A new rat model of transplant arteriosclerosis accelerated by ischemia/reperfusion injury.
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Animals↗
Biomedical subjects
I Wang
Publications and source records attributed to I Wang.
Characterization of Corn1 mice: Alteration of epithelial and stromal cell gene expression.
PURPOSE: Corn1 is an autosomal recessive mutation characterized by corneal epithelial hyperplasia and stromal neovascularization. The aim of the present study is to examine the expression patterns of specific epithelial and stromal proteins in corn/corn1 mutant mice. METHODS: Immunohistochemistry with antibodies directed against keratins 1, 4, 5, 12, and 14 as well as loricrin, filaggrin, and involucrin were performed in corn1/corn1 and wild type, A.By/SnJ strain, mice at 4 weeks of age. Western blot hybridization was performed to confirm the presence of involucrin in corneas. In situ and northern blot hybridization were used to evaluate the expression of keratin 12, lumican, and keratocan in these mice. RESULTS: In corn1/corn1 mice, focal areas of corneal epithelial hyperplasia alternate with epithelium with normal appearance. Both regions of normal and hyperplastic corneal epithelium were labeled by anti-keratin 12 antibodies through all corneal epithelial layers. The anti-keratin 14 antibody only labeled the basal cell layer in normal epithelial areas, whereas it labeled both basal and suprabasal cell layers in hyperplastic areas. In wild type mice, anti-keratin 12 antibodies labeled all corneal epithelial layers, whereas anti-keratin 14 labeled the basal corneal epithelial cells only. Positive staining by anti-involucrin antibody was demonstrated in the basal corneal epithelial layer of wild type mice and normal areas of corn1/corn1 mice. Similarly, as observed with anti-keratin 14 antibody, the anti-involucrin antibody labeled both basal and suprabasal cell layers of hyperplastic corneal epithelium of corn1/corn1 mice. Antibodies against keratin 1, keratin 4, loricrin, and fillagrin did not label the corneas of wild type mice or corn1/corn1 mice. Northern hybridization indicated that the expressions of keratocan and lumican mRNA levels were up regulated in corn1/corn1 mice, but keratin 12 mRNA remained similar to that of the wild type mice. In situ hybridization revealed that the lumican mRNA was detected in epithelial and stromal cells of corn1/corn1 mice, whereas keratocan mRNA was only detected in stromal cells. CONCLUSIONS: Hyperproliferative epithelial cells of corn1/corn1 mice have increased levels of expression of keratin 14 and involucrin, but do not exhibit the phenotypical characteristics of cornification. These observations indicate that factors associated with the phenotypes of corn1/corn1 mice do not alter the cornea-type epithelial differentiation of keratin 12 expression, but cause aberrant expression of lumican by corneal epithelial cells.
Animals↗
Experimental study on AT1-receptor-peptide-induced myocardial immune damage in rat.
In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n = 12), each rat was immunized with 150 micrograms AT1-receptor peptide coupled to bovine serum albumin, together with Freund's adjuvant. Control group (n = 6), sham-immunized, "immunized liquid" was same as immunized-group except AT1-receptor peptide. Systolic blood pressure (SBP) was measured by using the tail-cuff technique, antibody against AT1-receptor peptide detected by using ELISA method, and left ventricular myocardium and renal cortex sections were observed under light and electron microscopy. There was no significant difference in SBP and light microscopic observation of the tissue sections between the immunized-group and control group. The O.D. value of anti-AT1-receptor peptide antiserum was significantly higher in the immunized-group than in the rats before immunization and control group (P < 0.01). Positive rate in the immunized-group was 100%, while 0% in the control group. Ultramicroscopic morphology showed potential myocardial injury, including: increase in number of mitochondria, swelling of many mitochondria with reduction in number or absence of their cristae and cristolysis, disorder of the cardiac myofibrils, and myofibrillar disruption and myocytolysis. And lysosomes were increased in renal tubular epithelia. The AT1-receptor peptide could induce to generate the antibody against AT1-receptor peptide and lead to myocardial and renal damage in rats.
Animals↗
Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial.
