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Biomedical subjects

F Ogushi

Publications and source records attributed to F Ogushi.

At least 73 records · Page 4Linked to original sources
PubMed1988

Chylothorax and chylous ascites in a patient with uterine cancer.

A 63-year-old woman, who had undergone radical hysterectomy and radiation therapy for cervical cancer of the uterus three years previously, was found to have pleural effusion and ascites. A diagnosis of chylothorax and chylous ascites was made on the basis of these fluids' characteristics. She received medium-chain triglyceride (MCT) in her diet and intra-venous hyperalimentation to decrease the leakages of chyle into the pleural and peritoneal cavities, but she died of respiratory and renal failures after six months. At autopsy, metastases from the cervical cancer of the uterus to the lymph nodes in the mediastinum and around the abdominal aorta were proved histologically. Lymph node swelling due to metastasis had caused a rupture of the thoracic duct, leading to chylothorax and chylous ascites. The diagnosis, evaluation and therapeutic modalities of the condition are outlined and the literature reviewed.

Carcinoma, Squamous Cell↗
PubMed1987

Characterization of the M1(Ala213) type of alpha 1-antitrypsin, a newly recognized, common "normal" alpha 1-antitrypsin haplotype.

alpha 1-Antitrypsin (alpha 1AT) is a highly pleomorphic 52-kDa serum glycoprotein that functions as the major inhibitor of neutrophil elastase. Of these, the most common normal alpha 1AT haplotypes identified by isoelectric focusing (IEF) of serum are those of the M family, including M1, M2, and M3. In the course of studying the alpha 1AT type Z gene, we identified a restriction endonuclease BstEII polymorphism in the M1 gene that predicted the existence of a previously unidentified, but relatively common, haplotype of M, referred to as M1(Ala213) [Nukiwa, T., Satoh, K., Brantly, M. L., Ogushi, F., Fells, G. A., Courtney, M., & Crystal, R. G. (1986) J. Biol. Chem. 261, 15989-15994]. In this study we have cloned both alpha 1AT genes from an individual heterozygous for the M1(Ala213) and M1(Val213) haplotypes. Sequencing of the coding exons of both demonstrated that they are identical except for the Ala-Val difference at residue 213. The codominant transmission of the M1(Ala213) gene was demonstrated in a family study. Evaluation of 39 genomic samples of Caucasians with the IEF haplotype M1 demonstrated haplotype frequencies of 68% for M1(Val213) and 32% for M1(Ala213). alpha 1AT serum levels of individuals inheriting the M1(Ala213) gene in a homozygous fashion were in the same range as those for homozygous M1(Val213) as was the rate of association of the M1(Ala213) protein with neutrophil elastase.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin.

To evaluate the potential use of recombinant DNA-produced alpha-1-antitrypsin (alpha-1-AT) to augment the lung antineutrophil elastase defenses in alpha-1-AT deficiency, we compared the kinetics of intravenously administered recombinant produced alpha-1-AT (r alpha-1-AT) and purified normal human plasma alpha-1-AT (p alpha-1-AT) in the blood and lung of rhesus monkeys. The r alpha-1-AT was produced in yeast transformed with an expressing plasmid containing a full-length human alpha-1-AT complementary deoxyribonucleic acid and purified to greater than 99% homogeneity. The r alpha-1-AT has a molecular weight of 45,000, no carbohydrates, and is identical in sequence to normal plasma alpha-1-AT except for an additional N-terminal acetylmethionine. Despite its lack of carbohydrates, the r alpha-1-AT inhibited human neutrophil elastase with an association rate constant similar to that of p alpha-1-AT. Rhesus monkeys were infused intravenously with 120 mg/kg of r alpha-1-AT (n = 13) or p alpha-1-AT (n = 12) and the serum, urine, and lung epithelial lining fluid (ELF) concentrations of these molecules quantified at various intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase.

Current concepts relating to the pathogenesis of emphysema associated with cigarette smoking is that an imbalance exists within the lower respiratory tract between neutrophil elastase and the local anti-neutrophil elastase screen, enabling uninhibited neutrophil elastase to destroy the alveolar structures over time. The possible role of alveolar macrophages in contributing to this imbalance was investigated by evaluating the ability of cigarette smokers' alveolar macrophages to inactivate alpha 1-antitrypsin (alpha 1AT), the major anti-neutrophil elastase of the human lower respiratory tract. In vitro, alveolar macrophages of smokers spontaneously released 2.5-fold more superoxide anion and eightfold more H2O2 than macrophages of nonsmokers (P less than 0.01, both comparisons). Using a model system that reproduced the relative amounts of alveolar macrophages and alpha 1AT found in the epithelial lining fluid of the lower respiratory tract, we observed that smokers' macrophages caused a 60 +/- 5% reduction in the ability of alpha 1AT to inhibit neutrophil elastase. In marked contrast, under the same conditions, nonsmokers' macrophages had no effect upon the anti-neutrophil elastase function of alpha 1AT. Addition of superoxide dismutase, catalase, mannitol, and methionine prevented inactivation of alpha 1AT by smokers' macrophages, implying that the release of oxidants mediated the inactivation of alpha 1AT. In addition, by utilizing a recombinant DNA produced modified form of alpha 1AT containing an active site substitution (met358----val), the inactivation of alpha 1AT by smokers' alveolar macrophages was prevented, suggesting that the smokers' macrophages inactivate alpha 1AT by oxidizing the active site of the alpha 1AT molecule. These results suggest that in cigarette smokers, the alveolar macrophage can modulate the activity of alpha 1AT as an inhibitor of neutrophil elastase and thus play a role in the pathogenesis of emphysema associated with cigarette smoking.

