Risk of skin cancer after ultraviolet phototherapy in patients with vitiligo: a systematic review and meta-analysis.

BACKGROUND: Although ultraviolet (UV) phototherapy is an effective treatment for vitiligo, its effect on the risk of skin cancer remains controversial. AIM: To investigate the association between UV phototherapy and skin cancer risk in patients with vitiligo. METHODS: A systematic review was performed for studies published before 5 May 2021 in the PubMed, Embase, Web of Science and Cochrane Library databases. The primary outcome was the association of UV phototherapy with the risk of skin cancer in patients with vitiligo. A meta-analysis with a random-effects model was conducted. RESULTS: Five retrospective cohort studies covering a total of 228 607 patients with vitiligo (110 038 who had been treated with UV phototherapy and 118 569 patients who had not) were included in the meta-analysis. The risk of nonmelanoma skin cancer [Mantel-Haenszel risk ratio (MHRR) = 0.95; 95% CI 0.44-2.05] and melanoma (MHRR = 1.11; 95% CI 0.33-3.82) did not significantly increase after phototherapy in patients with vitiligo. In the subgroup analysis, we also found no significant association between phototherapy with narrowband UVB phototherapy specifically and risk of skin cancer in patients with vitiligo. There was no significant difference in risk of skin cancer between patients from Europe and those from East Asia and the risk was not affected by the number of narrowband UVB phototherapy sessions. CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that UV phototherapy is a safe treatment for vitiligo with no significant risk of skin cancer.

Birth month and risk of atopic dermatitis: a nationwide population-based study.

BACKGROUND: An individual's birth month has been associated with allergic diseases, but little is known about the association between birth month and atopic dermatitis (AD). OBJECTIVE: The aim of this study was to investigate the risk of AD in children born in various months. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a case-control study that included 31 237 AD cases and 124 948 age- and gender-matched controls without AD. Data regarding sociodemographic factors and coexisting medical conditions were collected and controlled in the multivariate logistic regression to determine the adjusted odds ratios and 95% confidence intervals for AD associated with the participant's birth month. RESULTS: Compared with people born in May, people born in December had the highest risk of AD (OR 1.17, 95% CI 1.10-1.25), followed by people born in October (OR 1.15, 95% CI 1.08-1.22) and November (OR 1.13, 95% CI 1.06-1.20). Low income (OR 1.28), asthma (OR 1.88), allergic rhinitis (OR 1.70), psoriasis (OR 2.36), vitiligo (OR 1.99), urticaria (OR 2.14), and systemic lupus erythematosus (OR 1.91) were significant coexisting medical conditions associated with AD. CONCLUSION: Being born in December, October, or November may be associated with an increased risk of AD. Future investigations are needed to evaluate the possible mechanism behind the association between birth month and AD.

Optical coupling from InGaAs subcell to InGaP subcell in InGaP/InGaAs/Ge multi-junction solar cells.

Spatially-resolved electroluminescence (EL) images in the triple-junction InGaP/InGaAs/Ge solar cell have been investigated to demonstrate the subcell coupling effect. Upon irradiating the infrared light with an energy below bandgap of the active layer in the top subcell, but above that in the middle subcell, the EL of the top subcell quenches. By analysis of EL intensity as a function of irradiation level, it is found that the coupled p-n junction structure and the photovoltaic effect are responsible for the observed EL quenching. With optical coupling and photoswitching effects in the multi-junction diode, a concept of infrared image sensors is proposed.

HLA-DM recognizes the flexible conformation of major histocompatibility complex class II.

DM facilitates formation of high affinity complexes of peptide-major histocompatibility complex (MHC) by release of class II MHC-associated invariant chain peptide (CLIP). This has been proposed to occur through discrimination of complex stability. By probing kinetic and conformational intermediates of the wild-type and mutant human histocompatibility leukocyte antigen (HLA)-DR1-peptide complexes, and examining their reactivities with DM, we propose that DM interacts with the flexible hydrophobic pocket 1 of DR1 and converts the molecule into a conformation that is highly peptide receptive. A more rigid conformation, generated upon filling of pocket 1, is less susceptible to DM effects. Thus, DM edits peptide-MHC by recognition of the flexibility rather than stability of the complex.

Factors leading to obstructive granulation tissue formation after ultraflex stenting in benign tracheal narrowing.

