Cochlear implantation in children with Mondini dysplasia: our experience.

OBJECTIVE: This study details the intra-operative complications, and compares auditory scales post-implantation of either profoundly deaf young children with radiologically normal inner ears (group A) or children with Mondini dysplasia (group B). METHODS: A retrospective survey was carried out of 338 patients with severe to profound sensorineural hearing loss who underwent cochlear implant surgery from February 2015 to May 2017. Patients were divided into 2 groups of 27 patients each. Both groups were followed up to three years post-implantation. RESULTS: Cerebrospinal fluid ooze developed in 12 patients, and 2 patients had a cerebrospinal fluid 'gusher', one of which had to be explored within 24 hours. After implant use for one year, both groups had similar speech perception scores. CONCLUSION: The cerebrospinal fluid gusher in Mondini dysplasia should be anticipated and adequately managed intra-operatively. This study highlights the tailoring of a post-implantation rehabilitation programme according to individual needs.

Antimicrobial activity of Alcaligenes sp. HPC 1271 against multidrug resistant bacteria.

Alcaligenes sp. HPC 1271 demonstrated antibacterial activity against multidrug resistant bacteria, Enterobacter sp., resistant to sulfamethoxazole, ampicillin, azithromycin, and tetracycline, as well as against Serratia sp. GMX1, resistant to the same antibiotics with the addition of netilmicin. The cell-free culture supernatant was analyzed for possible antibacterials by HPLC, and the active fraction was further identified by LC-MS. Results suggest the production of tunicamycin, a nucleoside antibiotic. The draft genome of this bacterial isolate was analyzed, and the 4.2 Mb sequence data revealed six secondary metabolite-producing clusters, identified using antiSMASH platform as ectoine, butyrolactone, phosphonate, terpene, polyketides, and nonribosomal peptide synthase (NRPS). Additionally, the draft genome demonstrated homology to the tunicamycin-producing gene cluster and also defined 30 ORFs linked to protein secretion that could also play a role in the antibacterial activity observed. Gene expression analysis demonstrated that both NRPS and dTDP-glucose 4,6-dehydratase gene clusters are functional and could be involved in antibacterial biosynthesis.

Identification of fruity aroma-producing compounds from Chryseobacterium sp. isolated from the Western Ghats, India.

A fruity aroma-producing strain WG4 was isolated from a water sample collected from the Western Ghats, India. The 16S rRNA gene sequence analysis of strain WG4 indicated that Chryseobacterium indologenes, a member of the family 'Flavobacteriaceae' is the closest related species with a pair-wise sequence similarity of 98.6%. Strain WG4 produces a fruity aroma when grown on nutrient or trypticase soy agar plates. The fruity aroma is more when the strain WG4 is grown on agar plates compared to their growth in broth. The aromatic compounds produced by the strain WG4 were identified as ester compounds and were confirmed as ethyl-2-methylbutyrate and ethyl-3-methylbutyrate based on Gas Chromatography-Mass Spectrometry (GC-MS) analysis and using standard reference compounds. Even after repeated subcultures strain WG4 produced the same aroma in high intensity. Thus, strain WG4 could serve as a source for the production of these flavour compounds.

Polarographic determination of certain cephalosporins in pharmaceutical preparations.

Polarographic methods have been developed for the determination of two cephalosporins namely cefotaxime (CTX) and ceftriaxone (CTR) in pharmaceutical formulations. Well defined peaks at potentials -1.432 V vs. SCE for CTX and -1.627 V vs. SCE for CTR were obtained in the presence of tungsten (VI). The method has been successfully applied for the determination of above mentioned cephalosporins in commercial dosage forms. The salient features of this investigation are presented in this communication.

Electroantennogram responses of the potato tuber moth, Phthorimaea operculella (Lepidoptera; Gelichiidae)to plant volatiles.