Adult↗
PubMed1987

Z-type alpha 1-antitrypsin is less competent than M1-type alpha 1-antitrypsin as an inhibitor of neutrophil elastase.

Alpha 1-antitrypsin (alpha 1AT) deficiency resulting from homozygous inheritance of the Z-type alpha 1AT gene is associated with serum alpha 1AT levels of less than 50 mg/dl and the development of emphysema in the third to fourth decades. Despite the overwhelming evidence that the emphysema of PiZZ individuals develops because of a "deficiency" of alpha 1AT and hence an insufficient antineutrophil elastase defense of the lung, epidemiologic evidence has shown that levels of alpha 1AT of only 80 mg/dl protect the lung from an increased risk of emphysema. With this background, we hypothesized that homozygous inheritance of the Z-type may confer an added risk beyond a simple deficiency of alpha 1AT by virtue of an inability of the Z-type alpha 1AT molecule to inhibit neutrophil elastase as effectively as the common M1-type molecule. To evaluate this hypothesis, the functional status of alpha 1AT from PiZZ individuals (n = 10) was compared with that of alpha 1AT from PiM1M1 individuals (n = 7) for its ability to inhibit neutrophil elastase (percent inhibition) as well as its association rate constant for neutrophil elastase (K association). Plasma alpha 1AT concentration, measured by radial immunodiffusion, was 34 +/- 1 mg/dl in PiZZ patients vs. 237 +/- 14 mg/dl for PiM1M1 plasma, a sevenfold difference. When titrated against neutrophil elastase, the present inhibition of PiZZ plasma was significantly less than Pi M1M1 plasma (ZZ 78 +/- 1% vs. M1M1 95 +/- 1%, P less than 0.001) as was purified Z type alpha 1AT (ZZ, 63 +/- 2% vs. M1M1 86 +/- 2%, P less than 0.001). Sodium dodecyl sulfate (SDS) gel comparisons of the complexes formed with M1-type alpha 1AT and Z-type alpha 1AT with elastase demonstrated the Z alpha 1AT-elastase complexes were less stable than the M1 alpha 1AT-elastase complexes, thus releasing some of the enzyme to continue to function as a protease. Consistent with these observations, the K association of purified Z-type alpha 1AT for neutrophil elastase was lower than that of M1-type alpha 1AT (ZZ 4.5 +/- 0.3 X 10(6) M-1s-1 vs. M1M1 9.7 +/- 0.4 X 10(6) M-1s-1, P less than 0.001), suggesting that for the population of alpha 1AT molecules, the active Z-type molecules take more than twice as long as the active M1-type alpha 1AT to inhibit neutrophil elastase. Consequently, not only is there less alpha1AT in PiZZ individuals, but the population of Z-type alpha1AT molecules is less competent as an inhibitor of neutrophil elastase than M1-type alpha1AT molecules. This combination of defects suggests that PiZZ individuals have far less functional antielastase protection than suggested by the reduced concentrations of alpha1AT alone, further explaining their profound risk for development of emphysema.

Adult↗
PubMed1987

PGE2 and PGF2 alpha content in bronchoalveolar lavage fluid obtained from patients with eosinophilic pneumonia.

Cell differential, prostaglandins (PGs) E2 and F2 alpha in the bronchoalveolar lavage fluid (BALF) in two patients with eosinophilic pneumonia were measured at different times in the course of the disease. Results showed markedly increased numbers of eosinophils and increased content of prostaglandin (PG) E2 in BALF obtained from the patients with eosinophilic pneumonia compared to that of normal volunteers. Interestingly, the increased content of PGE2 in BALF obtained from the patients reverted to normal range with corticosteroid treatment. This change in PGE2 content in BALF was accompanied by normalization of number and percentage of eosinophils in BALF. These findings indicated that PGE2 level in lower respiratory tract of patients with eosinophilic pneumonia may be related to an increased number of eosinophils.