BACKGROUND: This retrospective study aimed to determine the factors leading to obstructive granulation tissue formation after the placement of a self-expandable metallic stent (SEMS) in patients with benign tracheal disease. METHODS: From 2001 to 2007, a total of 67 patients (age: 62.1 +/- 15.4 years; range: 23-87 years) with benign tracheal disease received 75 ultraflex SEMS in our institution. RESULTS: There were 35 SEMSs complicated by obstructive granulation tissue formation out of the 75 stents placed in patients with tracheal disease, giving an incidence of 47.8 % (32/67 patients). The median time until developing granulation tissue was 106 days (IQR, 46-396). Structural airway obstruction prior to SEMS implantation independently predicted obstructive granulation tissue formation after SEMS implantation (odds ratio: 3.84; 95 % CI: 1.01-8.7; P = 0.04). Time to granulation tissue detection was shorter in patients with structural airway obstruction before SEMS implantation (structural airway obstruction vs. dynamic collapse airway: median [IQR] 95 [38-224, n = 26] vs. 396 days [73-994, n = 9]; P = 0.02). CONCLUSIONS: Obstructive granulation tissue formation is not uncommon after SEMS implantation and structural airway obstruction prior to SEMS implantation is an independent predictor. Although SEMS implantation should be restricted to a select population, it may be placed in patients not suitable for surgical intervention or rigid bronchoscopy with anesthesia because of poor pulmonary function.

Auditory brainstem potentials in chronic alcoholics.

Auditory brainstem potentials were recorded from abstinent chronic alcoholics and control subjects. The latencies of peaks II, III, IV, and V were significantly delayed in the alcoholic patients compared to control subjects. Brainstem transmission time was longer in alcoholics than in controls. This study provides systematic evidence that chronic alcohol abuse results in brainstem deficits suggesting possible demyelination of auditory tracts.

Metallic stent and flexible bronchoscopy without fluoroscopy for acute respiratory failure.

Stent implantation has been reported to facilitate liberation from mechanical ventilation in patients with respiratory failure due to central airway disease. The present retrospective cohort study sought to evaluate the risk and benefit of stent implantation via bronchoscopy without fluoroscopic guidance in mechanically ventilated patients. From July 2001 to September 2006, 26 patients with acute respiratory failure were recruited. A bronchoscope was inserted through a mouth guard into the space between the tracheal wall and the endotracheal tube. A guide wire was inserted via the flexible bronchoscope to the lesion site. The bronchoscope was reintroduced through the endotracheal tube. Under bronchoscopic visualisation, the delivery catheter was advanced over the guide wire to deploy the stent. These procedures were successfully performed in 26 patients, with 22 stents placed in the trachea and seven in the main bronchus. Of the 26 patients, 14 (53.8%) became ventilator independent during their stay in the intensive care unit. Severe pneumonia was the most common cause, in seven (58.3%) out of 12 patients, for continued ventilator dependence after stenting. Granulation tissue formation was found in seven patients during the follow-up period. It is concluded that metallic stents can be safely implanted without fluoroscopic guidance in patients with respiratory failure, to facilitate ventilator independence.

Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking.

To evaluate the possible role of a putative vesicle-targeting protein, syntaxin-4, in vasopressin-regulated trafficking of aquaporin-2 water channel vesicles to the apical plasma membrane of renal collecting duct cells, we have carried out immunoblotting, immunocytochemistry, and reverse transcription (RT)-PCR experiments in rat kidney. Immunochemical studies used an affinity-purified, peptide-directed polyclonal antibody to rat syntaxin-4. Immunoblots using membrane fractions from inner medullary collecting duct (IMCD) cell suspensions revealed a solitary protein of 36 kD, the expected molecular mass of syntaxin-4. This protein was enriched in a plasma membrane-enriched membrane fraction from IMCD cells. Immunoperoxidase immunocytochemistry in 0.85-microm cryosections from rat inner medulla revealed discrete labeling of the apical plasma membrane of IMCD cells. RT-PCR demonstrated the presence of syntaxin-4 mRNA in microdissected IMCD segments, confirmed by direct sequencing of the PCR product. In addition, RT-PCR experiments demonstrated syntaxin-4 mRNA in glomeruli, vasa recta, connecting tubules, and thin descending limbs of Henle's loops. The demonstrated localization of syntaxin-4 in the apical plasma membrane of collecting duct principal cells, coupled with previous demonstration of syntaxin-4's putative cognate receptor VAMP2 in aquaporin-2-containing vesicles, supports the view that these proteins could play a role of aquaporin-2 vesicle targeting to the apical plasma membrane.

Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice.

It has been controversial whether high water permeability in the thin descending limb of Henle (TDLH) is required for formation of a concentrated urine by the kidney. Freeze-fracture electron microscopy (FFEM) of rat TDLH has shown an exceptionally high density of intramembrane particles (IMPs), which were proposed to consist of tetramers of aquaporin-1 (AQP1) water channels. In this study, transepithelial osmotic water permeability (Pf) was measured in isolated perfused segments (0.5-1 mm) of TDLH in wild-type (+/+), AQP1 heterozygous (+/-), and AQP1 null (-/-) mice. Pf was measured at 37 degrees C using a 100 mM bath-to-lumen osmotic gradient of raffinose, and fluorescein isothiocyanate (FITC)-dextran as the luminal volume marker. Pf was (in cm/s): 0.26 +/- 0.02 ([+/+]; SE, n = 9 tubules), 0.21 +/- 0.01 ([+/-]; n = 12), and 0.031 +/- 0.007 ([-/-]; n = 6) (P < 0.02, [+/+] vs. [+/-]; P < 0.0001, [+/+] vs. [-/-]). FFEM of kidney medulla showed remarkably fewer IMPs in TDLH from (-/-) vs. (+/+) and (+/-) mice. IMP densities were (in microm-2, SD, 5-12 micrographs): 5,880 +/- 238 (+/+); 5,780 +/- 450 (+/-); and 877 +/- 420 (-/-). IMP size distribution analysis revealed mean IMP diameters of 8.4 nm ([+/+] and [+/-]) and 5.2 nm ([-/-]). These results demonstrate that AQP1 is the principal water channel in TDLH and support the view that osmotic equilibration along TDLH by water transport plays a key role in the renal countercurrent concentrating mechanism. The similar Pf and AQP1 expression in TDLH of (+/+) and (+/-) mice was an unexpected finding that probably accounts for the unimpaired urinary concentrating ability in (+/-) mice.

Intron sequences determine the expression of kappa light chain genes.

Alterations in kappa light chain expression were demonstrated to originate from genomic changes in the L-V intron (L-IVS) which changed the splicing pattern of the kappa mRNA. In R15, a mutant of mouse myeloma W3129 which produces no kappa light chain, a 358 bp novel sequence element (R15ns) of unknown origin replaced 19 bases of wild-type L-IVS, both altering the normal splicing pattern and activating a cryptic polyadenylation site. Subclones of R15 which reverted to kappa light chain production contained genomic deletions of R15ns and/or the surrounding intron. These deletions led to partial or full restoration of wild type kappa mRNA levels due to further changes in the pattern of mRNA processing. Two cryptic splice acceptor sites and a polyadenylation signal exist in the L-IVS; a cryptic splice acceptor sequence also exists in V kappa. These cryptic sites can be activated by changing the genomic context. It is thus possible to influence light chain expression without altering either the exon sequences or the known regulatory elements. Alterations in splicing patterns also serve to produce kappa light chains with novel variable region sequences and thereby could contribute to antibody diversity. Surprisingly, in the cell line producing this novel kappa light chain, intact alpha heavy chains were secreted in the absence of an apparent association with light chain. These studies also demonstrate that it is not possible to distinguish functional from non-functional genes solely by sequence analysis and that genes can both be inactivated and activated by changes in intron sequences.

Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets.

The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Two types of voltage-gated K channels in carotid body cells of adult cats.

The purpose of this study was to investigate if the oxygen-sensitive K channel is present in the carotid body cells of adult cats, and if all carotid body cells express the oxygen-sensitive K channel. A standard patch-clamp technique with a whole-cell configuration was applied to cultured carotid body cells from adult cats. The cells were continuously perfused with Krebs equilibrated with 5% CO2/air or 5% CO2/argon at room temperature. The results showed that electrophysiologically at least two types of cells existed in cultured cat carotid body cells. One type expressed the oxygen-sensitive K channel and the other expressed the oxygen-insensitive K channel. The oxygen-sensitive K channel was voltage-dependent with a threshold potential of -30 mV. No inactivation was observed during 40 ms of stimulation. The slope of the steady-state current-voltage curve was almost linear in the range from -30 mV to +50 mV. Hypoxia (pO2 = 25 mmHg) reversibly depressed the K current by 22%. The current was inhibited by 4-aminopyridine (10 mM) and tetraethylammonium (4-25 mM), but insensitive to charybdotoxin (100 nM). The oxygen-insensitive K channel showed similar characteristics to that of the oxygen-sensitive K channel in the threshold and the speed of activation, and the shape of I-V curve. The cat is the third species in which the oxygen-sensitive K channel was found in the carotid body. The sensitivity of K channels to oxygen may be a unique feature of chemosensory cells, but the properties of the oxygen-sensitive K channels are different among cats, rats, and rabbits.

