Oncocytic lipoadenoma of the parotid gland with sebaceous differentiation. Study of its keratin profile

Oncocytic lipoadenomas of salivary gland are extremely rare tumors with only two previously reported cases. In this paper, we describe an additional example of oncocytic lipoadenoma showing sebaceous differentiation, a hitherto unreported occurrence. The tumor was encapsulated and measured 3 × 2.5 × 2 cm. Microscopically, the tumor comprised a mixture of oncocytes with “light” and “dark” cells intimately associated with mature adipose tissue. The oncocytes were positive for low molecular keratin, epithelial membrane antigen (EMA), and keratin 7, with only a small subgroup of cells expressing high-molecular-weight keratin, keratin 5/6, keratin 19, and p63. Terminally differentiated sebaceous cells were positive for EMA and keratin 14 only. Calponin and actins were negative, indicating a lack of myoepithelial cells in the tumor. The keratin profile and p63 expression of this oncocytic lipoadenoma suggest the presence of a dual cell population somewhat similar to the dual cell population described in some ultrastructural studies of pure salivary gland oncocytomas and may represent partial basal-cell differentiation. The presence and nature of a dual cell population in oncocytic neoplasms of salivary glands merit further investigation to confirm these observations.     

Transthoracic fine-needle aspiration in the aetiological diagnosis of community-acquired pneumonia

To investigate the safety and practicability of conducting transthoracic fine-needle aspiration (TFNA) in a general hospital setting, we applied the TFNA procedure to 20 patients hospitalized with community-acquired pneumonia (CAP) within 36 h of admission. Also, a preliminary assessment was made of the potential value of adding TFNA to conventional methods of diagnostic microbiology. TFNA was easy to perform and caused little discomfort, and no serious adverse events were observed. In spite of ongoing antimicrobial treatment, a likely aetiological diagnosis was established for 14 of 20 (70%) of the patients. TFNA may provide important additional information on the aetiology of CAP.     

Biomechanical Evaluation of Equine Masticatory Action: Position and Curvature of Equine Cheek Teeth and Age‐Related Changes

The equine cheek tooth battery is part of a very dynamic system. The aim of this study was to investigate whether the curvature and position of the teeth are also involved in such dynamical processes. The alveolar crest was labelled with a radiodense marker (48 cadaver heads, 15 skulls) and laterolateral radiographs were taken. Then a geometrical method was elaborated to determine a cheek tooth's curvature and its position by means of specific angles. This method respects the remarkable changes of the equine dentition throughout life by considering two items: (1) the alveolar crest was taken as a constant landmark, (2) the central axis of the curved dental crown was determined by calculation of a linear regression equation. This equation considered several geometrically determined points on the curved dental crown which had been marked in the radiographs. Our study yielded the following results: Mandibular cheek teeth became more curved with age, but their positions (represented by the so‐called mesio‐occlusal angle between tooth and alveolar crest) did not change significantly. In maxillary cheek teeth, however, the mesio‐occlusal angle became larger with age (indication of change of dental position), while their curvature did not change. Even though changes of the dental position were not always statistically significant, they are discussed as being biologically/functionally relevant. The mandibular anticlinal tooth, i.e. the tooth positioned at a mesio‐occlusal angle of about 90°, was not in contact with the maxillary anticlinal tooth. Interestingly, the maxillary anticlinal tooth is known to cause most clinical dental problems. Anat Rec, 291:565–570, 2008. © 2008 Wiley‐Liss, Inc.     

The zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells

The pancreatic and intestinal primordia contain epithelial progenitor cells that generate many cell types. During development, specific programs of gene expression restrict the developmental potential of such progenitors and promote their differentiation. The Insm1 (insulinoma-associated 1, IA-1) gene encodes a Zinc-finger factor that was discovered in an insulinoma cDNA library. We show that pancreatic and intestinal endocrine cells express Insm1 and require Insm1 for their development. In the pancreas of Insm1 mutant mice, endocrine precursors are formed, but only few insulin-positive beta cells are generated. Instead, endocrine precursor cells accumulate that express none of the pancreatic hormones. A similar change is observed in the development of intestine, where endocrine precursor cells are formed but do not differentiate correctly. A hallmark of endocrine cell differentiation is the accumulation of proteins that participate in secretion and vesicle transport, and we find many of the corresponding genes to be down-regulated in Insm1 mutant mice. Insm1 thus controls a gene expression program that comprises hormones and proteins of the secretory machinery. Our genetic analysis has revealed a key role of Insm1 in differentiation of pancreatic and intestinal endocrine cells.     

Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages

In order to identify cellular genes which interfere with HIV-1 replication in monocyte-derived macrophages (MAC), cells were stimulated with interferon (IFN) or lipopolysaccharide (LPS) leading to a pronounced inhibition of HIV-1 infection in these cells, and the resulting gene expression was analyzed. Using the microarray technology we identified a gene named Stimulated Trans-Acting Factor of 50 kDa (Staf50), which is known to repress the activity of the HIV-1 LTR. Analysis of the Staf50 expression by real-time PCR showed an overexpression in IFNalpha (up to 20-fold) and LPS (up to 10-fold)-stimulated MAC as well as in infected cells (up to 3-fold). For stable overexpression, 293 T cells and primary macrophages were transduced with Staf50-IRES-GFP bicistronic pseudotype viruses. After transduction, 293 T CD4/CCR5 and MAC were infected with HIV-1, and virus replication was monitored by p24 ELISA. Overexpression of Staf50 inhibited the HIV-1 infection between 50% and 90% in 293 T CD4/CCR5 as well as in MAC. Our findings suggest that host genetic effects in combination with viral properties determine the susceptibility of an appropriate target cell for HIV-1 infection as well as the replication potential of the virus in the cell resulting in an overall productive infection.     

Caveolin-1 Is Down-Regulated in Human Ovarian Carcinoma and Acts as a Candidate Tumor Suppressor Gene

To identify novel markers differentially expressed in ovarian cancer versus normal ovary, we hybridized microarrays with cDNAs derived from normal human ovaries and advanced stage ovarian carcinomas. This analysis revealed down-regulation of the caveolin-1 gene (CAV1) in ovarian carcinoma samples. Suppression of CAV1 in ovarian carcinomas was confirmed using a tumor tissue array consisting of 68 cDNA pools from different matched human tumor and normal tissues. Immunohistochemistry demonstrated expression of caveolin-1 in normal and benign ovarian epithelial cells, but loss of expression in serous ovarian carcinomas. In low-grade carcinomas, redistribution of caveolin-1 from a membrane-associated pattern observed in normal epithelium to a cytoplasmic localization pattern was observed. No expression of caveolin-1 was detectable in four of six ovarian carcinoma cell lines investigated. In SKOV-3 and ES-2 carcinoma cells, which express high levels of the caveolin-1 protein, phosphorylation of the 22-kd caveolin-1 isoform was detected. Inhibition of both DNA methylation and histone deacetylation using 5-aza-2'deoxycytidine and Trichostatin A, respectively, relieves down-regulation of caveolin-1 in OAW42 and OVCAR-3 cells which is in part mediated by direct regulation at the mRNA level. Expression of CAV1 in the ovarian carcinoma cell line OVCAR-3, resulted in suppression of tumor cell survival in vitro, suggesting that the CAV1 gene is likely to act as a tumor suppressor gene in human ovarian epithelium.     

Parallel pathways mediate inhibitory effects of vasoactive intestinal polypeptide and nitric oxide in canine fundus.

1. The gastric adaptation reflex is activated by the release of non-adrenergic, non-cholinergic (NANC) inhibitory transmitters, including nitric oxide (NO) and vasoactive intestinal polypeptide (VIP). The role of NO in this reflex is not disputed, but some investigators suggest that NO synthesis is stimulated by VIP in post-junctional cells or in nerve terminals. We investigated whether the effects of these transmitters are mediated by independent pathways in the canine gastric fundus. 2. VIP and NO produced concentration-dependent relaxation of the canine fundus. Nomega-nitro-L-arginine (L-NNA) reduced relaxation induced by electrical field stimulation (EFS; 0.5-8 Hz), but had no effect on responses to exogenous VIP and sodium nitroprusside (SNP, 10 microM). 3. Oxyhaemoglobin reduced relaxations produced by EFS and SNP. Oxyhaemoglobin also reduced relaxation responses to low concentrations of VIP (<10 nM), but these effects were non-specific and mimicked by methaemoglobin which had no effect on nitrergic responses. 4. A blocker of guanylyl cyclase, 1H-[1,2,4]oxidiazolo [4,3,-a]quinoxalin-1-one, (ODQ) inhibited responses to EFS, SNP and DETA/NONOate (an NO.donor), but had no effect on responses to VIP. cis-N-(2-phenylcyclopentil)-azacyclotridec-1en-2-amine monohydrochloride (MDL 12,330A), a blocker of adenylyl cyclase, reduced responses to EFS, VIP and forskolin, but did not affect responses to SNP. 5. Levels of cyclic GMP were enhanced by the NO donor S-nitroso-n-acetylpenicillamine (SNAP) but were unaffected by VIP (1 microM). The increase in cyclic GMP in response to SNAP was blocked by ODQ. 6. The results suggest that at least two transmitters, possibly NO and VIP, mediate relaxation responses in the canine fundus. NO and VIP mediate responses via cyclic GMP- and cyclic AMP-dependent mechanisms, respectively. No evidence was found for a serial cascade in which VIP is coupled to NO-dependent responses.     

