Normal gonadal development in mice lacking GPBOX, a homeobox protein expressed in germ cells at the onset of sexual dimorphism.

Gpbox is a paired-like homeobox gene that colocalizes with two other members of the family, PsxI and Pem, on the proximal portion of the mouse X chromosome. Gpbox is expressed in the extraembryonic placenta and within the germ cells of the embryonic gonad. Beginning with the onset of sexual dimorphism (embryonic day [E]11.5 to 12.5), GPBOX transcripts accumulate faster in female than in male germ cells but disappear later in embryogenesis (E16) and have not been reported in adult tissues. To investigate the function of Gpbox, mouse cell lines lacking GPBOX were established using targeted mutagenesis in embryonic stem cells. Both homozygous Gpbox null female and hemizygous Gpbox null male mice were fertile and reproduced normally. Additionally, the development of male and female gonads in the null background was indistinguishable from that observed in normal littermates. The lack of an obvious phenotype raises the possibility that another member of this homeobox gene family provides the absent Gpbox function.

Gpbox (Psx2), a homeobox gene preferentially expressed in female germ cells at the onset of sexual dimorphism in mice.

XX gonads differentiate into ovaries, a morphologic event evident by embryonic day 13.5 (E13.5) in mice. To identify early markers of oogenesis, sex-specific urogenital ridge cDNA libraries were constructed from E12-13 embryos. After mass excision and isolation of plasmid DNA, approximately 4800 expressed sequence tags were determined and compared to existing databases. Few cDNAs were specifically expressed in the urogenital ridge, but one, designated GPBOX, encodes a 227-amino-acid homeobox protein that is first expressed at E10.5 in the embryo as well as in the extraembryonic tissues. The Gpbox gene is single copy in the mouse genome and is located on the X chromosome in close proximity to two other homeobox genes, Pem and Psx1. Within the embryo, its expression is limited to the gonad, and transcripts are not detected in adult tissues. Although comparable levels are initially present in both sexes, GPBOX transcripts accumulate faster in female germ cells and peak at E12.5 when they are present in fivefold greater abundance than in males. The persistence of GPBOX transcripts in female germ cells until E15.5 and their virtual disappearance in males by E13.5 suggest that Gpbox may play a role in mammalian oogenesis.

Detection of the ongoing sorting of ancestrally polymorphic SINEs toward fixation or loss in populations of two species of charr during speciation.

The FokI family of short interspersed repetitive elements (SINEs) has been found only in the genomes of charr fishes (genus Salvelinus). In an analysis of the insertion of FokI SINEs using PCR, we characterized six loci at which FokI SINEs have been inserted into the genomes of Salvelinus alpinus (Arctic charr) and/or S. malma (Dolly Varden). An analysis of one locus (Fok-223) suggested that a sister relationship exists between S. alpinus and S. malma and the SINE at this locus might have been inserted in a common ancestor of these two species, being fixed in all extant populations examined. By contrast, SINEs at two other loci (Fok-211 and Fok-206) were present specifically in the genome of S. alpinus, with polymorphism among populations of this species. Moreover, the presence or absence of the SINEs of the other three loci (Fok-214, Fok-217, and Fok-600) varied among populations of these two species. The most plausible interpretation of this result is that SINEs, which were ancestrally polymorphic in the genome of a common ancestor of these two species, are involved in an ongoing process of differential sorting and subsequent fixation in the various populations of each species.

[Retroperitoneal Castleman's disease occurred around the bilateral upper ureters. A case report].

A 45-year-old woman with a history of right regional dull pain was referred to our hospital for evaluation of right hydronephrosis. CT and MRI showed a solitary mass (1 x 1 cm, L1-L2 level) at the right upper ureter. Laboratory data were within the normal range. A right nephrectomy was carried out under a clinical diagnosis of primary right ureteral tumor. The pathohistological diagnosis of surgical specimen was plasma cell type of Castleman's disease. One year after surgery, the patient was rehospitalized for azotemia and left hydronephrosis. Abdominal CT revealed a solitary mass (1.5 x 1.5 cm) located at left upper ureter similar to that on her right side. We diagnosed that the mass lesion was due to asynchronous Castleman's disease, so we performed steroid therapy. After the treatment, mass had disappeared. The patient is uneventful for two years. This is the first case reported in the Japanese literature describing Castleman's disease occurred around the bilateral upper ureters.

