[Analysis of the prognosis of thymoma from long-term follow-up].
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Biomedical subjects
Publications and source records attributed to J Hashimoto.
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Of 134 patients with thymoma, 79 (59%) also had myasthenia gravis (MG). The thymoma with MG differed from that in the absence of MG in the following aspects: The ratio of lymphocytes to epithelial cells in the tumor was larger, the polygonal cell type was more prominent (i.e., in 83% of the MG patients this cell type predominated), and the differentiation of epithelial cells in the tumor was more advanced in the group with MG than in the group without MG. Furthermore, the clinical stage of thymoma was earlier, the recurrence rate was lower, and the survival curve was better in the group with MG than in the group without MG. These findings suggest that the thymoma with MG is less malignant than that without MG.
The effect of tumor necrosis factor alpha (TNF-alpha) on ectopic endochondral bone formation was studied in an experimental system for bone induction using murine osteosarcoma-derived bone-inducing substance. Ectopic new bone formation was inhibited by daily administration of recombinant human TNF-alpha (20-200 micrograms/kg body weight per day, intraperitoneally) after subcutaneous implantation of the bone-inducing substance into mice. Histological examination revealed that TNF-alpha prevented mesenchymal cells from differentiating into chondrocytes in the process of endochondral bone formation. The inhibitory effect of TNF-alpha continued during the period of its administration, but not after its administration was stopped. The bone induced in a three week period after discontinuation of TNF-alpha administration was histologically normal, but smaller than that induced in control animals. These findings suggested that TNF-alpha reversibly inhibits the biological activity of the bone-inducing substance or impairs the ability of cells to respond to the bone-inducing substance at an early stage of ectopic bone formation.
To evaluate the correlation between predicted postoperative lung function and postoperative respiratory morbidity, 156 patients with lung cancer who underwent resection were classified into four groups based on the degree of postoperative problems: Group 1--no problems (116 patients); Group 2--retention of sputum or atelectasis requiring bronchofiberscopy two or more times (17 patients); Group 3--tracheostomy or mechanical ventilation for more than 2 days or both (14 patients); and Group 4--postoperative death (9 patients). The mean ages of Groups 2, 3, and 4 were significantly (p less than 0.05) higher than the mean age of Group 1. The predicted postoperative lung function (F) was assessed by the formula F = [1-(b-n)/(42-n)] x f, where f is the preoperative vital capacity or forced expiratory volume in one second, b is the number of subsegments of the resected lung lobe, and n is the number of subsegments obstructed by the tumor, which was assessed by the findings on the chest tomogram, on the bronchogram, at bronchofiberscopy, or a combination of these. The total number of subsegments was assumed to be 42. The predicted postoperative % FEV1 was 65.1 +/- 19.3% in Group 1,55.3 +/- 10.6% in Group 2,37.6 +/- 12.1% in Group 3, and 42.3 +/- 18.4% in Group 4. It was significantly (p less than 0.05) different between all the groups except between Groups 3 and 4. All 10 patients with a predicted postoperative % FEV1 of less than 30% were in Groups 3 and 4. We conclude that special attention to postoperative management is needed for patients whose predicted postoperative %FEV1 is lower than 30%.
The complete amino acid sequence of ribonuclease U1 (RNase U1), a guanine-specific ribonuclease from a fungus, Ustilago sphaerogena, was determined by conventional protein sequencing, using peptide fragments obtained by several enzymatic cleavages of the performic acid-oxidized protein. The oxidized protein was first cleaved by trypsin and the resulting peptides were purified and their amino acid sequences were determined. These tryptic peptides were aligned with the aid of overlapping peptides isolated from a chymotryptic digest of the oxidized protein. The amino acid sequence thus deduced was further confirmed by isolation and analysis of peptides obtained by digestion of the oxidized protein with lysyl endopeptidase. The location of the disulfide bonds was deduced by isolation and analysis of cystine-containing peptides from a chymotryptic digest of heat-denatured RNase U1. These results showed that the protein is composed of a single polypeptide chain of 105 amino acid residues cross-linked by two disulfide bonds, having a molecular weight of 11,235, and that the NH2-terminus is blocked by a pyroglutamate residue. It has an overall homology with other guanine-specific or related ribonucleases, and shows 48% identity with RNase T1 and 38% identity with RNase U2.
