Cell nuclear DNA ploidy patterns were examined using cytofluorometry in hepatocellular carcinomas (HCC) induced by diethylnitrosamine (DEN) in rat and human HCC. These ploidy patterns were compared with histopathological and/or immunohistochemical studies of HCC using anti-bromodeoxyuridine monoclonal antibody. The results are summarized as follows. HCC of rats induced by DEN was occurred in 74(65.5%) of 113 rats. Intravascular invasion of the livers were seen in 31 of 74(41.9%). Metastasis was in 25 of 74(33.8%). The ploidy patterns of HCC in rats were classified into three types (types I, II and III). These ploidy patterns were closely connected with histological types of HCC in Edmondson's classification, and in order of types changing from type I to type III, 6c over polyploid cells, mitotic indices (MI) and labeling indices (LI) had a tendency to increase. In human HCC, cell nuclear DNA ploidy patterns were classified into three types similarly to experimental HCC. These ploidy patterns were closely related to histological types in Edmondson's classification. MI and 6c over polyploid cells were tendency to increase similarly to HCC of experimental rats. From the above results, measurement of DNA ploidy patterns and LI are considered a valuable parameter in examining the biological activity of HCC.

A case of Burkitt's type of acute lymphoblastic leukemia (FAB L3) in an 80-year-old male patient is reported. At the time of diagnosis, 74% of the bone marrow cells were lymphoblastoid cells, which were large and homogeneous in size, and whose cytoplasm was abundant and intensely basophilic containing many vacuoles. Lambda-light chains were detected as surface immunoglobulin (Ig), but not heavy chains or kappa-light chains. Epstein-Barr (EB) viral genome was detected in the cultured bone marrow cells by spot hybridization method. Chromosomal banding studies of bone marrow cells revealed t(8; 22) (q24; q11) in all the 18 metaphases examined. This translocation brings the Ig lambda-light chain gene on chromosome 22q11 to chromosome 8q24 where the c-myc proto-oncogene is localized, which is thought to be closely associated with the leukemogenesis of this disorder, whereas EB viral genome is observed in African Burkitt's lymphoma. To our best knowledge, however, there have been no reported Japanese patients with L3 ALL in whom t(8; 22) or EB viral genome was observed.

To investigate the effects of pregnancy and delivery on stomach carcinogenesis, we have conducted a case-control study. The cases consisted of females aged 34 or below who had been histologically diagnosed as having a stomach cancer, covering a period from 1967 to 1986 at the Center for Adult Diseases, Osaka. Our birth-year-matched controls were selected from female examinees who had undergone a gastroendoscopy in 1986. In this manner, a total of 79 cases and 158 controls were obtained. For women in the age group from 30 to 34, a history of their pregnancies and deliveries seemed to have protective effects on stomach carcinogenesis (RR = 0.36, P less than 0.05), whereas for those in the age group under 30, it appeared to be a risk factor for stage IV stomach cancer (RR = 4.42, P less than 0.05).

A 25-year-old man had multiple subcutaneous nodules on the neck, trunk and extremities. Those nodules first appeared in the right popliteal fossa about 15 years ago and thereafter gradually increased in the number with hearing loss, tinnitus, and vertigo. The tumors had smooth surfaces and were elastic hard without any adhesion to the overlying skin or to subcutaneous tissue. Histological examination revealed, in most parts of the lesion, Antoni type A neurilemmoma and the Antoni type B picture at the periphery. As extracutaneous lesion, there were bilateral cerebello-pontine angle neurilemmomas, and spinal and adrenal tumors. Similar subcutaneous tumors have been recognized in 6 of 17 family members of the previous four generations of his family. According to a statistical analysis of 119 cases, including this one, in the Japanese dermatological field, of 75 cases of solitary neurilemmoma and 44 cases of multiple ones, the latter showed male predominance and lower age of the onset. Many of them had tumors not only in the skin but also in extracutaneous sites.

