Effects of retinoic acid on keratinocyte proliferation and differentiation in a psoriatic skin model

Psoriasis is a skin disease characterized by the presence of red plaques on the skin. This pathology is well-known to be a retinoid-sensitive disease. Previous investigations have shown that retinoids can modulate epidermal proliferation with an antiproliferative potential in hyperproliferative skins. The aim of this study was to compare the development of psoriatic substitutes cultured in a retinoic acid supplemented medium with those cultured in medium receiving no supplement, to define the effects of this growth factor on keratinocyte proliferation and differentiation. The self-assembly method was used to create substitutes. Characterization of the psoriatic substitutes was performed by histological and immunolabeling analyses. Results showed that psoriatic keratinocyte substitutes cultured with retinoic acid have a thinner epidermis compared with psoriatic keratinocyte substitutes cultured without this supplement. Further, the expression of all tested cell differentiation markers was restored in psoriatic keratinocyte substitutes cultured in presence of retinoic acid. No significant change in epidermal thickness or in the expression of late differentiation markers was observed in healthy keratinocyte substitutes cultured with or without retinoic acid; however, some changes were reported for proliferation and early differentiation markers. Results suggest that retinoic acid can modulate epidermal differentiation and proliferation with an antiproliferative potential in psoriatic substitutes such as observed in psoriatic skin in vivo.     

Notch Signaling May Be Involved in the Abnormal Differentiation of Epidermal Keratinocytes in Psoriasis

Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions.     

Revisiting the Koebner phenomenon: role of NGF and its receptor system in the pathogenesis of psoriasis

Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n = 12), a marked up-regulation of NGF in Koebner-positive lesions (n = 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.     

Lipid profile in maintenance haemodialysis

INTRODUCTION: The chronic kidney failure is a source of dyslipidemia and accelerated atherosclerosis. No changes in the lipoprotein profile could be reversed by dialysis. OBJECTIVE: Our aim was to study the lipid disturbances characteristics in end stage renal disease in order to assess their theorical atherogenic potential. SUBJECTS AND METHODS: The patient population consisted of 36 patients on maintenance haemodialysis. Matched control subjects were recruited among apparently healthy normolipidemic Tunisians. Total cholesterol, triglycerides, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B concentrations were measured. RESULTS: The triglycerides levels were significantly higher in patient group, unlike the high-density-lipoprotein cholesterol and apolipoprotein AI levels that were significantly reduced. We saw no increase in the levels of low-density-lipoprotein cholesterol and apolipoprotein B. The low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio result wasn't helpful in the evaluation of the atherogenic risk. CONCLUSION: We confirm the quantitative lipid disorders associated with maintenance haemodialysis. The assessment of cardiovascular risk on the basis of these disorders seems difficult.     

Candidate genes involved in cardiovascular risk factors by a family-based association study on the island of Kosrae,Federated States of Micronesia

Altered plasma levels of lipids and lipoproteins, obesity, hypertension, and diabetes are major risk factors for atherosclerotic cardiovascular disease. To identify genes that affect these traits and disorders, we looked for association between markers in candidate genes (apolipoprotein AII (apo AII), apolipoprotein AI-CIII-AIV gene cluster (apo AI-CIII-AIV), apolipoprotein E (apo E), cholesteryl ester transfer protein (CETP), cholesterol 7alpha-hydroxylase (CYP7a), hepatic lipase (HL), and microsomal triglyceride transfer protein (MTP)) and known risk factors (triglycerides (Tg), total cholesterol (TC), apolipoprotein AI (apo AI), apolipoprotein AII (apo AII), apolipoprotein B (apo B), body mass index (BMI), blood pressure (BP), leptin, and fasting blood sugar (FBS) levels.) A total of 1,102 individuals from the Pacific island of Kosrae were genotyped for the following markers: Apo AII/MspI, Apo CIII/SstI, Apo AI/XmnI, Apo E/HhaI, CETP/TaqIB, CYP7a/BsaI, HL/DraI, and MTP/HhpI. After testing for population stratification, family-based association analysis was carried out. Novel associations found were: 1) the apo AII/MspI with apo AI and BP levels, 2) the CYP7a/BsaI with apo AI and BMI levels. We also confirmed the following associations: 1) the apo AII/MspI with Tg level; 2) the apo CIII/SstI with Tg, TC, and apo B levels; 3) the Apo E/HhaI E2, E3, and E4 alleles with TC, apo AI, and apo B levels; and 4) the CETP/TaqIB with apo AI level. We further confirmed the connection between the apo AII gene and Tg level by a nonparametric linkage analysis. We therefore conclude that many of these candidate genes may play a significant role in susceptibility to heart disease.     

