Phase II trial of high dose recombinant gamma-interferon in advanced hepatocellular carcinoma.
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Adult↗
Biomedical subjects
N Okazaki
Publications and source records attributed to N Okazaki.
Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices.
The addition of a new compound containing platinum, 254-S, an antineoplastic agent, to medium had no effect on p-aminohippurate (PAH) accumulation, gluconeogenesis, or potassium and ATP concentrations in rat kidney cortical slices at the concentrations tested, up to 10 mM. At 1 mM, cisplatin, used for comparison, significantly decreased all of these biochemical indices in the slices. Administration of 254-S at a low dose (10 mg/kg i.v.) to rats decreased the ability of the slices to accumulate PAH and to maintain the potassium concentration, without affecting levels of urea or creatinine in blood plasma. 254-S at a high dose (20 mg/kg i.v.) or cisplatin at 5 mg/kg (i.v.) also decreased these indices in the slices, and affected urea and creatinine in blood plasma. These results suggested that use of the renal slice technique gives data useful for the evaluation of the nephrotoxicity of 254-S, and that PAH accumulation and the potassium concentration in slices from rats treated with 254-S are indicators of nephrotoxic damage.
Adenosine Triphosphate↗
Pilot phase II study of cis-diamminedichloroplatinum (II) against metastatic gastric cancers.
Fifty patients with metastatic gastric cancer were entered for a phase II study of Cis-diamminedichloroplatinum (II) (CDDP), 45 of whom were able to have their responses evaluated. CDDP was given intravenously at a dose of 80 mg/m2 over two hours every three weeks. There were four partial responses (25%) among the 16 patients who had had no prior chemotherapy, and three partial responses (10%) among the 29 patients who had had prior chemotherapy. The total response rate was 16%. The chief manifestations of toxicity were gastrointestinal symptoms, such as nausea and/or vomiting. Severe nephrotoxicity was not observed. From these data, the administration of CDDP at a dose of 80 mg/m2 every three weeks was considered tolerable, and CDDP as a single agent was considered effective against metastatic gastric cancers. In addition, three of the 29 pretreated patients who responded suggested that CDDP could be given as a second-line chemotherapy when initial treatment with other active agents, i.e. fluorinated pyrimidine or mitomycin C, fails to obtain a response.
Adult↗
Detection of hepatitis C virus RNA in sera and liver tissues of non-A, non-B hepatitis patients using the polymerase chain reaction.
Sera obtained from patients with non-A, non-B hepatitis were examined for the presence of hepatitis C virus (HCV) genome by using the reverse transcription-polymerase chain reaction assay, as well as for antibody to HCV (anti-HCV) by using an enzyme-linked immunosorbent assay (ELISA). We also examined the presence of HCV RNA in liver tissue obtained by surgical resection of hepatocellular carcinoma. Among 33 patients, HCV RNA was detectable in 21 (64%), and the antibody was also positive in 21 (64%). Eighteen (55%) patients were positive for both assays. The two assays gave inconsistent results in 3 patients who were positive for HCV RNA but negative for anti-HCV, and in 3 other patients who were negative for HCV RNA and positive for anti-HCV. HCV RNA was also detected in 6 out of 10 non-cancerous liver tissue specimens and in 3 out of 7 tumor tissue specimens. Using the polymerase chain reaction, the HCV genome was detected directly in many specimens obtained from patients with non-A, non-B hepatitis, suggesting the presence of replicating virus in patients positive for anti-HCV. In addition, the differing results of the two assay systems suggest that the application of both is important for evaluation of the status of HCV infection.
Adult↗
[ELISA diagnosis for Mycoplasma pneumoniae infection with human normal immunoglobulin products as control sera].
It was found that the human normal immunoglobulin G product, prepared from pooled plasma of at least 1,000 normal human donors, contained some specific IgG antibodies to Mycoplasma pneumoniae by Western blotting. M. pneumoniae-ELISA OD values increased linearly from 25 to 800 micrograms/ml in the concentration of the product, there were no differences in the M. pneumoniae-ELISA OD value of the products among lots. Then we used this product as control serum for measurement of IgG antibodies to M. pneumoniae in human sera by ELISA and compared the results with those obtained by complement fixation (CF) and indirect hemadosorption (IHA) tests. ELISA titers determined by this method had a mutual relation with CF and IHA titers.
Antibodies, Bacterial↗
Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung.
