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Biomedical subjects

H Kunikane

Publications and source records attributed to H Kunikane.

At least 37 records · Page 2Linked to original sources

Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis.

BACKGROUND: It is commonly assumed that some immunological disorder may play a part in the pathogenesis of sarcoidosis. Previous studies by several groups have shown a significant association with HLA-DR antigens in patients with sarcoidosis. In this study, restriction fragment length polymorphism (RFLP) analysis of the HLA-DR gene was designed to confirm the association at the gene level and to look for a gene rearrangement which may influence susceptibility to sarcoidosis. METHODS: Thirty two unrelated Japanese patients with sarcoidosis were tested for HLA antigens and subjected to RFLP analysis after digestion with Eco RI, Pst I, Bam HI, Pvu II, and Hind III by using an HLA-DR beta cDNA probe. A group of 47 unrelated healthy Japanese subjects served as controls. Frequencies of each restriction fragment were compared between the patients and the control subjects. Correlation between fragment frequencies and clinical features were also analysed. RESULTS: No restriction fragments of HLA-DR beta gene were found specific to the patients with sarcoidosis. The RFLP analysis could detect polymorphism of HLA-DR beta genes that was not distinguishable by conventional serological methods. Several restriction fragments of the DR beta gene were seen only in DRw52 positive individuals, and showed higher frequencies in the patients than in control subjects. The patients with these DNA fragments were likely to have limited stage disease with no ophthalmic involvement. CONCLUSIONS: An association between HLA and sarcoidosis was noted at the DNA level, although no restriction fragments were specific for this disease. RFLP analysis of the HLA gene is a more useful method than the usual HLA typing, and should be the first step in identifying the gene sequence which is connected with susceptibility to sarcoidosis.

Adolescent↗

Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it. PATIENTS AND METHODS: Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy. RESULTS: Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown). CONCLUSION: The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.

Adult↗

Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma.

BACKGROUND: The value of nucleolar organizer regions (NOR) visualized by silver staining (AgNOR) for the histologic differentiation, pathologic staging, and estimation of growth rate was assessed by the investigation of paraffin sections from 58 lung adenocarcinomas. AgNOR consist of NOR-associated proteins, and the number of AgNOR might be related to proliferative activity. METHODS: In lung adenocarcinoma, the growth rate can be measured by means of chest radiographs. Using this technique, the authors studied the correlation between the mean number of AgNOR and growth rate. RESULTS: The mean number of AgNOR ranged from 1.8 to 6.3 (mean +/- standard deviation, 4.0 +/- 0.8). Neither the degree of histologic differentiation nor the pathologic staging was related to the AgNOR count. The tumor growth rate was estimated on the basis of the doubling time in the chest radiographs of 13 patients. The doubling time ranged from 80 to 760 days. There was a high inverse correlation between the AgNOR count and the doubling time (r = -0.910; P less than 0.001). CONCLUSIONS: Thus, it appears to be possible to use the mean number of AgNOR as an index of proliferative activity.

Adenocarcinoma↗

Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).

Adult↗

Nucleolar organiser regions as a marker of growth rate in squamous cell carcinoma of the lung.

BACKGROUND: The numbers of nucleolar organiser regions (AgNORs) per cell has been considered as an indicator of the cellular proliferative activity. A study was carried out to examine whether AgNOR numbers relate to the growth rate in squamous cell carcinoma of the lung. METHODS: AgNORs were stained by a one step silver method, and examined in representative paraffin sections from 45 cases of squamous cell carcinoma of the lung treated by surgical resection of the primary tumour. RESULTS: The mean (SD) AgNOR numbers per cell in squamous cell carcinomas (5.3 (0.9)) were significantly higher than those in normal bronchial epithelium (1.2 (0.1)). There was no statistical difference among tumours of different post-surgical stages (stage I = 5.2 (0.8), II = 5.9 (1.4), III A = 5.5 (1.3)). The tumour volume doubling time in these cases ranged from 74 to 208 days (120.7 (40.4)). There was a high inverse correlation between the AgNOR numbers and doubling time. CONCLUSION: The AgNOR numbers were related to the growth rate of squamous cell carcinoma of the lung. Thus the AgNOR count could be used as a useful marker for investigating the cellular proliferative activity.

Aged↗

[A case of bronchial actinomycosis associated with bronchoscopically removed broncholith].

A 57-year-old woman with bronchial actinomycosis associated with broncholith is presented. She had suffered from fever and productive cough for 7 years. Her chest roentgenograms showed atelectasis of the middle lobe and calcification in the middle lobe bronchus. Bronchoscopic examination revealed a broncholith covered with pus and granulomatous tissue. The biopsy specimen revealed sulfur granules containing a partially calcified lesion, and it was diagnosed as actinomycosis. After treatment with antibiotics, the broncholith became movable, and it was removed bronchoscopically. Its shape was like a molding of the right middle lobe bronchus. We speculate that the growth of this broncholith partially resulted from chronic inflammation associated with actinomycelial infection.

Actinomycosis↗

Nucleolar organizer regions in precancerous and cancerous lesions of the bronchus.