[Priapism treated by caverno-glandular shunt, caverno-saphenous shunt and caverno-spongiosum shunt: report of a case].

A 44-year-old man visited a local urologist complaining of continuous pain and tumescence at penis persisting for 3 days. He was diagnosed with priapism. A caverno-glandular and caverno-saphenous shunt was performed. He presented to our hospital 3 days later, because the symptoms especially tumescence continued. We confirmed the diagnosis of low-flow priapism from cavernosography and intracavenal blood-gasometry and performed caverno-spongiosum shunt. Detumescence was finally achieved after the operation.

[Primary cardiac non-Hodgkin's lymphoma].

A 69-year-old man who initially presented with lumbago developed heart failure during an MRI scan on the day of admission. A chest X-ray showed cardiomegaly and bilateral pleural effusion. Echocardiogram and computed tomography (CT) scan of the chest revealed a large tumor mass encompassing the heart with much pericardial effusion was demonstrated. The cytology of the effusion obtained by pericardiocentesis was consistent with non-Hodgkin's lymphoma, diffuse large B cell type. As CT scans of the abdomen and pelvis were negative, he was considered to have primary cardiac lymphoma. Although he responded remarkably to therapy with vincristine, cyclophosphamide and prednisolone and, he developed acute respiratory failure on the seventh month after admission. Although incidence of primary cardiac lymphoma is very low, it is necessary to investigate the mechanism of this disease in order to establish appropriate diagnostic and therapeutic approaches.

The salmon SmaI family of short interspersed repetitive elements (SINEs): interspecific and intraspecific variation of the insertion of SINEs in the genomes of chum and pink salmon.

The genomes of chum salmon and pink salmon contain a family of short interspersed repetitive elements (SINEs), designated the salmon SmaI family. It is restricted to these two species, a distribution that suggests that this SINE family might have been generated in their common ancestor. When insertions of the SmaI SINEs at 10 orthologous loci of these species were analyzed, however, it was found that there were no shared insertion sites between chum and pink salmon. Furthermore, at six loci where SmaI SINEs have been species-specifically inserted in chum salmon, insertions of SINEs were polymorphic among populations of chum salmon. By contrast, at four loci where SmaI SINEs had been species-specifically inserted in pink salmon, the SINEs were fixed among all populations of pink salmon. The interspecific and intraspecific variation of the SmaI SINEs cannot be explained by the assumption that the SmaI family was amplified in a common ancestor of these two species. To interpret these observations, we propose several possible models, including introgression and the horizontal transfer of SINEs from pink salmon to chum salmon during evolution.

Management conditions during dialysis therapy influence the occurrence of complications after renal transplantation?

We investigated whether the management condition of patients during dialysis therapy has an influence on the occurrence of complications after renal transplantation. Thirty-one patients who underwent renal transplantation were investigated: thirteen received kidneys from living related donors and 18 received cadaveric transplants. The relations between weight gain ratio, cardiothoracic ratio (CTR) and blood pressure during dialysis and the rate of episodes of acute rejection or infection after renal transplantation were analyzed. The rate of acute rejection tended to be higher among patients whose CTR was less than 45% than in those whose CTR was 45% or more. There was no relation found between the rate of infection after transplantation and weight gain ratio. CTR, or blood pressure during dialysis therapy. These results suggest the possibility that the management condition of patients during dialysis therapy influences the rate of acute rejection after these patients undergo renal transplantation.

Details of retropositional genome dynamics that provide a rationale for a generic division: the distinct branching of all the pacific salmon and trout (Oncorhynchus) from the Atlantic salmon and trout (Salmo).

