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今回，膵癌の小腸転移により小腸穿孔を来した1例を経験したので本邦文献報告例の検討および文献的考察を加え報告した．症例は84歳，女性．急性腹症の精査にてFree airおよび膵尾部腫瘍を指摘された．開腹所見では空腸に全周性腫瘍が存在し，同部で穿孔を認めた．空腸部分切除および腫大した幽門上リンパ節（#5）のサンプリングを行なった．術後病理所見にて小腸腫瘍および#5リンパ節は中分化腺癌で同一の組織像であり，小腸腫瘍は転移性腫瘍の形態を示したことから膵原発と考えられた．膵癌からの小腸転移は極めて稀である．我々が検索しえた限り，膵癌小腸転移の本邦文献報告例は自験例を含めわずか6例であった．平均年齢66.2歳，男性5例，女性1例であった．転移は全例空腸であり，穿孔例は3例で，5例で小腸切除がなされていた．転移経路は血行性3例，播種性3例であった．全例とも予後不良であった．

A 57-year-old woman with a complaint of a right upper quadrant mass was referred to our hospital. Multimodal studies such as PET-CT revealed large hepatic tumors and swollen para-aortic lymph nodes, the origin of which was unclear. Pathological analysis of a biopsy specimen obtained from the liver tumor led to a diagnosis of neuroendocrine carcinoma. After 4 CDDP/CPT-11 chemotherapy treatment courses, remarkable shrinkage of liver tumors and disappearance of the swollen lymph nodes were achieved. Subsequently, liver tumor and extrahepatic bile duct resection and lymphatic dissection were performed. Pathological analysis of the resected specimens revealed that the liver tumors and metastatic lymph nodes originated from the gallbladder, leading to a diagnosis of mixed adenoneuroendocrine carcinoma. After 5 courses of adjuvant chemotherapy using the same regimen, the patient has remained disease free for 24 months since the initialdiagnosis.

Reduction intermediate prepared in situ from chiral lactam alcohol 3 and borane at room temperature was found to catalyze the borane reduction of various prochiral ketones with high enantioselectivity up to 98% ee.

局所再発を繰り返し,最終的に多中心性に発生したと考えられる乳腺葉状腫瘍を経験したので報告する.症例は40歳,女性,左乳房腫瘤を主訴とし,当院を受診した.病歴に, 28歳, 32歳, 38歳時,左乳房C領域の腫瘤切除の既往があり,いずれも線維腺腫/葉状腫瘍と診断されている. 39歳時の同部腫瘤切除で,良性葉状腫瘍と診断された.今回,再度,同部に腫瘤を触知し,超音波, CT検査から,多中心性に発生した葉状腫瘍と術前診断された.腫瘍組織は左乳腺をほぼ占拠しており,左乳房単純切除をすすめたが,本人の強い希望もあり,多発乳房腫瘍摘出術(wide excision)が行われた.病理学的に核異型や細胞分裂像などの悪性所見は認められず,良性の葉状腫瘍と診断された.乳腺葉状腫瘍におけるetiology, すなわち線維腺腫との関連性,葉状腫瘍の多中心性発生のmechanism,悪性化,予後などに関して,検討を加え報告する.

S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only.

Ehlers-Danlos症候群(以下, EDS)IV型は出血型, 動脈型として知られ, 動脈性出血や消化管穿孔を起こし死亡率が高い. 今回, 腹腔内出血にて発見されたEDSIV型の1例を経験したので報告する. 症例は49歳の男性. 1997年12月5日頃より右下腹部痛, 下痢が出現, 12月8日当科受診後, 入院となる. 入院時, 腹部CT検査にて腹腔内出血を認め緊急手術を施行した. 術中所見にて回腸腸間膜に母指頭大の腫瘤を認め同部よりの出血が確認されたため腫瘤を含む小腸部分切除術を施行した. 腹腔内出血量は1, 144mlであった. 術後病理診断は回腸動脈瘤破裂であった. 症例は大動脈弁閉鎖不全症, 脊柱側弯症, 皮膚の過伸展, 関節の過可動性を有しておりEDSIV型の回腸動脈瘤破裂による腹腔内出血と最終的に診断された. EDSIV型の本邦報告例は自験例を含め31例に過ぎず, さらに腹腔内出血の報告は無くきわめてまれであると考えられた.