T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. We hypothesized that these cells produce colony-stimulating factors (CSFs), which have been shown to affect the proliferation and function of monocyte-/macrophage-lineage cells. To test this hypothesis, we tried to detect mRNA encoding CSFs in cells obtained by bronchoalveolar lavage using a reverse transcription-polymerase chain reaction. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in five of six patients with pulmonary sarcoidosis, whereas it was detected in none of the five normal controls. Macrophage-CSF mRNA was detected in all subjects examined, and interleukin-3 mRNA in none. These results suggest some relation of GM-CSF to sarcoid lesion formation.
Base Sequence↗
Modulation of accessory molecules on lung T cells.
Stimulation of T cells via the CD3/TCR complex is associated with the reduced expression of accessory molecules, a phenomenon called modulation. To investigate whether the modulation is implicated in the pathogenic mechanism of pulmonary disease, we determined the MFI of CD3, CD4 and CD8 on lung and blood lymphocytes in ten normal subjects and 54 patients with various pulmonary and extrapulmonary diseases. Although there were no significant differences in MFI of these accessory molecules on lung lymphocytes among the groups, MFI of CD3 on lung lymphocytes was significantly decreased compared with that on blood lymphocytes in all groups, demonstrating the modulation of CD3 on lung lymphocytes. Since it has been shown that T cells whose CD3/TCR is modulated are hyporesponsive to various mitogenic signals, our observation seems to represent another aspect of the mechanism whereby the local pulmonary milieu maintains the autoregulation of immune response.
Adult↗
The diagnosis of small hepatocellular carcinomas: efficacy of various imaging procedures in 100 patients.
The efficacy of various imaging procedures used for the diagnosis of small hepatocellular carcinomas (HCCs) (lesions no larger than 3 cm in diameter) was evaluated in a retrospective study of 100 patients. Seven patients with hepatic adenomatous hyperplastic nodules containing HCC foci were also assessed. In 89 patients, the lesion was initially detected during follow-up of chronic liver disease. In 21 patients, it was first diagnosed on the basis of elevated serum alpha-fetoprotein; in the remaining 79 it was diagnosed incidentally with imaging procedures. The overall sensitivities of sonography (84%), CT (84%), and angiography (81%) were compared with those of arterial angiographic CT (82%), portal angiographic CT (91%), lipiodol CT (93%), and intraoperative sonography (96%). The differences in sensitivity between angiography and lipiodol CT (p less than .05) and between intraoperative sonography and the other studies (p less than .01) were statistically significant. In 22 lesions smaller than 1 cm, the sensitivities of lipiodol CT and intraoperative sonography were high (83% and 86%, respectively). Adenomatous hyperplasias containing HCC foci were frequently detected by arterial angiographic CT and intraoperative sonography. These results show that sonography or CT and alpha-fetoprotein are useful in detecting small HCCs in screening programs of patients with chronic liver disease. Lipiodol CT and intraoperative sonography are necessary in patients who are candidates for surgery.
Adult↗
[Detection of metabolic inhibition antibody to Mycoplasma pneumoniae by new method with guinea-pig complement].
Improvement of the fermentation-inhibition (FI) test for Mycoplasma pneumoniae was attempted. The sensitivity of detecting the FI antibody to M. pneumoniae in the homologous immune rabbit serum was notably elevated, when such FI medium containing gamma globulin-free horse serum and guinea-pig complement in substitution for unheated horse serum was used. The M. pneumoniae suspension was filtered to remove aggregates of the organisms and used as the antigen for this new FI test. In detection of the serum antibody of patients with M. pneumoniae infections, the new FI test showed much higher sensitivity than conventional FI test and strongly correlated (r = 0.84) with high density particle agglutination test known to detect both IgG and IgM antibodies.
Animals↗
Early diagnosis of hepatocellular carcinoma.
We describe the results of our study on the early detection of the development of hepatocellular carcinoma among patients with chronic liver disease. Over a period of 18 years, 33 patients were diagnosed as having hepatocellular carcinoma. From 1970 to 1978, we used serum alpha-fetoprotein determination, liver palpation, and radionuclide liver scans. In addition to alpha-fetoprotein determination, computed tomography and ultrasonography were introduced in 1979. However, we did not have any general guidelines for the use of these imaging modalities. From 1984 onwards, ultrasonography and serum alpha-fetoprotein determination have been performed every three months and computed tomography every year in patients whose right hepatic lobe had atrophied due to liver cirrhosis. On the basis of this screening program, 50% of the detected hepatocellular carcinoma (9/18) were found to be smaller than 1.9 cm in diameter, and tumor resection was performed in 11 out of 18 patients (61%).
