Biomedical subjects
Publications and source records attributed to Y Minami.
We report a case of transitional cell carcinoma of the ureter and bladder that produced carbohydrate antigen 19-9 and carcinoembryonic antigen. The serum levels of these antigens were elevated in this patient and an immunohistochemical examination revealed that the carcinoma cells stained positively for both antigens.
To determine whether the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) immunoreactivities in prostatic carcinoma are reliable prognostic factors, the PSA and PAP immunohistochemical distribution was examined in needle biopsy specimens of 80 patients with advanced prostatic carcinoma. Our results indicated a higher cancer-specific survival rate in patients with a greater PSA or PAP immunostaining. Furthermore, a multivariate analysis of possible prognostic factors, that is patient age, clinical stage, Gleason score, serum PAP, PSA and PAP immunostaining scores, and the initial treatment, has confirmed that the difference in PAP immunoreactivity is the most important prognostic factor (p < 0.01) for advanced prostatic carcinoma, with the Gleason score (p = 0.06), clinical stage (p = 0.09) and PSA immunoreactivity (p = 0.48) being the second, third and fifth prognostic factors, respectively.
It is well known that IL-2 stimulates natural killer (NK) cells to express lymphokine activated killer (LAK) activity and that this stimulation prompts the acquisition of the ability to lyse previously insensitive target cells. The possible role of adhesion molecules in the IL-2 activation process was probed by focussing on a lymphocyte function-associated antigen (LFA)-1-dependent model system. A mAb to the LFA-1 beta chain abrogated LAK activity, but only moderately suppressed NK activity, suggesting a differential role for LFA-1 beta in LAK compared with NK mediated lysis. Orthophosphate labeling demonstrated that the LFA-1 beta chain was strongly phosphorylated in LAK but not NK cells; in contrast, the alpha chain was phosphorylated similarly in both effector cell types. At least a portion of the phosphorylation of the beta chain was on tyrosine residues, as shown by Western blotting with anti-phosphotyrosine antibody of LFA-1 beta immunoprecipitates. Crosslinking of the LFA-1 beta chain with plastic-adhered antibody stimulated Ca(2+)-dependent release of cytoplasmic lytic granules and induced phosphatidyl inositol turnover in LAK but not NK cells. We conclude that the IL-2-induced phosphorylation of the beta chain of the LFA-1 adhesion molecule in LAK cells and associated alteration in signal transduction may be important in the stimulation of LAK cell activity in NK cells.
Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific receptor following T lymphocyte activation. The receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2-induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF-B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src-family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface receptor to the nuclear events.
Some follicle cells organize thyroid follicles through proliferation of single cells in collagen gel culture. The aim of this study was to clarify whether two or more (plural) cells can form follicles through aggregation and linkage in this culture system. To address this question, we performed collagen gel culture of porcine follicle cells, using cell labeling with PKH 2 dye. A mixture of dye-labeled and nonlabeled cells was cultured in collagen gel. Organized follicles consisted of both dyed and nondyed cells. This suggested that plural cells reconstructed follicles through aggregation and linkage. To further confirm this finding, cells embedded in collagen gel were cultured in inhibition of cell proliferation with 2 micrograms/ml aphidicolin. Forty to 60 percent of the cells formed follicles, which did not grow larger. Electron microscopy showed that intracytoplasmic cavities appeared in the cells. In contrast, 20-30% of the embedded cells developed into cavity-embracing single cells, which remained signet rings. These results indicate that follicle cells organize follicles in collagen gel culture by two means: through cell division of cavity-embracing single cells and through aggregation and linkage of plural cells.
1-beta-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined. The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-beta-allylated compounds (2a-c). The regiochemistry and the beta-stereochemistry of the 1-allyl group were confirmed by comparison of the 13C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-beta-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b. None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-beta-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-beta-(2,3-Dihydroxypropyl) compounds (5 and 8) and 1-beta-(2,3-diacetoxypropyl) compounds (6 and 7) showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.
