Biomedical subjects
Publications and source records attributed to M Ohsawa.
We report a primary non-Hodgkin's B-cell lymphoma of the urethra in a 78-year-old female. Serum antibodies for Epstein-Barr virus (EBV) were negative, but there was a 40-fold increase in antibodies to EBV-associated nuclear antigen. Using PCR and in situ hybridization techniques, EBV genome was found in the tumour cell nuclei.
AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.
AIMS: To determine the presence of Epstein-Barr virus (EBV) genome in six patients (three with gastric and three with breast carcinoma) with severe small lymphoid cell infiltration. METHODS: The polymerase chain reaction and in situ hybridisation were used to detect EBV genome. The number and distribution of T and B lymphocytes were evaluated by immunohistochemistry. RESULTS: Histologically all of the patients had poorly differentiated tumours. Immunohistochemistry showed that T cells predominated in three cases, B cell in two, and almost equal numbers in one case. PCR showed that the EBV genome was present in two cases each of gastric and breast carcinoma. In situ hybridisation for EBV genome provided positive signals only in the small lymphoid cells in one gastric and two breast carcinomas giving a positive reaction for EBV genome by PCR. The gastric and breast cancer cells did not give positive signals. CONCLUSIONS: Severe lymphoid cell infiltration in gastric and breast carcinoma does not necessarily indicate that these tumours are associated with EBV. Larger numbers of cases will need to be studied to confirm this.
In our previous study, we suggested that long-standing pleural inflammation might be an etiological factor for development of pleural soft-tissue sarcomas, especially malignant fibrous histiocytoma and angiosarcoma (AS). To study the etiological importance of chronic pyothorax for development of pleural AS, a nationwide study of AS in Japan was carried out. Histological and clinical findings in 99 collected cases with AS were reviewed. Six (6%) of the 99 cases were chronic pyothorax-associated AS. Another three cases of pyothorax-associated AS previously reported by us were also included. They were eight males and one female from 45 to 74 yr of age (median 65 yr). All patients had a 15- to 40- (mean 30) yr history of chronic tuberculous pyothorax. Histologically, the tumors contained irregular, occasionally dilated vascular channels, which were invested by tumor cells with an epithelioid appearance. From the statistical data reported previously, annual incidence of AS is probably 0.01 to 0.02 per 100,000 population. Meanwhile, there was an incidence rate of pyothorax-associated AS among chronic pyothorax patients of 0.036 per 100 patients. Thus, the frequency rate of pyothorax-associated AS is supposedly over 3600-fold higher than that in normal population. The present study shows that chronic tuberculous pyothorax is one of the causes of AS development.
Interleukin-6 (IL-6) is a novel cytokine with activities that can affect hematopoietic cells including those of the megakaryocytic lineage. We have examined the effects of monomethoxy polyethylene glycol-modified recombinant human interleukin-6 (Peg-IL-6) on thrombopoiesis in vivo. To compare the thrombopoietic activity between Peg-IL-6 and unmodified IL-6, each was administered subcutaneously to mice every 24 hours at various doses. A dose-response experiment showed that Peg-IL-6 and IL-6 increased platelet counts in a dose-dependent fashion at a plateau stimulation level of 0.5 micrograms/day and 10 micrograms/day, respectively. This dose of Peg-IL-6 and IL-6 induced the elevated platelet counts by approximately 140% to 160% and 50% to 60%, respectively. Peg-IL-6 treatment (0.5 micrograms/day) for x-ray (6.0 Gy) irradiated mice induced an increase in the rate of platelet recovery, and a higher dosage (5 micrograms/day) completely blocked the induction of thrombocytopenia in this model. In contrast, IL-6 (10 micrograms/day) could not protect the animals from platelet nadir but reduced the period of thrombocytopenia after x-ray irradiation. Furthermore, when administered to 5-fluorouracil-treated mice, 5 micrograms/day of Peg-IL-6 diminished the platelet nadir and increased platelet counts on individual days during the recovery phase. The potent thrombopoietic activity of Peg-IL-6 were due to prolongation of circulating IL-6 levels that were reverted from Peg-IL-6 in vivo. These findings indicate that reduction of total body clearance of IL-6 induces potent thrombopoiesis and that Peg-IL-6 may be a useful thrombopoietic agent.