Adult↗
[A case of elderly (83-year-old) woman with possible left atrial myxoma].
A 78-year-old woman with exertional dyspnea (Hugh-Jones Grade III) and dry cough was admitted to our hospital in April, 1983. She had marked cardiac cachexia and a loss of body weight due to long term heart failure. On physical examination a systolic ejection murmur and a diastolic rumbling murmur were heard without the opening snap sound. Chest radiography revealed pleural effusion and cardiomegaly. M-mode and two dimensional echocardiography demonstrated abnormal echoes in the left atrium, the density being 22.7 Hounsfield Unit. Radionuclide angiography and magnetic resonance imaging (MRI) provided similar findings. No other mass lesion existed in the other chambers. Based on these findings, the mass was diagnosed as a left atrial myxoma. She has been well except for periodic congestive heart failure, for about five years since her discharge. The course of her ailment is interesting because her treatment is mainly symptomatic.
Aged↗
[The serial changes of antibody production, macrophage migration inhibition test (MIT) and histopathologic examination in an experimental hypersensitivity pneumonitis in rabbits].
We developed a hypersensitivity pneumonitis model by sensitizing rabbits intratracheally (IT) twice after two subcutaneous sensitizations (SS), and investigated the serial changes in the production of antibody against micropolyspora faeni (Mf), macrophage migration inhibition test (MIT), and histopathologic features. On the third day after the last IT, the proportions of neutrophils in bronchoalveolar lavage fluid (BALF) increased. The antibody levels of Mf specific-antigen in BALF decreased transiently, but those in serum began to increase. The number of AFC in spleen increased rapidly. Histopathologic examination revealed alveolitis and prominent acute pneumonia. On the seventh day after the last IT, the proportion of lymphocytes in BALF, the antibody levels of Mf specific-antigen in BALF, the number of AFC in BALF, and the percent inhibition of MIT were highest. Histopathologic features were characterized by the formation of prominent epithelioid granulomas. On the fourteenth day after the last IT, these features returned to the state of untreated group. These results indicate that the lesions in this HP model are formed by both type III and type IV immune reactions (Coombs-Gall). It was concluded that the seventh day after the last IT was most appropriate for the study of pathophysiology of human HP.
Actinomycetales↗
Clinical and radiologic assessments of the results of hepatectomy for small hepatocellular carcinoma and therapeutic arterial embolization for postoperative recurrence.
To study the prognostic significance of the state of the residual liver after hepatectomy for small hepatocellular carcinoma (s-HCC) no larger than 5 cm in diameter, 123 patients were followed for periods from 9 months to 9 years and 1 month. The following results were obtained: (1) recurrence occurred in the residual liver in 58 patients (54.2%) after an average of 14.9 months from hepatectomy; (2) at recurrence diagnosed by imaging, 12 of 48 recurrent patients showed negative alpha-fetoprotein; (3) computed tomography (CT) had a high sensitivity (71.4%) in detecting recurrence; (4) 5-year survivals for all patients (n = 123) who had hepatectomy, and for those without recurrence (n = 49) or with recurrence (n = 58) were 19.1%, 48.9%, and 11.0%, respectively; and (5) survivals for the patients who developed recurrence and who did and did not receive embolization treatment (n = 32, 23, respectively) were 70.3% and 37.1% at 1 year, 45.0% and 0% at 3 years, and 14.9% and 0% at 5 years, respectively. It is important to recognize that the patient who has undergone surgery even for s-HCC should be followed as a super high-risk patient at regular intervals using CT. Therapeutic embolization for recurrent patients improved the survival after recurrence.
Adult↗
Evaluation of the prognosis for small hepatocellular carcinoma based on tumor volume doubling time. A preliminary report.