Adult↗
PubMed1986

Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene.

This study reports the entire nucleotide sequence of the protein coding region sequence of the alpha 1-antitrypsin (alpha 1AT) Z gene, a common form of the alpha 1AT gene associated with serum alpha 1AT deficiency. In addition to Glu342 to Lys342 mutation in exon V which has been previously identified by peptide analysis, another point mutation (GTG to GCG in exon III) in the gene sequence predicts a second amino acid substitution (Val213 to Ala213) in the Z protein. This Val213 to Ala213 mutation was confirmed to be a general finding in Z type alpha 1AT gene by evaluating genomic DNA from 40 Z haplotypes using synthetic oligonucleotide gene probes directed toward the mutated exon III sequences in the Z gene. Furthermore, the exon III Val213 to Ala213 mutation eliminates a BstEII restriction endonuclease site in the alpha 1AT Z gene, allowing rapid identification of this Val213 to Ala213 substitution at the genomic DNA level. Surprisingly, when genomic DNA samples from individuals thought to be homozygous for the M1 gene (the most common alpha 1AT normal haplotype) were evaluated with BstEII, 23% of the M1 haplotypes were BstEII site negative, thus identifying a new form of M1 (i.e. M1(Ala213], likely identical to M1 but with an isoelectric focusing "silent" amino acid substitution (Val213 to Ala213). Although the relative importance of the newly identified exon III Val213 to Ala213 mutation to the pathogenesis of the abnormalities associated with the Z gene is not known, it is likely that M1(Ala213) gene represents a common "normal" polymorphism of the alpha 1AT gene that served as an evolutionary intermediate between the M1(Val213) and Z genes.

Base Sequence↗
PubMed1986

Structure and properties of albumin Tokushima and its proteolytic processing by cathepsin B in vitro.

Albumin Tokushima is a Japanese genetic variant of human serum albumin. Two homozygous and 6 heterozygous subjects with this variant were found in a family. Albumin Tokushima was purified from sera of the homozygous subjects. Its amino acid composition and amino-terminal sequence were determined and compared with those of a normal serum albumin. Albumin Tokushima with the amino-terminal sequence of Arg-Gly-Val-Phe-His-Arg-Asp-Ala-His-Lys-Ser-Glu-Val-Ala-His-Arg-Phe-Lys- Asp- Leu-Gly-Glu-Glu-Asn-Phe was found to be the same abnormal proalbumin as proalbumin Lille (Abdo, Y. et al. (1981) FEBS Lett. 131, 286-288). The isoelectric points of albumin Tokushima were pH 4.70 and 4.90 as compared with pH 5.05 and 5.25 of a normal serum albumin. Albumin Tokushima was converted to normal serum albumin by purified cathepsin B in vitro. Albumin Tokushima can bind Ni2+ at 4 degrees C but binds little at 37 degrees C.

Amino Acid Sequence↗
PubMed1985

Plasma-cell dyscrasia with polyneuropathy and endocrine disorders associated with dysfunction of salivary glands.

A case of plasma-cell dyscrasia with polyneuropathy and endocrine disorders that showed dysfunction of the salivary glands is reported. A 49-year-old Japanese man noticed swelling of the cervical lymph nodes and numbness in the lower extremities in May 1983. Histological examination of the enlarged cervical lymph nodes revealed many follicles penetrated by radial capillaries and proliferation of capillaries and plasma cells in the interfollicular area, forming Castleman disease-like lesions. The patient complained of a dry mouth and noticed swelling of the submandibular salivary gland in April 1984. Microscopic examination of this gland revealed an angiofollicular lymphoid lesion resembling that in the lymph nodes. He also suffered from an endocrine disturbance characterized by increased serum adrenocorticotropic hormone and impotence. This is the second reported case of plasma-cell dyscrasia with polyneuropathy and endocrine disorders that showed dysfunction of exocrine secretion. This case indicates that attention must be paid to organs of exocrine secretion as well as of endocrine secretion in this disease.

Endocrine System Diseases↗
PubMed1985

Comparison of cell profiles of bronchial and bronchoalveolar lavage fluids between normal subjects and patients with idiopathic pulmonary fibrosis.

The cell profiles of bronchial and bronchoalveolar lavage fluids (BLF and BALF) of patients with idiopathic pulmonary fibrosis (IPF) were compared with those of normal volunteers (NV) and age-matched control patients (CP), to characterize the cell profiles of the bronchoalveolar region in normals and patients with IPF. In BALF of nonsmokers from both control groups (NV and CP), alveolar macrophages (AM) were predominant and the percentage of neutrophil leukocytes and that of eosinophil leukocytes below 1% of the total cells. The percentage of neutrophils and that of bronchial epithelial cells were higher in BLF than in BALF of both control groups. Of the immune and inflammatory cells in BLF, the mean percentage of neutrophils was 12% in NV group and 42% in CP group. The percentage of neutrophils and that of eosinophils in BALF were higher in IPF group than in CP group, but the percentage of neutrophils in BLF of IPF group was comparable to that of CP group. In the IPF group, the percentage of neutrophils in BALF was lower than that in BLF. These results indicated that even in healthy subjects, a considerable number of neutrophils are present in the bronchial region and that the cell profile of the lavage fluid of the bronchoalveolar tree changes depending on the method of lavage. Presumably the higher percentage of neutrophils in BALF of patients with IPF is partly due to derangements of the alveolar structure, because the amount of saline infused into this region is limited.

