Healing of Fournier's gangrene of the scrotum in a haemodialysis patient after conservative therapy alone.
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Biomedical subjects
Publications and source records attributed to M Noguchi.
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Mating-type (MAT) loci were cloned from two asexual (mitosporic) phytopathogenic ascomycetes, Fusarium oxysporum (a pyrenomycete) and Alternaria alternata (a loculoascomycete), by a polymerase chain reaction (PCR)-based strategy. The conserved high mobility group (HMG) box domain found in the MAT1-2-1 protein was used as a starting point for cloning and sequencing the entire MAT1-2 idiomorph plus flanking regions. Primer pairs designed to both flanking regions were used to amplify the opposite MAT1-1 idiomorph. The MAT1-1 and MAT1-2 idiomorphs were approximately 4.6 and 3.8 kb in F. oxysporum and approximately 1.9 and 2.2 kb in A. alternata, respectively. In both species, the MAT1-1 idiomorph contains at least one gene that encodes a protein with a putative alpha box domain and the MAT1-2 idiomorph contains one gene that encodes a protein with a putative HMG box domain. MAT-specific primers were used to assess the mating type of F. oxysporum and A. alternata field isolates by PCR. MAT genes from A. alternata were expressed. The A. alternata genes were confirmed to be functional in a close sexual relative, Cochliobolus heterostrophus, by heterologous expression.
Clonal expansion of the germinal center B cells of human reactive lymph nodes was analyzed. By micromanipulation, 28 germinal centers were microdissected from three nonneoplastic lymph nodes that had been fixed with formalin. Immunoglobulin heavy chain variable (V) region gene rearrangement was examined by seminested polymerase chain reaction (PCR) using two sets of primers (FR2-J and FR3A-J). An oligoclonal development (one to five clones) was found in each germinal center. Depending on the primer used, four or five (16%) of the germinal centers showed a single rearrangement band. The average number of B-cell clones in each germinal center was approximately 2.5. Next, the authors analyzed 50 endoscopic biopsy specimens from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric lymphoma, 25 patients with chronic gastritis, and 19 patients with nonspecific colitis. In addition to the samples from the 6 patients with malignant lymphoma, 8 of 44 biopsy samples (18.2%) from patients diagnosed as having chronic gastritis or nonspecific colitis showed one or two amplified bands. These results indicate that PCR analysis of immunoglobulin heavy chain V region gene rearrangement in small biopsy specimens could be misleading, causing overdiagnosis of reactive lymphoid tissue as B-cell clonal proliferation.
OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.
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The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.
The molecular behavior of water in normal and regenerating tendons was analyzed using the transverse relaxation time (T(2)) measured by spin-echo proton nuclear magnetic resonance ((1)H-NMR) spectroscopy at 2.34 T (25 degrees C). A section of the Achilles tendon was dissected from an anesthetized Japanese white rabbit, and its longitudinal axis was oriented at 0, 35, 54.7, 75, and 90 degrees to the static magnetic field. In the normal tendon, the T(2) relaxation of water presented biexponential relaxation and anisotropy in both the long T(2) (5.41 to 6.21 ms) and short T(2) (0.41 to 1.43 ms) components, in which the greatest values were obtained at 54.7 degrees. However, the range of the anisotropy was much narrower than we expected from the (1)H dipolar interaction of water bound to the collagen fibers in the tendon. The apparent fractions of water proton density also varied with orientation: the fraction of the longer T(2) components was at its maximum at 54.7 degrees. These results suggest that a simple two-compartment model could not be applicable to orientational dependency of the T(2) value of the tendon, and the well ordered water in the short T(2) relaxation component may show an elongated T(2) relaxation time that falls in the range of the long T(2) relaxation component at 54.7 degrees. This hypothesis can explain both the narrower range of the T(2) relaxation time and the orientational dependency on the apparent fraction of (1)H density. Regenerating processes of the Achilles tendon were followed for 18 weeks by analyzing the T(2) relaxation time. There is only a long T(2) relaxation time component (21.8 to 28.0 ms) up to 3 weeks after transection. Biexponential relaxation is revealed at 6 weeks and thereafter, whereby (i) the T(2) relaxation times become shorter, (ii) there is anisotropy in the short and long T(2) values, and (iii) the orientational dependency of the apparent fraction of water proton density becomes evident with maturation of the regenerating tendon. From these results, the (1)H T(2) relaxation time of water might be used to monitor the healing process of collagen structures of the tendon non-invasively.
