Differentiation of blast cells from a Down's syndrome patient with transient myeloproliferative disorder

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.     

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.     

Aldosterone production and hormone responsiveness in adrenal glomerulosa cells from cows of different ages

Aldosterone production by suspensions of adrenal glomerulosa cells obtained from young and old cows was measured. Basal steroidogenesis was lower in cells from old cows, as were the responses to angiotensin II (AII), potassium, ACTH and dibutyryl cyclic AMP. Receptors for AII and aldosterone production from added progesterone were the same in old and young cells. Synthesis of pregnenolone from endogenous precursor, the 'early pathway' of aldosteronogenesis, was lower in old cells than in young. AII-stimulated incorporation of 32P into phosphatidylinositol and the change in 45Ca2+ flux induced by AII were diminished in old cells. Overall protein synthesis, measured by 3H leucine incorporation, was lower in old cells than young, but was not affected by AII in either. Diminished responsiveness of adrenal glomerulosa cells from old animals results from a change in postreceptor events that affect the early pathway of aldosteronogenesis.     

Evaluation of an improved fiberoptics luminescence skin monitor with background correction

In this work, an improved version of a fiberoptics luminescence monitor, the prototype luminoscope II, is evaluated for in situ quantitative measurements. The instrument was developed to detect traces of luminescing organic contaminants on skin. An electronic background-nulling system was designed and incorporated into the instrument to compensate for various skin background emissions. A dose-response curve for a coal liquid spotted on mouse skin was established. The results illustrated the usefulness of the instrument for in vivo detection of organic materials on laboratory mouse skin.     

A case-referent study of lung cancer, occupational exposures and smoking. II. Role of asbestos exposure

In a hospital-based case-referent study of 176 incident lung cancer cases, ascertained during a five-year period from two county hospitals, the role of asbestos exposure and smoking has been studied. Information on asbestos exposure was obtained from personal interviews, and allocated to four exposure categories, according to the intensity and duration of the exposure. Twenty-five percent of the cases and 10% of the referents had been moderately to heavily exposed to asbestos during their working career. A statistically significant trend in risk ratio related to the degree of exposure was observed, with a more than fourfold risk among the heavily exposed. The strongest association was found between asbestos exposure and small cell carcinoma, and the weakest association between asbestos exposure and adenocarcinoma. Very high risk ratios were observed among asbestos-exposed subjects who were heavy smokers, and the interaction observed between asbestos and smoking conformed more closely to a multiplicative model than to an additive one. The results suggest that the observed association between lung cancer and occupational exposures in this study was, to a large extent, due to asbestos exposure. Information on such exposure was missing in 90% of the medical records of these patients.     

Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit.

The effects of discrete bilateral ibotenic acid lesions to 3 areas of striatum were examined on a conditional visual discrimination task involving temporal frequency (SLOW vs FAST flashes) that had previously been shown to be sensitive to the effects of dorsal striatal dopamine depletion. Two of the groups, namely, those with nucleus accumbens (ACC) and lateral caudate-putamen (LCP) lesions, were very disrupted in the acquisition of the task. The nature of the respective impairments of the 2 groups was dissociable, however. The performance of the ACC group could be improved either by manipulations of stimulus duration or inter-stimulus interval, implying an attentional deficit. In contrast, the rats with lesions of the LCP were not significantly improved by any of the behavioural challenges. Their performance was characterised by a bias to respond to the SLOW discriminandum. Under conditions of non-reward, the LCP group extinguished their responding at a similar rate to control rats whereas the ACC group were very much more persistent. Lesions of the medial caudate-putamen failed to affect any index of performance significantly. These data suggest that the LCP is necessary for the acquisition of arbitrary stimulus-response rules and that damage to an equivalent area in humans, such as in Huntington's disease, may explain deficits of procedural memory. The second part of the experiment investigated the effects of ACC lesions on established performance of the schedule. The lesioned group behaved identically to the ACC group that had been lesioned prior to acquisition, both in terms of accuracy and degree of persistence in extinction, further implying the role of attentional factors and inflexibility in the lesion-induced deficit.