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Biomedical subjects

I Willis

Publications and source records attributed to I Willis.

At least 19 recordsLinked to original sources
PubMed2003

Effect of UV on the susceptibility of acid-soluble Skh-1 hairless mouse collagen to collagenase.

BACKGROUND/PURPOSE: Photoaging of the skin is a result of chronic exposure to environmental ultraviolet radiation (UV). The milieu provided by the extracellular matrix, which significantly influences the behaviour of resident fibroblasts, depends critically on the supermolecular collagen structure. We ask whether direct photochemical treatment of type I collagen with solar wavelengths capable of reaching the dermis can modify the substrate's susceptibility to collagenase in a model in vitro system. METHODS: Acid- extracted Skh-1 hairless mouse collagen samples were irradiated with 0-140 J/cm2 of radiation from bank of filtered FS lamp (UVB/UVA = 0.33, fluence rate = 0.81 mW/cm2). Subsequent to UV irradiation, collagen samples were coupled with fluorescein isothiocyanate (FITC) and assayed for susceptibility to bacterial collagenase by monitoring the appearance of supernatant FITC fluorescence (a measure of lysed collagen) over time of incubation. As a 'reference', unirradiated commercial FITC-labelled citrate-soluble collagen (Elastin Products, Owensville, MO 65066, USA) was similarly analysed. RESULTS: Unirradiated mouse collagen had a lower rate of cleavage than did the calfskin sample. Irradiation of unlabelled mouse collagen for 0-48 h (0-140 J/cm2 total UV) rendered the sample more soluble, with concomitant chain degradation, cross-linking and loss of intrinsic collagen fluorescence. At irradiation time's >/= 4 h (>/=11.7 J/cm2), the irradiated collagen was significantly more susceptible to bacterial collagenase digestion. DISCUSSION: It appears that the rate of cleavage depends on the superstructure of the collagen, since the kinetics of collagen cleavage differ for two collagen samples having essentially the same primary structure. Cleavage kinetics may depend on the 'maturity' (solubility) of the collagen. The observation that UV-damaged mouse collagen is a better substrate for collagenase than the intact sample may be illustrative of a mechanism whereby damaged collagen targets itself for selective attack by collagenase.

Animals↗
PubMed2001

Intraoperative sentinel lymph node mapping in patients with colon cancer.

BACKGROUND: The sentinel lymph node (SLN) mapping technique has been used in breast cancer and melanoma, and was recently described for colon cancer. METHODS: Thirty-five patients with colon cancer underwent intraoperative SLN mapping. One milliliter of 1% isosulfan blue was injected subserosally around the tumor. The first nodal area that was highlighted with blue was identified as the SLN. All lymph nodes underwent examination with hematoxylin and eosin (H&E) stain. SLNs underwent additional sectioning and were stained with CAM 5.2. RESULTS: Lymphatic mapping adequately identified the SLN in 25 patients (71%). In the 15 cases where the SLNs were negative for metastases, all other non-SLNs were also negative (0% false negative rate). The SLN was the only site of metastases in 6 (17%) of 35 patients. CAM 5.2 staining provided the only evidence of micrometastases in 4 (11%) of 35 patients. CONCLUSIONS: Intraoperative SLN mapping is a feasible technique with a reasonable SLN identification rate (71%). The absence of metastases in the SLNs accurately predicts the status of the non-SLNs. Tumors in 11% of patients were upstaged by the demonstration of micrometastatic involvement, and these patients may benefit from further adjuvant chemotherapy.

Adenocarcinoma↗
PubMed2001

Effect of UV irradiation on type I collagen fibril formation in neutral collagen solutions.

