Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3

The release of mitochondrial cytochrome c by genotoxic stress induces the formation of a cytosolic complex with Apaf-1 (mammalian CED4 homolog) and thereby the activation of procaspase-3 (cas-3) and procaspase-9 (cas-9). Here we demonstrate that heat-shock protein 27 (Hsp27) inhibits cytochrome c (cyt c)-dependent activation of cas-3. Hsp27 had no effect on cyt c release, Apaf-1 and cas-9 activation. By contrast, our results show that Hsp27 associates with cas-3, but not Apaf-1 or cas-9, and inhibits activation of cas-3 by cas-9-mediated proteolysis. Furthermore, the present results demonstrate that immunodepletion of Hsp27 depletes cas-3. Importantly, treatment of cells with DNA damaging agents dissociates the Hsp27/cas-3 complex and relieves inhibition of cas-3 activation. These findings define a novel function for Hsp27 and provide the first evidence that a heat shock protein represses cas-3 activation.     

Allergic fungal sinusitis: expanding the clinicopathologic spectrum.

OBJECTIVE: We sought to determine whether histologic tissue invasion occurs in allergic fungal sinusitis (AFS) and, if so, to identify clinical indicators for the same.Study design and setting We conducted a retrospective case record review of all 28 AFS cases identified by histology over a 32-month period at a tertiary care referral center. All histologic specimens were reevaluated for features of invasive pathology, and case records were correlated for clinical, radiologic, or laboratory parameters associated with such invasion. RESULTS: In addition to the universal finding of the characteristic allergic mucin with fungal elements on histopathologic examination of the sinus luminal contents, 6 cases (21%) had additional evidence of mucosal invasion as indicated by granulomatous inflammation and branching septate fungal hyphae in the submucosal tissues. Such coexistent invasion was associated with advanced disease as indicated by a higher incidence of orbital involvement on clinical evaluation (P = 0.024), and extrasinus spread (intraorbital or intracranial spread) on the computed tomography evaluation (P = 0.003). The single death that occurred on follow-up was in a patient with coexistent invasion. CONCLUSION: Advanced AFS may be complicated by histologic evidence of tissue invasion. SIGNIFICANCE: The noninvasive and invasive forms of fungal sinusitis are not necessarily discrete and may coexist in the same patient. Clinical features of orbital involvement or computed tomography manifestations of extrasinus spread should alert the clinician to the possibility of invasion.     

Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism

Homozygous HbE [beta26(B8)Glu-->Lys] is a clinically mild disorder with no significant symptoms. However, we have frequently noted hyperbilirubinemia among patients with homozygous HbE in the Indian population, with jaundice being the major complaint at presentation. A study of the UGT1A1 gene polymorphism shows that the variant TA7 in the promoter region of the UGT1A1 gene is associated with hyperbilirubinemia in homozygous HbE patients.     

Robot-assisted radical cystectomy and urinary diversion in female patients: technique with preservation of the uterus and vagina

BACKGROUND: After performing more than 500 robotic radical prostatectomy and robotic radical cystoprostatectomy in men, we attempted to develop the technique of robot-assisted radical cystectomy in women. This article describes two techniques of robot-assisted radical cystectomy for women, conventional and with preservation of the uterus and vagina. To the best of our knowledge, this is the first case series of robot-assisted radical cystectomy and urinary diversion in women. STUDY DESIGN: Robot-assisted radical cystectomy was undertaken in three female patients with transitional cell carcinoma of the urinary bladder. The operation was performed with the conventional anterior approach in one patient and with a new technique in two patients, which allows preservation of urethra, uterus, vagina, and both ovaries. As planned, the radical cystectomy was done robotically, using the da Vinci Surgical System (Intuitive Surgical). The bladder was entrapped in an Endocatch bag and removed through a small subumbilical incision. Urinary reconstruction was performed extracorporeally after exteriorizing the bowel through the incision used for retrieving the specimen. In two patients, the reconstructed pouch was placed in the pelvis and the abdominal incision was closed. Urethroneovesical anastomosis was done robotically, using a technique described previously for men. RESULTS: The average operating time for the robotic radical cystectomy was 160 minutes and the mean operating times for ileal conduit and orthotopic neobladder were 130 minutes and 180 minutes, respectively. The mean blood loss was less than 100 mL. The mean number of lymph nodes removed was 12 (range 3 to 21). Surgical margins were free of tumor in all three patients. CONCLUSIONS: This approach incorporates advantages of minimally invasive and open surgery. Performing the radical cystectomy with the robot allows precise and rapid removal of the bladder with minimal blood loss. Extracorporeal reconstruction of the urinary tract reduces operative time at this stage of evolution of laparoscopic and robotic instrumentation. In the future, with the development of technology, instrumentation, and with additional refinement of our technique, the entire procedure may be done completely intracorporeally with equal efficiency.     

Mother-to-child transmission of hepatitis E virus infection

Objectives : Water borne or enterically transmitted non-A-non-B hepatitis is a major public health problem in India. Many of these cases carry fatal outcome. The hepatitis E virus (HEV) has been considered to be the most important causative agent of this entity. The severity and fatality rates of HEV infection are reported to be rather more in pregnant women. However, there is meager information from India, on mother to child transmission of this agent.Methods : During 1997-98, we studied 60 pregnant women suspected to have acute viral hepatitis to understand the frequency of various viral etiologies, disease course and outcome of the pregnancy. Six cord blood samples were tested for IgG, and IgM antibodies against hepatropic viral agents and also for hepatitis E virus RNA by RT-nested PCR using ORF-1 as target.Results : Of the 60 pregnant patients hospitalised at All India Institute of Medical Sciences, New Delhi for acute hepatitis, 22 (37%) were positive for IgM anti-HEV antibodies and 10% were infected with hepatitis B virus. Co-infection of HEV with Hepatitis B and C was seen in 1 and 2 patients, respectively. Most (72%) of the HEV infected patients were in third trimester of pregnancy (P<0.05). Of the 6 cord blood samples tested 3 (50%) were positive for HEV RNA. Though, all mothers were RNA positive, half of the babies did not get infectedin utero with HEV. Fourteen of the 22 (63.6%) HEV infected mothers developed fulminant hepatic failure and all died.Conclusion : The mortality rate in HIV infected mothers was 100%. Mother to child transmission of hepatitis E virus infection was established in 50%