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Biomedical subjects

K M Halprin

Publications and source records attributed to K M Halprin.

At least 73 records · Page 4Linked to original sources
PubMed1978

Cyclic nucleotide-phosphodiesterase in the uninvolved and involved skin of psoriasis.

In the present study we have compared cyclic nucleotide-phosphodiesterase activities and affinity of phosphodiesterase for substrates (Km) in enzyme preparations obtained from the involved and uninvolved skin of psoriatic patients. With crude skin homogenates we consistently obtained two Km values (high and low) for both the involved and uninvolved, and both Km values were nearly identical between the involved and uninvolved. The same conclusion is also drawn from the Km determinations with partially purified preparations. Cyclic AMP-phosphodiesterase activities with crude homogenates showed no statistically significant differences between the involved and the uninvolved skin. However, when cyclic AMP- and cyclic GMP-phosphodiesterase activities were compared with a highly sensitive assay method in "pure" epidermal samples, which were microdissected free from stratum corneum, dermis and skin appendages, the involved skin contained 40% more activity of the low Km enzyme and 100% more of the high Km enzyme of both cyclic AMP- and cyclic GMP-phosphodiesterase. It is suggested that this may be due to a higher proportion of germinative cells in the lesional epidermis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Cyclic AMP accumulation in psoriatic skin: differential responses to histamine, AMP, and einephrine by the uninvolved and involved epidermis.

Using the uninvolved and involved skin from psoriatic patients, we investigated the effects of histamine and AMP (or adenosine) in vitro on the intracellular cyclic AMP levels. Both agents activated adenylate cyclase of the uninvolved and involved resulting in the accumulation of cyclic AMP. Without a cyclic nucleotide phosphodiesterase (PDE) inhibitor, these responses were biphasic and the maximal accumulation was observed in 5 min. With the PDE inhibitor both responses were markedly potentiated and high levels of cyclic AMP were observed for more than 20 min. The response to histamine by the involved skin was much greater than that by the uninvolved. The degree of the response to adenosine was approximately equal. In accordance with our previous work, the response to epinephrine by the involved skin was much less than that by the uninvolved. Thus adenylate cyclases of involved skin from psoriatic patients exhibit a markedly diminished response to epinephrine while at the same time exhibiting a markedly enhanced response to histamine. This precludes the possibility that the unresponsiveness to epinephrine can be due to a generalized inability of the epidermal psoriatic plaque cell to make a functioning cell membrane.

Adenosine Monophosphate↗
PubMed1977

Specific refractoriness of adenylate cyclase in skin to epinephrine, prostaglandin E, histamine and AMP.

The cyclic AMP level in pig skin (epidermis) increases markedly after incubation with epinephrine, prostaglandin E, histamine or adenosine 5'-monophosphate. This increase is transient and "spiking" is the consistent response to these four stimulators. The "spiking" is due to a non-responsiveness or refractoriness which develops within minutes and is specific to any one stimulating hormone but not to the others. The addition of inhibitors of protein syntheses did not prevent the development of the refractoriness. Adenylate cyclase and phosphodiesterase activities measured in skin homogenates prepared from skin samples taken before, during and after the "spiking" did not change significantly. The hormone-induced refractoriness in this skin system appears to be due to a specific, localized loss of function of the adenylate cyclase system.

Adenosine Monophosphate↗
PubMed1977

Epidermal adenylate cyclase systems: the retention of hormone responsiveness after enzymatic separation of pure epidermis.

Although it has been shown that keratome-sliced skin contains active adenylate cyclase systems which respond to various hormones and drugs, unequivocal proof that the epidermis contains these hormone-responsive systems is still lacking. We demonstrate in this study that "pure" epidermis obtained after either collagenase or trypsin treatment does contain the hormone-sensitive adenylate cyclase systems.

Adenosine Monophosphate↗
PubMed1977

Epidermal adenylate cyclase: stimulation of the histamine (H2) receptor by tolazoline.

Tolazoline (2-benzyl-2-imidazoline) activated adenylate cyclase in pig epidermal slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, theophylline. Specific histamine (H2) receptor inhibitors (metiamide and cimetidine) completely blocked the tolazoline activation of adenylate cylase. At low concentrations (10-100 micrometer), a histamine (H1) receptor inhibitor (diphenhydramine) and a beta-adrenergic blocker (propranolol) did not inhibit this effect. The stimulation of cyclic AMP formation by the combination of tolazoline and histamine was about the same as the stimulation by histamine alone (nonadditive), whereas the stimulatory effects by tolazoline and epinephrine were additive. These data suggest that tolazoline, an alpha-adrenergic blocker, also activates adenylate cyclase at the histamine (H2) receptor site which is distinct from the beta-adrenergic receptor site. Another alpha-adrenergic blocker, phentolamine, did not have this effect.

Adenylyl Cyclases↗
PubMed1977

Methotrexate uptake by psoriatic epidermis.

Psoriatic epidermis has been shown to be more sensitive to the effects of methotrexate than normal epidermis. One possible explanation for this observation is more rapid active transport of methotrexate into psoriatic cells. This study compares the uptake of methotrexate by normal and psoriatic epidermis and demonstrates the influence of extracellular pH on this process. Methotrexate uptake was not found to be greater in psoriatic epidermis than normal. A possible explanation for this unexpected finding is discussed.

Acid-Base Equilibrium↗
PubMed1977

Systemic antibiotic therapy of secondary infected dermatitis.

