Chronic thrombocytopenia is induced in dogs by development of cross-reacting antibodies to the MpL ligand.

The MpL ligand (ML) is a potent stimulus for thrombocytopoiesis. To create an in vivo model of ML deficiency, we injected dogs with a recombinant human ML (rhML) to determine whether cross-reacting antibodies would develop and cause thrombocytopenia. RhML was administered subcutaneously for 8 weeks to three normal dogs (mean platelets, 197 +/- 5.5 x 10(3)/microL). Within 5 days their platelet counts were twice baseline and greater than 4 times baseline by day 21. Then, uniformly, chronic thrombocytopenia developed. At 1 week after terminating rhML, mean platelets were 0.5 times baseline and at 2 months 0.25 times baseline. Early in treatment, marrow biopsies showed increased megakaryocyte number and ploidy, which decreased as platelets declined. Paralleling these changes, high titer anti-rhML antibodies developed. Autologous 51Cr-labeled platelet recovery and survival measurements indicated that the thrombocytopenia was principally due to decreased production. Infusion of plasma from the thrombocytopenic dogs into two normal dogs and one dog previously made thrombocytopenic with rhML caused platelet counts to fall gradually. These studies show that dogs with anti-rhML antibodies develop thrombocytopenia, presumably because the cross-reacting antibodies neutralize endogenous canine ML. The results strongly suggest that ML plays an essential role in maintaining normal platelet levels.

A brief history of positron emission tomography.

Shortly before the time of this writing, Michael Ter-Pogossian, PhD, passed away at the age of 71. He was considered by many to be the father of PET and is best known for experiments beginning in the 1950s, which led to the development of PET as a practical diagnostic tool (Fig. 1). In my research of the literature for this article, Dr. Ter-Pogossian's name appeared frequently on many of the landmark publications and I have drawn heavily from his work as a historian and scientist. His death is a great loss to the nuclear medicine community. It is with his achievements in mind, as well as the achievements of many other outstanding scientists, that I have written this article. I have tried to be as accurate as possible in my documentation of events as well as in my interpretation of their significance. I trust that the reader will gain as much as I have from this endeavor.

Maternal age and parity correlates of handedness: gender, but no parental handedness modulation of effects.

Mothers supplied information on the handedness of a total of 1079 children (238 left handed, 841 right handed), and also reported information on the handedness of the biological parents, parental ages when each child was born, parity, and birth complications. A MANOVA, employing offspring handedness and parental handedness (presence versus absence of at least one left handed) as the bases of classification, and parity, maternal age, paternal age, and a birth stress composite score as dependent measures, was applied to the data of female and male offspring separately. For females, there was a significant multivariate effect for handedness, but no effect of parental handedness nor any interaction of the handedness and parental handedness factors. Univariate ANOVAs, following the multivariate analysis, showed significant effects of handedness for the maternal age and parity measures, but not for paternal age or birth stress composite score. The analysis for males showed no significant multivariate or univariate effects. The data suggest, that in the absence of high risk parity and maternal age over 32, only about 7.8% of females are left handed. This implies that as many as 29% or so of female left handers may owe their sinistrality to factors associated with high risk parity and maternal ages over 32.

Social isolation does not alter brain regional benzodiazepine binding site numbers, affinity and coupling in the rat.

Male Sprague-Dawley rats were differentially housed for 21 days immediately after weaning. Isolated animals showed a selective suppression of exploration of the light side of a two compartment box; spending significantly less time in the light, and making fewer transitions between the light and dark compartments compared to socially reared controls. However, both basal and GABA-stimulated [3H] flunitrazepam binding was unaltered in the frontal cortex, hippocampus, amygdala and cerebellum following social isolation. These results are discussed in relation to other studies on central benzodiazepine receptor changes following a variety of experimental stressors.

Left handedness and immune disorders.

The Geschwind-Behan hypothesis that immune disorder (IMD) is more common among left than among right handed persons was tested in a sample of 3080 college students. Subjects indicated, for each of a list of IMDs, whether they: (1) had no reason to believe they had the disorder; (2) thought they might have the disorder; (3) had the disorder diagnosed by a physician; or (4) had had a disorder diagnosed and treated by a physician. Females reported significantly more IMDs than did males. Among females, the distribution of responses across the four response categories was not different for left and right handers, but IMD was significantly higher among left handed females when only the extreme categories were considered. Among males, no handedness effect was seen across the four categories, nor when only the extreme categories were considered. Laterality quotients, from the Edinburgh Handedness Inventory, were unrelated to IMD reports in both sexes. Results provide no real support for the Geschwind-Behan hypothesis. Even in the case of the extreme categories of IMD reports of females, the association of left handedness (for writing) and IMD accounts for only three-tenths of one percent of the variance.

An investigation of immune system disorder as a "marker" for anomalous dominance.

Geschwind and Galaburda (1987) proposed that immune disorder (ID) susceptibility, along with left handedness and familial sinistrality (FS), is a "marker" for anomalous dominance. The theory predicts lesser left lateralization for language processes, lessened left hemisphere abilities, and enhanced right hemisphere abilities. We assessed language laterality (dichotic consonant vowel task) and performances on spatial and verbal tasks. Subjects were 128 college students. The factors of handedness, sex, FS, and immune disorder history (negative or positive) were perfectly counterbalanced. Left-handers were significantly less lateralized for language and scored lower than right-handers on the spatial tasks. Females scored lower on mental rotation than males, but performed comparably to males on the spatial relations task. The only effect of ID was by way of interaction with FS on both spatial tasks--subjects who were either negative or positive on both FS and ID status factors scored significantly higher than subjects negative for one but positive for the other factor. A speculative explanatory model for this interaction was proposed. The model incorporates the notion that FS and ID factors are comparably correlated, but in opposite directions, with hormonal factors implicated by other research as relevant for spatial ability differences. Finally, no support for the "anomalous dominance" hypothesis predictions was found.

Dual radionuclide subtraction imaging of the spleen.

Dual radionuclide subtraction imaging of the spleen using 67Ga citrate and 99mTc is useful in further delineating lesions that are identified on either a routine radiogallium survey or on a conventional sulfur colloid liver-spleen image. Better anatomic localization of left subphrenic abscesses may be obtained. Differentiation of tumors and abscesses from less serious lesions such as cysts, infarcts, and hematomas is possible. We have found this technique to be generally applicable to any organ that can be selectively imaged using a technetium radiopharmaceutical, including the liver, bones, and kidneys. In addition, we are currently evaluating thallium-pertechnetate subtraction imaging in the evaluation of parathyroid adenomata.

Computerized double-tracer subtraction scanning with gallium-67 citrate in inflammatory diseases.

A gallium-67/technetium-99m subtraction technique was used with a variable weighting factor. That is, each image was separately set to 100%. Varying amounts of the Tc-99m images were subtracted from those of Ga-67. A total of 95 patients who had radiogallium scanning for suspected inflammatory disease were studied by the subtraction technique. Thirty of these patients had abnormal Tc-99m pyrophosphate bone scans, while 20 had abnormal radiogallium abdominal foci; 45 had defects in liver, spleen, or kidney images. The subtraction technique with variable weighting was highly successful in enhancing hot-spot visibility, and in providing information as to the anatomic location of the defect.