Many new members of the S-100 genes are known to be associated with cell differentiation, malignant transformation, and cell cycle. Of the S-100 genes examined in the present study, calcyclin, calpactin I light chain and calvasculin were expressed in most human epithelial tumor cells, and their expression levels differed according to various growth conditions. Their transcribed levels differed depending on each cell line, but their expression patterns were similarly changed under growth-modulatory conditions. Their messenger RNA levels increased parallel to the S phase population of cells, and decreased at G1/G2 phases. In contrast, this expression diminished in tumor cells under growth-inhibitory conditions, such as treatment with topoisomerase II inhibitor VP-16 or phorbol 12-myristate 13-acetate.

Deletion of certain chromosomal regions can be demonstrated in malignant cells. Chromosome 16q is one of the regions where allelic loss is frequently detected in carcinoma of the breast and many other tumors, suggesting that gene(s) which retard tumor growth may exist here. To elucidate the clinico-pathological significance of chromosome 16q, loss of heterozygosity (LOH) was investigated using microsatellite polymorphism analysis in 58 patients with endometrial lesions (50 with endometrial carcinoma and 8 who had hyperplasia with or without atypia). When 11 regions of chromosome 16q were examined, LOH was found in 20 patients with carcinoma (40%) and none of the patients with hyperplasia. The tumors of 9 of the 20 patients (45%) showed total loss of 16q, while the others (55%) showed partial deletion. Tumors with LOH were histologically less differentiated than those without LOH (P = 0.038, x 2 test). Patients with tumors showing LOH of 16q had a worse prognosis than those without LOH according to Kaplan-Meier survival analysis (P=0.0158, log-rank test). In addition, LOH of 16q showed a significant relationship to prognosis by Cox regression analysis. Deletion mapping of 16q demonstrated that two regions (16q22.1 and 16q22.2-23.1) were frequently involved. Patients with 16q22.1 LOH had a poorer prognosis than those with intact 16q22.1 (P=0.0003, log-rank test). These findings suggest that gene(s) of which defect is possibly related to the aggressiveness of endometrial cancer are localized on a limited region of 16q that includes 16q22.1.

Changes of surface sugar residues in the large intestinal mucosa may be associated with malignant transformation and may be of importance in differentiating borderline lesions. To compare these changes in normal mucosa, adenomas, and carcinomas of the large intestine, we investigated modifications of carbohydrate composition, such as those of N-acetyl-galactosamine (GalNac), L-fucose, and o-acetylated sialic acid, by histochemical staining with Dolichos biflorus agglutinin (DBA) and Ulex europaeus agglutinin-1 (UEA-1) lectins, and with Culling's periodic acid-thionin Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS), respectively. For stable staining, the sections stained with DBA and UEA-1 were pretreated with potassium hydroxide and neuraminidase. We conclude that the pattern of the two lectin stainings in carcinomas is quite different from that in normal mucosa and adenomas, and that it shows the carcinomatous features in some cases of adenoma with severe atypia (borderline lesions). In contrast, PAT/KOH/PAS staining demonstrates differences between normal mucosa and adenomas rather than differences between adenomas and carcinomas.

Protein-bound polysaccharide K (PSK) has been used as a chemoimmunotherapy agent for the treatment of colorectal cancer. Recently, PSK was reported to be able to decrease some adverse effects of FOLFOX therapy, including neutropenia and peripheral neurotoxicity. Here, we report 2 patients with metastatic colorectal cancer, who unexpectedly were able to receive many courses of PSK+mFOLFOX6 therapy for a prolonged period. We speculate that FOLFOX therapy may achieve long-term tumor control with the aid of PSK without serious side effects for metastatic colorectal cancer patients.

