Masaki Q. Fujita

Cancer risk after renal transplantation in Japan

Excess of cancer in patients receiving renal transplantation is well‐known in Western countries, but information in Japan remains limited. Our study examined whether excess risk is found in patients receiving renal transplantation in Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal transplantation in 6 hospitals, and a total of 12,982 person‐years of observation was accumulated. Malignancies developed in 2.6% of patients; O/E ration was 2.78. Median interval from renal transplantation to tumor development was 58 months. The interval in the patients receiving medication with cyclosporine‐A (CyA) (median, 42.5 months) was significantly shorter than that with non‐CyA (median, 95.5 months). Median age at the diagnosis of malignancy was 40 years, which is much younger than that in the general population. Relative risk was highest in renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer. A distribution of malignancies was different from that reported from Western countries. These findings showed the excess risk of malignancies in Japan with renal transplants, especially in male patients, similar to that observed in Western countries, though the types of malignancy were different. Int. J. Cancer 71:517‐520, 1997.

Structure of the dnaA region of Micrococcus luteus: conservation and variations among eubacteria

A phylogenetic tree constructed by 5S rRNA analysis is composed of three major branches in eubacteria: high G + C Gram+, low G + C Gram+ and Gram- [Hori and Osawa, Mol. Biol. Evol. 4 (1987) 445-472]. We have shown that the characteristic dnaA region is common among Escherichia coli (Gram-), Pseudomonas putida (Gram-), and Bacillus subtilis (low G + C Gram+). We have now determined the structure of the dnaA region of Micrococcus luteus, as a representative of the last branch, high G + C Gram+. The dnaA gene and at least three other genes, rnpA, rpmH and dnaN were found to be conserved in M. luteus. Large nontranslatable regions were found flanking the dnaA gene. The upstream region is conserved in the four bacteria so far examined. On the other hand, the downstream region is conserved only in Gram+ bacteria, M. luteus and B. subtilis. The consensus sequence of the DnaA box in M. luteus seems to be TTGTCCACA, in contrast to TTATCCACA of other bacteria. These results confirm our hypothesis that the dnaA region is the replication origin of the ancestral bacteria and that the essential feature of the DnaA protein and DnaA-box combination is conserved in eubacteria.

Structure of the dnaA region of Pseudomonas putida: Conservation among three bacteria, Bacillus subtilis, Escherichia coli and P. putida

SummaryWe have cloned from Pseudomonas putida a gene homologous to Escherichia coli dnaA, and determined the sequence of the gene and its neighboring region. The dnaA gene and at least three other genes, dnaN, recF and gyrB, were found to be highly homologous to the genes in the dnaA regions of the E. coli and Bacillus subtilis chromosomes. A non-translatable region of some 600 bp immediately upstream of the dnaA gene is also conserved in the three bacteria and contains 3, 12, and 14 DnaA-boxes (TTATCCACA and closely related sequences) in E. coli, P. putida and B. subtilis, respectively. The present results confirm our hypothesis that the dnaA region is the replication origin region of the ancestral bacterium and that the essential feature of the dnaA and DnaA-box combination is conserved in most eubacteria and plays a central role in initiation of chromosomal replication.

Structure of the dnaA and DnaA-box region in the Mycoplasma capricolum chromosome: conservation and variations in the course of evolution

We have previously shown that the dnaA gene and the DnaA-box region were conserved in bacteria representative of all three major branches of the eubacterial phylogenic tree: high G + C Gram+, low-G + C Gram+ and Gram-. In the present work, we determined the structure of the dnaA region of Mycoplasma capricolum and found that the dnaA gene and at least two other genes, rpmH and dnaN, were conserved in this bacterium. An unusually high level of amino acid (aa) substitutions was observed in M. capricolum DnaA. It was the case even in those aa which were well conserved in other bacterial species. The nontranslatable region upstream from the dnaA gene was also conserved in this bacterium, as it was universally found in both Gram+ and Gram- bacteria. An additional nontranslatable region downstream from the dnaA gene, which is common to Gram+ bacteria, was also found in M. capricolum, consistent with the proposal that M. capricolum is Gram+ in origin. These regions were rich in A + T and contained ten DnaA-box-like sequences (9-mers that differ from TTATCCACA by one or two bases).

Clinicopathological study of livers from brain-dead patients treated with a combination of vasopressin and epinephrine

Studies were made on the pathological lesions and biochemical indices of the livers of 22 patients in whom normal hemodynamics was maintained for 0-48 days after brain death by administration of vasopressin and epinephrine. Thirty-one specimens of liver tissues were obtained by percutaneous biopsy or at autopsy. The degrees of central venous congestion, central fibrosis, focal fibrosis, fatty metamorphosis, piecemeal necrosis, periportal fibrosis, and intrahepatic cholangitis in livers on various days after brain death were compared with those on the day of brain death (day 0). Central venous congestion was extensive on days 0-4, significantly less on days 5-14, and then again extensive on days 15-48. Central fibrosis and focal fibrosis showed no remarkable change during the 48-day period. Fatty metamorphosis, piecemeal necrosis, and periportal fibrosis showed no significant changes until day 16, but spread extensively on days 40-48. Intrahepatic cholangitis was scarcely observed on day 0 but began to increase after day 3, and spread extensively after day 5. The level of serum glutamic pyruvic transaminase did not increase in most patients until day 15. The mean value of prothrombin activity also did not decrease until day 15. However, the mean value of serum alkaline phosphatase increased gradually after day 3, and was correlated with cholangitis. The present study showed that during prolonged hemodynamic maintenance of brain-dead patients, pathological lesions did not spread or diminished and that biochemical indices did not become worse, or improved, in the first 2 weeks, except for increases in cholangitis and the serum alkaline phosphatase level.

