[Standard values and prediction equations for respiratory function measurements (III). Closing volume measurements in healthy Japanese].
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Biomedical subjects
Publications and source records attributed to M Hirota.
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A 68-year-old male patient without any previous thyroidal disease developed three times of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Because of his diabetes mellitus, alcoholic hepatitis, chronic pancreatitis and blind loop syndrome, his nutritional balance was easily disturbed leading to PCM. Although he recurrently developed primary hypothyroidism associated with PCM, this condition was completely restored by protein-calorie repletion. The possibility of dietary iodine deficiency was negated by the observation that his daily urinary iodine secretion was more than 4 mg/day. Plasma amino acid analysis revealed severe depletion of phenylalanine, tyrosine and other essential amino acids and raised the possibility that this hypothyroidism was caused by amino acid deficiency. In order to clarify the mechanisms of this primary hypothyroidism, we have investigated the change of thyroid functions during protein-calorie repletion by total parenteral nutrition (TPN). We then removed iodine from the nutrients for TPN to ascertain that iodine deficiency was not the cause of the primary hypothyroidism in the present case. In spite of the removal of iodine, serum T4 and T3 suddenly increased from 1.1 micrograms/dl and less than 25 ng/dl to 3.5 micrograms/dl and 59 ng/dl, respectively, in a few days after the beginning of TPN. They continued to increase thereafter and reached 6.3 micrograms/dl and 115 ng/dl in 6 weeks. Serum free T4 also showed a sudden increase from 0.56 ng/dl to 1.7 ng/dl after TPN and remained above 1.3 ng/dl thereafter. Serum reverse T3 showed a rapid increase after TPN, but, 4 weeks later, returned to the previous level before TPN. Serum TSH decreased from 120 microU/ml to 17 microU/ml in a few days after TPN and reached a level within normal range in 4 weeks. Serum TBG gradually increased from 10.7 micrograms/ml to 29.2 micrograms/ml in 6 weeks. These results show that the T4 synthesis was extremely impaired by PCM in spite of the strong stimulation by TSH and that this suppression of T4 synthesis by PCM led the patient recurrently to the primary hypothyroidism. We have next investigated the possibility whether the deficiency of phenylalanine and tyrosine could cause a suppression of T4 synthesis because tyrosine is an important substrate of T4. For this purpose we removed phenylalanine and tyrosine from TPN and added iodine to prevent iodine deficiency due to prolonged iodine-depleted nutrition. Reduction of phenylalanine and tyrosine resulted in a marked decrease in serum T4, T3 and TBG in 7 weeks, but gave no change to free T4. Serum TSH remained within normal range.(ABSTRACT TRUNCATED AT 400 WORDS)
Four monoclonal antibodies to Legionella pneumophila Philadelphia 1 were produced by the fusion of immunized BALB/c lymphocytes to a murine myeloma cell line. Two (Lp1-1 and Lp1-3) of the four monoclonal antibodies reacted with 14 L. pneumophila serogroup 1 strains, and the other (Lp1-2 and Lp1-4) reacted with only three out of 20 strains tested. These four monoclonal antibodies did not bind to any strains of L. pneumophila serogroup 2-7 and other Legionella species. In addition, it has been shown that these monoclonal antibodies may be useful not only for subserotyping of L. pneumophila but also for retrospective diagnosis using immunopathological methods.
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One hundred sixty-one sera from lung cancer patients, including 46 samples from patients who had not yet received treatment were screened for tumor-associated antigens with 3 monoclonal antibodies, CSLEX1, CSLEA1, and CLEX5, by a new cell binding inhibition assay. We had previously determined that the antigens recognized by CSLEX1 and CSLEA1 are sialosylated Lewisx and sialosylated Lewisa, respectively. Either of these two antibodies alone reacted with about 65% of the 46 untreated patients' sera. Eighty-seven % of the 46 showed positive results with at least one of the two antibodies. The CLEX5 monoclonal antibody is presented here as recognizing a potential tumor-associated antigen. CLEX5 reacted with 54% of the 46 sera from nontreated lung cancer patients. When the results for all three antibodies were combined, the percentage of positive sera was 89% (of 46). Some interesting patterns in the serum levels of the antigens detected by these antibodies were observed. Levels of sialosylated Lewisx were significantly higher in sera from nontreated advanced stage (III and IV) patients (P less than 0.0003). In addition, levels of the antigens detected by CSLEX1 and CSLEA1 were dependent on whether or not the patient had been receiving treatment. These observations suggest potential applications of monoclonal antibodies to diagnosis and monitoring of therapies.
