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K Nakakuki

Publications and source records attributed to K Nakakuki.

At least 37 records · Page 2Linked to original sources

Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas.

The frequency of H-ras, K-ras, and N-ras mutations and the presence of high-risk human papillomavirus (HPV 16, 18, and 33) DNA were studied in 75 paraffin-embedded specimens obtained from 68 Japanese patients with a variety of prostate carcinomas by using polymerase chain reaction and DNA hybridization with sequence-specific oligonucleotides. Ten specimens each of normal and benign hyperplastic prostatic tissues from the same number of patients were also examined for this analysis. Of 68 carcinoma cases, ras gene mutations were present in 16 cases (24%) and HPV DNAs in 28 cases (41%). Eleven mutations were detected in codon 61 of H-ras, 4 in codon 12 of N-ras, and 2 in codon 61 of K-ras. HPV 16, 18, and 33 DNAs were found in 11, 17, and 5 cases, respectively. Eight of the 16 cases with ras mutation also harbored HPV DNAs. The frequency of ras mutations and the HPV infection increased in patients with advanced stages of the tumor and with the higher Gleason score. There was the predominant presence of H-ras codon 61.2 (CAG-->CTG) mutation and HPV 18 DNA in prostatic carcinomas metastasizing to the bone. None of the normal or benign hyperplastic prostatic specimens contained either ras mutation or HPV DNA. Our results suggest that ras gene mutations and HPV infections are relatively frequent, at least in prostate carcinoma of Japanese patients. These two factors appear to be related to the progression of the tumor. Moreover, H-ras codon 61.2 mutation and HPV 18 infection may have some predictive roles for bone metastasis in prostate carcinoma.

Aged↗

High frequency of human papillomavirus infection in carcinoma of the urinary bladder.

BACKGROUND AND METHODS: The prevalence of type 6, 11, 16, 18, and 33 human papillomavirus (HPV) was investigated with the polymerase chain reaction (PCR) on formalin-fixed, paraffin wax-embedded material, including 48 neoplastic and 21 normal urinary bladder specimens. The PCR-amplified DNA were analyzed by gel electrophoresis and dot blot and Southern blot hybridization. Some tissues were tested further by nonisotopic in situ hybridization. RESULTS: HPV DNA was detected in 39 (81%) of 48 carcinomas and 7 (33%) of 21 normal urinary bladder specimens. The presence of high-risk HPV (types 16, 18, and 33) was increased significantly in carcinoma cases (62%) as compared with normal specimens (14%) (P less than 0.01). Similarly, multiple HPV infections were significantly higher in carcinoma (60%) than in the normal tissues (5%) (P less than 0.01). The overall and high-risk HPV infections in both neoplastic and normal specimens were distributed almost equally in male and female patients. There was no significant correlation between positive results for HPV and histologic grades of the carcinoma. CONCLUSIONS: These results demonstrate that the urinary bladder in both sexes is another site where infection with the common genital tract HPV may carry a risk of malignant transformation.

Carcinoma↗

Detection of HPV DNA in neoplastic and non-neoplastic cervical specimens from Pakistan and Japan by non-isotopic in situ hybridization.

In order to determine the prevalence and type-specific distribution of human papillomavirus (HPV) in women from Pakistan, a country with a low cervical cancer rate (hospital-based data), and to compare these results with their counter-parts in Japan, we studied 56 non-neoplastic cervical tissues and 162 cervical carcinoma cases from both countries. HPV infection was defined by in situ hybridization in paraffin-embedded tissues using biotinylated HPV 6/11, 16 and 18 probes. The overall positivity rates in non-neoplastic and neoplastic cervical tissues from Pakistan were 33% and 88%, while in those from Japan the rates were 46% and 80%, respectively. High-risk HPVs (16 & 18) were found in 17% of the non-neoplastic specimens and in 69% of cervical carcinoma cases from Pakistan, while Japanese figures in this respect were 19% and 68%, respectively. No correlation was found between the type-specific distribution or prevalence of HPV and the geographic location of the cases examined in the 2 countries. However, in comparison to Japanese women, the incidence of HPV-16-positive cervical carcinoma in Pakistani women decreased significantly (p less than 0.05) in the oldest age group as compared to the youngest age group.

