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At least 1,081 records · Page 60Linked to original sources
PubMed2002

Bacterial infection of a model insect: Photorhabdus luminescens and Manduca sexta.

Invertebrates, including insects, are being developed as model systems for the study of bacterial virulence. However, we understand little of the interaction between bacteria and specific invertebrate tissues or the immune system. To establish an infection model for Photorhabdus, which is released directly into the insect blood system by its nematode symbiont, we document the number and location of recoverable bacteria found during infection of Manduca sexta. After injection into the insect larva, P. luminescens multiplies in both the midgut and haemolymph, only later colonizing the fat body and the remaining tissues of the cadaver. Bacteria persist by suppressing haemocyte-mediated phagocytosis and culture supernatants grown in vitro, as well as plasma from infected insects, suppress phagocytosis of P. luminescens. Using GFP-labelled bacteria, we show that colonization of the gut begins at the anterior of the midgut and proceeds posteriorly. Within the midgut, P. luminescens occupies a specific niche between the extracellular matrix and basal membrane (lamina) of the folded midgut epithelium. Here, the bacteria express the gut-active Toxin complex A (Tca) and an RTX-like metalloprotease PrtA. This close association of the bacteria with the gut, and the production of toxins and protease, triggers a massive programmed cell death of the midgut epithelium.

Animals↗
PubMed1984

The prevalence of diet-induced migraine.

Nineteen percent of about 490 patients with classical or common migraine reported that headaches can be precipitated by chocolate, 18% by cheese and 11% by citrus fruit, and a highly significant majority of these patients were sensitive to all three foods. Twenty-nine percent of the patients reported sensitivity to alcohol; again this was significantly associated with sensitivity to the three food stuffs, though a substantial number of patients were sensitive to alcohol but not foods. Thirty-one percent of 331 female patients believed that oral contraceptives precipitated headaches, but this could not be related to any dietary response. Patients with affected relatives were significantly more likely to report sensitivity to alcohol and chocolate; sensitivity to cheese and citrus fruit was less strongly related, and there was no relationship at all for oral contraceptives. These correlations suggest that food induced headaches are mediated by chemical constituents common to these foods.

Alcoholic Beverages↗
PubMed1992

Relationship between fetal acidemia at cordocentesis and subsequent neurodevelopment.

To determine whether there is a relationship between chronic fetal acidemia and subsequent neurodevelopment, a follow-up study was undertaken of 36 children with normal karyotype and morphology, who had prenatal cordocentesis for severe growth retardation. The main outcome measure was the Griffiths neurodevelopmental quotient. The children who had acidemia as fetuses (n = 13) had a significantly lower developmental quotient (mean = 91.8, SD = 6.3) than those with normal (n = 23) fetal blood pH (mean = 100.3, SD = 10.3; t = -2.68, p = 0.011). There was also a significant correlation between developmental quotient and the degree of fetal acidemia (r = 0.41, n = 36, p = 0.012). The pregnancies with acidemic fetuses had similar epidemiological characteristics to those with fetuses with a normal pH, except for a higher incidence of smoking. There was no significant correlation between the degree of growth retardation (birth weight expressed as multiples of SD from the mean for gestational age and sex) and fetal acidemia (r = -0.23, n = 36, NS) or subsequent Griffiths developmental quotient (r = -0.005, n = 36, NS). The results show an association between chronic fetal acidemia and subsequent impaired neurodevelopment. This observation suggests that future preventative interventions may be possible.

Journal Article↗
PubMed2000

Nitric oxide inhibits cornified envelope formation in human keratinocytes by inactivating transglutaminases and activating protein 1.

Epidermal keratinocytes undergo terminal differentiation to form the stratum corneum, which consists of many layers of flat dead cells. These cells assemble an insoluble cornified envelope composed of specific proteins deposited on the intracellular surface of the cell membrane. The proteins are crosslinked by the action of transglutaminases, which catalyze the formation of isodipeptide bonds between the epsilon-NH2 side chain of a lysine residue and the gamma-amide side chain of a glutamine residue. Transglutaminases share a conserved, highly reactive cysteine in their active site. In this study, we found that nitric-oxide-releasing compounds inhibited cornified envelope formation in cultured keratinocytes and the in vitro crosslinking of loricrin, a natural substrate of transglutaminases. The NO donors inhibited transglutaminase catalytic activity in a dose-dependent manner, in both purified enzymes and keratinocyte extracts. Titration of thiol groups of transglutaminases indicated that NO regulates their enzymatic activity by chemically modifying a cysteine residue, possibly by S-nitrosylation. NO was also found to inhibit DNA-binding activity of activating protein 1 in keratinocyte nuclear extracts, and to interfere with the transactivation of activating protein 1 responsive genes such as transglutaminase 1, involucrin, and loricrin, whose expression is regulated during epidermal differentiation. In conclusion, we propose that NO may inhibit keratinocyte differentiation, acting both at transcriptional level (inactivation of activating protein 1) and at post-translational level (inhibition of transglutaminase activity).