Adult↗
PubMed1984

Carcinoembryonic antigen (CEA) levels in pleural effusions and sera of lung cancer patients.

For determining the value of carcinoembryonic antigen (CEA) levels in diagnosis of malignant tumors of the lung, the CEA levels in 187 specimens of pleural fluid and sera obtained simultaneously from patients with pleural fluid were measured. In all 70 patients with benign diseases, the CEA levels in the effusions were less than the cut-off value of 5 ng/ml (mean +/- SD: 1.44 +/- 1.01 ng/ml). In contrast, in 88 of 117 patients (75.2%) with malignant diseases, the CEA levels in the effusions were over 5 ng/ml (25.3 +/- 24.5 ng/ml) and in 58 of the 117 patients (50.4%), the CEA levels in the serum were values of 5 ng/ml or more (11.9 +/- 18.4 ng/ml). There was a significant correlation between the CEA levels in the effusions and in the sera. The CEA levels in effusions in patients with malignant lung tumors were usually much higher than those in their sera. The incidence of CEA levels of 5 ng/ml or more in both the serum and effusion was highest in the patients with adenocarcinoma. These data indicate that determination of the CEA level in effusions, when done in combination with cytological examinations, may have additional value in diagnosis of lung cancer.

Adenocarcinoma↗
PubMed1984

[Combination chemotherapy for small cell carcinoma of the lung: AVN-DVC therapy].

Comparative studies of alternating non-cross resistant chemotherapy, A.V.N.-D.V.C. (ACNU + VCR + PCZ-ADM + VCR + CPA) was carried out on 19 patients with small cell lung cancer. A.V.N. (A. V.F.) therapy on 45 patients and D.V.C. therapy on 19 patients were used as historical control, respectively. A.V.N. (A.V.F.) therapy was composed of ACNU (2.5 mg/kg, day 1), VCR (0.02 mg/kg, once every week) and PCZ (1 mg/kg, daily) (or FT-207 (15 mg/kg, daily], and duration of one course was 6 to 8 weeks. D.V.C. therapy was composed of ADM (1 mg/kg, day 1) VCR (0.02 mg/kg, days 1 and 5) and CPA (2 mg/kg, days 1 to 5), and repeated every 4 weeks. A.V.N.-D.V.C. therapy was done by a timely alternation of one course of A.V.N. and two course of D.V.C. Reduction rate of tumor size was 84% in A.V.N.-D.V.C. therapy, 62% in A.V.N. (A.V.F.) therapy and 26% in D.V.C. therapy, respectively. Median survival time was 13 months on A.V.N.-D.N.C. therapy, 8.5 months and A.V.N. (A. V.F.) therapy and 4 months on D.V.C. therapy. Significant prolongation of median survival time was obtained in A.V.N.-D.V.C. therapy in comparison with that of historical controls. Major toxicity in A.V.N.-D.V.C. therapy was slight bone marrow suppression.

Aged↗
PubMed1984

Potential value of liposomes containing muramyl dipeptide for augmenting the tumoricidal activity of human alveolar macrophages.

Potentiation of the tumoricidal activity of human alveolar macrophages (AM) by muramyl dipeptide (MDP) and MDP in liposomes (liposome-MDP) was examined. Significant increase in AM-mediated cytotoxicity against allogeneic melanoma cells required the interaction of AM with liposome-MDP for a minimum of 4 h. The uptake by human AM of liposomes containing fluorescent quinacrine was examined. A linear correlation was found between the amount of liposomes added to AM monolayers and their phagocytosis of liposome-entrapped quinacrine. Addition of phosphatidylserine to liposomes composed of phosphatidylcholine enhanced both the phagocytosis of liposomes and the ability of liposome-MDP to potentiate the tumoricidal activity of human AM. In experiments on the dose response of liposomes containing 10 micrograms/ml MDP, 50 nmol of liposomes/10(5) AM caused maximal activation of human AM, and greater than 100 nmol of liposomes was less effective. These results show that multilamellar vesicle liposomes containing MDP are more effective than free MDP in potentiating the tumoricidal activity of human AM during culture for 4 h.

Acetylmuramyl-Alanyl-Isoglutamine↗