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Biomedical subjects

K Blessing

Publications and source records attributed to K Blessing.

At least 19 recordsLinked to original sources
PubMed2000

Relative importance of aldose reductase versus nonenzymatic glycosylation on sugar cataract formation in diabetic rats.

The relative importance of sorbitol formation versus nonenzymatic glycosylation and advanced glycosylation end products (AGEs) on sugar cataract formation was examined in diabetic rats. Diabetes was experimentally induced in young, 50 g rats with streptozotocin, and aldose reductase inhibitors were administered in the diet for up to 8 weeks at concentrations of 0.06% for tolrestat or ponalrestat and 0.0125% for AL-1576. Cataract formation was monitored by hand-held slit lamp for up to 11 weeks. Lens polyol levels were monitored by GLC, glycosylated protein levels were spectrophotometrically determined, and AGE products were estimated by fluorescence measurements and ELISA. Sugar cataract formation was observed in all untreated diabetic rats while cataract formation was inhibited in all diabetic rats treated with the AR inhibitors. Lens sorbitol levels were reduced in all ARI-treated rats. Glycosylated lens protein levels were elevated in the diabetic rats, and these levels were not significantly lower in the non-cataractous lenses from ARI-treated diabetic rats. Fluorescence measurements of the lens proteins revealed increased lens AGE levels in all diabetic rats, and these were slightly reduced in the aldose reductase inhibitor treated diabetics. With ELISA, immunoreactive AGEs were only detected in cataractous lenses from the untreated diabetic rats. Immunoreactive AGEs were not detected in the clear lenses of the aldose reductase inhibitor treated diabetics or in the non-diabetic controls. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalyzed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.

Aldehyde Reductase↗
PubMed2000

Problematic pigmented lesions: approach to diagnosis.

A number of pigmented lesions are difficult to classify and raise the possibility of a melanoma diagnosis. Care should be exercised to exclude non-melanocytic lesions, and benign melanocytic entities, both of which can mimic melanoma histologically. In addition, the possibility of the lesion being a melanoma variant or epidermotropic metastasis should be considered. There will still be some cases that are difficult to resolve. These usually fall into one of three categories: atypical junctional melanocytic lesion versus early melanoma; naevus versus naevoid melanoma; and atypical Spitz, cellular blue, and deep penetrating naevi versus thick melanoma. These will pose problems even for experts. The atypical Spitz lesions are perhaps the most important category because they tend to be from younger individuals, the differential diagnosis is thick melanoma, and there is no single discriminating histological feature.

Age Factors↗
PubMed2000

Small cell malignant melanoma: a variant of naevoid melanoma. Clinicopathological features and histological differential diagnosis.

AIMS: To describe the clinical and histopathological features of a rare variant of naevoid melanoma, small cell melanoma, and discuss the histological differential diagnoses. METHODS: The clinical and histological features of cases of malignant melanoma with the histological features of small (non-Merkel like) melanoma were reviewed and documented. In addition, five cases had available material for immunohistochemistry and this was performed using antibodies to the S100 protein and melan-A, and the HMB-45 antibody. RESULTS: There were 15 cases of small cell melanoma from 14 (10 female, four male) patients, aged between 30 and 77 (mean, 48.6) years. The trunk was the most common location. In more than half the cases, the provisional diagnosis was melanoma/borderline lesion. All shared similar histological appearances of an intraepidermal component of in situ melanoma and a dermal component of nests of cells with hyperchromatic nuclei and scanty cytoplasm, usually in tightly packed nests. All components (junctional and intradermal) of the lesions investigated by immunohistochemistry were positive both for S100 protein and melan-A. All junctional components were positive with HMB-45, but with variable staining of the dermal components with this antibody. CONCLUSIONS: Small cell malignant melanoma is postulated to be a distinct histopathological entity and a rare variant of naevoid melanoma. Such lesions can be difficult to interpret and easily missed at scanning magnification because the cells of the dermal component mimic benign naevus cells.

Adult↗
PubMed1999

Benign atypical naevi: diagnostic difficulties and continued controversy.

Benign melanocytic naevi exhibit a wide spectrum of histological appearances. Some share significant clinical and histological features and are recognized as entities. Included among these are pagetoid/junctional Spitz naevus, pigmented spindle cell naevus, halo naevus, recurrent and traumatized naevus, ultraviolet (UV) irradiated naevus, naevus in infants, acral naevus, genital naevus and naevi from other specific anatomic locations. However, there still remains a diagnostic grey area of acquired predominantly junctional naevi with architectural and cytological atypia. Only a small percentage of these will fulfil the criteria for dysplastic naevus if criteria are strictly applied. Therefore, there exists a group of otherwise ordinary acquired naevi with atypical junctional activity, mostly mild, whose biological significance is unclear. In older individuals, although junctional activity in otherwise benign naevi does occur, extra care should be exercised in order to prevent the diagnosis of melanoma in situ being overlooked.