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A micro-enzyme-linked immunosorbent assay (ELISA) test and an ELISA inhibition test were developed and used to detect 4 monoclonal antibodies potentially useful for serodiagnosis of cancer. The 4 antibodies used in conjunction detected 73% of 71 sera from cancer patients and 8% of 42 sera from normal persons. Separately, the 4 antibodies reacted to tumors from various sites such as lung, breast, colon, stomach, and ovary. The ELISA inhibition assay may be useful for detecting culture supernatants reactive against tumor-associated serum antigens. Eventually, a panel of monoclonal antibodies detecting various tumors may be obtainable.
A new cell-binding inhibition assay to detect tumor-associated antigens in sera was developed. This assay determined that sialosylated Lewisx, as detected by the CSLEX1 monoclonal antibody, is present in the sera of 95% of patients with advanced lung adenocarcinomas. Sera with inhibition titers of 1:16 or higher were presumed to contain sialosylated Lewisx. Tests of over 900 sera samples from both malignant and benign disease patients yielded the following percentages of positive inhibition: lung cancers, 43.8%; stomach cancer, 26.0%; colon cancer, 44.4%; gall bladder and bile duct cancers, 47.8%; pancreas cancer, 37.5%; breast cancer, 26.7%; cancers of the hematopoietic system, 2.9%; benign diseases, 0.9% (332 sera); and normal healthy donors, 0.7% (280 sera). Within the lung cancer group, 95% of the sera from 21 advanced (Stages III and IV) nontreated adenocarcinoma patients gave positive results with high inhibition titers, whereas only 27% of sera from treated advanced adenocarcinoma patients yielded positive results. The sensitivity of the cell-binding inhibition assay is similar to those of the solid-phase radioimmunosandwich and reverse passive-hemagglutination assays. Reproducibility tests yielded an r value of 0.90. These results suggest that this simple cell-binding inhibition assay could be applied with monoclonal antibodies, such as CSLEX1, to monitor cancer.
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A new monoclonal antibody, CSLEX1, directed against sialylated Lewisx was tested in parallel with a monoclonal antibody, CSLEA1, directed against sialylated Lewisa antigen. In tests with a solid-phase radioimmune sandwich assay, the sialylated Lewisx monoclonal antibody detected sera from certain cancer patients that were negative with the sialylated Lewisa monoclonal antibody. Some sera from cancer patients showed the reverse reaction. We conclude that the combined use of these two monoclonal antibodies detects a wider range of sera from cancer patients than the use of a single antibody alone. It should be possible in the future to use multiple monoclonal antibodies to increase detection.
A 79-year-old woman with primary liposarcoma of the heart, an extremely rare malignancy, coexistent with Brenner tumor was reported. The histological features of the sarcoma on the routine histological slides were so varied that it was necessary to differentiate the histology from that of malignant fibrous histiocytoma or pleomorphic rhabdomyosarcoma. Most of the tumor cells including fibroblastic and bizarre giant cells, however, were stained intensely with histochemical methods for lipids and consequently diagnosed as pleomorphic liposarcoma originated from the epicardium. Electron microscopically, lipid droplets were demonstrated in the cytoplasm of the tumor cells, supporting the histological diagnosis. No distant or nodal metastases were noted.
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A monoclonal antibody CSLEX1 which reacts with sialosyl Lex but not with sialosyl Lea has been produced. The CSLEX1 antigen has a tissue distribution similar to that of Lex, appearing characteristically in the proximal tubules of the kidney and on granulocytes. It is tumor associated in that 14 of 34 (41%) of tumor lines tested reacted with the CSLEX1 antibody, and 50 of 74 (68%) of tumor tissues tested reacted with the antibody. Loss of immunoperoxidase staining of tissues after neuraminidase treatment showed that the antibody is reacting to sialyl derivatives. The antibody reacted in solid-phase radioimmunoassay to sialosyllactofucopentaosyl(III)ceramide and sialosyldifucosylganglioside (6B). These results indicate that the CSLEX1 epitope has the following structure: (formula: see text) This structure had not previously been known to be tumor associated.
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