Injection-site granulomas resulting from the administration of both leuprorelin acetate and goserelin acetate for the treatment of prostatic cancer.

Although injection-site granulomas caused by leuprorelin acetate have been reported, there have been no reports of granulomas caused by both leuprorelin acetate and goserelin acetate. An 81-year-old man presented with subcutaneous nodules of the abdominal wall and upper arm, where 11.25 mg of leuprorelin acetate had been injected for the treatment of prostate cancer. Because of these nodules, treatment was changed to goserelin acetate. Nevertheless, he presented with another subcutaneous nodule at the injection site. Histological examination showed that these nodules consisted of numerous giant cells that were CD3-positive T lymphocytes and CD68-positive histiocytes associated with granulomatous changes. The granulomas had likely been caused by delayed-type hypersensitivity to leuprorelin acetate injection. The granuloma that formed after goserelin acetate injection might thus have developed owing to the immunogenicity of the previous leuprorelin acetate injections. The patient underwent surgical castration. The present case suggests that both leuprorelin acetate and goserelin acetate can cause injection-site disorders.     

Identification of p46 Shc expressed in the nuclei of hepatocytes with high proliferating activity: Study of regenerating rat liver

The adaptor molecule Shc is a proto-oncogene product, and it is known to be associated with cell proliferation. However, the role of Shc in the proliferation and regeneration of hepatocytes remains unknown. In the present study, we report that p46 Shc is specifically expressed in the nuclei of proliferative (or regenerative) hepatocytes, suggesting that p46 Shc protein plays a role in hepatocellular proliferation. The expression of Shc was analyzed in liver tissue after partial hepatectomy (PH) or sham operation in Wistar rats by using immunohistochemistry and/or Western blot analysis. In addition, the expression of various cell cycle-related proteins, such as Cdk4, cyclin D1, PCNA, and Cdk1 was analyzed in the tissues of regenerating rat liver. Furthermore, the tyrosine phosphorylation of Shc was studied in liver tissue after PH or sham operation by immunoprecipitation using a monoclonal phosphotyrosine antibody. Although the protein levels of p52 Shc were unchanged in liver tissues after PH or sham operation, tyrosine phosphorylation was detected only in the regenerating rat liver after PH. The levels of p46 Shc protein were markedly increased in liver tissues during the liver regenerative process. In contrast, p66 Shc was not detected in the liver tissues after PH or sham operation. Western blotting and immunohistochemistry showed that the main location of p46 Shc was in the nuclei of proliferating hepatocytes after PH. These data suggest that p46 Shc expressed in hepatocellular nuclei may be closely related to the proliferation of hepatocytes. Therefore, it is suggested that p46 Shc expressed in hepatocellular nuclei may be a useful marker for detecting hepatocytes with high proliferative activity.     

Vinyl polymerization with dimethylaniline/cupric nitrate system

A study of vinyl polymerizations initiated with the system of dimethylaniline (DMA) and cupric [Cu(II)] nitrate has been made. This initiator system was found to induce the polymerization of vinyl monomers having an electron-attracting substituent such as methyl methacrylate (MMA) and acrylonitrile, but it does not initiate the styrene and vinyl acetate polymerizations. The rate of polymerization (R_p) of MMA with this system was expressed by the following Eqs., depending upon the Cu(II) concentration used: The apparent activation energy for this polymerization was found to be 16.5 and 14.4 kcal/mole for the above two Cu(II) concn. ranges, respectively. The polymer of MMA obtained by this system was found to contain an endgroup similar to dimethylaniline, probably a methylanilinomethyl group, from the determination of its UV spectrum.     

Cytogenetic studies of Hynobiidae (Urodela) XIX. Morphological variation of sex chromosomes pairing behavior of sex lampbrush chromosomes in <Emphasis Type="Italic">Hynobius quelpaertensis</Emphasis> (Mori) from Cheju Island,South Korea

Using Giemsa staining, C-banding and Ag-NOR staining techniques, we analyzed chromosomes in adult male and female Hynobius quelpaertensis and in embryos of this species in egg sacs collected from eight localities of Cheju Island, South Korea. Chromosome pair 21 was consistently homomorphic in male specimens, while it was heteromorphic in female specimens, suggesting the occurrence of ZZ/ZW sex chromosome constitution in this species. The W chromosome, being much larger than the Z chromosome, was of three morphologically distinct types: W^A, W^B and W^C. Lampbrush chromosomes examined in the oocytes of one female specimen having the W^A chromosome showed that the short arm of the W^A chromosome and the long arm of the Z chromosome paired closely and hence are genetically homologous. We also tried to analyze the structural relationship among the three types of W chromosomes based on their C-banding and Ag-NOR patterns.     