Adult↗
PubMed1999

Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours.

AIMS: Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenins, in a full range of benign and malignant excised melanocytic tumours. METHODS: Using immunohistochemistry and western blotting after tissue fractionation, the pattern of expression of cadherins/catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to stage III cutaneous metastatic malignant melanoma. RESULTS: Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma and primary vertical growth phase malignant melanoma. Loss of membranous E-cadherin is seen in a small number of vertical growth phase melanomas only when metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A minority of metastatic melanomas show de novo membranous N-cadherin expression in comparison with dysplastic naevi and primary melanoma. Membranous expression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm of cells in dysplastic naevi and metastatic malignant melanoma, with an implied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, implying obligatory transmembrane binding of cadherins to beta catenin for maintenance of adhesive function. CONCLUSIONS: The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.

Blotting, Western↗
PubMed1998

Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats.

Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine , SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.

Aldehyde Reductase↗
PubMed1998

Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants.

AIMS: The staining pattern of the recently described antibody melan-A was compared with those of S100 protein and HMB-45 in a variety of melanocytic lesions to assess the specificity and sensitivity of these antibodies. METHODS AND RESULTS: Immunohistochemical staining of paraffin sections of a range of melanocytic lesions was carried out following a high temperature antigen retrieval technique. The pattern and intensity of staining was semiquantitatively scored. S100 remains the most sensitive marker of melanocytic differentiation being diffusely positive in all benign and all primary and secondary malignant lesions including naevoid melanomas, and in most desmoplastic/spindle cell melanomas. Of the two more specific melanocytic markers melan-A stains the majority of benign and malignant lesions diffusely but with occasional patchy positivity only in some secondary melanoma deposits and with little staining of desmoplastic/spindle cell melanomas. HMB-45 is the least sensitive of the three showing little positivity of benign mature naevus cells, only variable patchy positivity of primary and secondary melanoma cells and limited positivity in naevoid, desmoplastic and metastatic melanomas. CONCLUSIONS: Melan-A is a useful addition to antibody panels as it is apparently specific for melanocytic lesions and is more sensitive than HMB-45; however, it has less value than S100 in the detection of spindle cell and desmoplastic melanomas.

Antibodies, Monoclonal↗
PubMed1997

Malignant melanoma in stasis dermatitis.

Two cases of malignant melanoma arising in established stasis dermatitis are described. One case was clinically thought to be melanocytic whereas the other was not. Histologically, both showed similar features with background varicose change of epidermal atrophy, sloughing of the epidermis, intense proliferation of small thick walled blood vessels, lymphocytic infiltrate and dermal fibrosis. In the superficial aspects of the biopsies there was little clue to the diagnosis of melanoma. In the deeper aspects of case 1, groups of melanocytes were present in the reticular dermis which mimicked benign naevus cells. S-100 protein staining confirmed the melanocytic nature of these lesions, their extent and the epidermal involvement. The latter features supported a malignant diagnosis. These lesions can be overlooked clinically as well as histologically.

Aged↗
PubMed1996

Expression of bcl-2 and p53 in Merkel cell carcinoma. An immunohistochemical study.

Bcl-2 is a protooncogene thought to play a role in oncogenesis by inhibiting programmed cell death. It may interact with p53, a tumor-suppressor gene which induces apoptosis in certain circumstances. We have studied these gene products by immunohistochemistry in 15 cases of Merkel cell carcinoma, a tumor characterised by prominent apoptosis. Five cases showed moderate/strong staining for p53, with moderate/strong bcl-2 staining in 10 patients. In seven cases abundance of p53 and bcl-2 expression was mutually exclusive. Two patients died within 1 year of diagnosis and six had nodal recurrences. Gene expression and survival appear unrelated. The role of Bcl-2 and p53 in tumorigenesis is complicated and may be inter-related with other genes known to be involved in programmed cell death.

Aged↗
PubMed1996

Expression of basic fibroblast growth factor in desmoplastic melanoma.

Basic fibroblast growth factor (bFGF) is an established growth factor for melanocytes and a potent angiogenic factor. The expression of bFGF was investigated in 23 desmoplastic melanomas. (DM) (12 males, median age 64 years, and 11 females, median age 54 years) by immunostaining of formalin-fixed, paraffin-embedded sections with high-affinity purified antibody raised against recombinant human bFGF (Scios Nova, Inc.). The tumors were characterized by level II invasion in 1 case (5%), level IV invasion in 11 cases (48%), level V invasion in 8 cases (35%), and indeterminate in 3 cases. bFGF expression was observed in 22 of 23 tumors (95%), either immune localized to tumor cell nuclei in 17 of 22 tumors (77%), or to the cytoplasm of tumor cells in 5 of 22 tumors (23%). Also in these cases, bFGF was strongly expressed in the nuclei of vascular endothelial cells. Maximal expression was noted in the peripheral blood vessels of 20 tumors (91%) versus intratumoral vessels of 13 DM (59%). In conclusion, the expression of predominantly nuclear bFGF by tumor cells in DM suggests a role in mediating the desmoplastic phenotype. In addition, the localization of bFGF to vascular endothelium, particularly at the periphery of the tumor, may be relevant to tumor angiogenesis.