Adenocarcinoma↗

[Study of incidental carcinoma of the prostate. II. Nuclear DNA analysis].

The clinical significance of cytofluorometric nuclear DNA analysis, ploidy pattern and DNA content, was investigated in 47 incidental prostatic carcinomas, 24 stage A1 and 23 stage A2 cases, 9 clinically advanced cases and 25 BPHs. The results were compared to clinical stage and histological differentiation. The mean nuclear DNA content of stage A1 cancer, which was similar to BPH, differed from that of stage A2 cases. The latter was almost identical to that of advanced cases. In moderately and poorly differentiated carcinomas it was higher than that of well differentiated ones. A non-diploid pattern was distributed in 33% of stage A1, 78% of stage A2 and 89% of clinically advanced cases. It was detected in 42% of the well-, 77% of the moderately- and 100% of the poorly differentiated adenocarcinomas. The DNA analysis of incidental prostatic cancer thus correlated well to the clinical and pathological parameters. If limited to well differentiated carcinomas, however, 17% of the stage A1 cases showed an aneuploid, and 29% of the stage A2 cases, a diploid pattern. No diploid pattern was detected in clinically advanced cases. Although we have not been able to prove any difference in prognosis in the present cases, these findings suggest that the nuclear DNA analysis is another parameter in defining the prognosis of incidental prostatic carcinoma. Further follow-up of the patients and accumulation of the data are necessary to determine the clinical validity of this method.

Adenocarcinoma↗

Kinetic analysis of amyloid fibril polymerization in vitro.

We investigated the polymerization kinetics of murine senile amyloid fibrils (fASSAM) in vitro. When sonicated murine senile amyloid fibrils was incubated with its constituent monomer protein, the extension of amyloid fibrils was observed in an electron microscopic analysis. Quantitative fluorometric analysis with thioflavine T (Naiki H, Higuchi K, Hosokawa M, Takeda T: Anal Biochem 177:244, 1989) revealed that (a) extension of amyloid fibrils occurred by a pseudo-first-order exponential increase in the fluorescence of thioflavine T; (b) the rate of extension was maximal around pH 7.5, and was inhibited with the increase in KCl or NaCl concentration in the reaction mixture; (c) the rate of polymerization was proportional to the product of the murine senile amyloid fibrils number concentration and the constituent monomer protein concentration; (d) the net rate of extension was the sum of the rates of polymerization and depolymerization with the equilibrium association constant K of 5 x 10(7) M-1. These results show that amyloid fibril formation can apparently be explained by a first-order kinetic model: that is, extension of amyloid fibrils proceeds by consecutive association of precursor proteins onto the ends of existing fibrils.

Aging↗

[Study of incidental carcinoma of the prostate. Part 1. Pathological analysis related to the clinical features].

To clarify the clinico-pathological characteristics of incidental carcinoma of the prostate, we investigated a total of 590 prostatic tissues which had been operated under the diagnosis of benign prostatic hyperplasia (BPH), including 12 whole prostatic specimens which were obtained by total cystectomy due to bladder cancer. Histological examination and estimation of the tumor volume were carried out by either a 3-mm step-section in 185 prostates obtained by open surgery, or by mounting whole specimens in 405 TUR cases. Incidental cancers were detected in 69 of the 590 patients (12%) with nearly equal numbers of stage A1 and stage A2 diseases. The age and the size of the prostate were significantly greater in the patients with cancer, compared to those without cancer. However, these parameters were not in agreement with each other. Histological analysis revealed that 46 of the 69 (67%) incidental cancers were well differentiated and nearly corresponded to Gleason's sum score of 2-4. In the analysis of the differentiation of the tumor cells and the tumor extension, nearly 80% of the 23 well differentiated cancers were manifest in a single lesion and were smaller than 0.3 cm3, whereas 90% of the 11 moderately or poorly differentiated cancers were diffusely invasive. Six of the 11 cases (55%) were larger than 0.3 cm3. The prognosis of the 16 incidental cancer patients who had survived more than 5 years after the surgery were compared with the controls. The controls were selected among the cases without incidental cancer, and matched for age and the time of operation in a 1 to 2 fashion without knowledge of their prognoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Clinico-pathological investigation on frequency and prognosis in patients with incidental prostatic carcinoma: preliminary report].

