SseBCD proteins are secreted by the type III secretion system of Salmonella pathogenicity island 2 and function as a translocon.

The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI2) is required for systemic infections and intracellular accumulation of Salmonella enterica. This system is induced by intracellular Salmonella and subsequently transfers effector proteins into the host cell. Growth conditions either inducing expression of the type III secretion system or the secretion of substrate proteins were defined. Here we report the identification of a set of substrate proteins consisting of SseB, SseC, and SseD that are secreted by the SPI2 system in vitro. Secretion was observed if bacterial cells were exposed to acidic pH after growth in minimal medium with limitation of Mg(2+) or phosphate. SseB, -C, and -D were isolated in a fraction detached from the bacterial cell surface by mechanical shearing, indicating that these proteins are predominantly assembled into complexes on the bacterial cell surface. The three proteins were required for the translocation of SPI2 effector proteins SspH1 and SspH2 into infected host cells. Thus, SseB, SseC, and SseD function as the translocon for effector proteins by intracellular Salmonella.

Right intrathoracic renal ectopia: a case report and review of the literature.

We report a case of right intrathoracic renal ectopia associated with a previously unreported congenital anomaly (trisomy 21) and review of the literature.

Complex renal cysts: findings on MR imaging.

OBJECTIVE: We retrospectively evaluated our experience with complex cystic renal masses on MR imaging, using T1-weighted, T2-weighted, and gadolinium-enhanced images, to determine whether imaging features could permit distinction between benign and malignant lesions. MATERIALS AND METHODS: Thirty-seven patients with complex cystic renal lesions were included in this retrospective study. The patients selected had undergone T1-weighted, T2-weighted, and gadolinium-enhanced MR imaging examinations using 1.5-T scanners, with at least one of the following findings: cyst fluid of heterogeneous signal intensity, mural irregularity, septa, mural masses or nodules, increased mural thickness, or intense mural enhancement. The diagnosis was established by histology in 19 patients and by follow-up studies in the remaining 18 patients. RESULTS: Fifty-five complex renal cystic lesions were present in the 37 patients. Among the 55 lesions, of 37 that contained fluid of a heterogeneous signal intensity, eight were malignant (22%); of 16 with irregular walls, 10 were malignant (63%); of four with septa, two were malignant (50%); of four with mural masses or nodules, three were malignant (75%); of 14 with a thick wall (>2 mm), 10 were malignant (71%); and of 32 with intense mural enhancement, 14 were malignant (44%). As independent variables, mural irregularity, mural masses or nodules, increased mural thickness, and intense mural enhancement each were highly associated with malignancy (p = .0003-.0022). The combination of mural irregularity and intense mural enhancement had the highest correlation with malignancy (p = .0002). CONCLUSION: The combination of mural irregularity and intense mural enhancement is a strong predictor of malignancy in renal cystic lesions. However, the appearance of benign and malignant lesions may overlap, suggesting that distinct separation of these entities is not currently possible in all cases with MR imaging.

Adrenal neuroblastoma in an adult with tumor thrombus in the inferior vena cava.

We describe the appearance of an adrenal neuroblastoma associated with tumor thrombus occurring in an adult patient. The tumor measured 14 x 12 x 12 cm, showed heterogeneous signal intensity on both T1-weighted and T2-weighted images, and displayed peripheral nodular enhancement on early post-gadolinium images. Tumor thrombus was identified within the inferior vena cava, which extended into the right atrium.

Intra-abdominal pulmonary sequestration: a benign suprarenal mass.

A 34-year-old white woman presented with an 8.5-cm left suprarenal mass. Evaluation revealed normal adrenal hormone function. Pathologic examination after surgical removal revealed a rare benign condition, intra-abdominal extralobar pulmonary sequestration (accessory lung).

A comparison of techniques for placement of double-lumen endobronchial tubes.