Expression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunologic functions of T-cells. However, a minor T-cell subset lacking both CD4 and CD8 molecules but bearing the usual form of T-cell receptor (TCR)-alpha beta (CD4-CD8-TCR-alpha beta+ T-cells) has recently been found not only in mice but also in humans, and the clinical relevance of this newly defined subpopulation to human diseases is now of considerable interest. The authors present a patient in whom CD4-CD8-TCR-alpha beta+ T-cells showed monoclonal proliferation in the peripheral blood for more than 3 years, then disappeared spontaneously, followed by subsequent development of Hodgkin's disease. The pathologic roles of double-negative T-cell proliferation in this case are discussed from the viewpoint of premalignancy in lymphoproliferative diseases.

Migration inhibitory factor-related proteins-8 (MRP8) and MRP14 comprise a heterodimeric molecule. This complex molecule consisting of 8kDa and 14kDa subunits (MRP8/14 complex) contains two chracteristic Ca2+-binding regions named EF hands in each subunit. The MRP8/14 complex is expressed mainly in peripheral blood neutrophils and monocytes but not in resting tissue macrophages. It is also induced in human cultured leukemia cells including HL-60 promyelocytic leukemia cells by treatment with differentiation-inducing agents. The MRP8/14 complex also appears in human sera. Its serum level is high in patients with cystic fibrosis, rheumatoid arthritis, sarcoidosis, and other chronic diseases. To date, several groups of investigators have demonstrated this complex's modulation of cellular kinase reactions, its configurational changes in a Ca2+-dependent manner, and its transition from the cytosol to the membrane during neutrophil activation. Such observations may be an important clue to understanding the functional role of MRP8 and MRP14.

The authors consider a decentralized H∞ control problem for multichannel linear time-invariant (LTI) descriptor systems. The aim is to design a low-order dynamic output feedback controller. The control problem is reduced to a feasibility problem of a bilinear matrix inequality (BMI) with respect to variables of a coefficient matrix defining the controller, a Lyapunov matrix, and a matrix related to the descriptor matrix. There is no globally effective method for solving general BMIs. In this article, under a matching condition between the descriptor matrix and the measurement output matrix (or the control input matrix), the authors propose to set the Lyapunov matrix in the BMI as block diagonal appropriately so that the BMI is reduced to LMIs.

Considers decentralized H/sub /spl infin// controller design problems for multi-channel linear time-invariant systems. Our interest is focused on dynamic output feedback, and our discussion concerns both continuous-time systems and discrete-time ones. The decentralized H/sub /spl infin// control problems are expressed as feasibility problems of bilinear matrix inequalities (BMIs) with respect to variables of a coefficient matrix defining the controller and a Lyapunov matrix. To deal with the BMIs, we propose to set the Lyapunov matrix as block diagonal appropriately according to the desired order of the controller so that the BMIs; are reduced to linear matrix inequalities (LMIs) which are sufficient to the BMIs but much more tractable.

(2003). Isolated torsion of haematosalpinx associated with tubal endometriosis. Journal of Obstetrics and Gynaecology: Vol. 23, No. 4, pp. 453-454.

Epstein–Barr virus (EBV) has been well documented in the aetiology of nasopharyngeal carcinoma (NPC), although its role as well as the genetic basis in the genesis of NPC have not been elucidated. The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV. Proliferating cell nuclear antigen (PCNA) has also been shown to be increased in NPC, suggesting its association among the overexpression of p53 and bcl-2 oncoprotein. We undertook this study to evaluate the correlation among these abnormalities in the development of NPC. The expression of p53 protein, bcl-2 oncoprotein, and the level of PCNA were investigated by immunohistochemistry in 53 patients with NPC. Twenty tissue samples from these patients were studied for p53 gene mutations by single strand conformation polymorphism (SSCP) and DNA sequencing as well as EBV genomes by polymerase chain reaction. Among the 53 specimens, 42 (79%) showed expression of p53 protein and 40 (75%) gave positive result for bcl-2 oncoprotein. A significant association was found between p53 expression and bcl-2 oncoprotein (P=0.002; Fisher's exact test) with 68% of the patients showing coexpression of both markers. The PCNA labelling index in the 53 patients varied from 5% to 80%. High PCNA labelling index was frequently found in the patients with overexpression of p53 protein and bcl-2 oncoprotein. The PCNA index in patients with p53 expression was significant higher than in those without p53 expression (P=0.002). Of the 20 patients, p53 mutations were found in four cases. EBV genomes were detected in 14 cases of which 12 cases showed overexpression of both p53 and bcl-2 and one case with only p53 expression and one case with bcl-2 expression. EBV genomes were detected in two cases with p53 mutations. We conclude that EBV is the important etiologic factor in NPC which may be involved in p53 and bcl-2 overexpression. The mutant p53 protein is correlated to deregulation of PCNA. p53 mutations participate in a small proportion of the tumorigenesis.

