação em Cadeia da Polimerase , Adulto , Sequência de Bases , Feminino , Herpesvirus Humano 3/genética , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Pessoa de Meia-Idade , Dados de Sequência Molecular
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