STUDY OBJECTIVE: To compare two methods of double-lumen endobronchial tube placement for thoracic surgery and to identify factors that provide a rational basis for placement method selection. DESIGN: Prospective, randomized study. SETTING: Teaching hospital. PATIENTS: 58 ASA physical status II, III, and IV patients scheduled for surgical procedures requiring elective left-sided endobronchial intubation. INTERVENTIONS: Patients were assigned randomly to either a group in which the initial placement method was the traditional approach of placing the endobronchial tube through the larynx and then advanced blindly into the left mainstem bronchus, or to a second group in which the left mainstem bronchus was intubated under direct vision using the fiberoptic bronchoscope. MEASUREMENTS AND MAIN RESULTS: Of the 32 patients who underwent the traditional approach, primary success occurred in 27 patients and eventual success in 30. In 27 patients undergoing the directed approach, primary success occurred in 21 patients and eventual success in 25. Two patients in each group required the alternative method. The blind approach took 88 (+/- 91) seconds and the directed approach took 181 (+/- 193) seconds (p = 0.029). Timing data were analyzed using analysis of variance with respect to method and secretions and then t-tests as appropriate. Categorical data were analyzed using the Kruskal-Wallis and Fisher's exact tests as appropriate. All values are reported as means +/- SD. CONCLUSION: Both the blind and directed approaches resulted in successful left mainstem placement of the endobronchial tube in the majority of patients but either method may fail when used alone. More time was required using the directed approach. Operator experience with both methods will increase the likelihood of success. The choice of the initial approach may be influenced by patient factors as well as available equipment and personnel.

Prognostic markers in bladder cancer: a contemporary review of the literature.

PURPOSE: We provide a contemporary review of bladder tumor markers and summarize their role as prognostic indicators. MATERIALS AND METHODS: A comprehensive review of the literature on prognostic markers for transitional cell carcinoma of the bladder was performed. RESULTS: Intense research efforts are being made to identify and characterize better various bladder cancers and their true biological potential. The need to predict which superficial tumors will recur or progress and which invasive tumors will metastasize has led to the identification of a variety of potential prognostic markers. Blood group antigens, tumor associated antigens, proliferating antigens, oncogenes, peptide growth factors and their receptors, cell adhesion molecules, tumor angiogenesis and angiogenesis inhibitors, and cell cycle regulatory proteins have recently been identified. The potential clinical applications of these tumor markers are under active investigation. Recent attention has focused on which tumor markers may predict the responsiveness of a particular bladder cancer to systemic chemotherapy. CONCLUSIONS: At present conventional histopathological evaluation of bladder cancer (tumor grade and stage) cannot predict accurately the behavior of most bladder tumors. With a better understanding of the cell cycle, and cell to cell and cell to extracellular matrix interactions as well as improved diagnostic techniques (immunohistochemistry), progress is being made to identify and characterize other potential prognostic markers for transitional cell carcinoma of the bladder. The ultimate goal is to develop reliable prognostic markers that will accurately predict not only the course but also the response of a tumor to therapy. This information may then be used to dictate more aggressive treatment for tumors that are likely to progress and less aggressive treatment for those that are unlikely to progress. In the future these biological markers may also be used in gene therapy for the treatment of bladder cancer.

Prospective pathologic analysis of female cystectomy specimens: risk factors for orthotopic diversion in women.

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.

Antitumor activity of novel octalactin A analogs in murine leukemia cells in vitro.

Octalactin A and B (code names K1 and K2) are eight-membered-ring lactones from a marine bacterium. K1 is reportedly cytotoxic. Since access to this natural product is severely limited, the entire synthesis of K1 has been achieved in K. Buszek's laboratory, and several of its structural and stereochemical analogs (code names K3-K9) have been tested for their ability to prevent murine L1210 leukemic cells from synthesizing macromolecules and growing in vitro. At 50 microM, K1 is inactive and the eight-membered lactone K4, an oxocene, is the only compound found to inhibit tumor cell growth by about 90% in the L1210 system. The long-term inhibition of L1210 cell growth by K4 is concentration dependent (IC50 around 10 microM) and not reversible following drug removal. The delayed and weaker cytotoxic effects of K4 suggest that the inhibition of tumor cell proliferation observed 1-4 days after K4 treatment is not solely caused by drug cytotoxicity. When compared to a spectrum of representative anticancer drugs, higher concentrations of K4 must be used to maximally inhibit tumor cell growth. In contrast to its antiproliferative activity, 50 microM K4 fails to alter the rates of DNA, RNA and protein synthesis in L1210 cells. This discrepancy between the ability of K4 to inhibit macromolecule synthesis and leukemic cell growth suggests that other molecular targets are involved in the antitumor action of this drug. At 50 microM, K4 inhibits the polymerization of purified tubulin by about 45%, and therefore may be a novel microtubule de-stabilizing drug weaker than vincristine. Even though other mechanisms may be involved in its antitumor action, the ability of K4 to partially disrupt microtubule dynamics indirectly suggests that this synthetic oxocene may be a cell cycle-specific anticancer drug that blocks mammalian cells in M-phase.

