Biomedical subjects
Publications and source records attributed to M J Marshall.
Progressive relaxation significantly moved elders toward a perception of internal locus of control. Progressive relaxation and activity programs significantly increased elders' self-esteem. Progressive relaxation was significantly more effective than the activity group in increasing self-esteem. Changes in locus of control and self-esteem were not correlated.
An immunocytochemical method using an antibody against 5-bromo-2'-deoxyuridine has been applied to the study of the kinetics of osteoclast nuclei on intact mouse parietal bones. Osteoclasts containing tartrate-resistant acid phosphatase show nuclei that are positive for the thymidine analogue within 24 hours of injection into four-day old mice. Labelled osteoclast nuclei decline in number with a half-life of 1.3 days, compatible with a random mechanism of cell death rather than a fixed lifespan. This is shorter than has previously been reported and the possible reasons for this are suggested. The main advantages compared with autoradiography are the shortened processing time and the large number of osteoclasts that can be examined per parietal bone.
A group of 5-day-old mice were injected intraperitoneally with (3-amino-1-hydroxypropylidine)-1,1-bisphosphonate (APD). Morphologic changes were observed in vitally stained osteoclasts on parietal bones 3 days later, and these were judged to be degenerative. At this time significantly increased numbers of nuclei per osteoclast and total numbers of osteoclast nuclei were observed. However, at 4 days after the injection of APD, the total numbers of osteoclasts were significantly reduced relative to controls. When parietal bones were maintained in culture, APD reduced osteoclast numbers and inhibited cell-mediated 45Ca2+ release. Exposure of bones to parathyroid hormone increased the number of osteoclasts counted 1 day later. This effect was not blocked by APD. Calcitonin prevented the reduction in osteoclast numbers due to APD in vitro. We conclude that APD has a direct effect on resorbing mouse osteoclasts.
Three experiments were conducted to assess the effects of the Stroop task (color-word incongruities) on observers' estimates of 30-sec. inspection periods. The experiments differed in psychophysical procedure; the three classic methods of production, reproduction, and verbal estimation were employed. Observers underestimated the passage of time, compared to doing nothing, when they were engaged on the Stroop task. However, judgments of duration on the Stroop task were shorter than those made in the control condition of naming color dots only when the method of production was employed. These findings are similar to results with mental arithmetic tasks and contribute to the understanding of the relationship between cognitive processing and time perception.
Osteoclasts were enumerated on the parietal bones of mice carrying combinations of alleles (mi, midi and +) at the microphthalmic locus. Homozygous mutants at this locus show varying degrees of osteopetrosis due to defective bone resorption. As the severity of the bone resorption defect increased across the genotypes, there was an increase in the total number of osteoclasts and also an increase in the proportion of uninucleate osteoclasts. In parietal bones incubated for 24 h with parathyroid hormone (PTH) there was no significant difference between osteopetrotic and normal bones in terms of the number of osteoclast nuclei that had taken part in fusion. When bones were incubated for 24 h in the absence of PTH the percentage of osteoclasts remaining was correlated inversely with the severity of the bone resorption defect. Thus, we suggest that the increased proportion of uninucleate osteoclasts in these mutants results from a shortened life span, reducing the time-dependent accumulation of nuclei. This implies a reduced efficiency of uninucleate osteoclasts over multinucleate ones and we speculate on the reason for this.
Osteoclastlike cells (OLCs) were recognized by their morphological, histochemical, and behavioral characteristics. These characteristics were initially observed in freshly isolated osteoclasts when neonatal rat bone cells were introduced into culture. Epithelioid cells proliferated during the first week to form a confluent layer. The cells' alkaline phosphatase content and ability to produce elevated levels of cyclic adenosine monophosphate in response to parathyroid hormone (PTH) led us to tentatively describe them as osteoblastlike cells. When a second addition of neonatal bone cells was made onto this confluent layer, OLCs were produced, their numbers increasing to a maximum 7 days later and dying out 3 weeks later. Mononuclear cells with similar characteristics to these multinuclear OLCs were observed and their production and disappearance closely paralleled that of the OLCs. Fusion of OLCs was observed. The conditions under which OLCs were produced are described.