Cross-Linking Reagents↗
PubMed2000

A glutamine insertion in the 1A alpha helical domain of the keratin 4 gene in a familial case of white sponge nevus.

White Sponge Nevus (WSN) is a rare, autosomal dominant disorder that predominantly affects noncornified stratified squamous epithelia. Clinically, it is characterized by the presence of soft, white, and "spongy" plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Mutations in keratin 4 (K4) and keratin 13 (K13) genes have already been demonstrated to be responsible for WSN; the identification of new keratin mutations in a stratified squamous epithelia closely related to epidermis is of relevance for the understanding of the biochemistry of intermediate filaments, and for genotype phenotype correlations. In this study we investigated a 27-y-old, female Italian patient, affected by white asymptomatic oral plaques. Sequence analysis revealed a 3 bp (ACA) heterozygous insertion localized in the helix initiation motif of the 1A alpha helical domain of K4. We report this new K4 gene mutation and describe an amino acid insertion, in the 1A domain, responsible for a keratin disease.

Adult↗
PubMed2000

A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus.

Palmoplantar keratodermas are a group of heterogeneous diseases characterized by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes: diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All forms are genetic diseases inherited as autosomal dominant disorders. We studied a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fit into any classes already described. We sequenced the keratin 16 cDNA derived from skin biopsy material from affected and non affected palms. The keratin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletion (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypeptide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygotic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, "unilateral palmoplantar verrucous nevus", rather than localized or focal epidermolytic palmoplantar keratodermas, as the lesions are present only on one side of the body and follow Blaschko's lines. This study is a report of a mosaic mutation in keratin 16 and also the association of a mutation in the V1 domain of a type I keratin associated with a human disease.

Adolescent↗
PubMed2002

Expression of transglutaminase 5 in normal and pathologic human epidermis.

To explore the expression and gain more information on the function of transglutaminase 5 enzyme in normal and defective human epidermis, we generated a rat antihuman transglutaminase 5 antiserum elicited against a purified active recombinant protein expressed in the baculovirus system. By use of Western blotting and immunofluorescence methods, the immunospecificity of the antibodies for transglutaminase 5 was tested; no crossreactivity with other transglutaminases (types 1, 2, and 3) was observed, thus allowing histochemistry studies. By indirect immunofluorescence analysis the antibodies decorated the upper layers of normal human epidermis, with consistent staining in the spinous and granular layers. We evaluated transglutaminase 5 expression in comparison with proliferating (keratin 14) and differentiating (transglutaminase 3) markers in different diseases, such as psoriasis, ichthyosis vulgaris, lamellar ichthyosis, and Darier's disease. We observed that transglutaminase 5 contributes, as a secondary effect, to the hyperkeratotic phenotype in ichthyosis (both vulgaris and lamellar) and in psoriasis. In Darier's disease, transglutaminase 5 expression, as well as transglutaminase 3, is completely missregulated, being overexpressed or totally absent in different areas of the same lesion.

Antibody Specificity↗
PubMed2004

Laryngo-upper esophageal sphincter contractile reflex in humans deteriorates with age.

BACKGROUND & AIMS: Recent studies have shown the existence of several reflex connections between the aerodigestive and upper gastrointestinal tracts. Our aim was to study the effect of laryngeal stimulation on upper esophageal sphincter (UES) pressure and to determine the reproducibility of this effect. METHODS: We studied 14 young and 10 elderly healthy nonsmoker volunteers and 7 patients with UES dysphagia using a concurrent manometric and video endoscopic technique. Three levels of laryngeal air stimulation were studied: 6 mm Hg/50 ms, 10 mm Hg/50 ms, and 6 mm Hg/2 s. Ten young subjects were studied twice. RESULTS: For 6-mm Hg/2-s and 6-mm Hg/50-ms duration stimuli, the frequency of UES response to air stimulation as evidenced by mucosal deflection (response/deflection ratio) in the elderly volunteers was significantly lower compared with that of young subjects (P < 0.05). The response/deflection ratio of the 6-mm Hg/2-s stimulus was significantly higher than those induced by stimuli of shorter duration (P < 0.01). Poststimulation UES pressure was significantly higher than prestimulation pressure (P < 0.05) in both groups. The magnitude of the increase in poststimulation UES pressure in the elderly volunteers was similar to that of the young subjects. Findings were similar in repeated studies. Four of 7 dysphagic patients exhibited an abnormal response. CONCLUSIONS: Afferent signals originating from the larynx reproducibly induce contraction of the UES: the laryngo-UES contractile reflex. This reflex is elicited most reliably by 6-mm Hg/2-s air stimulation. Frequency elicitation of this reflex decreases significantly with age while the magnitude of change in UES pressure remains unchanged, indicating a deleterious effect of aging on the afferent arm of this reflex. This reflex is altered in some dysphagic patients.