Angioimmunoblastic lymphadenopathy. Review of 44 patients with emphasis on prognostic behavior

In order to investigate the relationship between histologic findings and clinical behavior in angioimmunoblastic lymphadenopathy (AILD), 44 patients with AILD were reviewed. These patients comprised 24 men and 20 women with age range from 25 to 84 years of age (median, 64 years). Lymphadenopathy was observed in all patients, systemic in 37, and localized in seven. Polyclonal hypergammaglobulinemia was present in 64% of patients. Histologically clear cells or convoluted cells were observed in 36% and 48% of the patients, respectively. Univariate analysis (log‐rank test) for prognostic factors revealed age, appetite, presence of clear cells, or convoluted cells were important factors. However, multivariate analysis revealed that there were no independent factors for prognosis. The presence of clear cells and/or convoluted cells were histologic signs for poor prognosis; autopsy showed that patients with the clear cells with or without convoluted cells mostly died of active disease of AILD with two cases progressing to non‐Hodgkins lymphomas and those with convoluted cells alone died of lung infection. From these findings, AILD could be divided into three groups: AILD with (1) clear cells with or without convoluted cells, (2) convoluted cells alone, or (3) neither cells. The first two groups showed poor prognosis, and the last a favorable prognosis.

INCIDENCE OF PROSTATIC INTRA-EPITHELIAL NEOPLASIA IN OSAKA, JAPAN

High‐grade prostatic intra‐epithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic carcinoma. A high incidence of its association with cancer has been reported in Western countries. On the other hand, information regarding its incidence is limited in Japan, where the mortality due to prostate cancer is much lower. We reviewed 53 clinical stage T2 or T3 prostatic cancers of Japanese patients living in Osaka, Japan (mean age, 67.2 years). These cases were subdivided into a pre‐operatively non‐castrated group (34 cases) and a medically or surgically castrated group (19 cases). HGPIN was found in 27 cases. The incidence of HGPIN was significantly lower in the castrated group (21.0%) compared with the non‐castrated group (67.6%). In the non‐castrated group, patient age, pathological stage, Gleason score, tumor size and serum prostate‐specific antigen showed no significant correlation with HGPIN. Advanced pathological stage and tumor size tended to decrease the incidence of HGPIN, although this was not statistically significant. When the study group was limited to stage T2 tumors of the non‐castrated group, the incidence of HGPIN was 81.0%. HGPIN in Japan may also be clinically and etiologically significant as a precursor of clinical cancer. Int. J. Cancer 73:808–811, 1997.

UTILITY OF IMMUNOHISTOCHEMICAL DETECTION OF HIGH MOLECULAR WEIGHT CYTOKERATIN FOR DIFFERENTIAL DIAGNOSIS OF PROLIFERATIVE CONDITIONS OF THE PROSTATE

Background: Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. lmmunohistochemistry using an antibody (34βE12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presenceor absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis.

Immunohistochemical determination of immunosuppressive acidic protein in reactive and neoplastic diseases of macrophage

Immunosuppressive acidic protein (IAP), a substance purified from cancer ascitic fluid, is released into the culture medium of macrophages and neutrophils, and is supposed to suppress an immune function of the host. Elevation of serum IAP in cancer patients has been reported. In the current study, presence of IAP in proliferating diseases of macrophage was examined. Macrophages in reactive proliferation, histiocytosis X, and neoplastic proliferation gave positive reaction for IAP. Diffuse cytoplasmic staining was usual, but dot‐like or globular and surface staining also were observed. Proliferating cells in malignant fibrous histiocytoma were more sensitively stained by IAP than by other ordinary used markers for macrophage. These findings provide useful information to understand the mechanism of elevation of serum IAP in cancer patients.

Clonal Composition of Malignant Fibrous Histiocytoma: Analysis by PCR-Based Assay of the Human Androgen Receptor Gene (HUMARA)

Malignant fibrous histiocytoma (MFH), the most common soft-tissue sarcoma, consists mainly of two different cell populations: histiocytelike and fibroblastlike cells. It has been suggested to contain a large amount of reactive histiocytes and fibroblasts hard to distinguish from the tumor cells. In this study, the clonality of MFH was determined by analyzing the patterns of X chromosome inactivation at the human androgen receptor gene (HUMARA) using DNA samples from archival snap-frozen and paraffin-embedded tissues. All the eleven informative female heterozygotes without severe inflammation showed the monoclonal pattern; 8 storiform-pleomorphic (6 distinct, 2 relative monoclonal pattern) and 3 myxoid (3 distinct monoclonal pattern) subtype. Although normal tissue DNA, amplifiable by the polymerase chain reaction, valid for the assay was not available in these cases, statistically at least 5 cases are monoclonal (p = 0.037 <0.05), even when markedly skewed lyonization were to primarily exist in the normal tissue at the highest rate as ever reported (33%). Experiments using the mixture of monoclonal and polyclonal DNA at varying ratios have suggested that a distinct monoclonal pattern is obtained only when the monoclonal component exceeds 80%. Our study demonstrates that most cells that are present in MFH are monoclonal in origin which may be the population of tumor cells.