In the course of our histological studies on the testes of idiopathically infertile men, we found an increased number of mast cells in the limiting membrane of the seminiferous tubule. In 16 patients with idiopathic infertility, quantification of mast cells within the limiting membrane of the seminiferous tubule was performed. There apparently was a tendency to increased numbers of mast cells in the seminiferous tubule wall with decreased sperm count and an average Johnsen score for each tubule. These findings suggest that quantification of mast cells in the seminiferous tubule wall may be a useful marker in the histopathological evaluation of testis biopsies in patients with idiopathic infertility.
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Testicular biopsy was performed on 51 patients with idiopathic male infertility and 13 normal fertile adults. The biopsied specimens were examined by light and electron microscopy. A quantitative evaluation of Leydig cell number was made by determining the mean number of Leydig cells per one cross section of seminiferous tubule in the entire histologic section of each specimen, which was defined as "Leydig cell index". In both oligospermic and azoospermic groups, the Leydig cell index was significantly elevated as compared with in that the normal group, which indicated the presence of Leydig cell hyperplasia in the infertile testis. In addition, this index significantly correlated with serum luteinizing hormone and follicle stimulating hormone levels but not with serum testosterone level. Leydig cells were classified into three types based upon their morphological characteristics. Type I Leydig cells were functionally active and mature ones, with a smooth-surfaced round or oval nucleus, had abundant smooth endoplasmic reticulum (SER), characteristic mitochondria and relatively few lysosomes. Type II Leydig cells were functionally less active, and contained an irregularly shaped nucleus, less abundant SER, mitochondria with undeveloped cristae and relatively few lysosomes. Type III Leydig cells included immature and regressive cells, which were considered to have almost no hormone secreting function. The immature Leydig cells were spindle-shaped and had few cell organelles. The regressive cells had poorly developed SER and many secondary lysosomes in the cytoplasm. In the normal group, type I Leydig cells are the most numerous but in the infertile groups type II Leydig cells are the most numerous. However, in the latter, there is no significant difference in relative number of each Leydig cell type among the groups classified according to the number of sperm or Leydig cell. In summary, Leydig cell hyperplasia observed in the testis of the infertile patients was supposed to be induced by the elevation of the serum LH. Despite of the significant increase in Leydig cell number, the serum testosterone was not elevated, and this was considered to be due to the fact that the hyperplastic cells are mainly composed of functionally less active type II Leydig cells. In addition, especially in the severe hyperplastic group, not only type II but also type I Leydig cells increased in number. However, in this group, the serum testosterone level was not elevated. Therefore, the function of type I Leydig cells was suggested to be impaired.
Cervical spondylotic myelopathy among older individuals was investigated radiographically in 42 patients over age 60 years, and compared with those of younger patients. The cervical spine in the aged patients displayed dynamic canal stenosis in addition to static canal stenosis based on the aging process. Myelography and computed tomography-myelography showed multisegmental lesions (average: 3.0 lesions), that contributed to the various clinical features of myelopathy. The upper disc levels of C3-4 and C4-5 had a tendency to be involved in the aged patients, and the spinal cords were extensively compressed as compared with the younger patients. Disc protrusion, posterior osteophyte, and retrolisthesis, in addition to ligamentous entrapments were the primary etiologic factors of myelopathy. Morphologically, the high prevalence of cord atrophy was seen on computed tomography-myelography in the aged patients. This indicated severe pathologic changes in the cervical spinal cord, and its prognosis was considered to be poor.
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A series of 141 patients with thymoma was studied with regard to the way in which complete resection followed by postoperative radiation therapy influenced prognosis according to the stage and histologic type of thymoma. Postoperative radiation therapy (30 Gy in 3 weeks to 50 Gy in 6 weeks) was performed in 73.1% of the patients. Thirty-five of 48 patients with thymoma invading the surrounding tissues (stage III) underwent complete resection, with survival rates of 100% at 5 years and 94.7% at 10 and 15 years. The prognosis in these patients was comparable with those in 45 patients with no invasion (stage I) and in 33 patients with capsular invasion (stage III), all of whom underwent complete resection. Complete resection was done in 18 of 26 patients with epithelial cell thymoma, and there were no deaths by tumor until 15 years after the operation. There were no statistically significant differences in the survival rates of patients undergoing complete resection according to cell type (33 of 36 patients with lymphocyte predominant type and 61 of 77 patients with mixed cell type). The survival rate in six patients with epithelial cell type who underwent subtotal resection was not significantly different from that of 12 patients who underwent biopsy alone. Our findings indicate that complete resection of thymoma followed by postoperative radiation therapy results in a "benign" postoperative course, regardless of the stage and histologic type. Therefore, an aggressive surgical approach, such as resection of the superior vena caval system followed by reconstruction with a ringed polytetrafluoroethylene graft and/or complete pleuropneumonectomy, is justified for advanced thymoma, although the long-term results of such extended operations are still unclear.