Histochemical demonstration of endogenous estrogen in breast carcinomas: Biochemical and clinical correlation

Summary In a study of 277 patients with breast carcinomas, the PAP immunoperoxidase method for demonstrating endogenous estrogen was correlated with the sucrose density gradient (SDG) assay and with histologic and clinical features. The results from the PAP method and SDG assay agreed in 59 of 84 patients (82.1%) on whom both methods were performed. Histologically, the PAP method was positive in 7 of 7 patients with non-invasive carcinomas, in 164 of 233 patients (70.4%) with common invasive ductal carcinoma, and in 21 of 22 of those with special histological types of invasive carcinomas not including Paget's disease, medullary or apocrine carcinoma, where only 5 of 14 were positive. Clinically, 15 of 18 patients with positive endogenous estrogen showed a response to endocrine therapy as opposed to 1 of 9 patients with a negative endogenous estrogen. The mean survival was 31.2 and 15.6 months, respectively for patients with positive and negative endogenous estrogen. Remission for longer than 2 years was seen more often in patients with positive endogenous estrogen. These results suggest a clinical utility of the present PAP method which, therefore, deserves a further trial as an alternative to histochemical methods aiming at the estrogen receptors.This work was supported by Grants-in Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (No. 56480119).This paper was presented at the 72nd Annual Meeding of International Academy of Pathology (United States-Canadian Division), Atlanta, Georgia, March 1, 1983.     

Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium

The endometrium is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.     

Histological evidence of the altered distribution of osteocytes and bone matrix synthesis in klotho-deficient mice

Mice homozygous for klotho gene deletion are well established aging models as they mimic certain aspects of human senescence e.g. osteoporosis. Induced senescence may affect cellular functions and alter the histological properties of the extracellular matrices. The present study examined the histological and ultrastructural features of osteocytes and the surrounding bone matrix in klotho-deficient mice. As expected, osteoblasts showed a flattened shape with a weak immunoreactivity for alkaline phosphatase, and the bone matrix contained many empty osteocytic lacunae. The walls of both normal and empty lacunae were intensely immunopositive for osteopontin and dentin matrix protein-1, but featured an inconsistent immunoreactivity for osteocalcin and type I collagen. Not surprisingly, TUNEL-positivity, indicative of apoptosis, was found in many osteoblasts, osteocytes, and bone marrow cells of the klotho-deficient mice. In transmission electron microscopy, an amorphous matrix containing non-collagenous organic materials was recognizable around osteoblasts and in the osteocytic lacunae. Some osteoblasts on the bone surface featured these amorphous materials in vacuoles associated with their trans-Golgi network, indicating that, under klotho-deficient conditions, they synthesize and secrete the non-collagenous structures. Some osteocytes displayed pyknosis or degenerative traits. Thus, our findings provide histological evidence that klotho gene deletion influences the spatial distribution of osteocytes and the synthesis of bone matrix proteins in addition to the accelerated aging of bone cells.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

Minimum-Dose,Short-Term Methotrexate With Tacrolimus for Graft-vs-Host Disease Prophylaxis Following Unrelated Cord Blood Transplantation in Adults: A Retrospective Analysis at a Single Institution

BackgroundMethotrexate (MTX) or mycophenolate mofetil with tacrolimus (TAC) is used for graft-vs-host disease (GVHD) prophylaxis in unrelated cord blood transplantation (CBT). However, there is no consensus regimen for GVHD prophylaxis in CBT. We aimed to assess the efficacy and feasibility of minimum-dose, short-term MTX (MS-MTX) for GVHD prophylaxis in CBT.MethodsWe retrospectively evaluated 35 consecutive adult patients who underwent CBT and received MS-MTX (6 mg/m² day 1; 3 mg/m² days 3 and 6, intravenously) with TAC for GVHD prophylaxis in our hospital between 2015 and 2019. Transplantation outcomes with respect to time to hematopoietic recovery, engraftment, incidence and severity of GVHD, adverse events, relapse, nonrelapse mortality (NRM), and overall survival were evaluated.ResultsThe median time to neutrophil, platelet, and reticulocyte recovery was 22, 38, and 32 days, respectively. Cumulative neutrophil engraftment was 91.4%. After a median 3.2-year follow-up, the 2-year overall survival was 64.3%. The 2-year cumulative incidence of relapse and NRM was 20.4% and 14.9%, respectively. The 100-day cumulative incidence of grade II-IV acute GVHD and 2-year cumulative incidence of chronic GVHD were 28.6% and 36.6%, respectively. No grade IV acute GVHD was observed. Sixteen patients experienced oral mucositis and/or pharyngeal pain (46%; grades 1-2, n = 15; grade 3 pharyngeal pain, n = 1). No patients suffered from human herpesvirus 6 encephalitis/myelitis.ConclusionsMS-MTX with TAC is feasible and safe and yields lower rates of severe oropharyngeal mucositis and human herpesvirus 6 encephalitis/myelitis without increasing GVHD, graft failure, relapse, or NRM.