We report a case of left ventricular rupture and left ventricular-right atrial communication after mitral valve re-replacement. A 53-year-old man was admitted to our hospital for a primary tissue failure of mitral xenograft. On June 4, 1997, he underwent mitral valve re-replacement. At 12 post operative day, he was suffered from unexpected dyspnea. The transesophageal echocardiography showed floated mitral valve and left ventricular-right atrial communication. The emergent operation was done. At the operation, posterior mitral annulus was disrupted and the disruption reached to a membranous septum. A communication was directly closed, mitral annulus was repaired with perigard and one size smaller mitral valve was implanted. The patient was discharged and returned to social life.
A 31-year-old man had received corticosteroids for 20 months for treatment of a brain tumor, and his blood eosinophil count ranged from 100/microliter to 1,000/microliter. On June 24th, 1998, he was re-admitted because of dyspnea secondary to left massive pleural effusion. Peripheral blood examination revealed an eosinophil count of 48,000/microliter. The eosinophils were hypersegmented, with abnormal distribution of eosinophilic granules and formation of cytoplasmic vacuoles. Blasts and basophils were not increased, hemoglobin was 13.4 g/dl, and the platelet count was 79,000/microliter. Bone marrow was slightly hypercellular with 55% eosinophils and 0.2% blasts. The patient's karyotype was normal, and Wilms' tumor gene was not detected. Serum IgE was normal and serum vitamin B12 and soluble IL-2 receptor were elevated. Serum levels of eosinophilopoietic cytokines, IL-3, IL-5, and GM-CSF, were low. Specimens of pleural fluid contained many eosinophils. Because the eosinophil count increased to 110,000/microliter on July 2nd, hydroxyurea was started without effect. On July 16th, the eosinophil count reached 167,000/microliter, and vincristine was added. The eosinophil count rose to 253,000/microliter the next day, and cytarabine and daunorubicin were administered, but the patient died of septic shock. Although the clinical course suggested eosinophilic leukemia, monoclonal proliferation of eosinophils was not demonstrated. To our knowledge, this is the highest peripheral blood eosinophil count reported in the literature to date.
PURPOSE: To improve our understanding of transition zone cancer in terms of the diagnosis and biological behavior we examined all morphological and clinical variables in 148 consecutive cases of untreated transition zone cancer after radical retropubic prostatectomy. We matched 79 cases by total cancer volume to 79 of pure peripheral zone cancer with no secondary tumors. MATERIALS AND METHODS: Using the Stanford technique of prospective 3 mm. step sections we identified 175 of 996 men (18%) with untreated transition zone cancer after radical retropubic prostatectomy who had the largest cancer volume in the transition zone. We excluded 27 patients from study due to previous transurethral prostatic resection or incomplete data. Preoperative serum prostate specific antigen (PSA) was determined by the Tosoh AIA-600 PSA assay. Postoperatively a PSA of 0.07 ng./ml. and increasing represented biochemical failure when the assay was done in the ultrasensitive mode. RESULTS: Of the 148 cases of transition zone cancer 80% had organ confined disease, 70% stage T1c impalpable disease, 63% a positive initial prostatic biopsy, 62% unilateral cancer in the transition zone, 52% a secondary tumor only in the peripheral zone, 61% serum PSA 10 ng./ml. or greater preoperatively, 36% cancer volume greater than 6 cc and 24% at least 50% Gleason grade 4/5 cancer. Only 20% of the tumors were located in the proximal third of the transition zone near the bladder. The number of secondary tumors in the transition zone ranged from 1 to 12 (median 3) and secondary tumor volume ranged from 0.01 to 4.8 cc (median 0.6). Mean distance plus or minus standard deviation from the posterior prostatic capsule to the posterior border of the transition zone cancer was 12. 0 +/- 7.6 mm. (median 12.3). While only 15% of patients had capsular penetration, 29% had anterior positive surgical margins, 2.7% seminal vesicle invasion and 3.4% lymph node metastasis. When 79 transition zone cancers were matched by volume with 79 peripheral zone cancers, there were no differences in percent Gleason grade 4/5, serum PSA or prostate weight, although differences in clinical stage T1c to T2c and organ confined cancer were highly significant (p <0.0001). Kaplan-Meier curves showed that at 5 years of followup 49.2% of the men with peripheral zone cancer had undetectable PSA compared with 71.5% of those with transition zone cancer (log rank test p = 0.0002). CONCLUSIONS: Our report should make it easier to diagnose transition zone cancer. The 72% biochemical PSA cure rate is significantly higher than the 49% cure rate for peripheral zone cancer. Since cancer volume and percent Gleason grade 4/5 disease were the same in these 2 groups matched by cancer volume, the differences in behavior of peripheral and transition zone cancers must be sought at the molecular level unless anatomical location alone explains the differences in progression. Pathologists should differentiate transition from peripheral zone cancer when analyzing radical prostatectomy specimens.
