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The release of cAMP and lactate from the HCG and PGE 1 stimulated prepubertal rat ovary has been studied using a superfusion technique. The continuous presence of HCG (50 IU/ml) or PGE 1 (10 μg/ml) in the medium led to an increased but transient release of cAMP. The release of lactate also rose as a consequence of the stimulus but in this case the release stayed at an elevated level during the whole experimental period. Experiments with HCG (10 IU/ml) applied as 40-minute pulses spaced 240 minutes apart showed the ovaries to be refractory to the second stimulus. Contrary to this PGE 1 (10 μg/ml) administered under the same conditions elicited a renewed response to the second pulse. Despite refractoriness to a second HCG pulse, PGE 1 applied after HCG, could evoke a new increased release of cAMP. HCG applied after PGE 1 also gave rise to a renewed response in accordance with the experiments with double PGE 1 pulses. In these double pulse experiments, the response to the second challenge was always considerably suppressed in relation to the first.

The actions of LH (NIH-LH-B8) and FSH (NIH-FSH-S9) on the cyclic AMP (cAMP) system in ovaries of 23–24 day old rats have been analyzed. An intravenous injection of LH increased ovarian cAMP levels in vivo after only 20 seconds. Maximal cAMP levels were seen after 15 min. Addition of LH or FSH in vitro to the isolated ovaries produced dose dependent increases of cAMP in the tissue as well as in the incubation medium. Low concentrations of LH caused a release of cAMP into the incubation medium without any detectable change in the tissue levels. The levels of cAMP in the incubation media for all concentrations of FSH were lower than the tissue levels, whereas for LH the opposite was found. In time-course experiments where the concentrations of LH (10 μg/ml) and FSH (100 μg/ml) were chosen to give similar tissue levels of cAMP, the release of the cyclic nucleotide into the incubation medium was approximately 2–3 times greater for LH than for FSH at the time periods studied (5–240 min). When LH and FSH were tested together in high concentrations, their effects were additive. When the ovaries were first incubated with FSH for 120 min followed by an incubation with LH, the stimulatory effect of LH was considerably reduced. When the order of the incubations was reversed, however, LH did not change the response to FSH. The results show that both LH and FSH have intrinsic effects on the cAMP system in the prepubertal rat ovary, but that the effects of the two gonadotrophins are not identical.

A new method is proposed for the determination of energies of activation of oxidation of metals and alloys. Metals are oxidized under conditions of linearly increasing temperature, and the activation energy may be determined from one single oxidation run. In addition the method also gives the approximate temperature regions in which different rate laws of oxidation are found. The described method has been applled to high-temperature oxidation of nickel, zirconium, copper, and titanium. (auth)

Prednimustine and chlorambucil induce dose- and time-dependent cell death in V79 Chinese hamster cells in vitro. Prednimustine was found to be 3-4 times more potent than either chlorambucil or an equimolar mixture of its components chlorambucil and prednisolone after 24 h treatment. Prednimustine was hydrolyzed to prednisolone and chlorambucil in the system, and the concentration of prednimustine was reduced by one half within 15 h. Prednisolone was not further metabolized, but chlorambucil was rapidly inactivated by dechlorination, the half-life being 2.5 h. No dechlorinated prednimustine was formed during the experiments. The higher stability of prednimustine than chlorambucil is probably due to protective binding to different serum proteins from those that bind chlorambucil. Substitution of fetal calf serum by human serum albumin revealed that hydrolysis of prednimustine is catalyzed by esterases present in the serum. In similar substitution experiments cell survival studies indicated that prednimustine itself was not cytotoxic. Rather, cytotoxicity was found to correlate with hydrolysis to chlorambucil. Thus, it appears that the prolonged availability of chlorambucil is responsible for the increased potency of prednimustine in this system.

THE PRESENT STUDY is part of a broad program to investigate the concept that schizophrenia is an immunologic disorder. We postulate that a unique globulin (antibody) in the serum of schizophrenic persons becomes attached to neural cell nuclei (antigen) in certain regions of the brain, principally the rostral forebrain region, to cause physiologic changes and associated psychotic behavior.1The specificity of this reaction and differences between the globulin demonstrated in schizophrenic patients and that found in patients with other diseases were described.1 Previous reports by Heath and co-workers2,3described the isolation of a protein fraction, labeled taraxein, from the serum of schizophrenic patients. When given intravenously, this substance induced catatonia and abnormal electroencephalograms (EEG) from the rostral forebrain region of Macaca rhesus monkeys, and caused symptoms of schizophrenia in prisoner-volunteers.4Another study compared the characteristics and activity of

OBSERVATIONS in our laboratories that sera of schizophrenic patients contain a unique globulin (probably antibody) capable of attachment to specific sites of the brain (antigen) support our postulate that schizophrenia is an immunologic disorder. 1-3 The findings, however, do not establish a causeand-effect relation between the globulin and clinical symptoms of the disease. We have injected serum globulins of schizophrenic patients, normal healthy control subjects, and control subjects with diseases other than schizophrenia into the ventricles of rhesus monkeys prepared with depth and cortical electrodes and intraventricular cannulas. 3-5 Abnormal electroencephalograms (EEG) from the septal region and basal caudate nucleus with concomitant abnormal behavior were induced consistently by serum globulins of acute schizophrenic patients, and sometimes by globulins of chronic schizophrenic patients. Similar aberrations followed intravenous injection of the serum globulins. Fluorescent antibody techniques showed that the brains of the monkey