Failure of oral inosiplex treatment of recurrent herpes simplex virus infections.

A compound, a mixture of acedoben, dimepranol, and inosine (inosiplex) was used to treat recurrent local herpes simplex virus (HSV) infections in a double-blind placebo-controlled crossover study. Altogether, 58 patients with a history of frequently recurrent HSV infections were examined. Eighteen selected patients participated in the drug trial. Ten patients received both inosiplex and placebo, three received only inosiplex, and five received only the placebo. Three patients received both placebo and inosiplex twice. No substantial differences between the treatments with inosiplex or placebo could be seen in the frequency of occurrence or healing of the local lesions, nor in the results of these patients' immunologic studies. An evident placebo effect was observed, since only 15 (26%) of the 58 subjects examined continued to have an often relapsing form of the disease when followed up regularly.

Separation and partial characterization of four cysteine proteinases from a human epidermal cell line.

Four different cysteine proteinases from a cultured human epidermal cell line (NCTC 2544) were partially purified and characterized. The biggest hydrolase was an endoaminopeptidase with the molecular weight of several hundred kilodaltons. It was a glycoprotein and had an almost neutral pH optimum. The three other hydrolases resembled lysosomal cathepsins B, H, and L in various respects except for somewhat higher molecular weight for cathepsin B (29 kDa) and the cathepsin H-like (70 kDa) hydrolase than those reported from most other tissues. Low molecular weight cysteine proteinase inhibitors ACPI (cystatin A) and NCPI (cystatin B) inhibited the cathepsins, but not the high molecular weight proteinase.

Cysteine proteinase inhibitors in psoriatic epidermis.

Human psoriatic epidermis and scales were demonstrated to contain two antigenically separate cysteine proteinase inhibitors, one acidic with an isoelectric point of 4.7-5.0 (ACPI) and one neutral with an isoelectric point of 6.0-6.5 (NCPI), while normal epidermis contains only ACPI. The total papain (cysteine proteinase) inhibiting activity of the psoriatic epidermis as calculated per mg protein was higher than that in normal epidermis. Both ACPI and NCPI were localized immunocytochemically, mainly in the highest spinous cell layers with less activity in the parakeratotic cells and lower layers of spinous cells. Basal cells were essentially negative.

Natural cysteine proteinase inhibitors reduce lectin induced lymphocyte stimulation.

Lymphocyte stimulation by lectins can be inhibited by several synthetic inhibitors of proteolytic enzymes, notably those of cysteine proteinases. The effects of naturally occurring enzyme inhibitors are less well known. The effect of the neutral low-molecular weight cysteine proteinase inhibitor (NCPI) recently purified from lymph nodes and spleen was therefore investigated. Cultured peripheral blood lymphocytes were stimulated by PHA or ConA in the presence or absence of NCPI and the incorporation of 3H-thymidine was measured. NCPI was found to inhibit these lymphocyte responses in these circumstances.

Cell-mediated immunity against herpes simplex virus envelope, capsid, excreted, and crude antigens.

Cell-mediated immunity to herpes simplex virus envelope, capsid, excreted, and crude antigens was studied by in vitro lymphocyte stimulation tests during 198 recurrent attacks in 69 patients. Excreted antigen caused no blast transformation. Envelope and capsid antigen-induced lymphocyte stimulation was at the maximum 7 to 14 days postinfection, declining thereafter to a rather constant level in 1 to 2 months. The lowest levels were measured just a few days before a new attack. In persons with frequent relapses, the fluctuation was more rapid and stimulation index levels stayed higher, although no protective level seemed to exist. Cultures stimulated with the crude antigen in autologous serum showed rapid increases and declines in the stimulation index values, contrary to those grown in agamma serum, in which the stimulation level stayed rather constant up to 1 year postinfection.

Cysteine proteinase inhibitors produced by mononuclear phagocytes.

Monocytes were separated from human peripheral blood and allowed to attach to culture flasks, after which the content and production of a number of cysteine proteinase inhibitors was assayed. These were: a low molecular weight (MW 12000) acid cysteine proteinase inhibitor (ACPI); a low-molecular weight inhibitor of the same size with neutral pH (NCPI), and alpha-cysteine proteinase inhibitor with a molecular weight around 90 000 (alpha-CPI). Only NCPI was detectable in the cultures at the beginning of the incubation, and it was synthesized and released into the incubation mixture during the incubation, especially if the cells were stimulated with silica. The amount of NCPI contained in and released from the cells was drastically decreased by puromycin. Immunoblots after cell electrophoresis in polyacrylamide gel revealed only one molecular form of NCPI with a molecular weight of 12 000 both in the cells and in the culture medium. No ACPI or alpha-CPI could be detected.