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Biomedical subjects

H Hammar

Publications and source records attributed to H Hammar.

At least 19 recordsLinked to original sources

Proliferation and interferon-gamma receptor expression in psoriatic and healthy keratinocytes are influenced by interactions between keratinocytes and fibroblasts in a skin equivalent model.

Epidermal-dermal interactions were studied in a skin equivalent model. Six combinations of keratinocytes and fibroblasts from healthy and psoriatic skin were used. TPA (12-O-tetradecanoylphorbol-13-acetate) was used to determine whether the expression of the IFN-gamma receptors in keratinocytes was related to epidermal differentiation and proliferation. These phenomena were assessed by immunohistochemistry. In all epidermal outgrowths, the epidermal growth factor receptor was expressed throughout the epidermis, cytokeratin 16 suprabasally, and filaggrin and involucrin in its superficial part. The IFN-gamma receptor was expressed throughout the epidermis, but was unevenly distributed. The expression of the IFN-gamma receptor was quantified by confocal laser scanning microscopy both in the whole of epidermis and in areas with the strongest intensity. The total amount varied to a minor degree in the epidermal outgrowths of different origins and was unaffected by TPA. In high-intensity areas interactions between keratinocytes and fibroblasts did influence the amount of IFN-gamma receptor expression and TPA decreased the expression by 13%. There was no correlation between the proliferation rate and the expression of the IFN-gamma receptor. Psoriatic and healthy keratinocytes were equally well differentiated in the skin equivalents. The interferon-gamma receptor was similarly expressed under these conditions. The growth rate, assessed by Ki-67-positive nuclei in the basal layer, was highest in healthy keratinocytes. Keratinocytes from psoriatic lesions increased their growth rate when cocultured with psoriatic fibroblasts compared with normal ones, indicating that fibroblasts may be of importance for epidermal hyperproliferation in psoriatic lesions.

Adult

Liver fibrosis quantified by image analysis in methotrexate-treated patients with psoriasis.

BACKGROUND: Histopathologic monitoring of the liver is mandatory during methotrexate (MTX) treatment. Fibrosis is an important histologic feature of liver damage. OBJECTIVE: Our purpose was to supply an independent measure to histopathologic grading of hepatic changes in MTX-treated patients with psoriasis. METHODS: Forty-six liver biopsy specimens from 26 patients with psoriasis evaluated for or treated with MTX were histopathologically classified and their collagen content quantified by image analysis after staining with Sirius Red F3BA. RESULTS: Fibrosis in normal liver biopsy specimens (controls) amounted to 0.9% +/- 0.1% and in patients with psoriasis varied between 9.3% +/- 1.4% and 24.0% +/- 4.9%. An effect of MTX on liver fibrosis was not discerned. No correlation was obtained between fibrosis and histologic grades, intake of alcohol, lean tissue mass, or age of the patient. CONCLUSION: Two changes occurred in the psoriatic liver; the collagen content was increased at least tenfold when compared with controls, and significant heterogeneity in collagen content was present among patients (p < 0.001).

Adult

Wound healing.

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Blood Platelets

Epidermal growth in the skin equivalent.

The skin equivalent (SE) has been validated as a model for studies on proliferation of keratinocytes. SEs were prepared from normal skin by implanting punch biopsies on dermal equivalents consisting of fibroblasts in a collagen matrix. The outgrowths were measured by planimetry. An immunohistochemical investigation with antibodies against markers associated with proliferation was performed on frozen sections from SEs during outgrowth at 3-6 days (SE6) as well as after completion of outgrowth at 21 days (SE21). Biopsies from normal controls and from uninvolved and involved skin in psoriatic patients were also studied. The antibodies used were Ki-67, cytokeratin 8.12, and antibodies against the receptors for epidermal growth factor (EGFr) and transferrin (TFr). The increase in area was linear during the first 7 days of culture and usually reached the edges of the dermal equivalent at this time. In SE6 TFr was expressed in the basal part of the outgrowth while the other markers were not observed. In SE21 and in psoriasis there was abundant epidermal staining of Ki-67-positive nuclei and cytokeratin 8.12 was detected in the suprabasal part of the epidermis. EGFr and TFr were seen in the basal layer in SE21. In the psoriatic lesions these receptors were found both in the basal and suprabasal layers. The lack of proliferation markers in SE6 indicates that the initial increase in the area of keratinocytes is due to migration from the punch biopsies. Increased cell proliferation is present in SE21, a finding in common with psoriasis and wound healing. The skin equivalents should therefore be an appropriate model for studies on these phenomena.

