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A Japanese woman with condyloma acuminatum of the urinary bladder is presented. The condyloma acuminatum lesion was resected endoscopically and human papillomavirus 6/11 DNA was detected. After treatment, there has been no recurrence of the disease.

A simple method has been developed for detecting a broad range of genital human papillomavirus (HPV) types using the polymerase chain reaction (PCR). We utilized two consensus sequence primer pairs within the E6 and E7 open reading frames to amplify HPV DNA; malignant HPV DNA (from HPV-16, -18, -31, -33, -52b and -58) was amplified using the pU-1M/pU-2R primer pair whereas benign HPV DNA (from HPV-6 and -11) was amplified using the pU-31B/pU-2R primer pair. Identification of the amplification product was confirmed by restriction enzyme digestion. In this study, a pU-1M/pU-2R-mediated PCR was successfully applied to 39 cervical carcinoma specimens; HPV-16 was detected in 19 cases, HPV-18 in five cases, HPV-31 in two cases, HPV-33 in two cases, HPV-52b in one case, HPV-58 in three cases, and an unknown type(s) was detected in four cases. Overall, the prevalence of HPV was 84.6%. The results indicate that this detection system is useful for the detection of HPVs not only of known types but also of new types.

Ninety-two cervical scrapes and tissues, obtained from cytologically or histologically normal cervices of Japanese women, were examined for the presence of human papillomavirus (HPV) 16, 18 and 33 DNA by the polymerase chain reaction (PCR) method. Five out of 92 cases were HPV 16 DNA-positive, but neither HPV 18 nor 33 DNA was detected. The HPV (type 16, 18 and 33) prevalence rate in pregnant women, including postpartum, was 10% (3/31), which was higher than that in non-pregnant women. In two HPV 16-positive cases, we detected HPV 16 DNA again 2 months later. HPV (type 16, 18 and 33) prevalence in normal cervices was shown to be relatively low. However, it is very important to follow up the HPV-positive cases in cytologically normal cervices in order to elucidate the relation between HPV infection and the progression of cervical cancer.

We have established a highly sensitive method for specific detection of human papillomavirus (HPV) 16, 18 and 33, by using the polymerase chain reaction (PCR). A HPV‐related sequence (140 bp) in the E6 transforming region was specifically amplified and detected by gel electrophoresis and by the use of a specific oligonucleotide probe. The PCR could detect 10‐5–10‐6 copies per cell (maximum sensitivity). Furthermore, HPV 16, 18 and 33 DNAs were synthesized in a common reaction solution and specifically detected by HPV type‐specific probes. The PCR detected the HPV sequence from tissues which were negative to Southern hybridization. This detection technique may contribute significantly to the precise analysis of HPV in small proliferative lesions in the cervix.

Variation in the nucleotide sequence of the HPV 16 E7 gene in preinvasive cervical intraepitherial neoplasia (CIN) and invasive cervical carcinoma specimens was analyzed. Direct DNA sequencing of PCR-amplified products with primers different from those used for PCR with 5'-end labeling generated distinct sequence ladders with a low background, even in specimens containing relatively low copy numbers of HPV. Of 14 cervical neoplasias, 11 cases showed sequence diversity from prototype HPV16, and a total of 22 nucleotide exchanges were detected. Nine of these led to single amino acid exchanges: [Thr5] to [Lys5] in one case and [Asn29] to [Ser29] in eight cases. The [Ser29] E7 was distributed uniformly among invasive carcinomas and precancerous legions, and was also found in a normal cervix. The [Lys5] E7 and [Ser29] E7 had transforming potential similar to the prototype E7 assessed by cooperation with the activated ras gene in rat embryo fibroblasts.

Using in situ hybridization, human papillomavirus (HPV 6, 16, 18, 31, 33) DNAs were detected in a cervical severe dysplasia accompanied by squamous metaplasia. It was found that, only HPV 31 DNA was harbored in the cervical severe dysplasia, but HPV DNAs were not identified in a lesion of squamous metaplasia. The in situ hybridization method will be of use, therefore, when dysplasia with squamous metaplasia or other lesions are examined for HPV DNA. In a cervical smear, HPV 31 DNA could be detected on the nuclei of dysplastic cells, so this method is applicable to cervical smears. If squamous metaplasia is to be considered as a precursor lesion to cervical dysplasia, the HPV DNA harbored in the dysplasia must also be detected in the accompanying squamous metaplasia. Our results suggested that not all squamous metaplasias were involved with HPV, as far as we were able to detect using five types of HPV DNA probe.