BACKGROUND: Collagens have the well-known ability to spontaneously self-associate to form fibrils at physiological temperature and neutral pH in vitro and in vivo. Because solar UV may photochemically alter collagen, the kinetics of fibril formation may be modified. Thus, we have begun a systematic study of the effect of various UV wavebands on fibril formation. METHODS: Citrate-soluble calf skin collagen (Elastin Products) was dissolved at 0.05% in 0.5 M HOAc, dialyzed over 2 days into two changes of 0.0327 M phosphate buffer, pH 7.0 at 4 degrees C, and centrifuged at 48,000 x g. Photolysis was carried out at 4 degrees C with either (a) UVC (UVG-11 lamp), (b) filtered solar-simulating radiation (SSR) or UVA (SSR or UVL-21 lamp filtered with a 2.0 mm Schott WG 345 filter). Gelation was commenced by rapidly raising the temperature from 8 degrees C to 33 degrees C. Nucleation and growth were followed by turbidimetric measurements at 400 nm. RESULTS: UVC radiation (0-17.3 J/cm2) resulted in a dose-dependent decrease in the rate of fibril growth. Under these conditions, concomitant collagen crosslinking and degradation occurred. Fibril nucleation, a prerequisite for growth, was rapid (threshold approximately 2 min) and was not affected by UVC, UVA or SSR. SSR (0-1,320 J/cm2) caused a small decrease in growth rate and in the degree of fibril formation. UVA radiation (0-1,080 J/cm2) had a similar effect. "Direct" photochemical damage thus paralleled absorption via various collagen chromophores, with UVC>SSR approximately UVA. The presence of riboflavin (RF) resulted in groundstate interactions that markedly altered both nucleation and growth kinetics. Irradiation with 29.6 J/ cm2 UVA in the presence of RF photosensitizer caused relatively minor additional changes in fibrillation kinetics. CONCLUSIONS: These results collectively indicate that fibril formation is markedly dependent on specific ground state interactions and relatively insensitive to nonspecific UV damage. On the other hand, fibrils thus formed from photochemically altered collagen may have altered structural properties that could have subtle but unfavorable effects on the local dermal milieu in vivo. Notwithstanding, the relative insensitivity of fibrillogenesis to non-specific photochemical damage probably represents a favorable adaptation, overall, which tends to conserve the mechanical integrity of the skin.

Animals↗
PubMed1998

Photoprotection of mammalian acid-soluble collagen by cuttlefish sepia melanin in vitro.

Several important clinical conditions can result in close association between the pigment melanin and dermal collagen. Because melanin and its precursors can be chemically reactive in ground and excited states, it is important to know whether the resulting melanin-collagen interaction results in photoprotection or photoaggression. Acidic and neutral air-saturated collagen suspensions (0.033%) were irradiated with 0-2.6 x 10(4) J/m2 UVC or with 0-83 x 10(4) J/m2 solar-simulating UV radiation (SSR). Photochemical destruction of a photolabile collagen fluorophore (lambda em 360 nm) and collagen chain degradation were monitored as functions of irradiation time in the presence and absence of added (0-100 micrograms) sepia eumelanin. Melanin retarded collagen photodamage but did not qualitatively alter the fluorescence fading kinetics. Both H2O2 and O2-. can be produced by UV irradiation of eumelanin. Added H2O2 and KO2 destroyed collagen fluorescence and caused 50% chain degradation at ca 10-20-fold molar excess. Previous studies have demonstrated that eumelanins efficiently scavenge O2-.. We demonstrated that eumelanin also efficiently scavenges H2O2 as evidenced by its ability to (a) compete with scopoletin for peroxide uptake and (b) directly take up H2O2 through a dialysis bag. The latter observation suggests that peroxide scavenging could occur in vivo by melanin sequestered in melanophages. Thus, neither UV-generated O2-. nor H2O2 are likely to be present in concentrations high enough to cause measurable collagen damage. Absorption and/or scattering of excitation radiation away from the target chromophore appears to be the primary photoprotection mechanism, although scavenging of active O2 intermediates may play an important, if subtle role.

Animals↗
PubMed1997

One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases. OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Administration, Topical↗
PubMed1997

Electron transfer and photoprotective properties of melanins in solution.

The polyquinoid nature of eumelanin(s) enables them to couple oxidation of electron donors with the reduction of electron acceptors. We have studied the ability of synthetic (Sigma) and "biological" (cuttlefish sepia) melanins to mediate electron transfer between hydroxybenzene donors (tyrosine, dopa, chemical depigmenters) and model acceptors (ferricyanide, tyrosinase). 1) Depending on the reductant, melanin either retards or accelerates ferricyanide reduction. Reaction kinetics are consistent with a mechanism involving non-interactive binding of both hydroxybenzene and ferricyanide to melanin prior to coupled electron transfer. 2) Melanins also act as an electron conduit in markedly accelerating the tyrosinase-catalyzed oxygenation of p-hydroxyanisole (MMEH). The active species appears to be a complex between melanin and MMEH. The magnitude of both effects depend on the type of melanin as well as its oxidation state. Sepia (eu)melanin appears to protect against UV-induced damage to acid-soluble collagen, as judged by irreversible loss of intrinsic collagen fluorescence. Photoprotection against this type of damage appears primarily to involve optical absorption/scattering by the pigment.