Lipoproteins and apolipoproteins. Composition, metabolism, and association with coronary heart disease

Apolipoproteins play major roles in regulating lipoprotein synthesis and catabolism. Apolipoprotein AI activates the lecithin cholesterol acyltransferase, apolipoprotein CII and CIII regulate the lipoprotein lipase, and apolipoprotein B-100, B-48, and E control the cholesterol uptake into hepatic and extrahepatic cells. Therefore, investigating the alterations of lipoprotein metabolism in disease states at the apolipoprotein level may give increased insight into the underlying mechanisms of lipoprotein changes and provide better understanding about the premature development of the atherogenic process.     

Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid

We investigated the effect of chenodeoxycholic acid on cerebrospinal fluid sterol and protein composition in six patients with cerebrotendinous xanthomatosis, a progressive neurologic disease, and in 11 control subjects. In the cerebrospinal fluid from the controls, the mean (+/- SD) levels of cholesterol and cholestanol were 400 +/- 300 and 4 +/- 7 micrograms per deciliter, respectively. The levels were almost 1.5 and 20 times higher in cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis. Cholestanol levels were also markedly elevated in the plasma of untreated patients, but their plasma cholesterol levels (215 +/- 61 mg per deciliter) were not different from control values. Treatment with chenodeoxycholic acid reduced cerebrospinal fluid cholesterol by 34 percent and cholestanol threefold. Plasma cholestanol levels also decreased sharply. Normal cerebrospinal fluid contained small quantities of albumin, apolipoproteins, and lecithin:cholesterol acyltransferase. In cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis, immunoreactive apolipoprotein B or apolipoprotein B fragment was increased about 100-fold and albumin about 3.5-fold; apolipoprotein AI, apolipoprotein D, and lecithin:cholesterol acyltransferase were 1.5 to 3 times more concentrated. Apolipoprotein AIV and apolipoprotein E concentrations were comparable to those in controls, and apolipoprotein AII was considerably decreased. During treatment, the concentrations of albumin and apolipoproteins AI and B declined. These results suggest that increased cerebrospinal fluid sterols are derived from plasma lipoproteins by means of a defective blood-brain barrier in patients with cerebrotendinous xanthomatosis. Therapy with chenodeoxycholic acid reestablished selective permeability of the blood-brain barrier and normalized the concentrations of sterol and apolipoprotein in the cerebrospinal fluid.     

Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy

Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share molecules and mechanisms pertaining to extracellular lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM, basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem and cryosectioned. Sections were stained with traditional lipid stains and filipin for esterified and unesterified cholesterol or probed with antibodies to apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and protein. Esterified and unesterified cholesterol was present in all drusen and basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained by traditional lipid stains and apolipoprotein antibodies than peripheral drusen. RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in sub-RPE deposits links ARM with important molecules and mechanisms in atherosclerosis initiation and progression. The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM.     

Keratinocytes express functional CARD18, a negative regulator of inflammasome activation,and its altered expression in psoriasis may contribute to disease pathogenesis

Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a negative regulatory molecule that inhibits inflammatory events by terminating inflammasome activation due to a direct interaction with pro-caspase-1.During the investigation of molecular mechanisms in keratinocytes that contribute to the pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18 expression was detected, which showed significant elevation in response to inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast, higher basal expression was observed in psoriatic non-involved skin, but no further induction could be detected.We demonstrated that keratinocytes express CARD18 both at mRNA and protein levels and the expression increased in parallel with differentiation. The investigation of cellular inflammatory processes revealed that psoriasis-associated danger signals triggered the expression of inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1β production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1β secretion, suggesting a negative regulatory role for CARD18 in keratinocyte inflammatory signaling.The differential regulation of CARD18 in healthy and psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis. Furthermore, our in vitro results indicate that CARD18 may contribute to the fine tuning of keratinocyte innate immune processes.     

Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation,proliferation, and keratinization

The cytoskeleton in keratinocytes is a complex of highly homologous structural proteins derived from two families of type I and type II polypeptides. Keratin K2e is a type II polypeptide that is expressed in epidermis late in differentiation. Here we report the influence of keratinocyte activation, proliferation, and keratinization on K2e expression in samples of cutaneous and oral lesions. The normal expression of K2e in the upper spinous and granular layers of interfollicular epidermis is increased in keloid scars but showed distinct down-regulation in psoriasis and hypertrophic scars where keratinocytes are known to undergo activation. Unlike normal and psoriatic skin, K2e expression in hypertrophic and keloid scars began in the deepest suprabasal layer. In cutaneous basal and squamous cell carcinomas, K2e was absent in most tumor islands but the overlying epidermis showed strong expression. No significant K2e expression in nonkeratinized or keratinized oral epithelia, including buccal mucosa, lateral border of tongue and gingiva was detected. In oral lichen planus K2e expression was undetectable, but in benign keratoses of lingual mucosa induction of K2e along with K1 and K10 was observed. In mild-to-moderate oral dysplasia with orthokeratinization, K2e was highly expressed compared with parakeratinized areas but in severe dysplasia as well as in oral squamous cell carcinoma, K2e expression was undetectable. Taken together, the data suggest that K2e expression in skin is sensitive to keratinocyte activation but its up-regulation in oral lesions is a reflection of the degree of orthokeratinization.     

Angiogenic properties of normal and psoriatic skin associate with epidermis, not dermis

Psoriasis is a chronic inflammatory and proliferative epidermal skin disease associated with prominent new vessels in the dermis. Heretofore, unresolved was the question which skin element causes stimulation of vessel formation in this lesion: the epidermis, the dermis, vessels themselves, inflammatory cells, and so forth. It has been argued that the dermis by means of its vessels is responsible for the rapid and prominent epidermal growth and that psoriasis is simply a dermal-induced epidermal disease. Recognizing that vascular proliferations do not occur in the absence of an angiogenic stimulus we asked where in psoriatic skin is that angiogenic element found. By using the rabbit cornea angiogenic assay, the vessel-stimulating properties of epidermis and dermis (separated after cold trypsinization overnight), collected from psoriatic-plaque skin and normal skin both nonpsoriatic and psoriatic patients, were measured. The corneas were examined on days 2, 4, 8, 10, and 12 and graded from 1 to 5+ for vessel growth. Psoriatic plaque epidermis revealed a 4 to 5+ stimulus (8 of 12 corneas). Epidermis from normal subjects or from nonlesional psoriatic patient skin also revealed a 4 to 5+ stimulus (3 of 5 and 5 of 8, respectively). In no case was the dermal implant from normal (7 implants) or psoriatic patients (3 implants of lesional skin) angiogenic. The angiogenic activity of epidermis is stable to freezing and boiling. This study indicates that the vessel-stimulating properties of psoriatic and nonpsoriatic skin are associated with the epidermis and that the developing psoriatic lesion may involve complex epidermal to dermal as well as dermal to epidermal signals.     

Apolipoprotein AI and CIII gene polymorphisms and their association with lipid levels in Italian, Greek and Anglo-Irish populations of Australia

PRIMARY OBJECTIVE: The apolipoprotein (apo) AI-CIII-AIV gene cluster on chromosome 11 has been identified as a candidate region for hyperlipidaemia and in particular for hypertriglyceridaemia. Our aim was to detect associations between the apo AI and CIII polymorphisms and the plasma lipids, total cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in normal, healthy, adults from three ethnic groups of Australia--Italian, Greek and Anglo-Irish, separately by gender. METHODS AND PROCEDURES: The SstI restriction fragment length polymorphisms (RFLP) in the 3' untranslated region of the apo CIII gene and the MspI RFLP in the third intron of the apo AI gene were scored and the lipid concentrations were ascertained using standard methodologies. t-tests were used to compare lipid levels between sexes and between populations, and multivariate ANOVA was used to detect if the two RFLPs had an effect on any of the lipid concentrations. MAIN OUTCOMES AND RESULTS: The two RFLPs exhibit strong linkage disequilibrium in all three populations (p < 0.001). There were some significant differences in allele frequencies among the populations: the minor S2 allele was more frequent in Italians (0.12) than Greeks (0.03) (p = 0.003), and the minor M2 allele was more common in Greeks (0.14) than Anglo-Irish (0.05) (p = 0.026). We found no significant association between either of the RFLPs and any of the lipid concentrations in either sex of all three populations. However, Kruskal-Wallis tests detected associations of borderline significance between apo AI MspI genotypes and triglycerides (p = 0.04) and between apo AI MspI genotypes and cholesterol levels (p = 0.03) in Anglo-Irish females. CONCLUSIONS: Because only two statistically significant associations were detected among a number of comparisons, our data suggest that the apo AI and CIII polymorphisms play only a very limited role in mediating variation in lipid concentrations in these three ethnic groups.     