Systemic cloxacillin therapy of secondarily infected dermatitis cloxacillin therapy become apparent produces a significant increase in healing when compared to a placebo. The effects of systemic after five days of treatment. A single pretreatment culture was not helpful in directing therapy.

Adolescent↗
PubMed1977

Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding.

Approximately 60% of methotrexate in serum is protein bound and this binding occurs primarily to serum albumin. The fraction of methotrexate bound remains relatively constant despite changes in free methotrexate concentrations over the range observed clinically. Indomethacin did not influence methotrexate-albumin binding, but salicylate in therapeutic concentrations produced a 20% to 60% decrease in binding. The clinical significance of these findings for patients requiring concomitant methotrexate and salicylate is discussed.

Binding, Competitive↗
PubMed1976

Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase.

Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Histamine (H2) receptor-adenylate cyclase system in pig skin (epidermis).

Histamine activated adenylate cyclase in pig skin (epidermal) slices, resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of cyclic AMP-phosphodiesterase inhibitors (theophylline, papaverine). A specific H2 receptor inhibitor (metiamide) inhibited the effect of histamine completely, while other antihistamines (diphenhydramine, acetophenazine, perphenazine, fluphenazine, promethazine) inhibited the effect of histamine to various lesser degrees. It has been shown that both epinephrine and prostaglandin E stimulate epidermal adenylate cyclase. Our data using specific blocking agents indicate that histamine, epinephrine and prostaglandin E2 act independently on the epidermal adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1976

Multiple forms of cyclic nucleotide phosphodiesterase in pig epidermis.

Pig epidermal cyclic nucleotide phosphodiesterases (EC 3.1.4.16) have been partially purified by DEAE-cellulose column chromatography. At least three different forms of the epidermal phosphodiesterases were identified. They were cyclic GMP-specific, cyclic GMP- and cyclic AMP-hydrolyzing and apparently a cyclic AMP-specific enzyme: the first two forms were soluble and the last was the particulate enzyme. The cyclic GMP-specific soluble fraction had a relatively low Km, the cyclic GMP- and cyclic AMP-hydrolyzing fraction had a high Km for the respective substrates and the third particulate enzyme had both high and low Km values for cyclic AMP. The cyclic GMP-hydrolyzing enzyme was localized almost entirely in the soluble fraction, whereas cyclic AMP-hydrolyzing enzyme was distributed to both soluble and particulate fractions. Thus, our studies show that the multiple forms of pig epidermal enzyme differ distinctly in their substrate affinity, specificity and subcellular distribution.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1976

Effects of short chain alcohols and hydrocarbon compounds on the adenylate cyclase of the skin.

The cyclic AMP content of epidermal slices is increased by incubation with ethanol, the effect of which is dose-dependent from I to 5% concentration in the incubation media. n-Propanol and acetone are also effective at a concentration equimolar to 5% ethanol. Experimental results suggest that this effect of ethanol is due to activation of adenylate cyclase, rather than to the inactivation of cyclic AMP-phosphodiesterase.

1-Propanol↗
PubMed1976

Intravenous desensitization to mechlorethamine in patients with psoriasis.

Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.

Administration, Topical↗
PubMed1975

Multiple sequential skin cancers. The risk of skin cancer in patients with previous skin cancer.

We reviewed all reports of skin biopsies that had been performed at the Miami Veterans Administration Hospital within a three-year period. A total of 1,115 biopsy specimens of basal cell and squamous cell carcinomas were identified for 558 patients. Patient names, diagnosis, and dates of biopsies were tabulated for computer analysis. We determined that 121 patients (22%) developed at least one new or recurrent skin cancer during the average follow-up period of 1 1/2 years. From a computer review of clinic appointments, we determined that half of the 558 patients were unavailable for follow-up during that three-year period. Thus, the true rate of new and recurrent skin cancer in patients who had at least one skin cancer is no less than 22% and may approach 50% in the first 18 months. This high rate of new occurrences and recurrences of basal cell and squamous cell carcinomas emphasizes the need for repeated examinations of all patients with a history of skin cancer.

Basal Cell Carcinoma↗
PubMed1975

Cyclic AMP and psoriasis.

Evidence that an adenyl cyclase system is present in all mammalian epidermis is reviewed. This adenyl cyclase is stimulated by at least two separate types of chemicals: catecholamines, which act at a beta-adrenergic receptor site, and prostaglandins of the E series, which act at a separate site. In the psoriatic lesion, the response to these stimulators, especially to the catecholamines, is reduced. Despite this lack of response to external agents which elevate cyclic AMP, the concentration of cyclic AMP within the epidermis of the psoriatic lesion is no lower than in noninvolved skin. How cyclic nucleotides act to control cell proliferation and cell differentiation remains unclear.

Adenosine Monophosphate↗
PubMed1975

Micro-determination of cyclic AMP levels in human epidermis, dermis and haif follicles.

In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.

Adenine Nucleotides↗
PubMed1975

Cyclic AMP in skin: effects of acute ischaemia.

The cyclic adenosine 3',5'-monophosphate (cyclic AMP) content of pig skin was measured several seconds to minutes after removal of the skin from the body. It increased very rapidly, reached a maximum by 2 min after removal (4 times higher than the initial level), then decreased very slowly. Propranolol injected into the animal before or added after the removal of the skin did not suppress this phenomenon. The practical significance of this finding (increase of cyclic AMP level in skin after ischaemia) is obvious-in order to measure cyclic AMP level in vivo, the sample must be frozen immediately to avoid an 'artificial' increase in cyclic AMP.

Animals↗