Collagen↗
PubMed1996

Microglandular carcinoma of the pancreas: immunohistochemical and ultrastructural study of an unusual variant of pancreatic carcinoma that may closely resemble a neuroendocrine neoplasm.

Two cases are described of an unusual form of primary adenocarcinoma of the pancreas characterized histologically by their striking resemblance with a neuroendocrine neoplasm. The tumors were composed of a population of relatively small, uniform cells arranged in sheets admixed with small microglandular structures resulting in a cribriform pattern of growth. The tumor cells displayed scant cytoplasm with indistinct cell borders and round to oval nuclei with irregular clumping of chromatin and small, inconspicuous nucleoli. Immunohistochemical studies in both cases showed positivity of the neoplastic cells with CAM 5.2 antibodies and negative staining with a battery of neuroendocrine-related markers including chromogranin, NSE and synaptophysin, as well as with a variety of peptide hormones including insulin, glucagon, vasoactive intestinal polypeptide, gastrin and serotonin. Ultrastructural examination revealed a cohesive population of cells forming abortive glandular lumens lined by imperfectly formed microvilli and showing well-developed junctional complexes. No dense core neurosecretory granules or zymogen granules could be identified in any of the cells, supporting a ductal type of differentiation for these tumors. The main importance of recognizing this rare variant of pancreatic adenocarcinoma lies in avoiding misdiagnosis with other primary and metastatic neuroendocrine neoplasms of this organ. Immunohistochemical and ultrastructural examination will be of value in such cases for differential diagnosis.

Adenocarcinoma↗
PubMed1996

Chronic exposure of Sk-1 hairless mice to narrow-band ultraviolet A (320-355 nm)

Several recent investigations collectively suggest that the role of ultraviolet A (UVA) in chronic actinic skin damage may be greater than originally thought. In the present work, the output of a xenon-arc solar-simulator passed through a Bausch & Lomb monochromator in conjunction with a 2-mm Schott WG-320 filter produced narrow-band UVA centered at 338 nm, half-band width 24 nm, I0 = 3.4 +/- 0.3 mW/cm2. We chronically irradiated 10 Sk-1 albino hairless mice 5 times per week for 18 weeks, starting with 1.25 J/cm2, for 33 irradiation days, sequentially followed by 1.50 J/cm2 (34 days), 1.8 J/cm2 (10 days), 2.0 J/cm2 (22 days) to afford a total UVA dose of 154.3 J/cm2 over 99 irradiation days. Erythema was noted clinically by day 6, which persisted throughout the irradiation. During the irradiation period, some scaling, consistent with mild epidermal hyperplasia was noted during irradiation days 37-56. This response later regressed despite continued chronic irradiation. Hematoxylin and eosin examination immediately after the final irradiation revealed a mild inflammatory response, with some dermal restructuring. At the end of the experiment, no significant signs of epidermal hyperplasia or (pre)malignant lesions were seen, although some stratum corneum thickening was noted. Marked dermal collagen damage and moderate elastosis was also evident. We believe that the observed differences in results reported in previous studies are in large part due to differences in light sources and irradiation protocols.

Animals↗
PubMed1995

Photochemistry of type I acid-soluble calf skin collagen: dependence on excitation wavelength.