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Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. A combination of dye- and gamma probe-guided methods can identify SLN more accurately and easily than either of these techniques alone. On the other hand, SLN biopsy is highly accurate and sensitive in patients with small tumors, and no false-negative SLN biopsy has been reported for a breast cancer < 1.0-1.5 cm. Moreover, extensive intraoperative examination of SLNs using frozen sections can attain a sensitivity comparable to that obtained by histologic examination on the permanent sections. In practice, therefore, axillary dissection can be avoided in patients with small tumors in whom the SLNs are negative.
We ranked prognostic factors to retrospectively evaluate the clinical significance of interferon alpha (IFN-alpha) therapy in patients with Robson stage IVB renal cell carcinoma. A total of 44 Robson stage IVB renal cancer patients were divided into 2 groups, one with more than 6 months administration of IFN-alpha (3-7 times a week: group A) and another without any IFN-alpha administration. The distribution of these 2 groups was not randomized. In addition to IFN-alpha therapy, survival was analyzed with respect to performance status (PS), mass reductive nephrectomy, concomitant use of other cytotoxic therapies, the number of metastatic organs, growth type, site of metastasis and the period of diagnosis, using a multivariate method with Cox proportional hazards regression. The multivariate analysis showed administration of IFN-alpha to be the most significant factor influencing a good prognosis. Improved survival was also significantly correlated with slow growing type and good PS. Among group A, a significant favorable prognosis was obtained in patients with the responses of no change (NC), partial response (PR) and complete remission (CR) 6 months after initiating administration of IFN-alpha, as well as with good PS and a slow growing type carcinoma. We conclude that IFN-alpha therapy might improve the prognosis of patients with Robson stage IVB renal cell carcinoma, especially, in cases when a greater than NC response is obtained after 6 months administration of IFN-alpha.
In May, 1998, a 63-year-old woman was admitted for treatment of relapsed malignant lymphoma. In March 1997, a diagnosis of diffuse large B-cell lymphoma(DLBL), clinical stage IIISE A, was made from a biopsy specimen of the tumor in the left buccal mucosa. Six cycles of CHOP regimen were given, and complete remission was achieved. However, relapse of the lymphoma was suspected, and the patient was transferred to our hospital. On admission, a right tosillar mass, 8 mm in diameter, was found, and a biopsy showed DLBL. The immunophenotype of the lymphoma cells was CD3- CD4- CD5- CD8+ CD10- CD19+ CD20+ CD23- CD25+ IgL (lambda)+, and dual staining confirmed that the cells were CD8+ and CD19+. The patient was an HTLV-1 carrier, but monoclonal integration of HTLV-1 proviral DNA into the lymphoma cells was not detected. She was diagnosed as having CD8+ DLBL, clinical stage IA. Because she responded to salvage chemotherapy, autologous peripheral blood stem cell transplantation was performed and complete remission was obtained. To our knowledge, this is the first report of CD8+ DLBL.