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NOR) were studied in paraffin sections of five specimens of normal bronchial epithelium, eight of atypical squamous metaplasia, five of carcinoma in situ, and seven of microinvasive squamous cell carcinoma. The mean number of Ag-NOR in the nucleus were normal epithelium 1.2 +/- 0.1 (mean +/- SD), atypical squamous metaplasia (borderline lesion) 2.2 +/- 0.5, carcinoma in situ 3.8 +/- 0.6, and microinvasive squamous cell carcinoma 4.8 +/- 1.1. There was a highly significant difference between the Ag-NOR numbers in the atypical squamous metaplasia and those in the carcinoma in situ (P less than 0.01). The Ag-NOR staining is a useful technique for the differential diagnosis of difficult borderline lesions in the bronchial epithelium.

Bronchial Neoplasms↗

Pulmonary nontuberculous mycobacteriosis showing wandering shadows in chest roentgenograms.

The case of a 68-year-old woman with pulmonary nontuberculous mycobacteriosis, whose chest roentgenograms showed unusual wandering shadows on separate occasions, is presented. Acid-fast bacilli were detected in her sputa and by bronchial washing, and were identified as Mycobacterium chelonae, subspecies abscessus. The findings of computed tomography and transbronchial lung biopsy were also unique because of multiple peribronchial inflammations. Chemotherapy with anti-tuberculosis agents and a new quinolone drug was successful in this case.

Aged↗

[Nucleolar organizer regions, nuclear DNA content, and proliferative activity in adenocarcinoma of the lung].

The relationship between the quantity of silver-binding nucleolar organizer regions (AgNORs), nuclear DNA content, and proliferative activity was studied in 61 patients with adenocarcinoma of the lung. The proliferative activity of adenocarcinoma was estimated by tumor volume doubling time based on chest X-ray findings. There was a high, inverse correlation between the AgNORs and the tumor doubling time (p less than 0.001, r = -0.815), and the contribution rate was high value (2 = 0.664). However, the AgNORs value was an independent prognostic factor for survival time. A better 5-year survival rate was observed in patients with DNA diploidy than in DNA aneuploidy, but there was no statistical difference between the two groups. There was an inverse correlation between the DNA index and tumor doubling time (p less than 0.05, r = -0.565), but the contribution rate had a low value (r2 = 0.319). These results indicate that the AgNORs value is important in providing an estimate of the proliferative activity of adenocarcinoma.

Adenocarcinoma↗

[A case of bronchial artery aneurysm demonstrating a mass shadow on chest X-ray film].

A 66-year-old woman was admitted on May 13, 1989, because of an abnormal round shadow in the right hilum on chest X-ray film. Bronchoscopy revealed a stenosis of the right B8 caused by a bulging lesion. An aortogram showed a large meandering bronchial artery and a saccular aneurysm. The aneurysm was about 25 mm in diameter and associated with a bronchopulmonary anastomosis. It was surgically removed by right lower lobectomy. Pathological examination proved that the resected lesion was an arterial aneurysm. Patchy arteriosclerotic change was present in the intima of the aneurysm, but there was no evidence of inflammatory change in the arterial wall and the adjacent alveoli and bronchi. Twenty-six cases of bronchial artery aneurysm have been previously reported in the literature, but this is the first case that appeared as a solitary nodule on conventional chest X-ray.

Aneurysm↗

[CT analysis of pulmonary emphysematous and fibrotic changes in patients with von Recklinghausen's disease].

Five cases of von Recklinghausen's disease were studied with regard to their association with chest diseases, especially pulmonary emphysematous and fibrotic changes. CT analysis revealed that four patients out of five had multiple pulmonary emphysematous lesions and that those lesions were seen in all segments. In two cases out of the four, it was difficult to detect their abnormalities by an ordinary chest roentgenogram, suggesting the possibility of higher incidence of emphysematous changes in von Recklinghausen's disease than has been expected. On the other hand, pulmonary fibrosis was observed in two cases. There were two patients who had no fibrosis but emphysematous lesions. TBLB was performed in one case, in whom no fibrotic changes were observed. Usually pulmonary fibrosis is associated with emphysematous bullae in patients with von Recklinghausen's disease. However, fibrotic and emphysematous changes may not always occur in combination in von Recklinghausen's disease.

Adolescent↗

[An autopsy case of rest stomach cancer accompanied by tongue cancer].

A case of rest stomach cancer, accompanied by tongue cancer, in a 57-year-old man is reported. The patient underwent a stomach resection 11 years earlier because of a discovered cancer. Most cases of rest stomach cancer appear after 10 years in cases of a stomach resection because of a stomach cancer. A double cancer, accompanied by tongue cancer, mostly occurs in people over 60 years old, and more than half such cases involve a cancer in the alimentary tract as well.

Adenocarcinoma↗

Detection of a novel HLA-DQ specificity: serological and immunochemical analyses by a monoclonal antibody.