The nature and frequency of occurrence of monocytoid B-lymphocytes (MBL) was examined in 118 cases of Hodgkin's disease. Monocytoid cells were present in six cases (5%), four nodular sclerosis and two mixed cellularity. These cells were CD20+, CD3-, CD45RO-, KP-1-, PGM1-, with occasional positive reaction for MB-1 and CD74, indicating their B-cell nature, i.e., MBL. The MBL were distributed in the periphery of the nodules of nodular sclerosis accompanying centrally located Reed-Sternberg cells, although Reed-Sternberg cells were observed in some MBL clusters. In the mixed cellularity, MBL were located in the para-follicular area occasionally adjoining the lymph follicles. Because previous studies suggested depressed immune function in autoimmune diseases, acquired immune deficiency syndrome, and older persons to be responsible for the occurrence of MBL, it is possible that in some patients development of foci of MBL under immunodeficient conditions progresses to Hodgkin's disease.
BACKGROUND: Uterine lymphoma is a rare disease; therefore, information regarding histologic type, immunophenotype of tumor cells, and etiologic factors are limited. METHODS: Seven patients with uterine lymphoma, three from the corpus and four from the cervix, were collected by a nationwide study in Japan. Selection of cases was preferentially made from the "Annual of Pathologic Autopsy Cases in Japan." RESULTS: All cases with cervical lymphoma presented with vaginal bleeding. Abdominal pain or backache was observed in patients with corpus lymphoma. The age ranges of patients with corpus and cervical lymphomas were 46-78 years of age (mean, 63 years) and 30-71 years of age (mean, 53 years), respectively. Information about clinical staging was available for six patients; two patients with Stage I, three patients with Stage II, and one patient with Stage III. A definite diagnosis of uterine lymphoma was made by biopsy in all cases. Total hysterectomy, with or without bilateral salpingo-oophorectomy, was carried out in three patients, and tumor resection was carried out in one patient. Adjuvant therapy was given in six cases. Follow-up showed that five patients died due to tumor within 1 year of treatment. Histologically, all cases were non-Hodgkin lymphoma showing a diffuse pattern of proliferation. All but one were diffuse large cell type. Immunohistochemistry revealed the tumor cells in all cases were of B-cell nature. Expression of HLA-DR antigen was evaluable in four cases, of these three showed an increased expression on the vascular endothelium. CONCLUSIONS: Uterine lymphoma comprises exclusively B-cell type.
BACKGROUND: The significance of long-standing cystitis has been postulated as a causal factor in malignant lymphoma of bladder. METHODS: The authors reviewed 3 cases of primary malignant lymphoma of the urinary bladder and an additional 27 cases described in the literature (25 from Western countries and 2 from Japan). Clinical and pathologic findings in the total 30 cases are summarized. RESULTS: The majority of patients presented with gross hematuria and were between 20 and 85 years of age (median age, 64 years). Marked female preponderance was found (male to female ratio, 1:6.5). Six patients (20%), all of whom were women, out of 30 had a history of chronic cystitis. Macroscopic findings showed a solitary mass (22 cases), multiple masses (6 cases), or a diffuse lesion without nodule formation (2 cases). The vast majority of bladder lymphoma were non-Hodgkin lymphoma (NHL) of B-cell type; among them, 14% were follicular lymphomas. Follow-up indicated that NHL of bladder had a favorable prognosis. CONCLUSIONS: Malignant lymphoma of bladder is characterized by a preponderance in women, who are occasionally affected by chronic cystitis.
Histological and immunohistological prognostic factors for well-differentiated oral squamous cell carcinoma (SCC) were examined in 31 patients. They included 18 males and 13 females aged 42-84 (median 63) years. The tumors were located in the tongue in 13 cases, gingiva in 7, floor of the mouth in 5, cheek mucosa in 4, and palate in 2. Advanced disease (stages III and IV) was found in 92% of patients; 22 were treated by radical surgery and nine by excisional or incisional biopsy, followed by adjuvant chemotherapy and external radiation. The 5-year survival rate in patients with stages III and IV disease was 58% and 33%, respectively. Histologic factors evaluated were tumor cell mitotic counts, degree of lymphocyte and eosinophil infiltration around the tumor, mast cell counts, HLA-DR expression on tumor cells, or surrounding lymphocytes. Multivariate analysis revealed that degree of eosinophilic infiltration and expression of HLA-DR antigen on the tumor cells were significant factors for prognosis (P < 0.05); i.e., heavy eosinophilic infiltration and expression of HLA-DR antigen on tumor cells were signs of an unfavorable prognosis. The interpretation of the present findings are discussed with a review of the literature.
