Native chymotrypsin and its polyethylene glycol (PEG) conjugates, obtained using the succinimidyl carbonate of methoxy-PEG (SC-PEG) as the amino group modifying reagent, were tested for their activity toward several low and high molecular weight substrates. Tripeptide and tetrapeptide p-nitroanilides either as N alpha-benzyloxycarbonyl derivatives or attached via their N-terminals to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers or to PEG, as well as the proteins albumin and azoalbumin, were used as substrates. Extensively modified chymotrypsin bearing on average of 14 PEG chains per chymotrypsin molecule (PEG14CHT) and a moderately modified one containing 10 PEG chains (PEG10CHT) both degraded the low molecular weight p-nitroanilides at rates comparable to, and in the case of PEG10CHT, greater than, the rates exhibited by the native enzyme. Synthetic high molecular weight substrates and azoalbumin were also degraded by the PEG-modified enzymes. However, rates of such enzymatic reactions were lower for the PEG-enzymes than for the native one. Native albumin, as compared to azoalbumin, resisted degradation by both PEGCHTs yet was readily digested by the native chymotrypsin. The results obtained indicate that substrate-size-dependent specificity of PEG-modified enzymes cannot be explained solely by steric hindrance considerations. The decreased activity of PEG-enzymes toward protein substrates is consistent with the well-documented ability of PEG to exclude proteins from its surroundings and with the influence of protein unfolding on the susceptibility to degradation.

Albumins↗

PubMedDate not supplied

Gemcitabine-induced acute lipodermatosclerosis-like reaction.

Gemcitabine is considered to be a well-tolerated and safe cytostatic drug because of the relative lack of side effects. Cutaneous reactions due to gemcitabine treatment, including alopecia and maculopapular eruption, are well known. We report one patient with squamous cell carcinoma of the lung who developed a gemcitabine-induced cutaneous reaction mimicking acute lipodermatosclerosis. This case has never been reported in the literature before.

Acute Disease↗

PubMedDate not supplied

Acrokeratosis paraneoplastica (Bazex's syndrome): unusual association with a peripheral T-cell lymphoma.

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Acrodermatitis↗

PubMedDate not supplied

Inflammation of seborrheic keratoses due to docetaxel treatment.

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Aged↗

PubMedDate not supplied

Association of HLA-DRw9 with myasthenia gravis in Chinese.

HLA phenotypes were studied in 59 Chinese myasthenia gravis (MG) patients. Unfractionated peripheral blood mononuclear cells were used for typing of HLA-A, B and C, and B-enriched lymphocytes for HLA-DR. Seventy-nine healthy subjects were included as controls. When compared with healthy controls, the patients showed significant increases in HLA-Bw46 (47.5% versus 14%, chi 2 = 18.7, P less than 0.001), HLA-DRw9 (59.3% versus 11%, chi 2 = 35.7, P less than 0.001), while HLA-DR3 was decreased (3.4% versus 32.9%, chi 2 = 18.2, P less than 0.001). Further analysis showed that the primary association was with DRw9 and the increase in Bw46 was secondary to it. Both HLA-Bw46 and -DRw9 were increased in all subgroups except where the age of onset was greater than 40 years. Finally, the HLA-A2-Bw46-DRw9 combination was also significantly increased in patients (25.4% versus 5.1%, chi 2 = 11.5, P less than 0.001), especially in the subgroups of MG with age of onset of less than 10 and males with age of onset of less than 40 years.

Adult↗

PubMedDate not supplied

Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Thrombin stimulates prostacyclin formation in cultured human endothelial cells. However, a countervailing process that prevents prostacyclin overproduction has not been described previously. In this study, we demonstrate that Factor Xa can inhibit prostacyclin synthesis induced by thrombin or sodium arachidonate. The required concentration of Factor Xa represents activation of only 2% of the Factor X in plasma. The inhibition is reversed by a human monoclonal antibody directed against the light chain of Factor Va (Mr = 78,000), which suggests that Factor Va is required for this down-regulation of prostacyclin production. Confluent human endothelial cells (10(7)) contained 1.4 to 2.2 micrograms of Factor V antigen as measured by a competitive enzyme-linked immunosorbent assay. The results indicate that in endothelial cells Factor Xa may play a regulatory role in prostacyclin formation through interaction with Factor Va.

Arachidonic Acid↗

PubMedDate not supplied

Expression of factor V on human umbilical vein endothelial cells is modulated by cell injury.

Since human endothelial cells synthesize Factor V but do not secrete it into the medium, we studied the effects of cell injury on the availability of Factor V at the surface of these cells. Human umbilical vein endothelial cells (HUVEC), grown to confluency and incubated with human 125I Factor Va, specifically bound 5000 to 7000 molecules per cell. In the absence of added Va, no antigen was detected on adherent HUVEC with either labeled anti-V(Va) monoclonal or polyclonal IgG. However, exogenous Va, not V, prebound to these cells allows binding of labeled 125I anti-V(Va). Immunodectectibility of bovine Factor V contributed by fetal calf serum in the concentration used in cultures is less than 0.1% of that detected in human plasma. HUVEC, suspended by scraping from dishes, specifically bound 4000 molecules/cell of 125/I monoclonal IgG against V(Va). Although undisturbed cells excluded trypan blue, dye uptake by many of the suspended HUVEC indicated cell injury. Quantitation of injury by 51Cr release after scraping followed by multiple passages through an 18 g needle showed that 51Cr release increased with number of manipulations up to 60% and was observed almost immediately after manipulation. We suggest that little Factor V(Va) is present on the surface of intact adherent HUVEC. However, mechanical injury to HUVEC released or exposed endogenous Factor V(Va), resulting in expression of V that might mediate Factor Xa binding as well as activation of protein C by thrombin. Thus, injured, but not intact, HUVEC could participate in both promoting and limiting blood coagulation.

Animals↗

PubMedDate not supplied

Neurocutaneous melanosis with epilepsy: report of one case.

Neurocutaneous melanosis is a rare congenital syndrome characterized by the association of large or multiple congenital melanocytic nevi and benign or malignant melanotic tumors in the central nervous system. Patients with neurocutaneous melanosis usually have neurological symptoms early in life that progress rapidly due to the development of increased intracranial pressure or malignant melanoma. We report a 2-month-old female infant with multiple congenital melanocytic nevi and frequent seizure attacks. Magnetic resonance imaging of the brain demonstrated several regions compatible with melanotic deposits. During follow-up for one year, she had normal development and was seizure-free under the treatment of phenobarbital and valproic acid. We suggest that infants with large or multiple congenital melanocytic nevi should receive regular clinical check-up and brain imaging to exclude the possibility of central nervous system lesions.

Epilepsy↗