Although previous studies have demonstrated that the predominant photochemistry of type I collagen under 254 nm irradiation may be attributed either to direct absorption by tyrosine/phenylalanine or to peptide bonds, direct collagen photochemistry via solar UV wavelengths is much more likely to involve several age- and tissue-related photolabile collagen fluorophores that absorb in the latter region. In this study, we compare and contrast results obtained from irradiation of a commercial preparation of acid-soluble calf skin type I collagen in solution with UVC (primarily 254 nm), UVA (335-400 nm) and broad-band solar-simulating radiation (SSR; 290-400 nm). Excitation spectroscopy and analysis of photochemically induced disappearance of fluorescence (fluorescence fading) indicates that this preparation has at least four photolabile fluorescent chromophores. In addition to tyrosine and L-3,4-dihydroxyphenylalanine, our sample contains two other fluorophores. Chromophore I, with emission maximum at 360 nm, appears to be derived from interacting aromatic moieties in close mutual proximity. Chromophore II, with broad emission at 430-435 nm, may be composed of one or more age-related molecules. Collagen fluorescence fading kinetics are sensitive to excitation wavelength and to conformation. Under UVC, chromophore I fluorescence disappears with second-order kinetics, indicating a reaction between two proximal like molecules. Adherence to second-order kinetics is abrogated by prior denaturation of the collagen sample. A new broad, weak fluorescence band at 400-420 nm, attributable to dityrosine, forms under UVC, but not under solar radiation. This band is photolabile to UVA and UVB wavelengths.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Protection against UV photocarcinogenesis by fabric materials.

BACKGROUND: Clothing fabrics have long been considered effective protection against short-term and long-term sun damage. Recently, special "highly UV-protective" fabrics have been developed specifically for photosensitive patients. OBJECTIVE: To determine if one such fabric will protect hairless mice against (pre)malignant lesions under conditions that will produce skin cancers through a typical summer fabric of moderate sun protection factor (SPF). METHODS: After prior determination of minimal erythemal dose, four sets of 10 animals were divided into the following groups: (A) dark control (no irradiation); (B) positive control (no fabric); (C) "typical summer" fabric (SPF = 6.5 +/- 1.0); and (D) "special" fabric (SPF > 30 across a broad spectrum). Mice were irradiated on the dorsal surface 5 days per week, with biweekly incremental increases (roughly 20% of the starting dose), for 12 weeks. Group B started at 6.3 J/cm2, with biweekly increases of 1.45 J/cm2 (total dose, 596 J/cm2); groups After irradiation, mice were observed for clinical and histologic signs of pre(malignant lesions for an additional 12 weeks. RESULTS: At the end of the 12-week irradiation period, nine mice in group B and six mice in group C had actinic keratosis-like lesions, whereas one mouse in group B and two mice in group C had squamous cell carcinoma. By week 24, all mice in groups B and C had squamous cell carcinoma. Mice in groups A and D showed no discernable reaction at any time. Biopsy specimens confirmed the clinical results. CONCLUSION: Typical summer clothing fabrics may offer inadequate protection against skin cancer and pose high risk to chronically photosensitive patients. The use of appropriate sun protective apparel should offer effective protection to photosensitive patients against short-term and long-term photodamage.

Animals↗
PubMed1994

A mutation in the second largest subunit of TFIIIC increases a rate-limiting step in transcription by RNA polymerase III.

In previous studies, we have shown that the PCF1-1 mutation of Saccharomyces cerevisiae suppresses the negative effect of a tRNA gene A block promoter mutation in vivo and increases the transcription of a variety of RNA polymerase III genes in vitro. Here, we report that PCF1 encodes the second largest subunit of transcription factor IIIC (TFIIIC) and that the PCF1-1 mutation causes an amino acid substitution in a novel protein structural motif, a tetratricopeptide repeat, in this subunit. In agreement with the nature of the mutation, in vitro transcription studies with crude extracts indicate that PCF1-1 facilitates the rate-limiting step in transcription, namely, the recruitment of TFIIIB to the template. Additionally, biochemical fractionation of wild-type and mutant cell extracts shows that PCF1-1 increases the amount of the 70-kDa TFIIIB subunit detectable by Western (immunoblot) analysis in purified TFIIIB fractions and the transcription activity of a TFIIIB" fraction containing the 90-kDa subunit of this factor. We suggest that the effect of PCF1-1 on TFIIIB activity in vitro is a consequence of its increased rate of recruitment in vivo.

Amino Acid Sequence↗
PubMed1994

Idiopathic fibrosing pancreatitis causing obstructive jaundice in young adults: two case reports and literature review.

Chronic pancreatitis is uncommon in children and adolescents. A rare syndrome of idiopathic fibrosing pancreatitis has been reported in 28 patients, ages 4 months to 17 yr. We report two young adults with this syndrome who presented with obstructive jaundice. Both were seen in adult gastroenterology practice, and one is the oldest reported patient at age 20. We review the clinical features, diagnosis, and treatment of this disorder, which merits attention by adult gastroenterologists.