The complete amino acid sequence of momordin-a, a ribosome-inactivating protein from the seeds of bitter gourd, has been analyzed. Twenty-two peptides were isolated from the tryptic digest of momordin-a and sequenced by the DABITC/PITC double coupling method. The alignment of these tryptic peptides was done by analyzing the amino acid sequences of the peptides derived from chymotryptic digestion and cyanogen bromide cleavage of momordin-a as well as V8 protease-digestion of the CNBr fragment. Momordin-a consisted of 250 amino acid residues and carbohydrate residues attached to Asn227, and its molecular mass was calculated to be 28,690 Da. The sequence comparison with ricin A-chain shows that 33% of the residues of momordin-a are identical to those of ricin A-chain and that the residues involved in the catalytic site of the ricin A-chain are conserved in momordin-a.
To investigate risk factors of systemic lupus erythematosus (SLE) in relation to diet and reproduction, a population-based case-control study was conducted during the period from October 1988 to October 1989 in Miyagi Prefecture in northeastern Japan. Included in the study were 52 female patients with the recent SLE onset. Two sex- and birth year-matched (+/- 2 years) controls for each patient were selected from the general population. The analysis on diet showed that the frequent intake of meat was associated with an increased risk (frequent vs. rare, relative risk (RR) 3.36; 95% confidence interval (CI) 1.10-10.24) and that the patients preferred fatty meat such as beef or pork. The analysis on menstrual history revealed that menstrual irregularity was also associated with an increased risk (RR 3.79; 95% CI 1.43-10.01). These results suggest that dietary and reproductive factors may be responsible for the onset and the progression of SLE.
PURPOSE: To report on an in vitro reconstruction of cornea composed of three main layers. METHODS: These layers were reconstructed from isolated bovine corneal cells in three-dimensional collagen gel culture conditions. RESULTS: The topmost layer, corneal epithelial cells on collagen gel, was treated by what was designated as the "air-liquid interface method," a method developed specifically for this study. The treatment induced proliferation and differentiation of this layer. Those epithelial cells were positively immunostained with anti-epithelial keratin (55-kD/64-kD) antibody, AE5, which was specific for in vivo corneal epithelial cells. The middle layer consisted of keratocytes in the three-dimensional collagen gel matrix. This layer was comparable to the stroma in vivo. The underlayer, the counterpart of in vivo endothelial layer, was composed of corneal endothelial cells. CONCLUSIONS: This culture system probably provides a physiologic environment for detailed investigations of corneal cells.
Two cases of adrenal ganglioneuroma discovered as "incidentaloma" are presented Case 1 was in a 29-year-old female who had a right adrenal tumor incidentally found by abdominal ultrasonography. The tumor was 26 g and 5.1 x 3.6 x 3.0 cm in size. She underwent surgical exploration and histopathologic examination revealed adrenal ganglioneuroma. Case 2 was in a 75-year-old man who had a right adrenal tumor detected during examination of microhematuria due to right renal stone by abdominal computed tomography. The tumor was 51 g in weight and 5.3 x 5.0 x 5.2 cm in size. He underwent right adrenalectomy and histopathologic examination showed adrenal ganglioneuroma. Both patients had no abnormal endocrinological findings and the DNA histogram showed a diploid pattern.
Two cases of nonpenetrating traumatic tricuspid regurgitation were reported. The first case, a 46-year-old man who had an episode of traffic accident 21 years ago, was admitted with complaints of peripheral edema and dyspnea on exertion. The second case was a 16-year-old man who noted to have cardiac murmur and cardiomegaly after 4 years of a traffic accident. In both cases, cardiac catheterization showed increased right atrial pressure with high v wave, and echocardiogram showed severe tricuspid regurgitation with ruptured chordae tendineae of the anterior leaflet. Tricuspid valve replacement was performed successfully in both the cases. Twenty-two operated cases of traumatic tricuspid regurgitation have been reported in Japan; 17 of ruptured chordae tendineae, 3 of ruptured papillary muscle, and 2 of primary laceration of anterior leaflet. The patients with ruptured papillary muscle were operated from 2 months to 7 years (average 4 years) after trauma, while those with ruptured chordae tendineae were operated from 5 months to 25 years (average 10 years) after trauma. Tricuspid valve replacement was performed in 17 of 22 cases. From the review of 22 cases, tricuspid valve replacement should be indicated for traumatic tricuspid regurgitation in consideration of the severity of valve destruction regardless of the interval after trauma.