Electrophysiological and immunocytological demonstration of cell-type specific responses to hypoxia in the adult cat carotid body.

We have recently shown two types of cat carotid body cells based on the oxygen sensitivity of voltage-gated potassium channels. In the present study, we attempted to determine the correlation between cell types (glomus cells, sheath cells, and subtypes of glomus cells) and oxygen sensitivity of potassium channels. Further, changes in membrane potentials in response to hypoxia were also examined. Carotid body cells harvested from adult cats were cultured, and a whole cell patch clamp method was applied to determine the oxygen sensitivity of outward current. The tested cells were identified by Lucifer Yellow in the patch pipette. Glomus cells and sheath cells were immunocytochemically identified using tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) as markers. The cells whose outward current was inhibited by hypoxia showed TH-immunoreactivity but not GFAP-immunoreactivity. The cells whose outward current was not sensitive to hypoxia were GFAP-positive or TH-negative. One TH-positive cell had oxygen-insensitive outward current. The resting membrane potentials of the cells having oxygen-sensitive outward current were significantly higher (-55+/-3 mV) than those of the cells having oxygen-insensitive outward current (-35+/-2 mV). The former type of cells was depolarized during hypoxia, but not the latter type of cells. These results suggest that most glomus cells of the adult cat carotid body possess oxygen-sensitive potassium channels and are depolarized in response to hypoxia. On the other hand, sheath cells and possibly a small fraction of glomus cells possess oxygen-insensitive potassium channels and their membrane potential is not affected by hypoxia.

Isolation and characterization of metal-binding proteins (metallothioneins) from lobster digestive gland (Homarus americanus).

Two metallothionein (low-molecular-weight, metal-binding proteins) preparations, MT-1 and MT-2, have been isolated from the digestive gland of American lobster (Homarus americanus) contaminated with Cd. MT-1 contains Cd- and Cu-binding proteins, whereas MT-2 is a reasonably pure Cd-binding protein. The properties of MT-1 and MT-2 with respect to amino acid and elemental compositions, heat stabilities, polarographic, high-performance liquid chromatography (HPLC), and isoelectric focussing behaviors are reported. Lobster metallothioneins share a number of similarities with mammalian metallothioneins with respect to the presence of Cd and Cu, apparent molecular weights, amino acid compositions, UV absorption spectra at various pH, and polarographic behavior, but differ substantially in their electrophoretic behavior.

The reactivity of EDTA, copper ion, and copper citrate with metallothioneins isolated from the digestive gland of cadmium-contaminated lobster (Homarus americanus).

The reactivity of EDTA, Cu2+, and copper citrate with two metallothionein preparations (MT-1 and MT-2) isolated from the digestive gland of Cd-contaminated American lobster (Homarus americanus) was studied. Under pseudo-first-order conditions, metallothioneins reacted with EDTA for removal of Cd2+ in a multiphasic manner. Cadmium(+II) removal by Cu2+ was complex and non-stoichiometric, suggesting different binding sites. Rabbit liver metallothionein reacted similarly. Cadmium removal from lobster metallothionein by copper citrate was slow and triphasic in nature. EDTA removed Cu2+ from lobster metallothionein very slowly.

Selection of bioindicators for monitoring marine environmental quality in the Bay of Fundy, Atlantic Canada.