PURPOSE: We compared pathological findings with prostate specific antigen (PSA) failure rates following radical prostatectomy for large volume cancers (6 cc or greater). MATERIALS AND METHODS: A total of 191 men whose radical prostatectomy specimen had a cancer volume of 6 cc or greater were followed for a mean of 3.6 years (range 0.3 to 11.1) and 112 (58.6%) had PSA failure (PSA 0.07 ng./ml. or greater and increasing). Percent Gleason grade 4/5 (the Stanford modified Gleason scale), cancer volume, seminal vesicle invasion, regional lymph nodes, capsular penetration, positive surgical margin, location of the largest cancer in the peripheral or transition zone, prostate weight, patient age, preoperative PSA and clinical stage were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: In univariate regression analysis percent Gleason grade 4/5, lymph node involvement, cancer volume, cancer location in the peripheral zone, capsular penetration and positive surgical margins were significant predictors of biochemical failure. Seminal vesicle invasion, preoperative serum PSA, patient age, prostate weight and clinical stage were not statistically significant. Forward stepwise, multivariate analysis showed that percent Gleason grade 4/5 (p <0.0001, relative risk ratio 2.498), cancer location in the peripheral zone (p = 0.0097, 1.887), cancer volume (p = 0.0157, 1.691) and lymph node involvement (p = 0.0317, 1. 666) were the only independent predictors of biochemical failure. When 52 men with organ confined, large volume prostate cancer were analyzed separately, univariate and multivariate analyses showed that only cancer location in the peripheral zone (p = 0.0021, relative risk ratio 13.473) and percent Gleason grade 4/5 (p = 0. 0449, 4.111) were independent predictors of failure. CONCLUSIONS: Percent Gleason grade 4/5, cancer location in the peripheral zone, cancer volume and lymph node involvement have prognostic value in large volume prostate cancer. Cancer location in the peripheral zone and percent Gleason grade 4/5 are the most powerful predictors of biochemical failure in men whose cancer is 6 cc or greater and contained in the prostatic capsule. Preoperative serum PSA is not helpful in distinguishing biochemical failure rates in these large volume cancers whether they are organ confined or not.
In October 1998, a 37-year-old man was admitted because of petechiae and thrombocytopenia following flu-like symptoms. On admission, there were numerous petechiae on the back and extremities. The WBC count was 3,700/microliter with 3% atypical lymphocytes, the lymphocyte CD4/CD8 ratio 0.37, and the platelet count 1,000/microliter. Mild splenomegaly was detected by CT. Results of blood chemistry and coagulation tests were normal. A bone marrow aspirate was normocellular with no signs of dysplasia, and the megakaryocyte count was normal. The patient was initially diagnosed as having virus infection-associated thrombocytopenia. Steroid therapy was started immediately, and the platelet count rose to 15 x 10(4)/microliter on day 21. The PA-IgG level was 652 ng/10(7) platelets. Mild liver dysfunction developed, and atypical lymphocytes increased in number thereafter. Because IgM anti-cytomegalovirus (CMV) antibody (Ab) was positive and IgG CMV Ab was negative, a diagnosis of CMV mononucleosis was made. Gancyclovir was therefore started. Four months later, steroid therapy was discontinued, and partial remission has since been maintained. In healthy individuals, CMV infection is usually latent, and the development of mononucleosis is rare. So far, 11 cases of CMV-induced mononucleosis associated with severe thrombocytopenia have been reported in immunocompetent adults.
To investigate the potential role of the PTEN tumor-suppressor gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations of the PTEN gene, using a laser-assisted microdissection method. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%) and 13 of 23 solitary endometrial cysts (56.5%). Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%) and 7 of 34 solitary endometrial cysts (20.6%). In 5 endometrioid carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In 7 clear cell carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In no cases there were LOH events in the endometriosis only. These results indicate that inactivation of the PTEN gene is an early event in the development of both endometrioid and clear cell carcinoma of the ovary. A laser-assisted microdissection method enables us to collect target cells without contamination by non-tumor cells. We expect that this technique will be very useful for investigating genetic alterations in cancerous or precancerous lesions. Early genetic alterations in various precancerous cells detected by light microscopy can be readily identified by the tissue-microdissection method.
The p16 (CDKN2/MTS-1/INK4A) tumor-suppressor gene is frequently inactivated by DNA methylation in lung carcinomas. To clarify whether background anthracosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16-promoter region by methylation-specific polymerase chain reaction, and p16 expression immunohistochemically, and compared the results with the level of background anthracosis which was measured by an original quantitative method. At autopsy, DNA methylation of the p16 gene was observed in 6/19 tumors (32%) from patients who had died of pulmonary adenocarcinoma. The degree of background anthracosis (the effect of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16-gene methylation was significantly higher than that without methylation (mean A value = 0.298). p16 expression was inactivated in all tumors with p16-gene methylation. The mean A value of black dust matter deposition in cases with normal expression of p16 (A = 0.151) was significantly lower than cases with abnormal expression of p16 (A = 0.531). These results indicate that the level of background anthracosis is closely associated with inactivation of p16 expression and also DNA methylation of the p16-gene promoter region in pulmonary adenocarcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:609-613, 1999.