Salmonid species contain numerous short interspersed repetitive elements (SINEs), known collectively as the HpaI family, in their genomes. Amplification and successive integration of individual SINEs into the genomes have occurred during the evolution of salmonids. We reported previously a strategy for determining the phylogenetic relationships among the Pacific salmonids in which these SINEs were used as temporal landmarks of evolution. Here, we provide evidence for extensive genomic rearrangements that involved retropositions and deletions in a common ancestor of all the Pacific salmon and trout. Our results provide genetic support for the recent phylogenetic reassignment of steelhead and related species from the genus Salmo to the genus Oncorhynchus. Several other informative loci identified by insertions of HpaI SINEs have been isolated, and previously proposed branching orders of the Oncorhynchus species have been confirmed. The authenticity of our phylogenetic tree is supported both by the isolation of more than two informative loci per branching point and by the congruence of all our data, which suggest that the period between successive speciations was sufficiently long for each SINE that had been amplified in the original species to become fixed in all individuals of that species.

Characterization of species-specifically amplified SINEs in three salmonid species--chum salmon, pink salmon, and kokanee: the local environment of the genome may be important for the generation of a dominant source gene at a newly retroposed locus.

Short interspersed repetitive elements (SINEs), known as the HpaI family, are present in the genomes of all salmonid species (Kido et al., Proc. Natl. Acad. Sci. USA 1991, 88: 2326-2330). Recently, we showed that the retropositional efficiency of the SINE family in the lineage of chum salmon is extraordinarily high in comparison with that in other salmonid lineages. (Takasaki et al., Proc. Natl. Acad. Sci. USA 1994, 91: 10153-10157). To investigate the reason for this high efficiency, we searched for members of the HpaI SINE family that have been amplified species-specifically in pink salmon. Since the efficiency of the species-specific amplification in pink salmon is not high and since other members of the same subfamily of SINEs were also amplified species-specifically in pink salmon, the actual sequence of this subfamily might not be the cause of the high retropositional efficiency of SINEs in chum salmon. Rather, it appears that a highly dominant source gene for the subfamily may have been newly created by retroposition, and some aspect of the local environment around the site of retroposition may have been responsible for the creation of this dominant source gene in chum salmon. Furthermore, a total of 11 sequences of HpaI SINEs that have been amplified species-specifically in three salmon lineages was compiled and characterized. Judging from the distribution of members of the same-sequence subfamily of SINEs in different lineages and from the distribution of the different-sequence subfamilies in the same lineage, we have concluded that multiple dispersed loci are responsible for the amplification of SINEs. We also discuss the additional possibility of horizontal transmission of SINEs between species. The availability of the sets of primers used for the detection of the species-specific amplifications of the SINEs provides a convenient and reliable method for identification of these salmonid species.

Sensitization interval and administration method alter the effect of 15-deoxyspergualin on heart transplantation in sensitized recipient rats.

We evaluated the effect of 15-deoxyspergualin (DSG) on accelerated rejection. Brown Norway rats (BN) served as organ donors and Lewis rats (LEW) as recipients. In an accelerated rejection model, after a LEW rat was sensitized with BN skin, a BN heart was transplanted. Various intervals between sensitization and heart transplantation were examined. The heart allografts in sensitized recipients were rejected earlier than those in unmodified recipients regardless of the sensitization interval. DSG (2.5 mg/kg per day), given to the recipients during the sensitization phase, significantly prolonged graft survival compared with the untreated hosts when the sensitization interval was short. When the recipients were treated with DSG after heart transplantation, heart graft survival was significantly prolonged regardless of the sensitization interval. Flow cytometric analysis and complement-dependent cytotoxicity tests revealed that DSG suppressed antidonor antibody formation and the postoperative administration of DSG significantly decreased the proliferation of B cells when the sensitization interval was short and the proliferation of class II antigen-positive cells when the sensitization interval was long.

[A case of testicular tumor associated with the contralateral undescended testis].

