A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton.

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products. Polycomb group gene homologs are conserved in vertebrates. Murine mel-18 and closely related bmi-1 are homologous to posterior sex combs and suppressor two of zeste. Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences. To gain further insight into the function of Mel-18, we have inactivated the mel-18 locus by homologous recombination. Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm. Surprisingly, mel-18-deficient phenotypes are reminiscent of bmi-1 mutants. These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development.

Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.

A novel peripheral T cell subset characterized by the expression of a NK marker and invariant TCR encoded by V alpha 14 J alpha 281 gene segments with a 1-base N-region was investigated in relation to autoimmune disease development. First, we observed that invariant V alpha 14+ NK T cells are specifically reduced with aging in C57BL/6 lpr/lpr or MRL lpr/lpr mice, whereas no change was observed in age-matched control C57BL/6 or MRL +/+ mice as determined by FACS analysis and RNase protection assay. This reduction precedes the disease development and could also be detected in other autoimmune disease-prone mice, such as C3H gld/gld and (NZB x NZW)F1 mice. These results suggest that the specific decrease in invariant V alpha 14+ NK T cells correlates strongly with the development of autoimmunity. Second, injection of MRL lpr/lpr mice with anti-V alpha 14 mAb resulted in the early onset and exacerbation of lymphosplenomegaly due to the accumulation of abnormal CD3+ B220+ CD4-CD8- T cells as well as an increase in the titers of anti-dsDNA autoantibodies. These results indicate that V alpha 14+ NK T cells regulate autoimmune responses and play a crucial role in controlling the development of autoimmune diseases.

Post-prostatectomy incontinence. A urodynamic and fluoroscopic point of view.

Sixty-three male patients suffering from post-prostatectomy incontinence were studied by urodynamics and fluoroscopy. In almost half the patients (49%) the sole cause of incontinence was detrusor instability. Incontinence due to damage of the sphincter mechanism was present in less than half of the patients (47%). However, almost half of these patients (53%) had concomitant detrusor instability. Only a small number of patients (4%) had incontinence due to other causes. It appears that post-prostatectomy incontinence is not always due to a surgical misadventure. Many older patients may have preexisting neurologic disorders (e.g., Parkinson disease, diabetic autonomic neuropathy, alcoholic neuropathy, and various spinal cord disorders) which can profoundly affect the outcome of prostatic surgery. Detrusor instability should be considered when evaluating post-prostatectomy incontinence.

Causes of post-prostatectomy retention.

Forty-eight patients in urinary retention following prostatectomy underwent urodynamic evaluation. Fifteen patients (31%) were found to have persistent residual obstruction, while 14 patients (29%) had detrusor hyporeflexia. In 9 patients (19%) a combination of outflow obstruction and detrusor hyporeflexia was demonstrated. In 6 patients (13%), urinary retention was due to compromised mental status. No abnormality was detected in remaining 4 patients (8%) on urodynamic evaluation. For proper evaluation of unsatisfactory voiding after prostatectomy cystoscopy is of limited value while urodynamic testing is essential.

Penile vein ligation for corporeal incompetence: an evaluation of short-term and long-term results.

Dynamic cavernosometry and cavernosography can be used to identify patients with corporeal venous incompetence as a cause of erectile dysfunction. We reviewed our series of 16 patients with venous leakage who underwent surgical correction of the specific abnormality identified on cavernosography. Short-term and long-term results were obtained, and while at least temporary improvement was noted in 89.5% of the patients the long-term results tended to show a reversion to the preoperative status in the majority.

[Bone marrow biopsy in non-Hodgkin's lymphomas, chronic lymphoid leukemia and mycosis fungoides. 1. Incidence and infiltration patterns]. / Biópsia de medula óssea nos linfomas não-Hodgkin, leucemia linfóide crônica e micose fungóide. 1. Incidência e padrões de infiltração.