S-100 proteins (S100) are characterized by calcium-binding ability with two structural EF hands. Several S100 are expressed in cardiomyocytes and thought to play a crucial role in calcium signaling. To examine whether the expression of S100 is a response to detectable myocardial damage or regeneration, we investigated, immunohistochemically, the expression of S100A4 and S100A11 in the isoproterenol (ISP)-treated rat heart. Definite expression of S100A4 and S100A11 was demonstrated in normal cardiomyocytes, and their staining patterns were enhanced in the ISP-treated rat heart, suggesting the possible involvement of S1-A4 and S100A11 in ISP-induced myocardial damage.

To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (???AGC???GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors. © 1996 Wiley-Liss, Inc.

A 68-year-old man, after having been diagnosed as having hepatic disease at about the age of 41 years, had been hospitalized frequently until his death. Blood sugar, iron, and copper had not increased during his illness. Although the diagnosis of liver cirrhosis had been made and he had been receiving therapy, various neurologic symptoms without disturbances of consciousness appeared six months before his death. Autopsy revealed hemochromatosis, liver cirrhosis, and pancreatic fibrosis. A large amount of iron had accumulated in the liver, the pancreas, and the thyroid gland, while considerable numbers of ceroid and lipofuscin pigment granules had accumulated diffusely in the brain. Abnormal astrocytes of the Alzheimer II type were diffusely distributed in the brain and contained no intranuclear glycogen which stained positive with the carmine stain. No spongy changes were seen in the deeper layers of the cerebral cortex. Chemical analyses for trace metals in the brain, liver, and kidneys revealed a large amount of iron and increased copper in the liver, and considerable quantities of copper, manganese, calcium, and mercury in the brain. Because of changes in the erythrocyte sedimentation rate and marked thymol turbidity seen before and after the occurrence of the neurologic symptoms, this man was suspected of having disorders of the trace-metal binding proteins and/or of their polymers.

Foam cells in the spleen, bone marrow, liver and lymph nodes were examined on the 73 reliably recorded and sampled leukemia autopsy cases encountered at Kobe University from 1958 to 1972. Although the substances stored in the foam cells were biochemically unknown, the foam cells in leukemia could be morphologically classified into two types: The one was identified with the Gaucher type, but the other was not identified with the sea-blue type and might be considered as to be the transitional type described in another report. Foam cells could be found in the spleen of 6 out of 12 cases of chronic myeloid leukemia, one out of 2 cases of chronic lymphatic leukemia, one out of 7 cases of leukemic lymphosarcoma, one out of 9 cases of acute lymphatic leukemia, and none in 3 cases of monocytic leukemia. In acute myeloid leukemia, the incidence of foam cells in the spleen was 47.5% in 40 cases, and acquired lipidoses were more frequently seen in cases under 19 years of age, in male cases, in cases with an enlarged spleen over 400 g, and in cases of over 4 months' duration.

A 52-year-old man with a clinical diagnosis of aortitis and heart failure died of brain thrombosis. Autopsy revealed many non-caseous sarcoid granulomas scattered in lymph nodes, lungs, heart, testes, liver, and meninges. An unusual finding of this case was the presence of sarcoid lesions in abdominal aorta and subclavian and common iliac arteries.