Primary malignant melanoma with rhabdoid features: a histologic and immunocytochemical study of three cases.

Malignant rhabdoid tumors are morphologically characterized by the presence of sheets of large polygonal cells with abundant cytoplasm containing eosinophilic inclusions. They have vesicular nuclei, often with prominent central nucleoli. The term rhabdoid tumor was originally coined to describe a group of rare, aggressive renal neoplasms of childhood. Since then, similar lesions, so-called extrarenal malignant rhabdoid tumors have been increasingly reported. The evidence to date suggests that, at least in extrarenal locations, rhabdoid tumors do not constitute a homogeneous entity, but rather represent the shared morphological pattern of a diverse range of malignant neoplasms. Although such rhabdoid features are not uncommon in metastatic malignant melanoma, they have only once been briefly described in a primary lesion. We report three further cases of cutaneous primary malignant melanoma with rhabdoid morphology.

Tricyclic pyrone analogs: a new class of microtubule-disrupting anticancer drugs effective against murine leukemia cells in vitro.

Novel 1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano [4,3-b][1]benzopyrans were synthesized in Hua's laboratory (code names H5, H10, H14 and H15) and tested for their ability to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. The aryl groups of these tricyclic pyrone (TP) analogs are either 3, 4-dimethoxyphenyl in H5 and H15 or 3-pyridyl in H10 and H14. Since 50 M H5 and H10 both inhibit DNA synthesis and tumor cell growth by 79-100%, concentrations 25 M were used in this study to assess the structure-activity relationships for this class of compounds. At 10-25 M, H5 and H14 are more potent inhibitors of DNA, RNA and protein synthesis than H10. In contrast, at 5-25 M, H10 is much more effective than H5 and H14 at inhibiting the growth of L1210 cells over a 4-day period. Interestingly, H15 inhibits DNA synthesis as much as H10 but fails to alter tumor cell growth. This discrepancy between the ability of TPs to inhibit macromolecule synthesis and leukemic cell growth suggests that other molecular targets may be involved in the antitumor action of these drugs. Their short-term inhibition of nucleic acid synthesis is reversible following drug removal but their long-term inhibition of tumor cell growth is not. Moreover, 25 M H5 and H10 are not cytotoxic at 2 days but equally decrease cell viability at 4 days, suggesting that the potent and irreversible inhibition of cell proliferation observed 1-4 days after H10 treatment is not solely caused by drug cytotoxicity. The effectiveness of H10 as inhibitor of L1210 cell growth is comparable to that of a spectrum of representative anticancer drugs. A critical finding is that 5 M H10 blocks the polymerization of purified tubulin by 90% and, therefore, may be a novel microtubule de-stabilizing drug. Indeed, H10 inhibits tubulin polymerization and L1210 cell growth as much as 5 M of vincristine (VCR). In contrast, 5 M H5 alters neither tubulin polymerization nor tumor cell growth. The ability of H10 to disrupt microtubule dynamics indirectly suggests that TPs may be novel cell cycle-specific anticancer drugs useful for arresting mammalian cells in mitosis.

Orthotopic lower urinary tract reconstruction in women using the Kock ileal neobladder: updated experience in 34 patients.

PURPOSE: Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients. MATERIALS AND METHODS: Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70). RESULTS: There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming. CONCLUSIONS: The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

Early cystectomy for clinical stage T1 transitional cell carcinoma of the bladder.

Early radical cystectomy for a high-grade tumor invading the lamina propria (T1) remains controversial. In 1997, we cannot identify accurately which of these high-risk tumors will progress to muscle-invasive disease and metastases. In the near future, urologists may be able to use the presence of genetic alterations, such as p53 mutations, to help make therapeutic decisions. Previous reports on superficial bladder cancer treated with intravesical bacillus Calmette-Guérin immunotherapy have demonstrated a decrease in recurrence and progression. Unfortunately, there is no reliable method to predict which patients with a high-grade T1 tumor will fail to respond to intravesical therapy. Failure of intravesical therapy to control these aggressive tumors is associated with a significant rate of pathological upstaging and metastases. Radical cystectomy will cure a high percentage of these T1 tumors with acceptable morbidity and low mortality. In an era of nerve-sparing cystectomy and orthotopic neobladder reconstruction, early radical cystectomy is an alternative that should be discussed with the patient before instituting intravesical therapy.