BACKGROUND: A previously reported randomized clinical trial showed treatment of Bowen's disease using photodynamic therapy (PDT) with topically applied delta-aminolaevulinic acid (ALA) to be at least as effective as cryosurgery and to be associated with fewer adverse effects. OBJECTIVES: To compare ALA-PDT and cryotherapy in the treatment of histopathologically verified basal cell carcinomas (BCCs) in a non-blinded, prospective phase III clinical trial. METHODS: One lesion from each of 88 patients was included. The BCCs were divided into superficial and nodular lesions. The follow-up period was restricted to 1 year with close follow-up for the first 3 months. Efficacy was assessed as the recurrence rate 12 months after the first treatment session, verified by histopathology. Tolerability was evaluated as the time of healing, pain and discomfort during and after the treatment, and final cosmetic outcome. RESULTS: Histopathologically verified recurrence rates in the two groups were statistically comparable and were 25% (11 of 44) for ALA-PDT and 15% (six of 39) for cryosurgery. However, clinical recurrence rates were only 5% (two of 44) for PDT and 13% (five of 39) for cryosurgery. Additional treatments, usually one, had to be performed in 30% of the lesions in the PDT group. The healing time was considerably shorter and the cosmetic outcome significantly better with PDT. Pain and discomfort during the treatment session and in the following week were low, and were equivalent with the two treatment modalities. CONCLUSIONS: In terms of efficacy, ALA-PDT is comparable with cryosurgery as a treatment modality for BCCs. Retreatments are more often required with PDT than with cryosurgery. This can easily be performed due to the shorter healing time, less scarring and better cosmetic outcome that follows ALA-PDT.
Adult↗
Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin.
BACKGROUND AND OBJECTIVE: Fluorescence techniques can provide powerful noninvasive means for medical diagnosis, based on the detection of either endogenous or exogenous fluorophores. The fluorescence of delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has already shown promise for the diagnosis of tumors. The aim of the study was to investigate the localization of skin tumors after the topical application of ALA, by detecting the PpIX fluorescence either in the spectral or in the time domain. STUDY DESIGN/MATERIALS N AND METHODS: Two fluorescence imaging systems were used to identify basal cell carcinomas of the skin in humans, after topical application of 20% ALA ointment. Both systems rely on the comparison between the exogenous and the endogenous fluorescence, performed either in the spectral domain or in the time domain. The first system works by using three images acquired through different spectral filters, whereas the second one measures the spatial map of the average fluorescence lifetime of the sample. RESULTS: A clear demarcation of skin malignancies was successfully performed in vivo noninvasively with both fluorescence imaging systems. CONCLUSION: The two complementary approaches considered in the present study show promise for skin tumor detection and delineation based on specific fluorescence features.
Adult↗
Phages will out: strategies of host cell lysis.
Most phages accomplish host lysis using a muralytic enzyme, or endolysin, and a holin, which permeabilizes the membrane at a programmed time and thus controls the length of the vegetative cycle. By contrast, lytic single-stranded RNA and DNA phages accomplish lysis by producing a single lysis protein without muralytic activity.
Amino Acid Sequence↗
Response from wang, humayun and taylor
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Journal Article↗
How does HIV cause AIDS? The homing theory.
The mechanism by which HIV causes depletion of CD4+ T cells in infected individuals remains unknown. Numerous theories have been proposed, but none can fully explain all of the events observed to occur in patients. Recent studies have shown that HIV binding to resting CD4+ T cells upregulates L-selectin, causing the cells to home from the blood into lymph nodes at an enhanced rate. It is possible that the disappearance of CD4+ T cells in the blood is actually the result of them leaving the blood, which can help explain the loss of CD4+ T cells in the blood occurring at a much faster rate than in lymphoid tissues. Furthermore, secondary signals through homing receptors received during the homing process induce many of these cells into apoptosis. These cells die in the lymph nodes without producing HIV particles, which can explain the 'bystander effect' observed in the lymph nodes of HIV infected individuals. If this scenario occurs in HIV+ patients, it might explain many of the clinical observations.
Acquired Immunodeficiency Syndrome↗
Adenovirus technology for gene manipulation and functional studies.
Recombinant adenoviral vectors are highly efficient at gene transfer in a broad spectrum of cell types and species, and have been used, both in vitro and in vivo, to achieve gain or loss of function in functional studies. In recent years, there have been several significant advances in adenovirus technologies, including new generations of vectors, improved production systems and sophisticated methods of delivery. In this review, recent progress and innovative applications are discussed to demonstrate the potential of the recombinant adenoviral vector as an effective tool in functional genomics.
Journal Article↗
Fluorescence diagnostics and kinetic studies in the head and neck region utilizing low-dose delta-aminolevulinic acid sensitization.