In the past 12 years, 102 cases of anterior communicating artery aneurysm have been operated upon in our institution. Two basic microsurgical approaches (pterional and interhemispheric) were used. The combined pterional and interhemispheric approach was performed in a few cases. The rational for each surgical approach is discussed in relation to anatomical factors such as the height of the aneurysm neck, the side of dominance of A1, the relationship between the bilateral proximal parts of A2s, and the projection of the aneurysm. The final outcome was correlated to the preoperative clinical grading and timing of surgery. The overall results were as follows; 82.4% good, 5.9% fair, 4.9% poor, and 6.8% mortality rate. The operative results for pterional and interhemispheric approach were comparable with each other. In the combined approach, we got poorer results which could be related to excessive brain retraction and unfavourable clinical grading.
An etiologically important role of chronic tuberculous empyema for development of pleural lymphocytic lymphoma of B-cell type has been suggested. To examine risk factors for development of pleural lymphoma in patients with chronic tuberculous empyema, a case-control study was carried out. Onset age of lung tuberculosis and empyema, presence of chemotherapy, surgical treatment, extent of empyema, presence of fistula, history of smoking, and height and weight of patients at first admission were compared in patients with empyema alone (70 controls) and empyema complicated with lymphoma (42 cases): the date of birth and sex were matched by group. The patients receiving artificial pneumothorax showed a significant increase in risk for development of pleural lymphoma (relative risk = 4.92, P < 0.05). We could not find any report describing development of pleural neoplasias in patients with chronic empyema receiving surgical resection of pleural pyogenic membrane. From these findings, it is suggested that artificial pneumothorax left chronic non-healing inflammation in the pleural cavity, which resulted in development of pleural lymphoma.
Two patients with unusually large dorsal internal carotid artery aneurysms manifesting as subarachnoid hemorrhage are described. Surgery in both cases resulted in intraoperative rupture of the sac. The outcome was poor in the first patient and excellent in the second. The importance of wide exposure of the proximal and distal vasculature to the aneurysm, subpial dissection of the frontal and temporal lobes not to injure the fragile aneurysmal dome, and parallel clipping was emphasized for this rare type of aneurysm.
Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and thus studies on its regulation are toxicologically important. Heavy metal-dependent induction of MT genes is mediated by metal responsive elements (MREs) located upstream of the genes. Zinc regulatory factor (ZRF) is a zinc-dependent MRE-binding protein that was originally detected in HeLa cell nuclear extracts using the most proximal MRE of the human MT-IIA gene (hMREa) as a probe. We show that ZRF in HeLa cell nuclear extracts can also bind to the most potent MRE of the mouse MT-I gene (mMREd). This finding was further confirmed by using partially purified ZRF. Moreover, cadmium could not promote complex formation between ZRF and mMREd at any concentration tested, as is also the case with ZRF and hMREa. These observations suggest that the transcriptional regulatory system of MT genes by zinc is conserved beyond species.
Clinical and pathologic features of 69 cases with primary hepatic lymphoma, 52 reported from Western countries and 17 cases from Japan, were summarized in terms of clinical findings including age and sex, past history, presenting symptoms, and physical findings, diagnostic procedures including imaging techniques and histopathology, and finally therapy and follow-up. The present cases included four patients with an acquired immunodeficiency syndrome and 12 with a history of chronic liver diseases. Histologically, all cases were non-Hodgkin's lymphoma with diffuse large cell type being the most common immunochemically about 80% were B-cell type. Follow-up showed that hepatic lymphoma had a relatively favourable prognosis provided early detection was possible.
Occurrence of monocytoid B-lymphocytes (MBL) in extranodal organs in various inflammatory diseases was examined. MBL were present in 5 (11.4%) of 44 patients with Graves' disease, 11 (36.7%) of 30 with Hashimoto's thyroiditis, 1 (8.3%) of 12 with lymphoid follicular hyperplasia (LFH) of stomach, 1 (10%) of 10 with cutaneous LFH, and 0 of 5 with LFH of lung. The MBL presented as irregularly shaped nodular collections of cells, directly surrounding secondary follicles. Immunohistochemistry revealed a B-cell nature of these cells which expressed the following antigens; CD3-, CD 15-, CD45RA+, CD45Ro-, CDw 75+, CD74+, Mx-PanB+, MB-1+, EMA-. There were no immunoglobulin light chain restriction among infiltrating lymphoid cells. MBL in 2 of 18 cases showed positive reaction for CD43. The patients with MBL were older than those without MBL in each organ site, though the difference was not statistically significant. These findings showed that the MBL could appear in nonlymphoid organs affected by long-standing inflammation. High frequency of the appearance of the MBL in Hashimoto's thyroiditis suggest that MBL proliferation correlates with an impaired immune status.