To investigate the relationship between some clinico-pathological features of incidental prostatic carcinoma and its prognosis, totally 96 consecutive cases with simple prostatectomy from 1968 to 1973 under the diagnosis of prostatic hypertrophy were examined by the 3 mm step-section technique. Twenty-one cases (21.9%) of incidental carcinoma were detected histologically. The age of the patients with or without prostatic carcinoma ranged from 59 to 81 years old, 72.0 years old on the average, and from 54 to 87 years old, 69.9 years old on the average, respectively. The weight of the specimen varied from 7 to 84 grams, 32.4 g on the average, for the patients with carcinoma, and 10 to 64 grams, 29.7 g on the average, for the patients without carcinoma. Fifteen of 21 cases showed well differentiated carcinoma. None of the Japanese histological differentiation, Gleason's classification and volume of carcinoma presumably affected the survival of the patients.

Aged↗

[A case of primary signet ring cell carcinoma of the bladder].

A 41-year-old man visited our clinic with complaints of gross hematuria and pain on urination. Cystoscopic examination revealed papillary and sessile tumor at the retrotrigone of the bladder and the specimen of the transurethral biopsy showed signet ring cell carcinoma. Since there was no primary tumor in any other organs, we diagnosed it as a primary signet ring cell carcinoma of the bladder. Total cystectomy with Kock continent ileal reservoir and post-operative chemotherapy consisting of cisplatinum, adriamycin and 5-FU were performed. The literature on the pathological findings of this disease are reviewed.

Adenocarcinoma, Mucinous↗

Implantation of colon cancer cells onto renal pelvic mucosa. A case report.

We report here on a patient with recurrent sigmoid colon carcinoma. Postmortem examination revealed a fist-sized tumor in the retroperitoneum, invasive to the left ureter obstructing its lumen causing hydronephrosis of the ipsilateral kidney. Histological examination of the kidney showed multiple foci of adenocarcinoma cells on the pelvic surface. Invasion into the underlying tissue was not observed, and there was no tumor in the submucosal tissue of the pelvis or in the parenchyma of the left kidney. Cancer cells on the renal pelvic mucosa showed strong immunoreactivities for CEA and CA 19-9. These findings suggest that the tumor foci in the pelvis are formed by the intraluminal implantation of colon cancer cells detached from the ureteric metastasis. Our case presents the possibility of the implantation of carcinoma cells in the human urinary tract.

Adenocarcinoma↗

Trends in frequency of latent prostate carcinoma in Japan from 1965-1979 to 1982-1986.

By analyzing serial step-sections of whole prostate obtained at autopsy, we determined the chronologic change of the frequency of latent prostate tumor in Japan in two periods: 1965-1979 and 1982-1986. Methods of specimen preparation and examination were identical for both periods. The frequency with which latent prostate carcinoma was found in the 660 samples for 1982-1986 was 34.6% and was significantly higher than the 22.5% seen in the 576 observed for 1965-1979 (P less than .0001). This significant finding can be attributed to an increase in the frequency of latent infiltrative tumor (LIT). However, the increase in the frequency of noninfiltrative tumor (LNT) was less significant (P = .045). Both sets of specimens were subsequently combined and reanalyzed according to the year of birth of the decedents. The LIT has progressively increased in frequency in each age-specific category. By morphometry, we determined that the mean tumor volume decreased due to an increase in the number of smaller tumors during the study periods. Although the frequency of latent prostate carcinoma and the LIT:LNT in the samples obtained most recently were comparable to those of U.S. whites, cancer incidence and mortality rates remain lower in Japan. Apparently, the initial step in the induction of prostate carcinoma in indigenous Japanese is now similar to that in U.S. whites. The rates of clinical carcinoma in Japan are still low when compared with those in the United States and countries in Western Europe, but our findings may presage a time when these differences may be greatly reduced or nonexistent.