A 36 year-old woman beginning with spastic paraparesis at her age of 11 visited us for evaluation of progressive muscular weakness of the distal portions of the upper extremities and difficulty in speaking at her age of 33. The neurological features at the present are as follows; fine horizontal gaze-nystagmus, impaired smooth pursuit ocular movement, highly spastic paraplegia with pes equino-varus necessitating canes and the wheel-chair, highly accentuated PTRs and ATRs associated with positive Babinski's sign, diminished or absent deep reflexes in the upper extremities, moderate muscular wasting with fasciculation on the tongue and distal portions of the upper extremities (rt less than lt). Sensory or cerebellar functions remain normal. No autonomic finding has been manifested. The HTLV-I antibody titers of serum (eg. PA method: x8192 ) and cerebrospinal fluid are highly positive in various methods. That of her mother (no blood-transfusion history) is positive. The provirus genome analysis on peripheral lymphocytes using the Southern blotting method by the cleaving enzyme Psi I was unable to discriminate that of an ATL patient. MRI of the central nervous system revealed higher signal area (short SE) at the C5/6 region and atrophy of C7/8 region. Neither a definite lesion in the lower brain stem, cerebellum nor cerebral hemispheres was identified. The skeletal muscle X-ray CT on the lower extremities revealed the atrophic flexor thighs and the anterior tibial and peroneal muscles. Needle EMG showed the prominent neurogenic changes in the atrophic muscles. Oral prednisolone therapy for four months relieved nystagmus and difficulty in walking, slightly. She, however, discontinued because of its side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow cytometric DNA analysis (FCM) of adrenal tumors was studied to evaluate whether FCM will be a useful examination for differentiating between benign and malignant adrenal tumors. 10 specimens of surgically resected (for renal cell carcinoma confined within the middle or lower pole) normal adrenal glands and 20 specimens of surgically resected adrenal tumors were submitted for the study. Hyperplastic adrenal cortex as well as normal adrenal gland showed normal diploid pattern. On the other hand, some of the cortical adenomas showed tetraploid patterns, which has been known to be an index of malignancy in most of the flow cytometric intervention to other solid tumors. Conn adenomas were especially apt to show this tendency, in which as much as 86% showed tetraploid pattern. Proliferation Index (PI) (ratio of S + G2 +M cells for the whole population of analyzed cells) were as much as 9.45 +/- 6.97% in normal adrenal cells, whereas it was much higher in cortical adenomas (17.75 +/- 8.53%). As a matter of fact, PI of hyperplastic adrenal cortex was within the same range as that of the normal adrenal glands. In pheochromocytomas, aneuploid pattern, which has been believed to be a definite index of malignancy, was shown in 60% of the cases, tetraploid pattern in 20%, and normal diploid pattern in only 20%. As a matter of fact, a case of non functioning cortical adenocarcinoma and a case of malignant pheochromocytoma were judged to show typical aneuploid pattern. Thus, the application of the flow cytometric diagnosis for adrenal tumors was supposed to require some refinement in understanding the significance of aneuploidy or tetraploidy.

A male with myelodysplastic syndrome (MDS) following aplastic anemia is reported. The patient had been diagnosed as aplastic anemia at 8 years of age, and treated with blood transfusions, anabolic and glucocorticoid steroid hormones. Over a period of subsequent twelve years, he had remission and deterioration. At the age of 21, the patient developed a sudden progression of severe anemia, when his bone marrow showed hyperplasia with prominent dyshematopoiesis and excess of blasts, compatible with MDS by the definition of FAB classification. He received low dose Ara-C therapy, which was ineffective. Nine months later he developed acute monocytic leukemia (M5b) and died. Chromosomal analysis revealed 46, XY at the onset of aplastic anemia, 46, XY, del (6) (q21 q27) at the MDS and 46, XY, -7, +21, 6q-/47, XY, +Y, -7, +21, 6q- at the acute leukemic stage.

A 34-year old female was admitted to our clinic because of fever and general fatigue on March 26, 1987. On admission, peripheral blood (PB) revealed pancytopenia. Bone marrow smears revealed 9. 0% of promyelocytic cells with or without Auer rods. Diagnosis of RAEB in transformation was made. Chromosome study of the bone marrow cells showed t(15; 17) in 3 out of 20 cells analysed. After 3 months, the leukemic cells were observed in PB and increased in number. Then the patient showed bleeding tendency and fibrin degradation products (FDP) increased up to 40 micrograms/ml. And the leukemic cells were over 30% in PB at the end of July, 1987. The diagnosis of APL with DIC was made. To our knowledge, this is the first case of APL with a history of MDS with t(15; 17).

Eight children with Philadelphia (Ph1) chromosome positive chronic myelocytic leukemia (CML) were available for cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis as compared to the features of adults with Ph1-positive CML. In chronic phase additional abnormalities other than Ph1 chromosome were found in none of our cases. On the other hand, in blastic crisis all of 6 cases had additional chromosomal abnormalities like as i(17q), double Ph1 and +8. The frequency of the appearance of additional chromosomal abnormalities, especially i(17q), is higher in children than in adult cases. In the DNA of 7 of 7 examined patients, rearrangement of bcr could be demonstrated by Southern blot analysis. These findings were similar to those observed in adults. An analysis of the location of the bcr breakpoint indicated that 5' breakpoints were found in four cases who were long-term survivors, and two of the other cases had blastic crisis from the onset of the disease. These findings showed the cytogenetic findings of children with Ph1+CML were different from those of the adult cases in the frequency of the appearance of the additional chromosomal abnormalities, and the location of the bcr breakpoint in children cases might be different from that in the adult cases and influence its prognosis.

