Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-kappaB mutations or activation of the CD30, CD40, and RANK receptors.

PURPOSE: The malignant Hodgkin and Reed-Sternberg cells of Hodgkin disease (HD) are known to constitutively express high levels of activated nuclear factor kappaB (NF-kappaB), which plays an important role in their survival. The proteasome inhibitor PS-341 has been recently shown to modulate tumor cell proliferation and survival by inhibiting NF-kappaB and modulating critical cellular regulatory proteins, but its activity in cells carrying IkappaBalpha gene mutations has not been reported previously. Experimental Design: The activity of PS-341 in four well-characterized, HD-derived cell lines. Cell proliferation and apoptosis were determined by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium (MTS) and Annexin-V binding methods, respectively. Cell cycle analysis was determined by flow cytometry. Intracellular protein levels were determined by Western blot. RESULTS: PS-341 demonstrated a strong antiproliferative activity, which was irrespective of the status of mutations in IkappaBalpha and even the presence of CD30, CD40, or RANK receptor activation. This effect was attributable to the induction of apoptosis and cell cycle arrest at the G(2)-M phase. PS-341 not only inhibited nuclear localization of NF-kappaB but also activated the caspase cascade, increased p21 and Bax levels, and decreased Bcl-2 levels. Furthermore, PS-341 enhanced the effect of gemcitabine chemotherapy and potentiated the effect of tumor necrosis factor-related apoptosis-inducing ligand/APO2L and two agonistic antibodies to tumor necrosis factor-related apoptosis-inducing ligand death receptors R1 and R2. CONCLUSIONS: The in vitro activity of PS-341 against HD-derived cell lines suggests that PS-341 may have a therapeutic value for the treatment of HD.     

Occurrence of co-colonization or co-infection with vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in a medical intensive care unit.

OBJECTIVE: To determine the occurrence of co-colonization or co-infection with VRE and MRSA among medical patients requiring intensive care. DESIGN: Prospective, single-center, observational study. SETTING: A 19-bed medical ICU in an urban teaching hospital. PATIENTS: Adult patients requiring at least 48 hours of intensive care and having at least one culture performed for microbiologic evaluation. RESULTS: Eight hundred seventy-eight consecutive patients were evaluated. Of these patients, 402 (45.8%) did not have microbiologic evidence of colonization or infection with either VRE or MRSA, 355 (40.4%) were colonized or infected with VRE, 38 (4.3%) were colonized or infected with MRSA, and 83 (9.5%) had co-colonization or co-infection with VRE and MRSA. Multiple logistic regression analysis demonstrated that increasing age, hospitalization during the preceding 6 months, and admission to a long-term-care facility were independently associated with colonization or infection due to VRE and co-colonization or co-infection with VRE and MRSA. The distributions of positive culture sites for VRE (stool, 86.7%; blood, 6.5%; urine, 4.8%; soft tissue or wound, 2.0%) and for MRSA (respiratory secretions, 34.1%; blood, 32.6%; urine, 17.1%; soft tissue or wound, 16.2%) were statistically different (P < .001). CONCLUSIONS: Co-colonization or co-infection with VRE and MRSA is common among medical patients requiring intensive care. The recent emergence of vancomycin-resistant Staphylococcus aureus and the presence of a patient population co-colonized or co-infected with VRE and MRSA support the need for aggressive infection control measures in the ICU.     

An amazing case of working wrist watch in the esophagus

Foreign bodies in the esophagus are commonly seen in otolaryngologic practice. We report the successful removal of a working wrist watch dial lodged for one month in the esophagus of an adult schizophrenic patient, which is a rare incident.     

Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development.

Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele. On the contrary, about 75% of the heterozygote Chinese breast cancer patients preferentially expressed the arg allele, which rarely contained any somatic mutations. Moreover, histologically normal tissues from Chinese heterozygote breast cancer patients showed selective expression of the arg allele, in contrast to the preferential expression of the pro allele in heterozygote healthy normal breast tissues. Together, the data suggest that the expression of the different p53 polymorphs is selectively regulated in different ethnic populations, and that the arg allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphs, rather than the genotypic status, might be a useful indicator for cancer susceptibility.     

Histological and immunohistochemical study of estrogen and progesterone receptors in normal human breast tissue in adult age groups vulnerable to malignancy

Analysis of receptor status has become standard procedure for assessing breast cancer patients. Estrogen causes epithelial proliferation in breast tissue via the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by the estrogen gene. Analyzing ER and PR together gives information regarding the likely response of carcinoma patients to hormonal therapy. The aim of the present study was to record the expression patterns of ER and PR in normal mammary tissue in different age groups to provide reference data to facilitate histological diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult female cadavers were examined after H & E staining. ER and PR were identified and examined by immunohistochemistry. The percentage area occupied by parenchyma relative to stromal tissue was calculated in different age groups and was about 4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and 9th, and 10th decades of life, respectively. Both ER and PR were present in all age groups and the numbers of both receptors were maximal during the 4th decade. The distribution and staining patterns for both ER and PR were recorded in different age groups. The contiguous pattern of ER, which is considered pathognomonic of breast carcinoma, was not seen except in one case in the 6th decade. Moderately stained ER and PR receptor sites predominated throughout. The study of normal breast tissue of similar age might provide comparisons that will help histopathologists to make clinical diagnoses from breast biopsies. Clin. Anat. 29:729–737, 2016. © 2016 Wiley Periodicals, Inc.     

Bronchial asthma with ABPA presenting as PTE

Allergic bronchopulmonary aspergillosis (ABPA), as a complication of asthma, is rare in children. The persistent and poorly-controlled asthma leading to cor pulmonale is not uncommon in adults but rarely described in the pediatric age group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo-embolism and cor pulmonale. To the best of our knowledge, such association has never been reported in the pediatric age group.