Allopurinol Treatment Reduces Arterial Wave Reflection in Stroke Survivors

The importance of xanthine oxidase and its products is being increasingly recognized in cardiovascular medicine. Patients who have had a stroke are at high risk of future cardiovascular events and this risk is higher in those with high urate levels. The aim of this pilot study was to see if inhibiting xanthine oxidase altered arterial wave reflection, determined from the augmentation index (AIx). In a double‐blind study, 30 patients with high urate (≥0.38 mmol/L) were randomized to 300 mg allopurinol or placebo for 8 weeks. AIx measurements were made before and after treatment using the validated SphygmoCor pulse waveform analysis system. For patients treated with allopurinol, there was a reduction in AIx from 26.08 ± 3.31% to 20.15 ± 2.23% compared with an increase in the placebo group from 23.57 ± 3.13% to 27.64 ± 3.44% (P= 0.031, ANOVA). The vascular benefits of allopurinol are rapidly emerging. We have demonstrated that allopurinol has beneficial effects on AIx, a validated measure of vascular function. A further larger study is warranted to look at whether a therapeutic intervention with allopurinol will impact positively on mortality and morbidity in stroke survivors.     

Comparative study of patch test using traditional method vs. prior skin abrading

BACKGROUND: The patch test is an essential procedure for the investigation of aetiologic diagnosis of allergic contact dermatitis, although it is not yet able to fully reproduce the events of the initial site of contact with the allergen. OBJECTIVES: The aims of the present study are (i) to assess whether removal of the superficial corneous layer results in test positivity differences vs. the traditional technique, (ii) to assess the probable and/or possible and past and/or present sensitivity and relevance for each method, and (iii) to compare specific relevance of nickel sulphate for each method. RESULTS: Concordance of positive reactions was 75.9% (66 of 87), with 21.8% (19 of 87) positivity results on the abraded side only and 2.3% (2 of 87) on the unabraded side (P < 0.05). Concordance of the substances with probable and/or possible and past and/or present relevance was 77.3% (58 of 75) for the abraded side and 21.3% (16 of 75) and 1.3% (1 of 75) for the unabraded side (P < 0.05). Analysis of isolated relevance for nickel sulphate showed 95.6% (22 of 23) concordance. CONCLUSIONS: (i) We found a greater number of positive substances on the abraded side, and when only the 2 + and 3 + reactions were considered, greater relative discordance was also observed; (ii) relevance analysis revealed a statistically significant difference between the two methods; (iii) differences in nickel sulphate test positivity and relevance for the two methods did not reach statistical significance.     

The high molecular mass allergen fraction of timothy grass pollen (Phleum pratense) between 50–60 kDa is comprised of two major allergens: Phl p 4 and Phl p 13

BACKGROUND: More than 70% of the patients allergic to grass pollen exhibit IgE-reactivity against the high molecular mass fraction between 50 and 60 kDa of timothy grass pollen extracts. One allergen from this fraction is Phl p 4 that has been described as a basic glycoprotein. A new 55/60 kDa allergen, Phl p 13, has recently been purified and characterized at the cDNA level. OBJECTIVE: The relative importance of the two high molecular mass allergens has been characterized with respect to their IgE-binding frequency and capacity. METHODS: Both high molecular mass allergens were biochemically purified and subjected to nitrocellulose strips. About 306 sera obtained from subjects allergic to grass pollens were used to determine specific IgE-binding frequency to Phl p 4 and Phl p 13. IgE-binding of allergens was quantified by ELISA measurements. Pre-adsorption of sera with purified allergens and subsequent incubation of nitrocellulose-blotted timothy grass pollen extract was performed to determine whether or not Phl p 4 and Phl p 13 represent the whole high molecular mass allergen fraction. Proteolytic stability of both allergens was investigated by addition of protease Glu-C. RESULTS: More than 50% of 300 patients displayed IgE-binding with both allergens. Clear differences concerning the immunological properties of Phl p 4 and Phl p 13 were confirmed by individual IgE reactivities. Quantification of specific IgE for both allergens revealed comparable values. For complete inhibiton of IgE-binding in the high molecular mass range preincubation of sera with both allergens was necessary. Interestingly, inhibition of strong reacting sera with Phl p 13 eliminated not only reactivity of the 55/60 kDa double band, but in addition a 'background smear'. Whilst undenatured Phl p 4 was resistent to proteolytic digestion with Glu-C, native Phl p 13 was degraded rapidly. CONCLUSION: Phl p 4 and Phl p 13 are immunologically different and must both be considered as major allergens. They are judged to be important candidates for potential recombinant therapeutics that may provide a basis for improved immunotherapy.