New technique of vaginal reconstruction following anterior exenteration.

Vaginal reconstruction is important in sexually active females undergoing anterior exenteration for malignant disease. We describe a technique for vaginal reconstruction used in two women who underwent radical cystectomy that required en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a pedicle graft of greater omentum creates the anterior 270 degrees and the apex of the neovagina. The technique is simple and adds to the urologist's armamentarium of reconstructive procedures that improve quality of life following exenterative surgery.

Rigid fixation and strain patterns in the pig zygomatic arch and suture.

PURPOSE: In orthognathic surgery, rigid fixation is routinely used to hold together bone fragments that may experience heavy force from attached masticatory muscles. Internal fixation plates are assumed to hold bony parts rigidly, but the mobility at such sites subjected to normal masticatory function has not been measured. The purpose of this study was to investigate in vivo the degree to which a linear plate immobilizes separated bones, specifically sutures. MATERIALS AND METHODS: Three female miniature pigs (Sus scrofa) had 1.3-mm Synthes titanium plates placed across the suture in the zygomatic arch. Foil strain gauges were used to record load deformation in the zygomatic and squamosal (temporal) bones and across the vertical and horizontal parts of the suture. Strain was recorded in vivo during mastication and in anesthetized pigs with electrical stimulation of masticatory muscles. RESULTS: Strain at the suture was not reduced from normal levels. The plate induced increases in strain within the bones, but the changes were slight. CONCLUSION: The results indicate that linear "rigid fixation" does not immobilize sutures.

Expectant management as an option for men with stage T1c prostate cancer: a preliminary study.

The outcome of patients selecting observation of clinical stage T1c prostate cancer is unknown. A total of 101 men with clinical stage T1c prostate cancer were evaluated, counseled, and monitored in a standard fashion. Altogether, 27 men who elected observation were older and had greater co-morbidity but similar tumor characteristics as compared with 74 men who elected radical prostatectomy. In all, 9 men demonstrated clinical or biochemical evidence of progression after a mean follow-up of 23 months; 4 men who underwent radical prostatectomy had specimen-confined disease and undetectable post-operative levels of PSA. Observation appears to be a viable option for some men with clinical stage T1c prostate cancer.

Orthotopic reconstruction in a woman following cystectomy and cutaneous urinary diversion. The 1st reported case.

Orthotopic lower urinary tract reconstruction has become the procedure of choice in selected male and female patients at our institution following cystectomy with excellent functional results. A natural extension of the orthotopic neobladder is undiversion to the intact native urethra in patients who had previously undergone cystectomy and cutaneous urinary diversion. Undiversion has been successfully performed in selected male patients; however, to our knowledge, undiversion has not been reported in women. Herein, we present the 1st case of undiversion in a female patient who had undergone prior cystectomy and cutaneous urinary diversion.

Renal cell cancer: incidence of hemorrhage on MR images in patients with chronic renal insufficiency.

This study describes the occurrence of hemorrhage in renal cancer in patients with chronic renal insufficiency as shown on MR images. Thirteen consecutive patients with chronic renal insufficiency who had histologically proven renal cancer and underwent MRI at 1.5 T were entered in the study. MR examinations included spoiled gradient echo (SGE) and T1-weighted fat-suppressed imaging pre- and postgadolinium administration. All renal cancers were well shown on MR images and were most clearly depicted on postgadolinium T1-weighted fat-suppressed images. Tumors in 12 of 13 patients had regions of high signal intensity on precontrast T1-weighted images. Histology demonstrated intratumoral hemorrhage in all 12 of these patients. Four hemorrhagic tumors were largely cystic on imaging studies. One of these cancers altered in appearance from largely cystic with extensive hemorrhage to largely solid with substantial enhancement after a 2.5-year interval. Renal cancers demonstrated minimal enhancement (11 patients) on early postgadolinium images and were minimally enhanced on delayed images in 10 of 13 tumors. Two renal cancers demonstrated intense enhancement. Renal cancers are well shown on MR images in patients with chronic renal insufficiency. Because of the common occurrence of hemorrhage into renal cancers in patients with renal insufficiency, caution should be exercised when evaluating hemorrhagic cystic lesions in these patients.