Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats.

Although the MHC class II 'u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II 'a' and 'u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II 'a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis.

[A case of bilateral renal cell carcinoma showing a rapid course of death in a long-term hemodialysis patient due to polycystic kidney].

A case of bilateral renal cell carcinoma in a 42-year-old polycystic kidney male is reported. He had been treated with hemodialysis for 22 years. An abnormal small mass was found in one of the left renal cystic lesions by screening ultrasonography and CT scan at the 19th year of the hemodialysis. Left radical nephrectomy was performed and the histological diagnosis was a renal cell carcinoma (RCC). There was no evidence of recurrence and metastasis, however, he presented with asymptomatic macrohematuria two years after the operation. CT scan demonstrated the rapidly progressing right renal tumor and multiple para-aortic lymph node swelling. Right nephrectomy and lymphadenectomy were performed and pathological examination showed the advanced RCC with multiple lymph node metastasis. Eleven months after the second operation followed by interferon therapy. he died of multiorgan metastasis of the RCC. This is the first bilateral RCC case in polycystic kidney patient treated with hemodialysis in Japan.

[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

[Two cases of primary carcinoma developed in a vesical diverticulum treated with ileal neobladder for total bladder replacement].

Two cases of carcinoma developed in vesical diverticulum were encountered. Both these males, the first, 66-year-old and the second case, 68-year-old gentleman, visited our clinic with a complaint of asymptomatic gross hematuria. Total cystectomy was performed, and an ileal neobladder was constructed for total bladder replacement in both two cases. Pathological examination of the first case revealed transitional cell carcinoma, and the second case showed adenocarcinoma mixed with transitional cell carcinoma. Although primary carcinoma developed in vesical diverticulum was initially reported by Williams in 1883, adenocarcinoma is very rare. The diagnosis is often challenging and the prognosis is dire. Both our cases were successfully treated with total cystectomy and an ileal neobladder was constructed for total bladder replacement. Careful management and aggressive therapy for such patients may make even cure possible.

[A case of malignant mesothelioma of the tunica vaginalis testis].

A case of malignant mesothelioma of tunica vaginalis testis experienced in an 83-year-old male who presented with a complaint of left intrascrotal pain is reported. The tentative diagnosis was acute epididymitis. Left epididymectomy was performed following the unsuccessful treatment with antibiotics. The histology of the surgical specimen revealed malignant mesothelioma. Radical excision of the left spermatic cord and scrotal content indicated locally advanced disease with positive surgical margin. Metastatic workup, including abdominal and chest computerized tomography scan, magnetic resonance imaging and bone scan demonstrated presence of metastasis to the paraaortic lymph nodes and the lumber spine. The patient is being followed conservatively in consideration of his age and advanced stage of the disease.

Alternative splicing of hepatitis B virus RNAs in HepG2 cells transfected with the viral DNA.

We identified a novel spliced RNA of 2.6 kb from a human hepatoma cell line HepG2 transfected with the hepatitis B virus (HBV) genome. The splicing acceptor site of the novel 2.6-kb RNA (position 489) was shown to be common to that of the previously described 2.1-kb spliced RNA which codes for an altered core antigen lacking the carboxy-terminal amino acid, cysteine. However, the donor site of the 2.6-kb RNA is different from any of the spliced RNA reported and located at 538 nucleotides (nt) downstream of the donor site of the 2.1-kb RNA. Introduction of single-base change mutations in the consensus sequence of the donor site of the 2.1-kb RNA maintained the splicing by using the cryptic donor site. The amount of the 2.6-kb spliced RNA was unchanged by these mutations. These results suggest independent regulations for the synthesis of the 2.1- and 2.6-kb spliced RNAs.

Detection and mapping of spliced RNA from a human hepatoma cell line transfected with the hepatitis B virus genome.

HepG2 cells, known to support the replication and virion formation of hepatitis B virus (HBV), were transfected with a cosmid constructed to contain 12 tandem head-to-tail repeats of the HBV genome for effective HBV genome expression. We detected previously identified RNAs of 3.3, 2.3, and 2.0 kilobases (kb) that code for core antigen, large surface antigen, and middle/major surface antigen, respectively. We also detected four additional RNAs of 2.1, 1.7, 1.1, and 0.7 kb [the lengths exclude the poly(A) tail]. S1 mapping and nucleotide sequencing data showed that the 2.1-kb RNA is a spliced RNA whose 5' and 3' ends are identical to those of the 3.3-kb RNA. The results suggest that the 2.1-kb RNA codes for an altered core antigen lacking the last amino acid, cysteine, and that expression of the 3.3-kb pregenomic RNA is regulated, at least in part, by splicing. The map positions of the 1.7- and 1.1-kb RNAs suggest that they code for the carboxyl-terminal portions of the putative polymerase, whereas the 0.7-kb RNA codes for the X protein.