Electroantennograms (EAGs)were recorded from males and females of the potato tuber moth,Phthorimaea operculella in response to a broad range of plant volatile compounds belonging to diverse chemical classes.The responses to 27 compounds were evaluated,which indicated significant differences in EAGs between chemicals as well as between sexes.The fatty acid derivatives comprising essentially green leaf volatile components elicited significantly greater responses in females.The response profile of males was,in general,lower than that of females.EAG responses to the oxygenated and hydrocarbon monoterpenes were lower in both males and females.Dose -response studies indicate differences in response between the sexes and concentrations,suggesting the existence of sexual dimorphism. Compounds belonging to the fatty acid derivatives class appear to be important for an oligophagous pest such as the potato tuber moth and the findings are discussed in relation to host plant selection in this species.

Association of ablation of Barrett's esophagus with high grade dysplasia and adenocarcinoma of the gastric cardia.

There has been increasing application of endoscopic ablation therapy for patients with high-grade dysplasia (HGD) and Barrett's esophagus (BE). Three cases are reported in which the patient developed adenocarcinoma of the gastric cardia after thermal ablation of HGD. A definition of BE including endoscopic abnormality and intestinal metaplasia by biopsy was used. Strict and standardized criteria were utilized for the endoscopic landmarks. Three cases are reported with long-segment BE and a nodule or mass in the endoscopic cardia post-thermal ablation. Biopsies documented adenocarcinoma of the gastric cardia. The development of adenocarcinoma of the cardia is unexpected. Speculation is offered as to the potential of increased proliferation and mutations at the new squamocolumnar interface after endoscopic ablation therapy to explain this association.

Evidence for presence of female produced pheromone components in male scent brush extract of castor semi-looper moth Achaea janata L.

Hexane extract of male terminalia (along with scent brushes) of castor semi-looper moth, Achaea janata L, elicited significant olfactory responses in both male and female insects by electroantennogram recording technique. However, male extract in the wind tunnel evoked noticeable behaviour responses in the female insects only. Orientation response of the males to the male extract was not evident in wind tunnel experiments. Two electrophysiologically-active compounds were identified from the male extract. Based on GC retention times and mass spectrometry the two compounds were confirmed as (Z,Z)-9,12-octadecadienal and (Z,Z,Z)-3,6,9-heneicosatriene. These two compounds are also constituents of female produced four-component blend of A. janata.

Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase.

We have investigated possible factors that underlie changes in the production of eicosanoids after prolonged exposure of mast cells to Ag. Ag stimulation of cultured RBL-2H3 mast cells resulted in increased expression of cyclooxygenase (COX-2) protein and message. Other eicosanoid-related enzymes, namely COX-1, 5-lipoxygenase, and cytosolic phospholipase A(2) were not induced. Activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein (MAP) kinase preceded the induction of COX-2, whereas phosphatidylinositol 3' kinase and its substrate, Akt, were constitutively activated in RBL-2H3 cells. Studies with pharmacologic inhibitors indicated that of these kinases, only p38 MAP kinase regulated expression of COX-2. The induction of COX-2 was blocked by the p38 MAP kinase inhibitor SB202190, even when added 12-16 h after stimulation with Ag when p38 MAP kinase activity had returned to near basal, but still minimally elevated, levels. Interestingly, expression of COX-2 as well as cytosolic phospholipase A(2) and 5-lipoxygenase were markedly reduced by SB202190 in unstimulated cells. Collectively, the results imply that p38 MAP kinase regulates expression of eicosanoid-related enzymes, passively or actively, at very low levels of activity in RBL-2H3 cells. Also, comparison with published data suggest that different MAP kinases regulate induction of COX-2 in inflammatory cells of different and even similar phenotype and suggest caution in extrapolating results from one type of cell to another.

Two-color, cytokeratin-labeled dna flow cytometric analysis of 332 breast cancers: lack of prognostic value with 12-year follow-up.

