Individual chaperones required for Yop secretion by Yersinia.

Pathogenic yersiniae secrete anti-host proteins called Yops, by a recently discovered Sec-independent pathway. The Yops do not have a classical signal peptide at their N terminus and they are not processed during membrane translocation. The secretion domain is nevertheless contained in their N-terminal part but these domains do not resemble each other in the different Yops. We have previously shown that YopE secretion requires SycE, a 15-kDa acidic protein acting as a specific cytosolic chaperone. Here we show that the gene downstream from yopH encodes a 16-kDa acidic protein that binds to hybrid proteins made of the N-terminal part of YopH and either the bacterial alkaline phosphatase or the cholera toxin B subunit. Loss of this protein by mutagenesis led to accumulation of YopH in the cytoplasm and to a severe and selective reduction of YopH secretion. This protein thus behaves like the counterpart of SycE and we called it SycH. We also engineered a mutation in lcrH, the gene upstream from yopB and yopD, known to encode a 19-kDa acidic protein. Although this mutation was nonpolar, the mutant no longer secreted YopB and YopD. The product of lcrH could be immunoprecipitated together with cytoplasmic YopD. lcrH therefore seems to encode a YopD-specific chaperone, which we called SycD. Determination of the dependence of YopB on SycD requires further investigation. SycE, SycH, and SycD appear to be members of a new family of cytosolic chaperones required for Yop secretion.     

Differential immunoreactivity of her-2/neu oncoprotein in prostatic tissues.

To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium.     

Perineal ectopic testis

The case of a 24-year-old patient is presented who was erroneously presumed to have unilateral testicular aplasia following inguinal exploration in early childhood. At the age of 24 years he underwent surgery for a soft perineal mass, which was found to be perineal testicular ectopia associated with a congenital hernia. Histological examination of the excised testicle revealed atrophy of the germinal epithelium. A survey of the literature yielded approximately 175 more cases of perineal testicular ectopia. This is the most frequent from of testicular ectopia with a relative incidence of less than 1% of all cases of undescended testes. Ectopic testes seem only to differ from undescended testes in terms of topography. Little difference can be observed in terms of histology or the incidence of concomitant hernias.     

Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization.

Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer.     

Intracoronary shunt reduces postoperative troponin leaks: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate whether intracoronary shunt usage reduced the myocardial damage on the basis of the cardiac markers when compared with the shuntless anastomosis in off-pump coronary artery bypass grafting (OPCABG) surgery of isolated left anterior descending artery lesions. METHODS: Forty patients who had stable angina with isolated left anterior descending (LAD) coronary artery lesion undergoing OPCABG surgery were randomized into two groups. Shunt group consisted of 20 patients who had OPCABG using intracoronary shunt, whereas the shuntless group consisted of 20 patients who underwent OPCABG without using intracoronary shunt. Cardiac troponin I, CK, and CK-MB before and 24h after the surgery were assessed in the groups. RESULTS: There were no deaths in the study. The two groups were similar with respect to sex and age. Duration of LIMA-LAD anastomosis was significantly higher in the shunt group (p=0.01). There was no significant difference between the groups concerning the preoperative and postoperative CK and CK-MB levels. The preoperative troponin I levels of the groups were not different (p=0.238; NS), whereas postoperative levels of this marker was significantly higher in the shuntless group (p=0.003). CONCLUSION: Intracoronary shunt reduced the postoperative troponin I levels significantly, so it may be indicated in the patients who are thought to be susceptible to transient ischemia.     

Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy.

Complications in a donor are a distressing but inevitable occurrence, since graft procurement is a major undertaking. Although the technique for procurement has some similarities to hepatic resection, a donor is very unlike a patient with malignancy. The risk factors identified in these patients cannot be extrapolated to donors. Donor hepatectomy carried out from June 1995 to March 2005 in Chang Gung Memorial Hospital, Kaohsiung Medical Center was reviewed with the aim of identifying risk factors for complications. There were 204 living donor liver transplants, with 205 donor hepatectomies, as 1 living donor liver transplantation was a dual graft. Ten donors (4.88%) suffered complications. There was no difference in terms of age, gender, body weight, operation, and parenchymal time between those who had complications and those who did not. There was also no difference in liver function tests between the 2 groups of donors, but the total bilirubin was significantly higher in donors with complications. The graft weight and remnant liver volume were also similar. The proportion of donors with fatty liver was the same between the 2 groups. The mean blood loss in donors with complications was 170 +/- 79 mL, and that for donors without complications was 95 +/- 77 mL. There was a statistically significant greater blood loss in donors with complications (P < 0.05). The number of segments removed in donors with complications was also higher compared to donors without complications (P < 0.03). Using multivariate analysis, intraoperative blood loss and the number of segments removed were found to be independent risk factors for donor complications. Intraoperative blood loss during graft procurement must be kept low to minimize complications in donors.     

Characteristics of apathy in Parkinson's disease.

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.     

Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments

ONE OF THE RISK FACTORS FOR HUMAN PAPILLOMAVIRUS (HPV) INFECTION and subsequent lower genital tract neoplasias and cancers is impaired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative women to have lower genital tract neoplasias. A corresponding increase in the risk of invasive vulvar and anal cancers, but not of cervical cancer, has also been observed among HIV-positive women. Treatment failure and recurrence of neoplasia occur much more frequently among HIV-positive than among HIV-negative women. In this review, we discuss recent advances in the understanding of the relation between HIV and HPV coinfection and the development of lower genital tract neoplasias and cancers in women. In addition, we present strategies for monitoring and treating noninvasive and invasive neoplasias of the lower genital tract in HIV-positive women.