A 36-year-old man visited the hospital complaining of painless swelling of the right scrotal contents. His left scrotal contents were absent in the scrotum. Right inguinal orchiectomy was performed on May 17, 1993 under the diagnosis of testicular tumor. The pathological diagnosis of the tumor was pure seminoma. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed the enlargement of para-aortic lymph nodes and there was a soft tissue signal in the left inguinal region which seemed to be the left testis in MRI. His serum testosterone level was low and gonadotropin level was high. The left orchiopexy was performed on June 24, 1993, but the left testis was finally removed because of methicillin-resistant Staphylococcus aureus (MRSA) infections. Radiation therapy was done against the metastatic lesion in the retroperitoneal lymph nodes and complete remission was obtained. The left undescended testis pathologically showed atrophy of germ cells but there was no appearance of atypia of Leydig cells or germ cells.

[Retroperitoneal lymph node dissection for patients with advanced testicular tumor].

We examined the indication for retroperitoneal lymph node dissection (RPLND) for 30 patients with advanced testicular tumor and made the following conclusion. The sequence of RPLND and primary chemotherapy made no difference in the therapeutic effect for patients with stage II A non-seminomatous germ cell tumor (NSGCT). However, we thought it better to administer primary chemotherapy prior to RPLND to prevent dissemination of tumor cells. Viable tumor cells often remained in retroperitoneal residual tumors even after chemotherapy in the patients with NSGCT advanced beyond stage II B. Therefore, RPLND seemed to be necessary if residual retroperitoneal tumors were found after the chemotherapy. In patients with seminoma, RPLND did not seem to be necessary if the residual tumor was less than 3 cm in diameter or the reduction rate of the retroperitoneal tumor was more than 80% after the initial therapy (chemotherapy or irradiation therapy.

Species-specific amplification of tRNA-derived short interspersed repetitive elements (SINEs) by retroposition: a process of parasitization of entire genomes during the evolution of salmonids.

Fourteen members of the Hpa I subfamilies of tRNA-derived SINEs in particular salmonid species were isolated from genomic libraries of chum salmon, kokanee, coho salmon, masu salmon, and steelhead. Alignment of the sequences of these 14 members, together with those of 4 members already published, 3 of which were previously demonstrated to have been amplified specifically in certain lineages, revealed the presence of five subfamilies with particular diagnostic nucleotides. The amplification of members of the same subfamily in different salmonid lineages and the amplification of members of different subfamilies in the same salmonid lineage suggest that multiple dispersed loci were responsible for amplification or, alternatively, that SINEs were transmitted horizontally between species. These two possibilities are not mutually exclusive. Our results also indicate that the Hpa I SINEs in salmonids behave like parasites. The amplification of these SINEs is ongoing and continues to shape the evolution of salmonid genomes.

Amplification of distinct subfamilies of short interspersed elements during evolution of the Salmonidae.

There are at least three different kinds of short interspersed repetitive elements in salmonid genomes. Of these, members of the HpaI family are found to be most widely distributed in salmonid species. The HpaI family is present with high copy numbers in all members of the subfamily Salmoninae, such as salmon, trout and charr. In order to determine whether the amplification of the Hpa sequence occurred rapidly within a short evolutionary period or gradually, over the long term, a search was made for Hpa sequences in primitive salmonids; namely, grayling and whitefish. A grayling species has fivefold fewer copies of these sequences than the Salmoninae species, whereas several whitefish species have 200-fold to 20-fold fewer copies than the Salmoniae species. Characterization of the Hpa sequences in these species allowed us to recognize two distinct Hpa subfamilies on the basis of diagnostic substitutions as well as a new short interspersed element with an Hpa-related sequence. The distribution of these sequences revealed that distinct members of the HpaI or Hpa-related family were amplified during establishment of each subfamily lineage in a manner very similar to the amplification of the human Alu family. We provide evidence for the validity of a model that involves "multiple source genes" to explain diagnostic substitutions of the Hpa subfamilies and the timing of their appearance during evolution.