Urological tumors were examined for the presence of human papillomavirus (HPV) DNA by using Southern blot hybridization. In 20 male patients with condyloma acuminatum, HPV type 6 was found at 85% (17/20), HPV type 11 at 95% (19/20), HPV type 16 at 5% (1/20) and HPV type 18 at 0% (0/20). In 2 female patients with condyloma acuminatum, HPV types 6, 11, 16 and 18 were found at 100% (2/2), 100% (2/2), 50% (1/2) and 0% (0/2), respectively. All 6 of the patients who were positive for HPV type 6, were also positive for HPV type 11. Two patients were positive for HPV types 6, 11 and 16, the last of which was frequently found in penile cancer and uterine cervical cancer. In 6 patients with penile cancer, two patients were positive for HPV type 16 and negative for HPV types 6, 11 and 18. The remaining 4 patients were negative for all these HPV types. One patient who was positive for HPV type 16 had penile cancer after three previous episodes of penile condyloma acuminatum. From this information, a malignant change in the condyloma acuminatum was assumed to indicate the possible association of HPV type 16 with the process of malignant degeneration. HPV types, 6, 11, 16 and 18 were not detected in a female patient with vulvar cancer. Although HPV was thought to participate in the development of urological tumors except for external genital tumors, all patients examined, consisting of 2 with benign prostatic hypertrophy, 5 with prostatic cancer and 24 with bladder cancer, were negative for HPV types 6, 11, 16 and 18. Eight patients with bladder cancer were negative for HPV type 33.

われわれは管理職者グループを対象に過去12年間にわたり健康管理を行なっているが, このグループ内における広範囲胃切除例の遠隔成績について年代別に比較検討し, 高年者群に対する術後管理上の注意などについて考察した.症例は広範囲胃切除術後1年以上6カ月間隔で定期的に術後管理をうけている72例である. 年代分布は40歳代以下18例, 50歳代28例, 60歳代以上26例で, 性別は男性71例, 女性1例, 術式はビルロートI法71例, ビルロートII法1例である. 原胃疾患は進行胃癌5例, 早期胃癌16例, 胃潰瘍23例, 十二脂腸潰瘍6例, 胃ポリープ15例, 胃炎6例, その他1例である.まず, 外科的遠隔疾患では, 胆石症が7例に認められたが, 60歳代以上の例ではみられないのが注目された. 症状については, 術後6カ月以上では全体に少なく年代的に著しい差はみられない. 摂食状況および就業状況についてもとくに高年者で不利とはいえないようである.術後体重の推移は, ほとんどの症例で術後5年以上経過すると安定しているが, 若年者ほど良好な経過を示し, 術前すでに標準体重±5.0kgの範囲より低下している高年者では, 体重の改善は期待できないようである. 血色素量の変動も術後5年以上で安定する例が多いが, 高年者群では低血色素状態の出現率が高い. 血清蛋白の推移は, 各年代とも良好で年代による差はほとんどみられず, 肝機能障害による影響が大きいと考えられる.したがって, 60歳代以上の高年者群に対しては体重, 血色素量の経過に注意し, とくに長期にわたる定期的健康管理が必要であると思われる.

A mixed intestinal adenocarcinoma-argentaffin carcinoma of the vagina in a 32-year-old woman is reported. Special stains showed the argentaffin and argyrophil reactions of the small cell population of this tumor. The small cells also contained serotonin as demonstrated by immunocytochemistry. Electron microscopy revealed characteristic cytoplasmic neurosecretory granules. The large cells were columnar and contained mucin droplets similar to those in Goblet cells in the intestines. The observations suggest that the tumor was mixed intestinal adenocarcinoma-argentaffin carcinoma (malignant carcinoid), which probably arose in aberrant intestinal epithelial cells in the vagina. The patient died with metastases of pure argentaffin carcinoma in 1 year.

A case of peritoneal melanosis secondary to a ruptured benign cystic teratoma in a 28-year-old woman is reported. The patient had no history of cutaneous or ocular malignant melanotic lesions. The section of the left ovary contained benign teratoid elements. The ultrastructure of the omental and peritoneal pigmented nodules confirmed that the lesions consisted of histiocytes phagocytizing massive melanin pigments. Although no melanocytic neoplasm was found in the ovarian cystic teratoma, circumstance suggests that the ovarian, omental, and peritoneal pigmented lesions were secondary reactions to melanin released from the ruptured cystic teratoma.