CONTEXT: DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of standardization and confirmatory studies. OBJECTIVE: To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference. DESIGN: Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospectively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions. These suspensions were dual fluorescence-labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium) and leukocyte common antigen (internal leukocyte control) for gated analysis of subpopulations. Multicycle software with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell-cycle quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations. RESULTS: DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival. Sixty-five percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of 206 cases in the low range (<13.4%), 36.4% in the intermediate range (>13.5 to <25.4%), and 27.6% in the high SPF (>25.5%) category. Aneuploid tumors tended to have a higher SPF. Univariate survival analysis showed prognostic significance of the following: tumor size, stage, TNM components, vascular invasion, nuclear grade, and histologic grade. Only T classification, presence of positive axillary lymph nodes, and distant metastases were significant independent predictors of survival in multivariate Cox regression models. Age and hormone receptor status showed no prognostic significance. Synthesis-phase fraction was significantly correlated with tumor size, stage, T classification, nuclear and histologic grade, presence of estrogen or progesterone receptors, and axillary lymph node status. None of the histologic parameters showed any significant association with DNA aneuploidy, except for high nuclear and histologic grade and the absence of estrogen receptors. CONCLUSIONS: Despite the use of state-of-the-art processing and flow cytometry analytic techniques, DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer. However, select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses. We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer.

Retrorectal cystic hamartoma: report of 5 cases with malignancy arising in 2.

BACKGROUND: Retrorectal cystic hamartomas, or tailgut cysts, are rare congenital lesions that typically present as presacral masses. These lesions are frequently clinically unrecognized and misdiagnosed. Malignant change is extremely rare. Only 10 additional cases with associated malignancy were recovered from the literature. We describe the clinicopathologic features of 5 cases, including 2 cases with malignant transformation. RESULTS: All patients were women (age range, 36-69 years). The most common symptoms were pain with defecation and rectal bleeding. One patient was asymptomatic. All lesions presented as multicystic presacral masses and all were surgically resected. The lesions varied in size from approximately 2 to 12 cm (average, 9.5 cm) and overall had similar histology composed of a variety of epithelial linings (stratified squamous, transitional, and simple or ciliated pseudostratified columnar). Skin adnexa, neural elements, and heterologous mesenchymal tissue, discriminators between retrorectal cystic hamartoma and teratoma, were not identified. Arising in association with the cysts was a focus of adenocarcinoma in one case and a neuroendocrine carcinoma in another. CONCLUSIONS: The clinical diagnoses in our cases were often delayed, which in part may be due to unfamiliarity with this entity. The main diagnostic difficulty is distinction from presacral mature cystic teratomas and rectal duplication cysts. Tailgut cysts require complete surgical excisions to prevent future recurrences and to preclude possible malignant transformation. Meticulous gross examination and adequate sampling are important to document the exact nature of these cysts and to rule out possible coexisting malignancies, which may be focal.

Salivary gland basal cell and canalicular adenomas: immunohistochemical demonstration of myoepithelial cell participation and morphogenetic considerations.

OBJECTIVE: To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation. DESIGN: Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas. SETTING: Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco. RESULTS: All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells. CONCLUSIONS: There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.

The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.

BACKGROUND: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas. OBJECTIVE: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors. DESIGN: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval. RESULTS: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer. CONCLUSION: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.

Inhibition of lipid peroxidation by selenium in chick embryos.

Toxic doses of Selenium (Se) (12.5 and 37.5 micro moles/Kg egg wt.) administered to 14 day old chick embryos reduced the level of lipid peroxides (LPO) significantly both in hepatic and brain tissues. However, the LPO formation was inhibited maximally at early hours after exposure (3 h and 6 h) and it was gradually increased thereafter to normal levels by 48 h. Further, the effect of Se on some of the antioxidant enzymes like glutathione peroxidase (GPx), glutathione transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase were studied. In hepatic tissues GPx, GST and SOD activities were increased at 6 h post treatment with no change in the activities of GR and catalase. However, at 48 h GST and catalase activities were found to be increased, while GPx, GR and SOD activities were not affected. In brain at 6 h increase in the activities of GPx, GST, GR and SOD and no change of catalase were observed. At 6 h glutathione (GSH) levels were reduced in both hepatic and brain tissues. Our results suggest that the elevated levels of antioxidant enzymes at early hours were successful in bringing LPO levels back to normal.

Inhibitory effect of selenium on enzymes involved in heme biosynthetic pathway in chick embryos.