We report a 50 year old male patient with an amphetamine psychosis who had anesthesia for a pneumonectomy. The patient had been intoxicated with methylamphetamine since 1976. After drug abuse for 2 years, he suffered from hallucination and delusion. He was diagnosed to have amphetamine psychosis by psychiatrists and treated with major tranquilizers. During the treatment for the psychosis, a squamous cell carcinoma in the lung was found. Pneumonectomy was scheduled. Anesthesia was induced with thiopental 300 mg and maintained with isoflurane, nitrous oxide, oxygen and epidural lidocaine. In the recovery room, he was injected with a major tranquilizer. Epidural buprenorphine was used to lighten the pain stress. Psychotic state did not appear after the surgery. We also discuss amphetamine psychosis in Japan.
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Interleukin 2 (IL-2) can stimulate the proliferation of various kinds of T-cell lines. The receptor for IL-2 is composed of at least two subunits (alpha and beta), of which beta subunit plays the major role in transducing growth signals into the cells. A nonreceptor-type tyrosine kinase, Lck, is associated with IL-2 receptor beta subunit, and the binding of IL-2 to its receptor induces the activation of Lck. On the other hand, it has been shown that stimulation of T-cells with IL-2 causes rapid activation of Ras protein. In this paper, we describe that both of the two regions in IL-2 receptor beta subunit, the indispensable region for the induction of cell growth (serine-rich region) and the binding region of Lck protein (acidic region), are required for the activation of Ras. These two regions are also required for tyrosine phosphorylation of an 85-kDa cellular protein (p85) and the accumulation of fos and jun mRNAs. This observation suggests also that the activation of a receptor-associated tyrosine kinase in response to IL-2-stimulation is primarily responsible for subsequent activation of the pathway through Ras to Fos and Jun.
Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer-specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation.
Cross-linking of the human homologue of the murine MEL-14 lymph node homing receptor (Selectin-1, LECAM-1, Leu 8) on both T and B cells results in modification of cell function. To investigate this phenomenon, we performed studies to determine if the Leu 8 molecule influences T cell activation via the TCR/CD3 complex. In initial studies, we treated T cells with immobilized anti-CD3 (OKT3 mAb) in the presence or absence of immobilized Leu 8 mAb. We found that although Leu 8 mAb alone had no effect on T cell proliferation, this antibody markedly augmented immobilized OKT3 mAb-induced proliferation. In further studies, we immunoprecipitated surface radioiodinated T cell lysates with OKT3 and Leu 8 mAb to determine if molecules in the TCR/CD3 complex associate with Leu 8 molecules. Although Leu 8 mAb immunoprecipitated only a single protein of approximately 80 kDa from T cell lysates treated with Nonidet P-40 under reducing condition, it coimmunoprecipitated additional proteins of 48, 42, 28, 24, and 22 kDa from T cell lysates treated with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate. These additional proteins were identified as the alpha-, beta-, gamma-, delta-, and epsilon-chains of the TCR/CD3 complex by one-dimensional and two-dimensional diagonal SDS-PAGE. Densitometric scanning showed that, on average, 18% of the TCR/CD3 complex associates with Leu 8. In a final study, we showed by immunoblotting analysis using anti-zeta peptide antibody that Leu 8 mAb coimmunoprecipitates the zeta-chain of CD3. These results indicate that the human lymph node homing receptor homologue (Leu 8) participates in the activation of T cells, probably via its association with the TCR/CD3 complex.
The prognosis of U.S.A. patients with prostate cancer based on reports from the American College of Surgeons and Roswell Park Cancer Institute was compared with that of Japanese in Nagasaki and Gunma. There was more than a 10% difference in survival rate between the two countries. Several clinical parameters were analyzed to determine the basis for this difference. In general, stage distribution, metastatic sites, bone pain and alkaline phosphatase in the USA patients with Stage D disease were more severe than in the Japanese patients. Moreover the prostate cancer death rate in the USA was higher than that in Japan. However, only the distribution of pathological grade in the USA was better than that in Japan. From these results, it is difficult to conclude that prostate cancer in the USA is more aggressive than in Japan. The possibility of selection bias in these studies is discussed.
A 38-year-old male was admitted due to severe chest pain. Echocardiography and CT revealed an acute dissecting aneurysm. Cabrol's operation was performed immediately in order to prevent a rupture of the ascending aortic aneurysm and the dissection extending to the heart. Intraoperative trans-esophageal echocardiography was useful to get detailed informations, such as an extent of the dissection and a site of the entry. He was discharged from hospital on 53rd day and returned to society.