Diagnostic measurements and pharmacokinetic studies were performed in 17 patients with various kinds of malignant, premalignant and benign lesions in the head and neck region by means of point monitoring laser-induced fluorescence. For marking different types of tissue, delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used. The ALA-induced PpIX synthesis was monitored at different time intervals after oral administration of ALA in low doses, 5 and 15 mg/kg b.w. Besides the porphyrin-related signal the tissue endogenous fluorescence was also recorded. The fluorescence spectra were evaluated at two different wavelengths corresponding to the specific drug-related fluorescence peak and the endogenous tissue fluorescence emission at 635 and 490 nm, respectively. The evaluated fluorescence data were correlated to the histopathological tissue investigation. A fall-off in the overall fluorescence intensity at 490 nm was obtained for all the malignant and premalignant areas, as well as an increased red fluorescence. A ratio between the red and the blue/green fluorescence intensity was formed for each time interval after the ALA administration. The lower drug dose seems to be sufficient to obtain a useful demarcation ratio between normal and diseased tissue with a very low PpIX fluorescence intensity in the normal tissue. A PpIX fluorescence maximum seems to occur between 3 and 4 h in normal tissues, whereas malignant tumour tissue shows a higher level for a longer period of time.
Administration, Oral↗
Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas.
Laser-induced fluorescence (LIF) investigations have been performed in connection with photodynamic therapy (PDT) of basal cell carcinomas and adjacent normal skin following topical application of 5-aminolaevulinic acid (ALA) in order to study the kinetics of the protoporphyrin IX (PpIX) build-up. Five superficial and 10 nodular lesions in 15 patients are included in the study. Fluorescence measurements are performed prior to the application of ALA, 2, 4 and 6 h post ALA application, immediately post PDT (60 J cm-2 at 635 nm), and 2 h after the treatment. Hence, the build-up, photobleaching and re-accumulation of PpIX can be followed. Superficial lesions show a maximum PpIX fluorescence 6 h post ALA application, whereas the intensity is already the highest 2-4 h after the application in nodular lesions. Immediately post PDT, the fluorescence contribution at 670 nm from the photoproducts is about 2% of the pre-PDT PpIX fluorescence at 635 nm. Two hours after the treatment, a uniform distribution of PpIX is found in the lesion and surrounding normal tissue. During the whole procedure, the autofluorescence of the lesions and the normal skin does not vary significantly from the values recorded before the application of ALA.
Administration, Topical↗
Photodynamic therapy utilising topical delta-aminolevulinic acid in non-melanoma skin malignancies of the eyelid and the periocular skin.
PURPOSE: Photodynamic therapy utilising delta-aminolevulinic acid-induced protoporphyrin IX photosensitisation, was evaluated as a treatment modality for nonmelanoma skin malignancies of the eyelids and the periocular skin. METHODS: Photodynamic therapy with laser light at 635 nm was performed in 13 patients with 19 basal cell carcinomas and one patient with 3 cutaneous T-cell lymphoma lesions. A topical application regimen was used and in median 3 treatment sessions were given to each lesion. RESULTS: A visually judged complete response was achieved in 42% (8/19) of the basal cell carcinomas and in 100% of the T-cell lymphoma lesions (3/3). Partial tumour response was seen in 42% (8/19) and no response in 16% (3/19) of the basal cell carcinomas. The median follow-up time was 12 months. No, or very little scarring and loss of cilia were induced by the treatment. CONCLUSION: Photodynamic therapy with delta-aminolevulinic acid can eradicate eye-close non-melanoma skin malignancies without compromising the function of the eyelids. Further development of the method is needed to reach the same cure rates as those of the conventional treatment modalities.
Administration, Topical↗
Laser-based spectroscopic methods in tissue characterization.
Laser-based spectroscopic techniques were developed for tumor tissue characterization utilizing different tumor-localizing substances. In particular, sensitization with the heme precursor delta-amino levulinic acid (ALA) administered topically, orally or intravenously was used for the induction of protoporphyrin IX (PpIX). The autofluorescence as well as the PpIX-related fluorescence signals were monitored, and tumor demarcation functions were calculated for different human malignant tumors, such as tumors in the urinary bladder and the prostatic gland, in the head and neck region, in the breast and in the gastrointestinal tract. In the gastrointestinal tract, colon tumors were examined as well as tumors and dysplastic lesions in the esophagus, where patients with Barrett's esophagus were examined. Time-integrated laser-induced fluorescence measurements utilizing a point monitoring fluorosensor and a multicolor fluorescence imaging system were performed in vivo in patients in different clinical specialities.