Adenocarcinoma↗

Cytogenetic demonstration of out-of-phase DNA synthesis in endoreduplicated CHO cells: evidence for partial endoreduplication.

Out-of-phase DNA synthesis, which is demonstrated cytogenetically as premature chromosome condensation (PCC), was analyzed in endoreduplicated Chinese hamster ovary (CHO) cells induced by colchicine or vincristine. Like conventional polyploid cells, endoreduplicated cells exhibited PCC in either S or G2. The former was more frequently observed in drug-treated cultures. In addition to these two types of PCC, other mitotic figures showing out-of-phase DNA synthesis were found. Such cells contained both conventional chromosomes (monochromosomes) and diplochromosomes. Differential FPG staining of chromatids in these cells showed that diplochromosomes incorporated BrdU twice while monochromosomes did so once, indicating the occurrence of partial endoreduplication in one of the sister nuclei of multinucleate cells. The possible mechanisms underlying induction of out-of-phase DNA synthesis and production of partial endoreduplication are discussed.

Animals↗

A positive difference in nature of envelopes of thymus- and uterus-derived leukemia viruses of AKR mice.

Thymus-derived leukemia virus of AKR/J mice was inactivated by anti-theta antiserum. But it was not inactiviated by the antiserum which had been absorbed with intact thymus cells of AKR/J or RF/J mice, and by anti-uterus-derived leukemia virus antiserum. In contrast, uterus-derived leukemia virus of the strain was not inactivated by anti-theta antiserum, but was neutralized by anti-uterus-derived leukemia virus antiserum. The results suggest the possibility that some constitutents of the envelope of thymus-derived leukemia virus are derived from the plasma membrane of thymus cells of AKR mice at the time of budding and that such constituents are not associated with the enveloped of uterus-derived leukemia virus.

AKR murine leukemia virus↗

[A case of neuro-Behcet's syndrome in a woman (author's transl)].

An autopsy case of Neuro-Behçet's syndrome is reported with review of the previous 13 cases. A 48-year-old woman who had recurrent oral aphthae and genital ulcers beginning at the age of 27 years suddenly developed several neurological symptoms including headache, paraplegia and disturbance of speech. She died of septicemia due to the urinary infection 22 years after the appearance of the first symptoms and one year after the neurological manifestation. Autopsy revealed a marked atrophy of the frontal lobes of the cerebral hemispheres. Microscopic changes in the central nervous system were consisted of edema and lymphocytic cuffing around the vessels, small foci of softening of the white matter and accumulation of fat-laden cells around these foci, and demyelination. These histologic lesions showed a diffuse distribution in the entire brain without a characteristic localisation, but involvement of the basilar nuclei and the pons was most intense in the present case as observed in most of the previous reports. Microscopic examination of other organs revealed severe pyelonephritis and fatty changes of the liver.

Atrophy↗

A spontaneous transplantable osteogenic sarcoma in AKR/Ms mice.

A transplantable osteogenic sarcoma originally arising in the right femur of an AKR/Ms male mouse is described. The original tumor showed a conspicuous bone and cartilage formation, but the capability of forming the bone was lost in the 4th transplant generation and that of cartilage formation was lost in the 7th generation. Alkaline phosphatase activity was histochemically demonstrated in only a few tumor cells, and the activity did not rise in the host serum. Intracisternal type-A particles of an average diameter of 70 nm were abundant in the rough endoplasmic reticulum, while type-C particles were rarely found to be budding from the cell surface or free in the extracellular spaces by electron microscopy. Three of the 27 thymectomized AKR mice that had been neonatally injected with cell-free material of the transplanted tumor developed osteomas, but no osteogenic sarcoma was found.

Alkaline Phosphatase↗