Localization of cellular oncogenes (c-onc) near the break points of translocations in tumor cells has indicated involvement of these genes in neoplastic growth. Enhanced transcription of the cellular homolog (c-abl) of the transforming sequence of Abelson murine leukemia virus was observed in K3D, which was one of the cloned cell lines of 7,12-dimethylbenz[a]anthracene-induced rat erythroblastic leukemia. Since the c-abl activation was not observed in the parent cell line (K2D) from which K3D was derived and the latter was different from the former in the presence of a new marker chromosome, t(3;12), this marker may play a role in the expression of c-abl in K3D cells. In contrast to the human c-onc assignments, few rat c-onc assignments have been reported. In situ molecular hybridization studies assigned c-abl to the 3q12 site of the normal chromosome 3 and to the break point of the translocation t(3;12) in K3D cells. Another break point in this translocation chromosome 12p11 involves the nucleolar region, and the 3;12 translocation may involve c-abl and nucleolar cistrons. These results provide evidence of secondary c-onc activation during karyotypic evolution of cloned malignant cells.

The gene dosage change of nucleolar cistrons (rDNA) in tumor cells has not been extensively studied. The present studies showed that increased dosage, as well as abnormal distribution of rDNA, was frequently associated with leukemia cells of SL/Ni and AKR mice. In normal SL cells, 37%, 39%, and 25% of rDNA was located in nucleolar organizer regions (NOR) of chromosomes #12, #18, and #19, respectively. Increase of rDNA/DNA was shown by hybridization on filter membranes in SL1, SL2, SL3, and M1 leukemia cells. Direct measurement of rDNA/DNA in G1 cells revealed an 11% increase in synchronized M1 cells. The increased rDNA dosage was explained by trisomy 12 in SL1 and SL2, the ectopic NOR of #9 in SL3, and the double t(X;19) marker chromosomes in M1. On the other hand, in normal AKR cells, 27%, 29%, and 45% of rDNA was assigned to NORs of chromosomes #15, #16, and #18, respectively. The relative rDNA distribution among NORs estimated by autoradiographic grain counting was suggested to be abnormal in AKR leukemia cells despite their normal karyotype; 36% rDNA was shown to be in chromosomes #15 and #16, respectively, by relative reduction in chromosome #18 in AKR1; the trisomy 15 explained the increased rDNA in AKR2; a relative increase was found in chromosome #15 in AKR3. These results were discussed with reference to the reported NOR involvement in chromosome translocation and amplification in tumor cells.

Two culture cell lines L615K and L7212K were established from transplanted murine leukemias L615 and L7212, which had been established and maintained in China for years. Based on morphological, immunological and gene rearrangement analyses, L7212K cells are considered to be of T‐cell origin while L615K cells might be immature T‐cells. Immunofluorescence assays of viable leukemia cells and fluorescence focus assays of their culture supernate for infectious viruses suggested that recombinant mink cell focus‐inducing viruses were significantly involved in both leukemic cell lines. Chromosome analysis of the L615K cells revealed a translocation t(12;17) which probably involved the c‐fos locus on chromosome 12, since the DNA rearrangement of c‐fos was demonstrated by Southern blot analysis with Hind III, and c‐fos has been assigned to this chromosome. Although the expression of this gene was not detected by RNA Northern blot analysis, c‐myc was slightly expressed in both L615K and L7212K cells.

The ribosomal cistrons (rDNA)/genome ratio was measured in five cell lines derived from three chemically induced erythroblastic leukemias (D-1, D-2, and NE26) in the Long-Evans (LE) rat and compared with values in the normal liver, bone marrow, and fetus. The ratio was 20-42% higher in the leukemias than in normal tissues. The number of autoradiographic silver grains of 125I-labeled rRNA hybridized in situ over three nucleolus organizer regions (NORs) of leukemia cells was determined and compared with that of the normal cells. Although the distribution of silver grains of normal cells averaged 44.6%, 25.9%, and 29.5% in NORs of chromosomes #3, #11, and #12, respectively, their distribution was abnormal in two of the leukemias examined; rDNA was amplified in chromosomes #12 of two sublines (K1DA and K1DB) of one leukemias (D-1), and in one chromosome #3 of two sublines (K2D and K3D) of another leukemia (D-2). We consider the possibility that these abnormal patterns of rDNA distribution are related to the increase in rDNA in leukemia cells.