Fluorescence↗
Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.
PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.
Adult↗
Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues.
Laser-induced fluorescence (LIF) for in vivo point monitoring and fluorescence microscopy incorporating a CCD camera were used to study the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in tumours. Fluorescence in a chemically-induced adenocarcinoma in the liver of rats and in an aggressive basal cell carcinoma in a patient were studied after intravenous injection of ALA at a dose of 30 mg/kg body weight. The LIF technique demonstrated slightly more ALA-induced PpIX fluorescence in the tumour than in the surrounding normal liver and abdominal muscle of rats. The visible parts of the human basal cell carcinoma exhibited strong ALA-induced fluorescence, while this fluorescence was much weaker in the necrotic areas of the tumour and in the surrounding normal skin.
Adenocarcinoma↗
Laser Doppler perfusion imaging: new technique for determination of perfusion and reperfusion of splanchnic organs and tumor tissue.
BACKGROUND AND OBJECTIVE: Several investigations indicated that laser Doppler flowmetry on the liver surface reflects relative changes of the total liver blood flow. In this study, Laser Doppler Perfusion Imaging (LDI), monitoring the surface only, was used for measurements of tissue perfusion of normal and/or impaired liver, pancreas, spleen, stomach and intestines, and the blood flow of hepatic tumors in rats. STUDY DESIGN/MATERIALS AND METHODS: Eighty Wistar/Furth rats were divided into five groups. Group I served as controls. Groups II and III underwent ischemic injury of the liver and intestine with or without the administration of WEB2170, a platelet-activating factor receptor antagonist. Laser-induced photodynamic therapy (PDT) utilizing delta-amino levulinic acid sensitization was performed in Groups IV and V. RESULTS: Normal pancreas and intestine had a high LDI perfusion value and the liver and stomach exhibited a medium perfusion value whereas the perfusion value from the spleen was low. WEB2170 improved the reperfusion of the postischemic liver and intestine. An immediate decrease in surface blood flow of hepatic tissue treated by laser-induced PDT and a decreased blood flow in large tumors were observed. CONCLUSION: LDI is a useful technique for the measurement of tissue perfusion of various splanchnic organs or tumor tissues.
Aminolevulinic Acid↗
Superficial blood flow following photodynamic therapy of malignant non-melanoma skin tumours measured by laser Doppler perfusion imaging.
Laser Doppler perfusion imaging offers a new modality for in vivo monitoring of the superficial blood perfusion in biological tissue. In this study, the superficial blood perfusion of malignant non-melanoma skin tumours and the surrounding normal skin was measured in conjunction with photodynamic therapy (PDT) using topical delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer. The results clearly show that, in contradiction to PDT with the intravenously administered photosensitizer Photofrin, no direct vascular damage can be seen. With the topical sensitization the blood perfusion is increased immediately after the treatment irradiation. The increased blood flow is seen up to a week after treatment, in a similar way as for an inflammatory reaction. Despite this, all basal cell carcinoma and squamous cell carcinoma in situ lesions in this study healed without any sign of residual tumour after the treatment, suggesting an efficient direct tumour cell destruction induced by PDT.
Adult↗
Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells.
We compared the expression of human alpha- and beta-defensins by various human tissues. mRNA for alpha-defensins HNP1-3, abundant in bone marrow, was detected in peripheral blood leukocytes, spleen and thymus by RT-PCR, which revealed alpha-defensins HD5 and HD6 only in the small intestine. In contrast, the pancreas and kidney expressed high levels of hBD-1 and lower levels of this beta-defensin were found in many organs by RT-PCR (salivary gland > trachea > prostate and placenta > thymus, testis, small intestine). hBD-1 mRNA was produced constitutively by cultured normal human epithelial cells derived from the trachea, bronchi, small airways and the mammary gland. These largely non-overlapping tissue distributions of human alpha- and beta-defensins suggest that hBD-1 may be positioned to defend epithelial cells and mucosae from infection, whereas expression of HNP1-3 in neutrophils and HD5 and HD6 in Paneth cells allows these alpha-defensins to participate in systemic and small intestinal host defenses, respectively.
Amino Acid Sequence↗