Adult

Expression of interferon-gamma receptors in normal and psoriatic skin.

Psoriatic keratinocytes have a reduced antiproliferative response to interferon (IFN)-gamma, and HLA-DR expression is usually not observed on keratinocytes in psoriatic plaques despite the presence of activated T cells. We have therefore compared the expression of IFN-gamma receptors in psoriatic skin with that of normal human skin. Using mouse monoclonal antibodies and immunoperoxidase staining on cryostat cut sections, we detected IFN-gamma receptors on keratinocytes throughout the epidermal layers except stratum corneum in normal skin (n = 11). Biopsy specimens from involved psoriatic skin (n = 17) consistently showed a staining pattern that differed from that of normal skin in that only the lower part of epidermis reacted with the antibodies to IFN-gamma receptors, whereas the upper layers showed no or minimal staining. Expression of IFN-gamma receptors in uninvolved psoriatic skin (n = 16) did not differ from that of healthy controls. Forty-five percent of the biopsies from lesional psoriatic skin displayed ICAM-1 positive keratinocytes, and only two specimens had a limited expression of HLA-DR reactive keratinocytes. The decreased binding of antibodies against the IFN-gamma receptors in the upper part of psoriatic epidermis might be secondary to abnormal maturation of psoriatic keratinocytes or a primary defect involving abnormal modulation of IFN-gamma receptors.

Adult

Group G streptococcal infections on a dermatological ward.

Groups A, B, C and G streptococci were cultured from 63 consecutive in-patients recruited between November 1987 and April 1988 and monitored until the end of July 1988. Chronic leg ulcers were present in 34 patients. Group G was found in 34 patients, 25 of whom had pyoderma and 3 had sepsis. Six of the patients had no signs of clinical infection, and treatment with antibiotics was therefore withheld. Recurrent phlegmon or erysipelas developed in 2 of 28 patients with clinical Group G infections. Erysipelas developed some 1-7 months later in 3 of the 6 patients who were not initially treated. No significant difference in severity or additional medical conditions was found between the patients with either Group G or Group A streptococci. In comparison, data on all streptococcal cultures at the Department indicated that Group G was isolated 2.6 times as often as Group A streptococci for the in-patients, compared with 1.1 for all patients seen. It is concluded that Group G streptococcal skin infections must be regarded with the same clinical vigilance as Group A infections.

Adult

A case report of acute febril neutrophilic dermatosis (Sweet's syndrome) and Crohn's disease.

A case of Crohn's disease complicated by Sweet's syndrome is presented. The main ultrastructural findings were the multiplication of basal lamina surrounding the venulea, interendothelial gaps and in perivascular locations mixed infiltrates of neutrophiles and erythrocytes. The changes indicate that the initial site of the reaction was the walls of the dermal vessels.

Acute Disease

The specificity and cellular origin of phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity in psoriatic skin.

Phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity has been found in psoriatic skin and in this study, PNMT-like immunoreactivity was investigated in the involved and uninvolved skin of six patients with lichen planus and four patients with lichen simplex. No PNMT immunoreactivity was observed in these diseases. Studies were carried out using cultured fibroblasts from two patients with psoriasis from uninvolved and involved areas of skin and from two controls using antibodies to PNMT, as well as antibodies to the chemical messengers somatostatin, substance P, parathyroid hormone and peptide histidine isoleucine amide. No immunoreactivity to these substances was found, and fibroblasts are unlikely to be the cellular origin of the PNMT-like immunoreactivity as seen in psoriatic skin.

Adolescent

Treatment of pemphigus vulgaris with cyclosporine. .