Distribution of metals, PAH's and PCB's in lobsters, mussels, and sediments were used to assess marine environmental quality of the Bay of Fundy. This study demonstrates that the lobster (Homarus americanus) is a better bioindicator for monitoring contaminants in the marine environment and has a greater capacity for the uptake and accumulation of contaminants than the mussel (Mytilus edulis) and sediments. A definite pattern in the spatial distribution of lobster Cu, Cd, and Ag was evident. The distribution of organic contaminants for both mussels and lobsters in the Bay of Fundy lacked a spatial trend, and organic contaminants were undetectable in sediments from all sites. The Gulf Watch Programme, which monitors chemicals in mussels in the Bay of Fundy, did not indicate a problem with high levels of Cu, Cd, and Zn in the ecosystem. Analytes below the detection limit, such as in mussels and sediments, increase the difficulties of chemical analysis and detection for environmental monitoring. Deficiencies of mussels in monitoring the Bay of Fundy were discussed.

A regression model using sediment chemistry for the evaluation of marine environmental impacts associated with salmon aquaculture cage wastes.

This study was undertaken to develop an approach for modelling changes of sediment chemistry related to the accumulation of aquaculture waste. Metal composition of sediment Al, Cu, Fe, Li, Mn, and Zn; organic carbon and < 63 microm particles were used to determine the extent of detectable effects around the cage. This study showed marked differences in the sediment chemistry between aquaculture sites and the natural background: (1) negative correlations between sediment Cu and Zn with Al, (2) poor correlations between metals and Li, and (3) concentrations of Fe and Mn decreased with increased accumulation of organic carbon. There is a trend among normalised metals, organic carbon and particles related to normal, hypoxic and anoxic sediment conditions. The trends are useful for detecting and assessing the cumulative effects from aquaculture wastes to the marine environment. Lithium is less interactive with other metals in aquaculture sediments compared with the natural background sediments. Principal components analysis (PCA) was carried out on the metals, organic carbon, and particles to cluster the similarities of the variables so as to establish the predicted or adjusted environmental monitoring program (EMP) ratings. This approach, using the adjusted EMP rating based on sediment chemistry, yields a regression model with R2 = 0.945 compared to R2= 0.653 for the regression model using unadjusted EMP for assessing the environmental conditions.

Metal contaminants for modelling lobster (Homarus americanus) migration patterns in the Inner Bay of Fundy, Atlantic Canada.

A method, which uses metal compositions in lobster digestive glands as natural environmental tags, has been developed to trace lobster movements. Lobsters were collected from three selected sites, Minas Channel, Minas Basin, and Cobequid Bay, Inner Bay of Fundy, New Brunswick, Canada, that were known to be contaminated with Cu. Five metal variables (Ag, Cd, Cu, Mn and Zn) were processed for principal component analysis (PCA). Metal concentration and burden models were investigated and PCA was able to differentiate lobsters from the respective catch sites. The method was applied to investigate the May and June lobsters collected at the three sites to determine the migration rate during this period of the fishing season. The results show a high level of mixing at Minas Basin and Cobequid Bay in June, and lobster movement inward toward the inner reaches of the bay, with very limited movement outward from the inner bay.

Aquaculture-related trace metals in sediments and lobsters and relevance to environmental monitoring program ratings for near-field effects.

The study was undertaken to assess the marine environmental effects from feed and waste associated with aquaculture activities. Metal compositions of sediment, lobster, and feed were used to evaluate the extent of detectable effects at 0 m (under the cage) and 50 m distance. Sediments that were collected under the cages and were characterised as hypoxic or anoxic, showed elevated levels of Cu, Zn, organic carbon, and % <63 microm particles, and low Mn and Fe. At 50 m there was a major reduction in waste chemical impact. Using lobster, a bioindicator species, as a tool for detecting near-field impacts, showed accumulations of high Cu associated with active aquaculture sites. Chemical compositions and metal ratios normalised with organic carbon, were used to assess the sediment conditions associated with environmental monitoring program ratings (EMP--normal, hypoxic, and anoxic). Principal component analysis (PCA) was used to explore chemical data at all sites for differentiating normal, hypoxic and anoxic sediment conditions. Selected variables (Cu, Zn, Fe, Mn, organic carbon, and particles <63 microm) were sufficient for the PCA approach with >90% explainable variance of first two components. The groupings based on PCA and cluster analysis were similar to EMP classifications with some exceptions of mis-identification by EMP. The sediment chemistry components were valid indicators for evaluating marine environmental conditions and for assessing aquaculture operating sites. The developed techniques, using chemical variables in combination with EMP and the statistical approach should be useful to predict the effects of aquaculture practices and the suitability of aquaculture operations.