Granulosa cells were obtained from human ovarian follicles. In cultured granulosa cells obtained from large follicles clear-cut ultrastructural features of steroid secreting cells were not observed due to the paucity of smooth endoplasmic reticulum. This is in keeping with their low progesterone secretion rate as measured by the RIA method and seems to indicate an early stage of luteinization. In cultured granulosa cells obtained from small follicles, oil-red-O-stained lipid droplets were observed mostly in stromal cell layers, while in large follicles under light microscopy these were located in the granulosa cell layers. These lipid droplets may play an important role in progesterone production, but the amount of lipid clearly does not always reflect active hormone secretion, since the above results indicated low progesterone secretion. Numerous intracellular microfilaments were seen under electron microscopy in cultured granulosa cells obtained from large follicles over a 3-day period. During this same time, progesterone production increased, and then decreased gradually. The microfilaments in granulosa cells may, therefore, be related to progesterone production.

Immunologic evaluations of women with genital neoplasia-papilloma syndrome demonstrated the presence of subclinical immunodeficiency when compared with results in 20 control women. All patients with genital neoplasia-papilloma syndrome were previously found to have human papillomavirus deoxyribonucleic acid in genital neoplasias or papillomas occurring either synchronously (in at least two genital organs at the same time) or metachronously (at different times during a period of months to years). Immunologic tests included blastogenic responses of lymphocytes to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen, and tetanus antigen) and lymphocyte phenotyping with the use of monoclonal antibodies (OKT3, OKT4, OKT8, and OKT11). As compared with those of control subjects, the responses of the lymphocytes of patients with genital neoplasia-papilloma syndrome to mitogens were significantly decreased. The group with genital neoplasia-papilloma syndrome had a significantly higher percentage of suppressor-cytotoxic T cells (OKT8-positive cells) when compared with that of control subjects (mean 33% versus 18%) and a lower proportion of helper T cells (OKT4-positive cells) when compared with that of control subjects (35% versus 50%). The mean helper-to-suppressor/cytotoxic T-cell ratio (mean OKT4/OKT8 ratio) in the human papillomavirus-infected women was 1.72 +/- 0.29 (SE) as compared with 3.21 +/- 0.33 (SE) in the control group, demonstrating a significant reduction of the ratio in the patients with genital neoplasia-papilloma syndrome. These findings suggest that patients with genital neoplasia-papilloma syndrome have a reduced suppressor/cytotoxic T-cell ratio (mean OKT4/OKT8 ratio; that in the human papillomavirus-infected women was 1.72 +/- 0.29 (SE) as compared with 3.21 +/- 0.33 (SE) in the control group, demonstrating a significant reduction of the ratio in patients with genital neoplasia-papilloma syndrome. These findings suggest that patients with genital neoplasia-papilloma syndrome have reduced immunocompetence of unknown etiology.

The spectrum of vulvar intraepithelial neoplasia (VIN) was investigated with human papillomavirus (HPV) DNA probes by Southern blot hybridization technique. The results of vulvar tissue examinations from 25 patients were compared to prior genital and systemic diseases, clinical presentation, and histopathologic manifestations. The presence of HPV DNA in these lesions was largely associated with multifocality of the lesions, the presence of synchronous and metachronous multicentric genital neoplasia, and depressed immunocompetence. These findings indicate that VIN is associated with HPV and may have an infectious etiology.

The sensitivity in detecting human papillomavirus (HPV) by histological observation of koilocytosis, immunocytochemistry, and electron microscopy with reference to the results of Southern blot deoxyribonucleic acid (DNA) hybridization were reviewed in 41 lesions (37 patients) of cervical and vaginal condylomata acuminata and intraepithelial neoplasia. Human papillomavirus DNA was demonstrated in fresh tissues by Southern blot DNA hybridization in all but one lesion of moderate dysplasia (98%). The rate of koilocytosis observed in tissue sections was 80% in condyloma, and ranged from 89-20% in cervical intraepithelial neoplasia (CIN), with steady reduction as the grade of CIN or vaginal intraepithelial neoplasia (VaIN) was higher. The immunocytochemistry for HPV capsid antigens was positive in 80% of condylomata and ranged from 61-0% in CIN or VaIN. The rate declined in inverse proportion to the grade of CIN or VaIN. Electron microscopy of preselected areas containing intranuclear inclusions in paraffin sections of 10 lesions demonstrated HPV-like particles in 90% of the lesions. Although immunocytochemistry and observation of koilocytosis may be useful in detecting HPV in condylomata acuminata and mild dysplasia, their sensitivity was poor in CIN or VaIN of higher grades. Electron microscopy on preselected areas in paraffin blocks showed better sensitivity, presumably due to its ability to detect immature virions.