Serum lipids, lipoproteins and apolipoproteins in pregnant non-diabetic patients.

AIMS--To investigate the effect of pregnancy on serum concentrations of lipids, lipoproteins, and apolipoproteins. METHODS--Fasting serum concentrations of total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), apolipoproteins AI, AII, and B, and lipoprotein (a) were measured in 178 women with normal glucose tolerance in the second and third trimesters of pregnancy and in a control group of 58 non-pregnant women of similar age. Data were analysed using the unpaired t test and by one-way analysis of variance. RESULTS--The pregnant women had significantly higher concentrations of total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and apolipoproteins AI and B (p < 0.001) and apolipoprotein AII (p = 0.003) than the control women. The ratio of apolipoprotein B:apolipoprotein AI was significantly higher in the pregnant women than in the controls (p < 0.001), but the total cholesterol:HDL cholesterol ratio was not significantly different. No significant difference was found in the concentration of lipoprotein (a). CONCLUSIONS--Hyperlipidaemia is common in the second half of pregnancy. This may be a purely physiological response to pregnancy or it may be indicative of pathology in some women. These results warrant a follow up study to investigate whether the hyperlipidaemic response to pregnancy is variable and if so, whether it can predict future hyperlipidaemia in a manner analogous to that of impaired glucose tolerance during pregnancy, predicting non-insulin dependent diabetes in later life.     

Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis.

The importance of immunologic mechanisms in psoriasis has been deduced from the ability of immunosuppressive therapies to ameliorate this common and chronic skin disease. Certainly the histology of psoriatic lesions suggests a dialogue between the hyperplastic keratinocytes and infiltrating T lymphocytes and macrophages. To begin dissecting the cytokine network involved in the pathophysiology of psoriasis, the location, in both epidermal and dermal compartments, of tumor necrosis factor-alpha, interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha at the protein and/or mRNA levels were identified. Tumor necrosis factor-alpha was selected as a potentially key regulatory cytokine, first because it induces cultured keratinocyte interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha production, and second because intercellular adhesion molecule-1 expression by keratinocytes in psoriatic epidermis had been identified previously. Using immunohistochemical localization, tumor necrosis factor-alpha was identified in 12 psoriatic lesions as intense and diffuse expression by dermal dendrocytes (macrophages) in the papillary dermis (without significant staining of endothelial cells, mast cells, or dermal Langerhans cells), and focally by keratinocytes and intraepidermal Langerhans cells. Functional interaction between the dermal dendrocytes and keratinocytes was suggested by the presence of interleukin-8 expression of suprabasal keratinocytes immediately above the tumor necrosis factor-alpha-positive dermal dendrocytes. Interleukin-8 mRNA and transforming growth factor-alpha mRNA were detectable in the epidermal roof of psoriatic lesions, but neither was detectable at the protein or mRNA levels in any normal skin specimens. Treatment of cultured human keratinocytes with phorbol ester (which experimentally produces psoriasiform changes on mouse skin) or tumor necrosis factor-alpha also increased interleukin-8 and transforming growth factor-alpha mRNAs. Further elucidation of the cellular and molecular basis for the genesis and evolution of psoriasis will provide the framework for a better evaluation of the cause and treatment of this skin disease.     

T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products

Psoriasis vulgaris has been recognized lately as an immunologically mediated inflammatory skin disease. To analyze the pathogenetic role of T lymphocytes in the generation of psoriatic skin lesions, 105 T cell clones (TCC) and 10 T cell lines (TCL) were differentially isolated from dermis and epidermis of psoriatic skin specimens. Supernatants prepared from these T cells were studied for their effects on keratinocyte proliferation in vitro. Conditioned media from 14 of 77 epidermal TCC, 7 of which were CD8⁺, and from 8 of 28 dermal TCC, 5 of which were CD8⁺, reproducibly enhanced keratinocyte proliferation, with more pronounced mitogenic activities found in dermal TCC. Another 9 epidermal and 3 dermal TCC did not affect keratinocyte growth and supernatants from the remaining clones, as well as from the 5 epidermal and 5 dermal TCL, inhibited keratinocyte replication to varying degrees. Both mitogenic and suppressive activities were largely abolished by addition of an antiserum to interferon-gamma (IFN-γ), while addition of epidermal growth factor or irradiated psoriatic TCL had little effect on the activities of the supernatants. These studies reveal that a subpopulation of lesional psoriatic T lymphocytes is capable of enhancing keratinocyte proliferation in vitro via secreted products. Their mitogenic capacity most likely requires IFN-γ, but the ultimate effect is apparently determined by the presence of additional cytokines. Activation of T cells secreting such combinations of factors in vivo may contribute to the keratinocyte alterations characteristic of psoriatic skin lesions.     