The chromosomal distribution of chromosome aberrations (CA) and sister chromatid exchanges (SCE) induced by various chemical carcinogens such as 7,12-dimethylbenz[a]anthracene, 7,8,12-trimethylbenz[a]anthracene, 1-butyl-1-nitrosourea, urethan, 4-nitroquinoline 1-oxide, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, and the antineoplastic compound mitomycin C was studied with the use of noninbred Long-Evans male rat bone marrow cells in vivo and in vitro. The CA and SCE induced by these structurally different chemicals were distributed in a similar pattern among and along chromosomes when the chemicals were given a short time (6 hr) before the metaphase cells were harvested. The specific distribution pattern of chemically induced CA and SCE along chromosomes was attributed to the late DNA replication of the vulnerable chromosome regions. Conversely, X-ray-induced CA were distributed more randomly. Thus the different chemical carcinogens were shown to exert a similar genetic effect at the chromosome level.

A 6-month-old boy, having suffered repeated convulsive seizures since birth, died of severe epilepsy, the disease remaining unknown. However, when a brother, born after the death of the present case, displayed the same clinical symptoms and was diagnosed clinically as having pyridoxine dependent convulsion, the deceased became suspected of having been a case of familial pyridoxine dependency. Pathologically, bilateral cerebellar hemorrhages were found accompanied by subdural and subarachnoidal hemorrhages. Histologically, neuronal loss and diffuse astrocyte hyperplasia were found hi the brain: Beside marginal gliosis, proliferations of astroglia and glial fibers were found, especially hi the pons, medulla oblongata, and cervical cord, although the fibrillary gliosis may be representative for a physiological intermediate state. Foamy cells were found in the lymph nodes, but not hi the brain. Observed hi the kidneys were substances deposited hi the glomeruli and Bowman's capsules and materials hi the tubular lumen.

A new embolic material has been devised to improve the therapeutic effect of ferromagnetic embolization upon tumors. Iron sponge microspheres (diameter 10-30 mu) were suspended in viscous, aqueous polysaccharide solution, dextran 40, and sodium carboxymethyl cellulose (Ferro-polysaccharide, FPS). Transcatheter embolization with FPS was performed under external magnetic control (2,800 gauss) in dog kidneys and VX2 carcinomas of rabbits, causing widespread, intraparenchymal vascular occlusion of target vessels. Neither recanalization nor collateral circulation was found to the infarcted areas, and the embolized tumors had extensive necrosis with resultant tumor regression. No significant untoward reaction or other undesirable embolization was noted serologically or histologically, even after intravenous administration of FPS. Clinical application to two patients, one with a hepatoma and the other with a renal cell carcinoma, resulted in excellent tumor infarction with no significant side effects.