Treatment of a few severe cases of pemphigus vulgaris with ciclosporin has been reported. We describe a patient with pemphigus vulgaris of more than 3 years' duration who did not respond to prednisolone treatment in high doses nor plasmapheresis or pulse therapy with methylprednisolone. When therapy with ciclosporin (5.0 mg/kg/day) in combination with prednisolone (1.4 mg/kg/day) was given, clinical improvement was present after 1 week, and almost complete remission was seen after 11 weeks. We did not observe any side effects during 1 year of treatment except hypertrichosis and hypomagnesemia.

Cyclosporins

Transferrin and epidermal growth.

Growth of keratinocytes in explant culture of mouse ear epidermis was studied. The addition of transferrin to the culture media improved growth. Transferrin fractionated from human and fetal calf serum increased outgrowths of the cultures when compared with commercially available transferrin. An acidic transferrin fraction was present in greater amount in human serum and in fetal calf serum than that found in commercial transferrin. This fraction was more abundant in serum from psoriatic patients than in serum of healthy subjects as shown by isotachophoresis. For the culture studies, preparation of this material was done by chromatography on DEAE-Sepharose 6B-CL columns. Further on, diferric transferrin was preferentially used in order to abolish variation due to iron saturation. Iron concentration higher than 5 microM was deleterious to cell growth. The basal culture medium contained transferrin depleted fetal calf serum in RPMI 1640 with 2 microM glutamine and antibiotics. Serum-free medium was used in some experiments. The additions were 1.7 microM insulin, 1.4 microM hydrocortisone, 10 microM ethanolamine and 10 microM phosphoethanolamine. A partially purified fraction of the acidic forms of transferrin (10-20 micrograms/ml medium) improved outgrowth when compared with a neutral fraction under these circumstances.

Animals

Complement C3 proteins in psoriasis.

A new polymorphism of the complement factor C3 in human plasma was demonstrated by isotachophoresis in agarose gels followed by immunodetection with rabbit anti-human C3c and C3d immunoglobulins. Four bands were detected in the immunoprint of freshly drawn EDTA-plasma, which were C3s1, C3s2, C3f1 and C3f2. At least four additional C3 components in Mg2+ -zymosan activated plasma were present, which were C3b1 to C3b4. The different forms of C3 in frozen and thawed heparin-plasma from 20 patients with psoriasis and 20 healthy individuals were studied from the immunoprint. The total content of C3 components was 29% greater in the patients with psoriasis than controls. The major difference was in the C3b components which were increased by 46%. In psoriatic patients, the two slow C3 components C3s1 and C3s2 were increased by 24 and 56% respectively, when compared with controls. The two fast C3 components C3f1 and C3f2 were decreased to 29 and 37%. The results suggest a direct involvement of the complement factor C3 in psoriasis.

Adult

Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group.

Sixty-nine patients with mycosis fungoides, plaque stage, were treated in an open study with photochemotherapy (PUVA) or the combination of oral retinoids and PUVA (RePUVA). The response rate of Re-PUVA was equal to that of PUVA, with complete remission in 73% and 72%, respectively. Remissions were obtained with fewer PUVA sessions, and with a lower UVA dosage, if PUVA was combined with retinoids. A lower UVA dosage was needed if treatment was given four times weekly in stead of twice weekly. The duration of the remissions tended to be prolonged if retinoids were given as maintenance therapy.

Adult

Epidermal growth.

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Arachidonic Acids

Analysis of epidermal growth. Tape stripping of skin and explant culture.

An explant culture model of epidermal cell growth is outlined. Based on sequential measurements of the radius of the outgrowth around the explant, the paper describes two phases of growth. In the first phase, growth depends on migration of cells out from the explant and on their subsequent proliferation by mitosis. This period occurs during the first week after explantation. At a certain point in time, migration ceases and during the following phase a linear increase in log cell number takes place. A mathematical analysis of the growth is outlined and necessary parameters described. In the system, migration and proliferation rates are determined and the latter related to cell kinetic parameters. This model of epidermal cell growth is used to describe the explant culture of pig skin after activating the skin in vivo by tape stripping. This leads to a mitotic burst which in the explants is shown by augmented migration of cells from the explant, when compared with control explants. The migration rate was no different from that of controls. The duration of migration was prolonged in the experimental group. The proliferation rate observed in these outgrowths was similar. Cell cycle time was 53 and 43 h in control and stripped skin cultures, respectively. An analysis of the model is given.

Animals

Phenylethanolamine N-methyltransferase-like immunoreactivity in psoriasis. An immunohistochemical study on catecholamine synthesizing enzymes and neuropeptides of the skin.

Immunoreactivity for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the conversion of norepinephrine to epinephrine, was present in the basal epidermis and upper dermis in 16 patients with psoriasis. The amount of immunoreactivity was increased tenfold in involved compared to uninvolved skin as characterized by computer-assisted image analysis. In skin from healthy volunteers no immunoreactivity could be found. In our subjects, no immunoreactivity was observed for the other catecholamine synthesizing enzymes (tyrosine hydroxylase; dopa-decarboxylase; dopamine-beta-hydroxylase), apart from single tyrosine hydroxylase positive adrenergic vascular nerves. Furthermore, in psoriasis, the immunoreactivity pattern of the peptides somatostatin, substance P, vasoactive intestinal polypeptide and bombesin was in agreement with skin from healthy volunteers.

Adult

Oral retinoids in mycosis fungoides and Sézary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group.

Thirty-nine patients with mycosis fungoides in various stages or Sézary syndrome were treated with isotretinoin and 29 with etretinate as single drug therapy. Complete remission within 2 months was obtained with isotretinoin in 8 cases (21%) and partial remission in another 15 cases (38%). Etretinate induced complete remission in 5 cases (21%) and partial remission in 11 (46%). Only 1 case with Sézary syndrome went into partial remission. The first sign of remission occurred in 2 to 4 weeks. During continued treatment remissions could not always be maintained. Isotretinoin and etretinate were considered to be of equal potency in the treatment of mycosis fungoides.

Drug Eruptions

Comparison of two enzyme immunoassays and an immunofluorescence test for detection of Chlamydia trachomatis.

Three rapid methods for the detection of Chlamydia trachomatis were compared: one immunofluorescence test and two enzyme immunoassays. Cervical and urethral specimens were obtained from 75 women in an outpatient clinic for therapeutic abortions and from 50 women in a sexually transmitted disease clinic. Urethral specimens were also obtained from 154 men in the same clinic. One hundred and nineteen cervical and 272 urethral specimens of a total 391 specimens were tested by the three methods. The direct immunofluorescence test detected Chlamydia trachomatis in 8% and the two enzyme immunoassays in 10% and 12% of the patients. The sensitivity of the immunofluorescence test was 76% compared to 91% and 80% for the two enzyme immunoassay tests. All three tests had a specificity of 99%. Dilution experiments confirmed that one immunoassay test, Chlamydiazyme, detected most of the positive specimens. The rapid and easily automated enzyme immunoassays are a valuable complement to the culture technique.

Cervix Uteri

Psoriasis treatment: faster clearance when UVB-dithranol is combined with topical clobetasol propionate.

Fifty patients with plaque psoriasis were treated with dithranol and UVB 5 days per week. Twenty-six of these patients also received 13 treatments (once daily in the 1st week, every other day in the 2nd week, twice in the 3rd week and once in the 4th week) with topical clobetasol propionate. The median time for clearance was 2.5 weeks for those on the clobetasol propionate-dithranol-UVB combination compared with 4 weeks when only dithranol-UVB was used. Scaling and induration of the lesions disappeared during the first 2 weeks of treatment with clobetasol propionate-dithranol-UVB which was a significant improvement compared with dithranol-UVB alone. The time of remission in patients completely cleared was the same in the two groups. Relapses occurred slightly more often in the clobetasol propionate treated than in the control group (during treatment 5 of 26 versus 2 of 24; after 6 months 7 of 18 versus 4 of 15) but the differences were not statistically significant. The study shows that addition of topical clobetasol propionate according to our schedule to the traditional dithranol-UVB regimen of psoriasis results in a more rapid clearance of lesions without undesirable side effects.

Administration, Topical