Adult↗
PubMed2006

Influence of sleep stages on esophago-upper esophageal sphincter contractile reflex and secondary esophageal peristalsis.

BACKGROUND & AIMS: Airways are most vulnerable to aspiration during sleep. Esophago-upper esophageal sphincter (UES) contractile reflex (EUCR) and secondary peristalsis (2P) have been proposed to protect the airway by reflexively contracting the UES and clearing the esophagus of refluxate, respectively. Our aim was to study EUCR and 2P elicitation in "awake" state, stage II, slow-wave (stage III/IV), and rapid eye movement (REM) sleep. METHODS: Thirteen healthy volunteers were studied in the supine position using concurrent UES and esophageal manometry and polysomnography. Threshold volume (Tvol) to trigger EUCR and 2P and changes in sleep stages were recorded during injection of 2.7 mL/min water into the proximal esophagus after sleep stages were confirmed. RESULTS: UES pressure progressively declined with deeper stages of sleep. Tvol for EUCR and 2P elicitation was not significantly different between the stage II and "awake" state (EUCR: 4.0 +/- 1.8 mL vs 6.1 +/- 3.6 mL stage II; 2P: 5.8 +/- 2.2 mL vs 8.0 +/- 4.0 mL stage II). Tvol for EUCR and 2P elicitation during REM sleep were significantly lower than during the stage II and "awake" state (REM EUCR: 2.2 +/- 1.1 mL; 2P: 3.5 +/- 1.2 mL). Arousal and cough preempted development of EUCR and 2P during slow-wave sleep. CONCLUSIONS: (1) EUCR/2P can be elicited in stage II and REM but is preempted by arousal in slow-wave sleep. (2) Tvol for EUCR/2P elicitation is significantly lower in REM, compared with the stage II and "awake" state, suggesting a heightened sensitivity of these reflexes during REM sleep. (3) Although UES pressure progressively declines with deeper stages of sleep, it can still reflexively contract during REM sleep, despite generalized hypotonia.

Adult↗
PubMed2006

Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients.

BACKGROUND & AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) patients has been documented by evaluation of perceived stimulations that can reflect abnormalities of both sensory neurocircuitry and cognitive processes. The presence of actual neurohypersensitivity in human beings has not been documented separately. Because subliminal stimulations are free from the influence of stimulus-related cognitive processes, functional magnetic resonance imaging (fMRI) cortical response to these stimuli can be considered a measure of activity of the neural circuitry alone. The aim of this study was to compare quantitatively the cerebral cortical fMRI activity response to equal subliminal stimulations between IBS patients and age-matched controls. METHODS: We studied 10 IBS patients and 10 healthy controls using a computerized barostat-controlled rectal distention device. fMRI activity volume and percent maximum signal intensity change for equal subliminal distention pressures were compared between controls and patients. RESULTS: Three levels of subliminal distention pressures (eg, 10, 15, and 20 mm Hg), were represented in both controls and patients and were analyzed for fMRI response. In all 3 distention levels the fMRI activity volume in IBS patients was significantly larger than age- and sex-matched controls (P < .05). The percent maximum signal intensity change was similar between IBS patients and controls. CONCLUSIONS: The volume of cerebral cortical activity response to equal subliminal distention pressures in IBS patients is significantly larger than in controls, documenting the existence of hypersensitivity of the neural circuitry in this patient group irrespective of stimulus-related cognitive processes.

Adult↗
PubMed2002

c-erbB 2 serum level as prognostic factor in hormonally treated advanced breast cancer patients.

To investigate whether c-erbB 2 serum levels may be predictive of clinical response, progression-free and overall survival in postmenopausal women with advanced breast cancer hormonally treated, 265 patients enrolled in previous clinical trials were evaluated. C-erbB 2 serum levels were assessed before the start of treatment and in a subgroup of patients also at the first response evaluation. In addition, serum CA 15.3 levels were determined. The role of c-erbB 2 was investigated by means of multiple regression models in which both c-erbB 2 and CA 15.3 values were modelled as continuous variables together with other known prognostic factors. The failure probability tended to be higher in the presence of high c-erbB 2 levels, but the trend was not statistically significant; in contrast, significant results were obtained for progression-free survival (PFS,P <0.001) and overall survival (OS, P=0.014). The within-patient c-erbB 2 variation significantly predicted PFS (P=0.006) and OS (P=0.040). It is worth noting that c-erbB 2 and CA 15.3 baseline levels were significantly correlated and that the prognostic effect of c-erbB 2 tended to disappear in the presence of high CA 15.3 levels for PFS and OS.

Journal Article↗