Occurrence of monocytoid B-lymphocytes (MBL) in spleens of 34 patients with gastric cancer was examined. Histologic findings of gastric cancer including classification, depth of invasion, and stage of disease were defined based on the General Rules for the Gastric Cancer Study (Japan). MBL were defined morphologically as having abundant pale cytoplasm with distinct cell borders and small nucleus often with reniform shape. Immunohistochemically, these cells were B-cell in nature, i.e., CD15-, CD43-, CD45RA+, CD45Ro-, CD68-, CD74+, CDw75+, Mx-PanB(L26)+, MBI+, EMA-, PG-MI-. Clusters of MBL were found in 14 of 34 (41%) patients: they were found to be directly adjoining to the periarterial sheath or apart from the white pulp. In the cases without MBL, zonation of mantle zone and marginal zone was apparent with distinct secondary follicles in 72% of cases. Meanwhile, in spleens with MBL, the mantle zone showed atrophy in a half of cases, resulting in indistinct zonation of the mantle zone and marginal zone. Secondary follicles were distinct in less than 30% of cases. Correlation of the occurrence of MBL, evaluated by Spearman's correlation coefficient, revealed that the age was the most important factor (R = -0.4852, P = 0.00364): the median age of patients with and without MBL was 75.7 and 61.7 yr, respectively. The MBL were increased in gastric cancer as compared with other cancers (P < 0.03) and with noncancer spleens (P < 0.1). The age of gastric cancer patients with MBL was older than those in other cancers and noncancer patients. Therefore occurrence of MBL in spleen might be a function of aging.
We report two non-surgical cases of pseudoaneurysm of the left ventricle after mitral valve replacement. Two patients underwent uncomplicated mitral valve replacement with Ionescu-Shiley and Carpentier-Edwards bioprosthesis respectively, and both had good early postoperative course with no symptoms. Left ventriculogram one month after operation showed subvalvular pseudoaneurysm of the left ventricle in both patients. Two patients were in New York Heart Association Functional Class I with digitalis and diuretics and have left ventriculogram had done five years postoperatively. Pseudoaneurysm of the left ventricle without a surgical repair disappeared in one patient, and revealed no enlargement in the other. There still remain controversies regarding the treatment of pseudoaneurysm of the left ventricle following mitral valve replacement.
Reactivities of Reed-Sternberg (RS) cells for antibodies against T-lymphocytes and B-lymphocytes together with CD30 and CD15 were examined in the sequential biopsies of Hodgkin's disease (HD). For this purpose, six patients with lymphocyte predominant (LP) HD, each three of nodular and diffuse types, and three with mixed cellularity (MC) HD were examined. Numbers of times of biopsy in these cases were 25, the intervals between each biopsy ranged from 1 to 92 (median 12) mo. Positive reactivities of the RS cells for CD20, 45R, w75, w74, and/or MB1 were observed in all but one with nodular LPHD. Five of six cass with LPHD showed positive reaction for CD30 and/or CD15. RS cells in all of the present MCHD cases showed a positive reaction for CD30 with each one case showing positive reaction for CD15, CD20, and w75. RS cells in two of three cases with MCHD showed a positive reaction for CD20 or w75. RS cells did not show positive reaction for any antibodies against T-lymphocytes. Sequential biopsy revealed that two of three cases with nodular LPHD and one of three with diffuse LPHD changed to MCHD and two of three with MCHD changed to LDHD. Reactivity of RS cells for CD30 was consistent even when the histologic subtypes changed. Expression of CD15 by RS cells was labile; appearance of disappearance of this antigen during sequential biopsy was frequent. Positive reactivities of RS cells for anti-B-lymphocytes antibodies in LPHD cases disappeared in two cases when histology changed to MCHD. In one case with MCHD, the RS cells became reactive for anti-B-lymphocytes antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)