This article reported a familial occurrence of intracerebral cavernous angioma in four members of one generation diagnosed by X-ray CT, MRI or operative specimen. Case 1, a 34-year-old female, was examined just after an episode of sudden convulsive seizure. On examination, she had a cutaneous angioma without any neurological deficit. X-ray CT revealed a high density mass lesion in the left frontal lobe, and MRI demonstrated a mass lesion in the chronic stage with an old hematoma circumscribed by hypointensity ring indicating peripheral hemosiderosis. Complete excision was carried out and a diagnosis of cavernous angioma was made after histological examination. Case 2, the 37-year-old brother of Case 1, suddenly developed left hemiparesis and hypesthesia with severe headache. X-ray CT revealed a high density mass in the right parietal lobe and two other calcifications. The right parietal lesion was excised and a histopathological diagnosis of cavernous angioma with intracerebral hematoma was made. Case 3, the 49-year-old sister of Case 1, suddenly fell into a coma and was admitted immediately. X-ray CT revealed a large pontine hemorrhage. She died on the 4th day of hospitalization without operative treatment. Necropsy was not carried out. Case 4, the 39-year-old sister of Case 1, was asymptomatic, however, she was examined on the supposition of a familial occurrence of intracerebral cavernous angioma. On examination, it was found she had multiple cavernous angioma without any neurological deficit. X-ray CT revealed parietal intracerebral calcification. MRI demonstrated a mass lesion with peripheral hypointensity ring in the right parietal lobe, and another small lesion in the pons.(ABSTRACT TRUNCATED AT 250 WORDS)

It seems to be important for the epidemiological study on cancer etiology to conduct molecular biological approach. IARC/WHO held "International Course on Molecular Biology for Epidemiologist" in order to promote the molecular epidemiology. I described here the content of the course and our study on lung cancer etiology using c-Ha-ras VTR marker of leukocyte DNA in peripheral blood, and discussed the possibility of molecular epidemiology.

The cisplatin (CDDP)-resistant subline TYK-nu (R) was developed by culturing TYK-nu (human ovarian cancer cell line in vitro) with exposure to CDDP in stepwise increasing concentrations. The characteristics of both cell lines were compared and the results were as follows; 1. Both cell lines formed a monolayer in a pavement-like arrangement and large cells were occasionally present in TYK-nu (R) rather than TYK-nu. The population doubling time of TYK-nu and TYK-nu (R) was 43 hr and 48 hr, respectively. 2. IC50 (microgram/ml) in 96 hr treatment with CDDP and carboplatin (CBDCA) was 0.035 and 0.5 in TYK-nu and 0.62 and 2.0 in TYK-nu (R), respectively. 3. In the intracellular CDDP concentration, there was no marked difference between TYK-nu and TYK-nu (R) after CDDP (2.0 micrograms/ml) treatment in 2hr. 4. After treatment with CDDP (0.2 microgram/ml) or CBDCA (2.0 micrograms/ml), a decrease in S and G2 + M compartments was observed in the pattern of the DNA histogram of TYK-nu, but not in that of TYK-nu (R). 5. The majority of chromosomes in both cell lines were in hyperdiploid areas and the mode of TYK-nu and TYK-nu (R) was 56 and 51, respectively. The karyotype of TYK-nu (R) showed deletion of chromosome 7q. Thus, compared to TYK-nu, TYK-nu (R) was 17.7 times more resistant to CDDP and 4 times more resistant to CBDCA. The results suggest that the mechanism of resistance to CDDP may be due to genetic changes at the cellular level.

Familial polyposis coli (FPC) is a genetic disorder, transmitted as an autosomal dominant trait, characterized by numerous colorectal adenomas. If untreated, most patients may develop colorectal adenocarcinomas. We investigated linkage between FPC and several DNA markers, and loss of heterozygosity in colorectal tumors by using RFLP analysis. We examined 15 pedigrees for linkage analysis and 31 FPC patients including 16 adenocarcinomas and 43 adenomas and 15 non-polyposis colorectal carcinomas (NPCC) for searching loss of heterozygosity. 1. Significant linkage was not observed with 26 polymorphic DNA probes. Maximum lod score of 0.301 at a recombination fraction of 0.0 was observed with the marker D5S71, which was reported to be tightly linked to the major gene for FPC in Caucasian. 2. Loss of heterozygosity was observed at the loci on 17 chromosomes in colorectal carcinomas from FPC patients, and on 6 chromosomes in NPCC. Thus, chromosomes in FPC patients may be unstable compared with those in patients with NPCC. 3. Frequent loss of heterozygosity in colorectal carcinomas from FPC patients was observed on chromosomes 5 (20%), 14 (22%), 17 (43%) and 22 (38%), and was also observed on chromosomes 5 (33%), 14 (38%), 17 (27%) and 22 (15%) in NPCC. These results suggest that tumor suppression genes may locate on these chromosomes. 4. Tumor suppression genes may play a role by dose dependent way.