The relationship of tumor volume doubling time to length of patient survival was investigated for 15 patients with small hepatocellular carcinoma smaller than 4.5 cm in diameter. The mean tumor volume doubling time of these 15 nodules was 102 +/- 77 days (mean +/- SD; range 41 to 305 days) before the initiation of a specific treatment for cancer. These doubling times tended to correlate with mitotic indexes of the tumors and the patients could be divided into two groups according to the therapeutic modalities used. Patients in Group A received systemic chemotherapy without response or nonspecific treatments for cancer. In this group, there was a positive correlation between tumor volume doubling time and survival length (r = 0.8812; P less than 0.025). Patients in Group B either received hepatectomy after transarterial embolization or systemic chemotherapy or received hepatectomy alone. In this group, early death occurred in patients who had shorter tumor volume doubling times. Three surgically treated patients in Group B were evaluated as having survived for a significantly long period as assessed from their tumor volume doubling times. These results indicate that tumor volume doubling time is one of the determining factors of survival length in patients with hepatocellular carcinoma, and, therefore, can be used in the evaluation of therapeutic efficacy.
Aged↗
Hepatic artery embolization for inoperable hepatocellular carcinoma; prognosis and risk factors.
During a 7-year period in our hospital, 69 patients with inoperable hepatocellular carcinoma (HCC) underwent 111 courses of transcatheter hepatic artery embolization (TAE) and/or chemoinfusion with lipiodol. Patient survival was 0.5-37 months following therapy and the factors affecting prognosis were evaluated. Survival rates at 1, 2 and 3 years after TAE were 53%, 24% and 15%, respectively. Survival rates at 1, 2 and 3 years in relation to tumor size were 100%, 100% and 100% in 5 patients (tumor size less than 2 cm in diameter), 81%, 33% and 16% in 23 patients (2.1-5.0 cm), and 35%, 9% and 0% in 41 patients (greater than 5.1 cm). An analysis of prognostic factors showed that the size of the main tumor significantly influenced the prognosis following TAE (P less than 0.01), whereas the frequency of TAE, intrahepatic metastasis and the degree of liver dysfunction showed a slight correlation (P less than 0.1). These results suggest that TAE has a significant potential for becoming the first choice of treatment for patients with small multiple HCCs (less than 2 cm), provided that neither severe hepatic dysfunction nor a tumor thrombus in the main portal vein is present.
Adult↗
[Mycoplasma pneumoniae isolation and IHA antibody detection in patients with M. pneumoniae infection].
Throat swab culture was compared with indirect hemagglutination (IHA) antibody detection for diagnosis of Mycoplasma pneumoniae infection. These two methods were tried on the patients several times for a long term after onset of the disease. For five years from 1982 to 1986 in Kanagawa prefecture, a total of 566 patients were tested and 141 (25%) were diagnosed as M. pneumoniae infection by either of the two test methods. Both culture and antibody detection were performed on 110 patients out of 141, revealing that 96 patients (87%) were positive by culture and 89 (81%) were positive by antibody detection. Most of the patients with M. pneumoniae infection showed positive culture within a week after onset of the disease, and half of the patients treated with antibiotics such as macrolides or tetracyclines showed positive for two or three months after the onset. Positive rate of IHA antibody detection in the patients with M. pneumoniae infection was 43% within a week after onset of the disease and reached the maximum (92%) in 15 to 21 days after the onset. The rate did not decrease to less than 70% three months after the onset. Geometric mean titer of the antibody reached the maximum at the same time as the antibody positive rate. Both antibody positive rate and geometric mean titer declined significantly four months after the onset. In general, IHA antibody of infants with M. pneumoniae infection increased satisfactorily day by day after onset of the disease. Nine percent of the patient with M. pneumoniae infection developed otitis media with effusion, and M. pneumoniae was isolated from two of six patient effusions.
Antibodies, Bacterial↗
Interleukin 1 production by alveolar macrophages is decreased in smokers.
To evaluate the mechanism by which cigarette smoking suppresses pulmonary immune responses, we determined the capacity of alveolar macrophages (AM) to produce interleukin 1 (IL-1 in 32 normal subjects and in 40 patients with pulmonary sarcoidosis. The amount of IL-1 released from LPS-stimulated AM from smokers was significantly decreased compared with that in nonsmokers in both normal and sarcoid groups. The addition of indomethacin to the cultures in 18 normal subjects and in 22 patients with pulmonary sarcoidosis yielded similar results, thus excluding the possibility that this difference resulted from a difference in the amount of cyclooxygenase metabolites released in the culture supernatants. Similar results were obtained by enzyme-linked immunosolvent assay. Because IL-1 is thought to induce the accumulation of T cells at the site of disease and contribute to local cellular and humoral immunity of the lung, our data suggest that the reduced capacity of AM to release IL-1 in smokers affords partial protection against the initiation of immune responses in the lung and the development of granulomatous lung diseases.
Adult↗