Prognostic factors determining response to antidepressant drugs in psychiatric out-patients and general practice

The outcome of antidepressant drug treatment was measured in 200 patients, 145 seen in psychiatric out-patient clinics and 55 in general practice, after 4 weeks of therapy. The results of the 200 patients taken together suggested that prognosis was largely determined by factors dependent on the natural history of the disorder and that clinical symptoms were unimportant, but when the results for patients in each drug group were analysed separately symptoms were more important than natural history factors. We conclude that clinical symptoms are only important predictors of response to antidepressant drugs when the patients studied are homogeneous with regard to natural history factors, particularly duration of illness.     

Identification of the major structural proteins of two BALB/c myeloma C-type viruses.

We have analyzed the structural proteins of the C-type viruses produced by cloned lines of the MOPC-21 and FLOPC-1 BALB/c murine myelomas. These viruses, designated MO₂₁-MuMAV and FL₁-MuMAV, respectively, have been shown to be composed of proteins with approximate molecular weights of 90,000, 75,000, 17,000, 12,000, and 10,000 daltons. In addition, these viruses contain a “doublet” with molecular weights of approximately 30,000 daltons. The 90,000- and 75,000-dalton proteins are glycosylated. The p30 “doublet” as well as the NB-ecotropism is retained upon subsequent virus cloning in SC-1 cells, passage through NIH-3T3, or BALB/3T3 cells, or microtiter plate cloning of SC-1 cells replicating cloned virus. The two cloned MuMAVs appeared to possess the p30 proteins of the endogenous BALB/c N- and B-tropic viruses described by Hopkins and co-workers (N. Hopkins, J. Schindler, and R. Hynes, 1977, J. Virol.21, 309–318; J. Schindler, R. Hynes, and N. Hopkins, 1977, J. Virol. 23, 700–707). Subsequent tryptic peptide analysis of the myeloma virus p30 proteins demonstrated that these proteins share extensive homology with, but not identity to, the two prototype BALB/c ecotropic endogenous virus p30 proteins.     

The effect of denervation of Merkel cells in cats

The morphology of Merkel cells in sinus hair follicles of the upper lip (vibrissae with a circular blood sinus), and in touch domes of the glabrous skin of the nose, was investigated in cats up to 12 weeks after resection of the infraorbital nerve. Even 12 weeks after denervation there was neither an ultrastructural alteration of Merkel cells nor a reduction of their number in sinus hair follicles. Also in touch domes the Merkel cells did not disappear.     

Evaluation of the Antioxidant Effects of Ziziphus Mauritiana Lam. Leaf Extracts Against Chronic Ethanol-Induced Hepatotoxicity in Rat Liver

Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.     

Studies of the antigenicity and allergenicity of phospholipase A2 of bee venom.

The antigenic and allergenic properties of phospholipase A2 (PLA2) and whole bee venom were compared by measuring the IgG and IgE antibody responses in animals and man. Precipitating antibodies raised in rabbits and reaginic and other antibodies raised in mice reacted about equally with both bee venom and PLA. The majority of human sera containing bee venom-specific IgE also contained PLA-specific IgE, although in somewhat lower titers. Similarly, most human sera with significant amounts of total antibodies reacting with bee venom also had antibodies reacting with PLA. Histamine and SRS-a release from leukocytes of sensitive patients followed challenge with whole bee venom and PLA in the majority of instances. However, mediator release from several patients' cells was obtained with bee venom only. These studies suggest that although PLA is a major allergen and antigen in bee venom, significant exceptions in patients' reactivity may limit its potential diagnostic and therapeutic usefulness.     

Effect of H+ and elevated PCO 2on membrane electrical properties of rat cerebral arteries

Some membrane electrical properties of muscle cells from the middle cerebral artery of the rat were recorded with intracellular microelectrodes. The resting membrane potential (E _m) of this preparation was –63 mV. Reduction of extracellular pH to 7.0 in the face of a constantP _{CO 2}of 40 mm Hg had no significant effect onE _m. Similarly the slope of the steady-state voltage/current curves was not different at pH 7.0 compared to control at pH 7.4. In marked contrast, whenP _{CO 2}was elevated to around 60 to 70 mm Hg there was a rapid hyperpolarization and reduction in the slope of the voltage current curve suggesting an increased conductance for one or more ionic species. In addition elevation ofP _{CO 2}increased the slope of theE _m vs. log[K]₀ curve from 46 mV/decade to 59 m V/decade which is in good agreement with a Nernstian potential for a K⁺ selective membrane. These data suggest that while the smooth muscle cells of rat cerebral arteries are relatively insensitive to a small reduction in extracellular pH; reduction of intracellular pH by elevatingP _{CO 2}induces hyperpolarization by increasing K⁺ conductance (g _k). However, it is not clear from these experiments if theP _{CO 2}effects are mediated entirely by changes in pH or if there is a direct membrane action of CO₂.This work is supported by Grant no. HL27862     

Leukocyte histamine release in Hymenoptera-allergic patients. Correlation with skin test reactivity and changes following hyposensitization therapy

We have studied 46 Hymenoptera-allergic patients and 11 nonallergic controls by grading the severity of their sting reaction, determining their skin test reactivity, and performing human leukocyte histamine release with a commercial mixed stinging insect extract. A significant correlation was found between increasing severity of sting reaction and increasing skin test reactivity (p < 0.001). In $\text{41}\text{46}$ allergic patients from 15 to 100 per cent release of total cellular histamine occurred, whereas in the 11 nonallergic controls no greater than 10 per cent release of total cellular histamine was observed. Skin test reactivity correlated significantly with cell sensitivity in the allergic patients (p < 0.001). Following hyposensitization therapy, cell sensitivity generally did not change, but significant increases in antigen-neutralizing capacity (A.N.C.) of allergic serum did occur in $\text{11}\text{15}$ Hymenoptera-allergic patients.     

Thymic stroma is required for the development of human T cell lineages in vitro

Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3^– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible.