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Biomedical subjects

H Hammar

Publications and source records attributed to H Hammar.

At least 19 recordsLinked to original sources

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

Palmoplantar lesions in psoriatic patients and their relation to inverse psoriasis, tinea infection and contact allergy.

One hundred and seven psoriatics with palmoplantar involvement were clinically examined. They were selected from 921 patients filed in 1976 with the diagnosis psoriasis. Fifty per cent of the patients with palmoplantar psoriasis had flexural changes. The frequency of palmar involvement in patients with inverse psoriasis compared to patients with psoriasis vulgaris was increased 5.3 times. Pustulosis palmoplantaris (PPP) in addition to psoriasis was diagnosed in 18 patients (17%). A dermatophyte infection was observed in 1 of 48 patients examined for tinea infection. Positive patch tests were obtained in 8 of 47 patients, 7 of whom had more than one test reaction. The result gives no evidence of tinea infection and contact allergy as important factors in maintaining palmoplantar psoriasis.

Adult

Coagulation and fibrinolytic systems during the course of erysipelas and necrotizing fasciitis and the effect of heparin.

Necrotizing fasciitis (NF) is a grave infection of the skin leading to gangrene of the integument and often having a complicated and prolonged course. Studies on blood coagulation and fibrinolysis were done in 15 patients with NF and compared with 5 cases of erysipelas (E). In both conditions local fibrin deposition occurred initially in their course, but it was quantitatively more pronounced in NF than in E. Fibrinolysis decreased and stayed low at the site of NF up to 5 months (median) after discharge from hospital. Fibrinogen and activities of several plasma serine proteinases modifying coagulation were increased during the course of both diseases and even at the follow-up. Factor XII was decreased during the first week in E but a transient drop was present in NF only on days 3 and 4. The treatment of NF consists of high doses of appropriate antibiotics instituted early in its course. A beneficial effect of 300-500 IU heparin/kg/day was suggested from this open study. The hard induration preceding the appearance of skin gangrene was inhibited, if heparin was given early in the course of NF. We conclude that the enhanced fibrin deposition and vascular occlusions in the skin are the basis for most complications present in NF.

Adult

The measurement of coenzyme A and a coenzyme A-dependent enzyme. In microdissected epidermal material using coupled enzyme and bioluminescent reactions.

A sensitive micromethod for the determination of Coenzyme A and its esters down to about 0.2 pmol in a volume of 10 microliters and of the activity of citrate synthase is outlined. Epidermal material from healthy and psoriatic skin was utilized in microgram quantity as tissue source. The assay utilizes the ketoglutarate dehydrogenase reaction to yield NADH on addition of free Coenzyme A and the subsequent measurement of NADH by a bioluminescent reaction with Acromobacter fischerii. The total Coenzyme A content in six healthy subjects measured in stratum Malpighii was 1.58 +/- 0.19 mmol per kg dry weight. In six psoriatic patients non-involved and involved epidermis contained 1.51 +/- 0.27 and 1.50 +/- 0.25 mmol/kg, respectively. Long-chain acyl-Coenzyme A comprised about 20% in lesion-free skin and 60% of total content in the involved psoriatic epidermis. The activity of citrate synthase in basal layers of healthy epidermis was 0.30 +/- 0.04 mkat/kg dry weight.

Animals

Measurement of the horny layer turnover after staining with dansyl chloride: description of a new method.

A simple non-radioactive technique is described. The corneal layers were stained with 5% dansyl chloride ointment during 24-48 h of occlusion. The number of newly formed corneal layers were counted on sections from punch biopsies obtained at various intervals after the staining. The rate of formation is given as layers formed per 24 hours. The technique makes it possible to detect an increase in the turnover rate when it is more than 15-32% above normal. The biological material can also be utilized for comparative studies utilizing biochemical and histological methods. The average rate of formation was 1.15+-0.09 (S.E.M.) layers per 24 hours in a group of 10 subjects.

Adult