A monoclonal antibody (mAb) with a novel human B-cell allospecificity was produced by immunizing a C3H/He mouse with the human B lymphoblastoid cell line EBV-Wa (HLA-DR4/Dw15/DQblank homozygous). The mAb, termed HU-46, reacted with B cells from not only DR4/Dw15-positive individuals but also certain DRw8/Dw8-positive ones whose DQ phenotypes had not yet been defined. Two-dimensional gel analyses indicated that the mAb recognized class II antigens which were encoded by the HLA-DQ locus. Furthermore, in genetic analysis, the gene encoding the class II antigen detected by HU-46 met the Hardy-Weinberg condition as a fourth allele of the DQ locus. We provisionally labeled this novel DQ specificity DQWa.

Alleles↗

A cytotoxic monoclonal antibody (HU-39) that detects DRw8 + DRw12.

A monoclonal antibody, HU-39, was produced by immunizing BALB/c mice with a cultured human B lymphoblastoid cell line, Shi-C3 (HLA-A24, A31, B51, Bw52, DR2, DRw12, DQw1, DQw3). Utilizing the complement-dependent cytotoxicity test, HU-39 was found to detect a polymorphic determinant common to HLA-DRw8 and HLA-DRw12, a split antigen of HLA-DR5. Although HU-39 reacted with the cells from all of nine DRw12 positive individuals, the cells from only 18 out of 21 DRw8 positive individuals reacted with HU-39 and the remaining three were negative for HU-39. The cytotoxicity of the antibody was reduced after the surface HLA-DR molecules of two cell lines, GI and EBV-Sh, typed as DRw8 and DRw12, respectively, were masked with F(ab')2, of anti-HLA-DR monoclonal antibody. The results of the sequential coprecipitation test and the two-dimensional gel electrophoresis by using EBV-Sh also indicated that HU-39 preferentially recognizes an epitope borne on the DR molecules, but not on the DQ molecules. Thus, HU-39 appeared to be of great value as a tissue typing reagent to define DRw8 and DRw12, the latter of which had been difficult to assign because of the lack of monospecific alloantisera.

Antibodies, Monoclonal↗

Chondroid syringoma (mixed tumor of the skin). A clinicopathological study of 13 cases.

The clinicopathology of 13 cases of chondroid syringoma were examined. The ages of the patients ranged from 26 to 86 years, with an average of 48 years. There were eight males and five females. Ten tumors out of the thirteen appeared on the face. Only one patient out of ten was suspected of recurrence in follow-up information. Histologically, all tumors consisted of epithelial cells, chondroid or myxoid matrix, and other strumal elements. The tumors were histologically classified into two types; twelve tumors had tubular and cystic lumina lined by two layers of epithelial cells, and only one case had small lumina lined by only a single layer. By an immunohistochemical study with a PAP method, positive stainings of keratin were observed in all cases, and S-100 protein in all but one. Ultrastructurally, the tumor cells showed features of an epithelial cell. Some ultrastructural differences were noted between two types of chondroid syringoma. Type I tumor cells had many tonofilaments in cytoplasm, but cytoplasmic filaments in type II were of the intermediate-type.

Adenoma, Sweat Gland↗

Role of HLA-DR antigens in Japanese patients with sarcoidosis.

Fifty-three Japanese patients with sarcoidosis were tested for HLA-A,B,C, DR, and DQ antigens in order to investigate immunogenetic mechanisms in the pathogenesis of sarcoidosis. All of the patients had abnormal shadows on their chest radiographs, and all had histologically confirmed sarcoidosis. Groups of 60 and 57 unrelated Japanese served as control subjects for HLA-A,B,C and HLA-D region antigens, respectively. The frequency of HLA-DRw52 was 79.2% (42 of 53) in the patient group compared with 50.9% (29 of 57) in the control group, and the difference was significant (chi 2 = 9.66, p less than 0.005, pc less than 0.05, relative risk = 3.69). On the other hand, no significant association was found with HLA-A,B,C antigens. When various clinical features of the patients were taken into account, there was a tendency for the frequency of DRw52 to be lower in the patients who were in an advanced stage or who had resisted treatment with steroids. Furthermore, 31 of the 32 patients without ophthalmic involvement were DRw52-positive, which was highly significant (96.9% as compared with 50.9% of the control group; chi 2 = 19.74, p less than 0.001, pc less than 0.01, relative risk = 29.93), whereas the frequency of DRw52 in the patients with ophthalmic involvement was almost the same as in the control group. These results suggest that HLA-DR antigens play a significant role in the pathogenesis of sarcoidosis, and there may be a heterogeneity in the clinical entity of sarcoidosis.

Adolescent↗

Association of HLA-DR with sarcoidosis. Correlation with clinical course.

HLA-DR typing was performed in 58 Japanese patients with sarcoidosis. We found a significantly increased frequency of HLA-DRw52 (p less than 0.0007; pc less than 0.009) and DR5J (p less than 0.004; pc less than 0.05). (Corrected probability value is given as pc.) In 34 of 58 patients the disease resolved spontaneously. There was no significant difference between the frequency of DRw52 and the resolution rate of disease. The frequency of DR5J was increased significantly in the unresolved cases. Our results also suggest that DRw52 is concerned with onset of sarcoidosis and DR5J antigen has an effect on the clinical course of this disease.

Adult↗