Seventy bone marrow biopsies belonging to 53 patients with non-Hodgkin lymphomas, chronic lymphocytic leukemia, and micosis fungoides were studied. Bone marrow involvement was analyzed in correlation to staging before and after treatment. Bone marrow involvement was most frequently seen in CLL and IL followed by WDLL and PDLL/N and PDLL/D. Highest incidences after treatment were in CLL, WDLL, and PDLL/N and PDLL/D. With respect to staging, WDLL disseminated to bone marrow only in the late stages (III or IV), whereas the nodular and diffuse forms of PDLL presented similar infiltration in all stages. HLL and IL presented a slight trend to infiltrate only in the later stages. The pattern of bone marrow infiltration was also analyzed considering staging before and after treatment. No clear correlation was observed between staging and a specific pattern of bone marrow involvement in most cases, and disease evolution and treatment do not seem to change infiltration pattern.

Relative usefulness of physical examination, urodynamics and roentgenography in the diagnosis of urinary stress incontinence.

Stress urinary incontinence is a common problem in women. Accurate diagnosis of this condition is necessary for successful surgical treatment. Currently, many tests are popular. The relative value of these tests, in terms of usefulness, accuracy and practicality, has not been tested in the past. With this aim, we have compared the results from three of the most commonly performed tests, namely physical examination, urodynamics and roentgenography. It is our opinion that physical examination in the standing position is the simplest and most accurate test. Cystometrogram is important, although the yield is small. We do not advise the routine use of urethral pressure profile. For accurate determination of anatomic deformity, roentgenographic examination is the most accurate test.

Diagnosis and grading of outflow obstruction.

Urodynamic data from 66 male patients with obstruction due to benign prostatic hyperplasia were analyzed. Criteria for grading the severity of outflow obstruction based on uroflowmetry, post void residual urine, maximum bladder contraction (Pmax), and pressure during voiding (Pvoid) were developed. In selected cases, voiding cystourethrography also may be needed. These criteria help determine the need for prostatectomy. Unnecessary prostatectomies can then be avoided and can lead to significant reduction in mortality, morbidity, and health care expenses.

Instability and rotation of silver silicone penile prosthesis.

Four cases of a similar complication in patients who have had the Jonas silver silicone prosthesis implanted are reported. The patients complain of instability and rotation of the prosthesis to a position that stands out from the body, no matter what the initial position of the prosthesis. The rotation causes difficulty with coitus. The explanation is one of a manufacturing and not a surgical defect.

Marfan syndrome and medullary sponge kidney: case report and speculation on pathogenesis.

The case of a 16 year old boy with Marfan syndrome, recurrent nephrolithiasis, and bilateral Medullary Sponge Kidney (MSKD) is described. This association was not previously described.

Alguns aspectos anatomopatologicos das leucemias. / Anatomopathological aspects of leukemias

Quinze autopsias de pacientes leucemicos foram estudadas. Os principais achados macro e microscopicos sao analisados quanto a frequencia e intensidade de acometimento de diferentes orgaos. As principais causas de obito sao comentadas, bem como a relacao entre terapeutica e o grau de infiltracao leucemica

Multicentric fibroepithelial ureteral polyp.

A case of a fibroepithelial ureteral polyp consisting of numerous separate ureteral growths is presented, and the preoperative diagnostic criteria are discussed. The latter are crucial in raising the suspicion of a benign process and thereby encouraging a conservative operative approach.

Postvoid film of intravenous pyelogram in diagnosis of urethral diverticulum.

Urethral diverticulum is a correctable cause of lower urinary tract symptoms in women. It has been found to be present in from 1.85 to 4.7 per cent of all females. The postvoid film of the intravenous urogram (IVP) is the simplest and least invasive method available to diagnose urethral diverticula. It should be a routine part of the IVP in women with lower urinary tract symptoms.

Renal failure in diabetes after intravenous urography.

A review of the literature reveals that patients with juvenile onset diabetes with azotemia, associated vascular disease, and proteinuria, are at great risk of sustaining acute renal failure following intravenous pyelography. Predisposing factors are identified, but the exact mechanism of acute renal failure remains obscure. Since no prophylactic measures or effective treatment exist, the benefits and risk must be weighed prior to the procedure.