[Adrenal ganglioneuroma: report of a case].

A 52-year-old man was hospitalized for a right adrenal tumor which had been incidentally found by abdominal CT scan for examination of colon cancer. Laboratory and endocrine findings were within the normal limits except for increased urinary concentrations of noradrenaline and dopamine. Adrenal angiography revealed that the feeding artery of the tumor was the inferior suprarenal artery. Adrenal venous blood sampling studies detected no abnormalities in the concentrations of catecholamine, cortisol or aldosterone. Right adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma. Ganglioneuroma is a benign tumor originating from the sympathetic nerve ganglion. The adrenal origin of the tumor is relatively rare and 60 cases of adrenal ganglioneuroma including our case have been reported in Japan.

Endobronchial metastasis from a primary uterine osteosarcoma in a patient with multiple myeloma: report of a case.

We present herein the case of a 75-year-old woman with multiple myeloma who underwent a left lower lobectomy for endobronchial metastasis from an uterine osteosarcoma. She had initially been admitted to our hospital for chemotherapy more than 1 year earlier, soon after which a primary uterine osteosarcoma was discovered and a total abdominal hysterectomy and bilateral salpingo-oophorectomy performed. One year after the operation, the patient developed hemoptysis. A flexible bronchofiberscopy demonstrated a polypoid mass obstructing the left basal bronchus, and computed tomographic scans showed three pulmonary nodules. Surgery was performed to control the hemoptysis. At thoracotomy, two metastatic nodules were identified in the left lower lobe, and the endobronchial extension of the tumor was resected en bloc with the left lower lobe. The tumor was diagnosed as lung metastasis from the uterine osteosarcoma. Although further lung tumors have recently appeared, the patient has remained well for the 3 years since her last operation without any hemoptysis.

[Congenital midureteral stricture with ectopic ureter: a case report].

A 7-year-old girl was hospitalized with urinary incontinence. Intravenous pyelography showed the dilatation of upper segment of the right kidney, in which slight radioisotopic accumulation was detected on renal scintigraphy with 99mTc-DMSA. On computerized tomographic (CT) scan, a cystic mass shadow occupied the retroperitoneal space. During surgery, the right kidney was found to be completely duplicated and the ectopic ureter opened in Vestibule vaginae accompanied with midureteral stricture. The ectopic ureter was incised above the strictural site and anastomosed with the ureter of the lower segment. Although approximately 700 cases of ectopic ureter have been reported in Japan, congenital midureteral stricture accompanying ectopic ureter is extremely rare.

Primary mucinous carcinoma of the renal pelvis.

A case of primary mucinous carcinoma originating in the renal pelvis associated with renal lithiasis is reported. The left kidney removed was mostly occupied by mucinous carcinoma with areas of signet ring cell carcinoma. The epithelium covering the pelvis consisted of a single layer of columnar epithelium with scattered goblet cells and mucous glands. A series of careful examinations of the abdominal viscera failed to disclose any other primary lesion. The patient died with multiple peritoneal tumor disseminations eight months after the operation despite additional chemotherapy.

Determination of the phylogenetic relationships among Pacific salmonids by using short interspersed elements (SINEs) as temporal landmarks of evolution.

Several subfamilies of the salmonid Hpa I short interspersed element (SINE) family were isolated from salmonid genomes and were sequenced. For each genomic locus that represented the subfamily, amplification by PCR of the orthologous loci in the 12 fish allowed us to determine the order of branching of the Pacific salmonid species. The deduced phylogeny suggests three evolutionary lines, namely, a line of chum salmon, pink salmon, and kokanee; a line of coho salmon and chinook salmon; and a line of steelhead trout. Our data also support a change in the phylogenetic assignment of steelhead trout from Salmo to Oncorhynchus. We present here an extensive phylogenetic tree constructed from an analysis of differential insertion of SINEs, and we propose that SINE insertion analysis is one of the best available methods for clarifying the order of divergence of closely related species.