Adolescent↗
PubMed1993

In vivo depigmentation by hydroxybenzene derivatives.

Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

The PCF1-1 mutation increases the activity of the transcription factor (TF) IIIB fraction from Saccharomyces cerevisiae.

PCF1-1 is a dominant suppressor of a tRNA gene A block promoter mutation (A19) in Saccharomyces cerevisiae. Transcriptional activation by PCF1-1 was examined in vitro using whole-cell extracts and purified factors derived from mutant and wild-type strains. These experiments show that PCF1 is a general activator of RNA polymerase III (pol III) gene transcription. The transcription of all pol III genes analyzed to date, including type I and numerous type II genes, is increased 3-7 fold in mutant cell extracts. Single round transcription assays indicate that the PCF1-1 mutation increases the number of functional preinitiation complexes and suggest that this is achieved by increasing the intrinsic activity of the encoded product rather than its amount. Point mutations throughout the A block of the sup3-e gene and numerous B block mutations fail to abolish transcriptional activation suggesting that interactions between TFIIIC and the internal promoter are unaffected by PCF1-1. Moreover, TFIIIC purified from the mutant strain is incapable of conferring PCF1-1 transcriptional activity to a reaction in which the remaining components are wild-type. In contrast, the activity of the TFIIIB fraction is increased in PCF1-1 extracts and can reconstitute mutant levels of transcription when added to wild-type TFIIIC and polymerase. We conclude that PCF1 is a component or regulator of TFIIIB.

Base Sequence↗
PubMed1992

Dose-response of chronic ultraviolet exposure on epidermal forward scattering-absorption in SK-1 hairless mouse skin.

This work provides a dose-response model of UV-induced epidermal-stratum corneum thickening induced by irradiation at wavelength lambda. This model assumes that photobiochemical reaction(s) can give rise to hyperplasia in a manner which is predictable from a simple photochemical kinetic scheme. In this work, we derive an equation which predicts an approximately linear relationship between the logarithm of the increase in optical skin thickening measured at 320 nm (delta OD320) and total cumulative dose (DT) seen by the target cells in or near the basal layer. For each excitation wavelength lambda, the slope R(lambda) of the log delta OD320 vs DT plot is proportional to epsilon(lambda) phi rx, where epsilon(lambda) is the extinction coefficient for the target chromophore at excitation wavelength, and phi rx is the quantum yield for the photochemical reaction(s) leading to hyperplasia. Our data previously obtained from irradiation of SK-1 hairless mice with "monochromatic" UV wavebands at 280, 290, 300, 307 and 313 nm (Menter et al., 1988, Photochem. Photobiol. 47, 225-260.) and data from Sterenborg and van der Leun at 254 and 313 nm (1988, Photodermatology 5, 71-82) are in good agreement with this model, except for 254 and 280 nm excitation, which are greatly attenuated by epidermis-stratum corneum. For excitation at the latter wavelengths, "dark" regressive processes successfully compete with the "light" reaction(s) which lead to (pre)cancerous lesion. This difficulty notwithstanding, the "intrinsic" action spectrum for hyperplasia derived from these measurements indicates that the target chromophore preferentially absorbs in the UV-C region.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Double-blind bilateral paired comparison of 0.05% halobetasol propionate cream and its vehicle in patients with chronic atopic dermatitis and other eczematous dermatoses.

Six investigators evaluated 0.05% halobetasol propionate cream and its vehicle in 111 patients with chronic atopic dermatitis and several other eczematous dermatoses. Patients applied treatment twice daily to bilateral lesions for 14 days. Investigators graded pruritus, erythema, scaling, papulation, and lichenification using 4-point severity scales on days 0, 7, and 14. On day 14 patients provided an assessment of efficacy for both treatments. Statistically significant differences favoring halobetasol propionate over the vehicle were seen for all signs and symptoms (p less than 0.001). Substantial improvements were achieved by the active treatment by day 7 (p less than 0.001). Patients assessments of efficacy were significantly higher for halobetasol cream than for vehicle (p less than 0.001). No instances of systemic effects or skin atrophy were reported and adverse experiences were limited to burning or stinging and other minor, nonspecific complaints distributed uniformly between active treatment and vehicle. These results demonstrate that 0.05% halobetasol propionate cream is highly effective in the treatment of atopic dermatitis and other eczematous dermatoses.

Administration, Cutaneous↗