Cytogenetic studies of bone marrow and extramedullary tissues and clinical course during metamorphosis of chronic myelocytic leukemia

Of 33 consecutive patients with chronic myelocytic leukemia, examined during metamorphosis, 82% showed chromosome abnormalities in addition to the Ph1. Aberrations most frequently encountered were +8 (39%), +22q - (30%), and i(17q) (18%). Translocations other than the Ph1 were observed in four cases and - Y clones in four cases. Discrepancies in the cytogenetic pattern between bone marrow and extramedullary tissues or blood were noted in a total of 15 patients. In six cases, transformation occurred in extramedullary organs at a time when it was not present in the marrow. In three cases the bone marrow transformation was preceded by a lymph node blastic infiltrate; in one case, by a skin infiltrate; and in one case, by a subdural blastoma. Clonal abnormalities additional to the Ph1 were identified in the tumor tissue from all these cases. Patients with primary extramedullary transformation tended to have a lower median age at onset of metamorphosis, shorter survival, and higher incidence of chromosome abnormalities than the cases without extramedullary involvement. Patients with only Ph1-positive cells and no other anomalies had a slightly longer duration of metamorphosis and longer total survival. Basophilia and thrombocytopenia were more marked in cases with i(17q) than in the rest of the series.     

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.     

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.     

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.     

Karyotyping chromosomes by electron microscopy. Condensation-inhibition of G bands in human and Chinese hamster chromosomes by a BrdU-Hoechst 33258 treatment

A BrdU-Hoechst 33258 treatment of living cells, which selectively induced condensation-inhibition of G-band chromatin in human and Chinese hamster chromosomes, is presented. As a consequence mitotic chromosomes showed high resolution R-banding patterns when examined by light and electron microscopy. Besides each whole chromosome identification, this procedure also permitted the electron microscopic study of specific structures, such as satellites, secondary constrictions, telomeres, centromeres, as well as G and R bands, some of them not visible by light microscopy. We have also observed that the chromatin of G and R bands behave as blocks of chromatin condensation and that G-band chromatin develops condensation along G₂. Under the BrdU-Hoechst 33258 treatment, chromatin fibers seem to invert their spontaneous pattern of condensation within the chromosomes.     

Plasma steroid concentrations during alternate-day treatment with prednisone

Plasma steroid concentrations were measured in asthmatic children 24 and 48 hours after administration of alternate-day treatment with prednisone, and the results were compared with those of control patients who did not receive corticosteroid treatment as well as those of patients who were treated with prednisone each day. It was found that 24 hours after administration of prednisone in any dose, plasma steroid concentrations were significantly lower than those of the control group. The degree of suppression in plasma steroid concentration was less marked in patients who received treatment on alternate days than in those who received the same doses of prednisone each day. Within 48 hours after administration of alternate-day treatment, plasma steroid concentrations approached the values observed in the control group and were independent of the magnitude of the prednisone dose. Although alternateday steroid treatment was associated with transient and incomplete suppression of pituitary-adrenal function, patients whose therapy was changed from a daily to an alternate-day regimen sometimes exhibited prolonged suppression of adrenal cortical function.     

Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus

During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release.     

Qualitative and quantitative evaluation of the exercise electrocardiogram in assessing the degree of coronary heart disease

Exercise-induced changes in the ST segments of the electrocardiogram were compared with the results of coronary arteriography in 73 consecutive patients referred for preoperative evaluation of coronary artery disease. Eighteen patients had single-, 25 double-, and 30 triple-vessel disease. Thirteen were taking digitalis alone, 28 were taking beta blockers alone, 21 had beta blockers and digitalis and 11 had no cardiac drugs. Exercise induced elevation of the ST segment in 11 patients, all with a predominant lesion in the left anterior descending coronary artery. ST depression with an upsloping ST segment was observed in patients with one-, two-, and three-vessel disease and it was the most common type of ST change in patients with single-vessel disease. Horizontal ST depression was most common in two-vessel disease and downsloping ST segment in three-vessel disease. There was a good correlation between the number of stenosed vessels and ST changes caused by exercise, expressed as the sum of ST segment displacements in twelve leads recorded immediately after the end of exercise (sigma/ST/) or as ST depression per unit increase in heart rate during exercise ("m" (ST/HR]. The latter was obtained by linear regression of ST displacement and heart rate measured at three or four different workloads in the lead with the greatest displacement of the ST segment. The mean values of sigma/ST/ were 0.58 +- 0.030 mV in single-vessel, 0.97 +- 0.41 mV in double-vessel and 1.58 +- 0. 46 mV in triple-vessel disease. The mean values of "m" (ST/HR) were 0.0024 +- 0.0013 mV X min-1 X beat-1 in single-vessel, 0.0042 +- 0.0012 in double-vessel, and 0.0078 +- 0.0033 in triple-vessel disease. These differences were highly significant (p less than 0.01 - 0.001) and there was only minimal overlap between the single- and triple-vessel groups. Digitalis caused a slight (statistically nonsignificant) increase in sigma/ST/ but not in "m" (ST/HR).     

Ejaculatory incompetence: a theoretical formulation and case illustration

Three theoretical formulations of ejaculatory incompetence have been proposed in the literature. They include: (1) aversive conditioned inhibition of the ejaculatory reflex, (2) an "autosexual" orientation associated with discrepant levels in the cognitive and physiological dimensions of sexual arousal, and (3) a discriminative learning model. These three models are discussed in relation to their theoretical and therapeutic implications. Clinical data supporting the discriminative view is presented.