Influence of apolipoprotein E genotype variation on the means, variances, and correlations of plasma lipids and apolipoproteins in children

The impact of the three most common apolipoprotein E ( APOE ) genotypes (ε32, ε33, and ε43) on means, variances, and correlations of nine plasma lipid and apolipoprotein traits (total cholesterol, lnTriglycerides, HDL cholesterol, and apolipoproteins AI, AII, B, CII, CIII, and lnE) was studied in 212 unrelated female and 219 unrelated male children aged 5–21.5 years from 278 pedigrees ascertained without regard to health status from Rochester, Minnesota. There was significant heterogeneity ( p ≤ 0.05) among genotypes for the mean plasma levels of lnApo E, Apo CII, Apo CIII, and lnTriglycerides (lnTrig) in females, and for the means of lnApo E, Apo B, and total cholesterol (Total-C) in males. Significant heterogeneity of intragenotypic variance was observed in males for Apo CII, lnTrig, and HDL-C; no significant heterogeneity was observed in females. Pairwise correlations between traits differed significantly among APOE genotypes in both females (6 of 36 pairs) and males (5 of 36 pairs). These results differ from those obtained from studies of the parental generation from the same sample of pedigrees. Our study further demonstrates that, with the exception of mean lnApo E levels, the univariate and bivariate distributions of traits that are measures of lipoprotein metabolism are influenced by variation in the APOE gene in a gender- and generation-dependent manner.     

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and Xba I polymorphisms, the apo E polymorphism and two polymorphisms of lipoprotein lipase (LPL) gene: Hind/ III and PvuII. Apo B signal peptide and Hind III/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p<0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and Pvul II/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The e4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p<0.01) have not previously been reported. LpAI:AII concentration was also influenced by Pvu II/LPL polymorphisms.     

Ultrastructure of psoriatic epidermis

The ultrastructure of human affected and unaffected psoriatic epidermis was studied in skin biopsies from 5 patients and 3 normal controls. Transmission electron microscopic investigations revealed abnormalities in all cell layers of the affected epidermis. Common to psoriatic keratinocytes from affected epidermis was the reduction of tonofilaments. The essential ultrastructural changes were located in the stratum granulosum and stratum corneum. Thus, absence of the fusion between the keratohyalin granules and the tonofilaments was found in stratum granulosum. The keratinocytes of the stratum corneum showed a large accumulation of ribosomes and vesicles resembling lipid vesicles.     

Plasma lipids, lipoproteins, and apolipoproteins in Nigerian diabetes mellitus, essential hypertension, and hypertensive-diabetic patients.

Plasma lipids, lipoproteins, and apolipoproteins were assessed in three groups of Nigerians at increased risk for atherosclerotic heart disease. The three patient groups, diabetes mellitus (n = 15), essential hypertension (n = 12), and hypertensive-diabetes mellitus (n = 11), were compared with age-matched, apparently healthy controls (n = 14). In subjects with diabetes mellitus, triglyceride and its related apolipoproteins CIII and CIII:NonB were significantly higher than controls. High-density lipoprotein cholesterol (HDL-C) was significantly lower; its related ratios, total/HDL-C and low-density lipoprotein cholesterol (LDL-C)/HDL-C were significantly higher than those for controls. Subjects with hypertension and hypertensive-diabetes mellitus had significantly higher values than controls for those lipids and lipid fractions considered atherogenic (total cholesterol, LDL-C, triglyceride, and the total/HDL-C and LDL-C/HDL-C ratios) as well as apolipoproteins B, CIII, and lipoprotein particles Lp(a) and CIII:NonB. Only hypertensive-diabetes mellitus subjects had lower HDL-C levels, while hypertension patients had significantly higher apolipoprotein AI and LpAI concentrations than controls. Subjects with hypertensive-diabetes mellitus had significantly worse lipid, lipoprotein, and apolipoprotein profiles both in terms of increased atherogenic and reduced anti-atherogenic parameters compared with subjects with diabetes mellitus or hypertension only. These studies suggest that Nigerians with diabetes, hypertension, and especially both hypertension and diabetes need to be fully evaluated from a lipid and lipoprotein standpoint, and any abnormalities detected need to be taken into consideration during therapy of this group of high-risk patients.