Adult↗
PubMed1996

The prognostic significance of basic fibroblast growth factor in cutaneous malignant melanoma.

Basic fibroblast growth factor (bFGF) is a growth factor and an angiogenesis factor which may play a role in the evolution of cutaneous malignant melanoma (CMM). In this study, we evaluated the distribution of bFGF in CMM using immunochemical methods and correlated the pattern of bFGF expression with the clinical course. Formalin-fixed, paraffin-embedded sections of 46 CMMs were immunostained with a high-affinity purified antibody raised against human bFGF. CMM were categorized into lesions that exhibited subsequent recurrence (local, regional and/or systemic) or recurrence-free lesions. The minimum follow-up time was 5 years. Expression of bFGF within the tumors and in peritumoral and intratumoral blood vessels was similar in the two groups. Comparable results were attained when 8 recurring vs 8 non-recurring CMM, selected from the above tumors, were matched for age, gender, anatomic site and tumor thickness. These results suggest that the biologic behavior of CMM may not be predicted by immunoreactivity to bFGF in CMM cells or in the local tumor vasculature.

Fibroblast Growth Factor 2↗
PubMed1995

Subepidermal calcified nodule in children: a clinicopathologic study of 21 cases.

Twenty-one cases of subepidermal calcific nodule are presented. These lesions occur twice as commonly in males compared to females, with the head (particularly the ear), and neck as favored locations. No case was identified correctly clinically and only 1 case had a history of trauma, which appeared unrelated to the lesion. Histologically, there was a variety of appearances, with two-thirds of specimens exhibiting a warty architecture. Younger lesions were composed of large, amorphous, calcific dermal deposits and were frequently associated with epidermal ulceration. The older lesions were not ulcerated and the calcium deposits were in small spherules. There was no evidence of pilomatrixoma or pre-existing nevus. It is hypothesized that subepidermal calcified nodule represents dystrophic calcification secondary to dermal injury-several in our series showed the architectural changes of verruca vulgaris.

Adolescent↗
PubMed1995

Tumor vascularity is not a prognostic factor for malignant melanoma of the skin.

Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most suitable vascular marker for this study. Our results indicate that there was no statistically significant difference between the two groups with regard to tumor vascularity. Even after identifying 15 cases of thin ( < 1.0 mm thick) melanoma, there was no significant difference in the number of microvessels between metastasizing and non-metastasizing tumors. Comparison of patterns of vascular microarchitecture also failed to discriminate between the two groups. Thus, our results indicate that tumor vascularity may not be an independent prognostic factor for cutaneous melanoma.

Adolescent↗
PubMed1994

The regressing keratoacanthoma.

The clinical and pathological features of 11 cases of regressing keratoacanthoma are presented. These lesions were from sun-exposed skin of individuals between the ages of 58 and 92 years and were of short clinical duration (2-12 months). Histologically, these lesions showed similar features and consisted of symmetrical shallow cup-shaped invaginations of thin atrophic epidermis with overhanging edges. The underlying papillary dermis demonstrated variable degrees of inflammatory infiltrate and scarring. It is important to recognize these features as representing regressed keratoacanthoma as they may be confused with other unrelated skin conditions.

Aged↗
PubMed1994

Pseudorheumatoid nodule (deep granuloma annulare) of childhood: clinicopathologic features of twenty patients.

Pseudorheumatoid nodule of childhood is seen uncommonly by pathologists and is thought to be a variant of granuloma annulare. We report a series of 20 patients (13 M, 7 F) age 1 to 17 years. Fourteen lesions arose on the front of the lower limb, and 14 children had numerous lesions at diagnosis. Seven developed some form of recurrence, except for one case occurring at the site of the original lesion. Only one patient had a weakly positive rheumatoid factor, and was the patient with remote recurrence. As a significant number of lesions arose around the foot when the child was beginning to walk or starting to wear shoes, it is suggested that trauma plays a role in the development of some of these lesions.

Adolescent↗
PubMed1993

A study of thin (< 1.5 mm) malignant melanomas with poor prognosis.

555 cases of malignant melanoma less than 1.5 mm in depth were studied. 30 recurred locally or metastasised during follow-up. The width and depth of excision was similar in those with and without recurrence. There were no local recurrences in tumours < 1.0 mm which had been completely excised, irrespective of the width of excision. Other variables, the size of the primary tumour (p < 0.03), the depth of uninvolved dermis deep to the lesion (p < 0.01), the Clark level (p < 0.03) and the presence of lesional regression (p < 0.001), identify a sub-group of thin melanomas which have a poor prognosis irrespective of local treatment.

Humans↗