Benz[ a ]anthracene (BA) and its derivatives containing methyl and/or ethyl groups in the 7 and/or 12 positions were tested for their ability to induce chromosome aberrations (CA) in rat bone marrow cells and for their mutagenicity to Salmonella typhimurium TA100 or TA98. The incidence of aberrant cells induced by the BA derivatives, given in lipid emulsion as a single-pulse dose of 50 mg/kg body weight into the caudal vein, was in the order: DMBA > EMBA > MEBA > other BA derivatives = control. The alkyl groups, at least 1 methyl group, at the 7 and 12 positions of BA seemed to be necessary to induce CA, although DEBA having ethyl groups at both the 7 and 12 positions of BA did not induce CA. DMBA or EMBA induced not only gaps and breaks but also exchanges and multiple CA, while the CA induced by other BA derivatives consisted of only gaps and breaks. 7MBA and 12MBA which exhibit carcinogenic activity intermediate between that of DMBA and BA induced few CA in the present system. However, the correlation coefficient between the logarithm incidence of aberrant cells and the carcinogenicity index calculated from the data of 9 BA derivatives including both 7MBA and 12MBA was 0.792. The relative mutagenicities of the BA derivatives with TA100 in the presence of hepatic S9 from polychlorinated biphenyl (PCB)-treated rats were in the order: BA > 7MBA > DMBA > 12MBA > 7EBA > EMBA > MEBA > 12EBA = DEBA = control. The results with TA98 were essentially the same as those with TA100. The results with TA100 in the presence of hepatic S9 from phenobarbital (PB)-treated rats were in the order: DMBA > 12MBA > 7MBA > 7EBA > BA > EMBA = MEBA > 12EBA = DEBA = control. These findings reveal no obvious relation between the mutagenic activities of the BA derivatives with the PCB-S9 or PB-S9 activating systems and their capacities to induce CA or their reported carcinogenicities. The incidence of CA induced by the dihydrodiols implicated as the metabolic precursors of the active diol epoxide metabolites of several of these BA derivatives was also tested. BA 3,4-dihydrodiol, like BA itself, induced few CA. However, the corresponding dihydrodiols of DMBA, 12MBA and 7MBA, induced relatively high levels of CA. The present results are consistent with the hypothesis that induction of CA by diol epoxide metabolites is involved in the mechanism of PAH carcinogenesis, but do not rule out the possibility that other electrophilic metabolites are also involved.

On 58 cases of D1 trisomy, which were classified as those with seven separate D chromosomes, including the one in this report, congenital brain and facial anomalies were reviewed and discussed. Congenital brain defects in this syndrome might be classified into three groups: (I) grossly normal brain, (II) absence of olfactory bulbi and tracts, but normally-separated cerebral hemisphere, and (III) completely or incompletely uncleaved hemispheres with absence of olfactory bulbi and tracts. 25.9% of the cases were found in group I, 56.9% in group II, and 17.2% in group III, respectively. Although facial anomalies predicted the brain defects in group III, malformations of the face were not concerned with the brain defects in group I and II. There were no cases with both, normal brain and face.

S100A4, one of the tandemly arranged S100 genes at chromosome 1q21, has been suggested to play a functional role in cell motility and invasiveness of tumor cell growth. We investigated the expression of S100A4 and the in vitro invasiveness of 4 human bile duct adenocarcinoma cell lines by the Matrigel assay. S100A4 was abundantly expressed in 2 adenocarcinoma cell lines whose growth pattern was highly invasive. Induction of antisense S100A4 into one of the cell lines decreased S100A4 mRNA levels and reduced invasiveness. In contrast, induction of sense S100A4 expression into non-invasive KMBC adenocarcinoma cells, which originally lacked S100A4 expression, resulted in apparent invasive potential in the transfected cells compared with the cells with the vector alone. These results suggest that S100A4 expression is well correlated with the invasiveness of human bile duct adenocarcinomas.

The calcium-binding protein S100A4 has been characterized as a metastasis-inducing molecule, and regulates cell motility and invasiveness of cancer cells. In order to clarify the significance of the expression of S100A4 as a prognostic factor in gallbladder cancer, S100A4 expression in resected gallbladder cancers were examined using an immunohistochemical staining technique. The relationship between S100A4 expression and clinicopathological factors including prognosis were evaluated. Twenty-five of 60 cases (42%) demonstrated positive staining for S100A4. There was no statistically significant association between S100A4 and histological grade, T, N, M factor, presence of stone, or stage. Kaplan-Meier method showed the 5-year survival rate of the group staining positive for S100A4 (31.5%) to be statistically poorer than that of the group staining negative for S100A4 (78.2%). Also in T2 cases, the 5-year survival rate of the group staining positive for S100A4 (57.1%) was statistically poorer than that of the group staining negative for S100A4 (83.3%). On univariate analysis, positive staining for S100A4 was a significant prognostic factor, and the hazard ratio was 4.05. On multivariate analysis, positive staining for S100A4 is also a significant predictor of prognosis second to T factor. These results indicate that positive staining for S100A4 is useful in assessing the prognosis of patients with gallbladder cancer as well as TNM factors.