Effect of different concentrations of selenium (Se) on heme biosynthesis was studied at different developmental stages of chick embryo. The first rate limiting enzyme ALA-synthase (ALA-S; E.C.2.3-1.37) activity was enhanced by selenium, while hepatic and blood ALA-dehydratase activity (ALA-d; E.C.3.2.1.24) was decreased. Hepatic and blood free-sulfhydryl (-SH) group contents were significantly decreased by Se. Further, hepatic aminolevulinic acid (ALA) and total blood porphyrin levels were enhanced and hepatic heme levels were depleted by selenium exposure. Heme biosynthesis was maximally inhibited in the E4 (4th day injected embryos) when compared to later periods.

Isolation of 75Se binding protein from hepatic tissues of chick embryos.

Distribution study using 75Se shows that maximum accumulation was in liver tissues after 24h of 75Se administration. Induction of selenium binding protein (Se-P) in hepatic tissues of chick embryo was observed. Chick embryo hepatic Se-P was isolated after 24h of 75Se treatment using Sephadex G-75 column chromatography. Fractions of induced protein shows the presence of maximum concentration of 75Se. This induced protein was found to have an approximate molecular weight of 56 KD on molecular sieve. It also showed an absorbance maxima at 254 nm, which indicates the presence of high concentrations of sulphydryl groups.

Cloning, sequence, and expression of mouse protoporphyrinogen oxidase.

Protoporphyrinogen oxidase (EC 1.3.3.4) is the penultimate enzyme in the heme biosynthetic pathway, catalyzing the six-electron oxidation of protoporphyrinogen to protoporphyrin. A dominantly inherited genetic deficiency in this enzyme results in the disease variegate porphyria. We now report the cloning, sequence, and expression of mouse protoporphyrinogen oxidase. The cDNA for mouse protoporphyrinogen oxidase was obtained by complementation of Escherichia coli SASX38, a protoporphyrinogen oxidase-deficient strain, with a mouse erythroleukemia (MEL) cell expression library. The sequence of this cDNA along with 5' untranslated sequence obtained by 5' rapid amplification of cDNA ends of MEL cell mRNA is 1814 bp in length and contains an open reading frame of 1431 bp. This encodes a protein of 477 amino acid residues with a calculated molecular weight of 50,870. The protein as expressed in E. coli is sensitive to inhibition by the diphenyl ether herbicide acifluorfen. Northern blot analyses of RNA from uninduced and induced MEL cells as well as mouse hepatoma cells all show two major mRNA species of 1.8 and 3.6 kb.

Generation of resistance to the diphenyl ether herbicide acifluorfen by MEL cells.

The diphenyl ether herbicide acifluorfen has been shown to act by inhibition of the terminal enzyme of the protoporphyrin biosynthetic pathway, protoporphyrinogen oxidase (E.C. 1.3.3.4) (PPO), in plant and animal cells. In the present study we show that long term maintenance of murine erythroleukemia (MEL) cells in acifluorfen, which is normally toxic to these cells at 5 microM concentration, results in cells that grow at a near normal rate in 100 microM acifluorfen. Acifluorfen resistant cells do not have increased levels of PPO activity, nor does the PPO made by these cells have increased resistance to acifluorfenin, but these cells accumulate porphyrin and have elevated levels of heme. Data is presented that suggests the resistance of these MEL cells to acifluorfen may be attributable to induction of a cytochrome P450(s).

Effect of cellular location on the function of ferrochelatase.

Ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, is a nuclear encoded protein that is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane. Since the product of the enzymatic reaction, protoheme IX, is utilized almost exclusively in the cytoplasmic compartment or on the cytoplasmic side of the inner mitochondrial membrane, it was of interest to determine if the intracellular location of ferrochelatase-deficient strain of the yeast Saccharomyces cerevisiae vectors that coded for full-length ferrochelatase and a truncated form of the enzyme that lacked the mitochondrial targeting sequence were expressed. Both of these transformed cells produce approximately equal total amounts of ferrochelatase, as determined by enzyme assays and Western blot analysis, but only with the full-length construct was ferrochelatase properly localized. In cells containing the truncated construct, ferrochelatase activity was found in all membrane fractions but was not located on the matrix side of the inner mitochondrial membrane. Cells containing either construct produced heme, although the amount of heme synthesized by cells with the truncated construct was significantly less. Interestingly in cells with improperly localized ferrochelatase the amount of b-type cytochrome decreased by 80% as opposed to c- and a-type cytochromes where the decreases were only 60 and 40%, respectively.