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The complete nucleotide sequence of apple scar skin viroid(ASSV) has been established, and a probable secondary structure is proposed. A single-stranded circular ASSV RNA consists of 330 nucleotides and can assume the rodlike conformation with extensive base-pairing characteristic of all the known viroids. ASSV shows low sequence homologies with other viroids and lacks the central conserved region. These indicate that ASSV should be allocated to a separate viroid group. However, homologous sequences with potato spindle tuber viroid(PSTV) in ASSV occur in limited and scattered regions of both viroids. These homologous regions fall within the particular domains in the viroid domain model which has been previously proposed by Keese and Symons(Proc. Natl. Acad. Sci. USA. 82, 4582-4586, 1985).
The prognosis of patients with stage III nonsmall cell lung cancer was studied, with special attention to their biologic status prior to lung resection. The biologic status was estimated from the neutrophil/lymphocyte ratio in the peripheral blood, serum albumin level, and erythrocyte sedimentation rate. Among 46 patients who underwent potentially curative operations, 31 cases of biologic status A or B (more than two parameters normal) revealed 37.6% of a 5-year survival rate, whereas there was no 5-year survivor in 15 cases of biologic status C or D (more than two parameters abnormal). Of the 5-year survival rate in T3N0 disease of biologic status A or B, the 60% surviving (of 10 cases) was in marked contrast to the same stage disease of biologic status C or D where only 1 patient (of 10 cases) was still surviving at more than 30 months. In 30 patients with T3N0, T3N1, and T2N2 diseases of biologic status A or B, where long-term survivors were derived, the 5-year survival rate in 30 patients of biologic status A or B was 36.6% in contrast to no long-term survivor in the same stage diseases of biologic status C or D (n = 25). We conclude that surgical results in stage III nonsmall cell lung cancer will be beneficial in patients of biologic status A or B, but nonbeneficial in patients with the same stage of biologic status C or D.
In an attempt to ascertain whether prostaglandins alter the in vitro contractile activity of the human seminiferous tubule, the effects of prostaglandins on the isolated human seminiferous tubule were examined by recording the intratubular pressure with a servonull pressure with a servonull pressure measuring device. We describe here the first response of the human seminiferous tubule to prostaglandins. Prostaglandin F2 alpha (10(-9) M to 10(-6) M) produced contractions of the seminiferous tubules in a dose-dependent manner. In contrast, prostaglandins F1 alpha (10(-8) M to 10(-6) M), E1 (10(-9) M to 10(-6) M) and E2 (10(-8) M to 10(-6) M) produced relaxations of the seminiferous tubules which were dose dependent. The results from these experiments suggest that prostaglandins modulate the in vitro contractility of the human seminiferous tubules and thus may regulate the transport of spermatozoa and tubular fluid to the rete testis.
Although the existence of the seminiferous tubule contractions attributed to myoid cells is established, the control of the contractions is poorly understood. Recently, we have suggested the possible neural control mechanism for contractility of the human seminiferous tubule. In an effort to identify the nerve supply to the myoid cells in the human seminiferous tubules, we studied the paraffin sections of biopsied testicular specimens using a protein silver impregnation technique (Bodian's method). Here we demonstrate evidence for the presence of nerve fibers close to the myoid cells. It is highly suggested that contraction of the human seminiferous tubule may play an important role in the transport of spermatozoa, and neurohumoral regulatory mechanism may partly exist in this connection.
Scanning electron microscopic observation of the basal surface of the basement membrane of the rat seminiferous tubule has revealed that the basement membrane appears to be like a tiled floor, and formation of meshwork structure of collagen fibrils is evident in some exfoliated areas of basement membrane. This meshwork structure is considered to ensure fluid regulation from the intertubular medium toward the lumen of the seminiferous tubules.