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A novel staining procedure for enumerating osteoclasts on neonatal mouse calvaria with the vital fluorescent dye acridine orange is described. It has the advantage over Barnicot's neutral-red method in that the nuclei and cytoplasm of the osteoclast are stained differentially. The osteopetrotic calvarium (mi/mi) has fewer multinucleate osteoclasts than its normal counterpart (mi/+) and they are differently distributed. The osteopetrotic calvarium has more mononucleate cells which stain like osteoclasts with acridine orange than the normal calvarium and these cells also are differently distributed. These mononuclear cells may be mononuclear osteoclasts or their precursors. These observations suggest that the defect resulting in this osteopetrosis lies with osteoclast differentiation.
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The response of T and B lymphocytes to the mitogens PHA and LPS was studied in the Fatty/Orl-op rat. Whereas T and B cells from op/op spleen showed no lack of responsiveness compared with that of normal (op/+) littermate rats, the response of thymic cells to the T cell mitogen was lower in op/op rats over 12 days of age compared with normal rats of the same age. Osteopetrotic rats of 10 days and younger did not show this T cell deficiency. The responsiveness of T cells from op/op lymph nodes to PHA was less than that of normal rats at 12 days and older. Thus, though splenic T and B cell populations were well maintained in the adult op/op rat despite the severe depletion of marrow cells in this mutant, the thymus and lymph node T cell populations were qualitatively or quantitatively deficient. Since osteopetrotic obliteration of the marrow cavities precedes the appearance of the immune deficiency we suggest that the immune deficiency may be caused by a failure of T cell supply to the thymus and lymph nodes.
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H2 compatible allogeneic bone marrow cultured for four weeks was effective in inducing bone resorption when injected intravenously into osteopetrotic mi mouse. The active cell line or its progenitors can therefore be established in culture and is probably derived from a haematopoietic stem cell (HSC).
The question of whether there is a single pluripotent haemopoietic stem cell or a variety of stem cells each with a capacity for self-replication is still unresolved. Evidence from radiation-chimaeras and from patients with marrow grafts indicates that haemopoietic stem cells are not a homogeneous population. It is suggested that in marrow there is a variety of stem cells, some controlled by recognised factors and others by as yet unknown factors. It is postulated that some of these cells are pluripotent, whereas others are differentiated for a single line, so both polyphyleticists and monophyleticists may have been partly right.
Resorption of petrotic bone in osteopetrotic (mi/mi) mice was brought about by transplantation of bone marrow to X-irradiated recipients. In an attempt to learn more about the donor cell line involved in this process, both normal and defective marrow were used. The consequent repopulation of the lympho-myeloid complex was monitored by isoenzymes of glucose phosphate isomerase. The progress of normal marrow grafts was contrasted with that of a defective marrow (We/Wv). Despite the observation with We/Wv marrow showed reduced ability to form colonies in the spleen of an irradiated recipient, this marrow was as effective as normal marrow in inducing resorption of petrotic bone. The primordial stem cell for the osteoclast (haematopoietic stem cell?) is thus not a CFUS. Chimaeras with resolution of osteopetrosis by We/Wv bone marrow may exhibit erythropoiesis from residual stem cells of the host but leucocytes and platelets from the donor.
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Electrophoresis of cytosol prepared from normal and malignant tissue samples of uterine cervix and endometrium revealed interesting differences which may be relevant to the characteristic alterations in glucose metabolism associated with tumour development. Hexokinase II was detected in 30% of the cancer material from both sources, but in none of the samples of normal cervix. A duplet band of 6-phosphogluconate dehydrognease was seen in the majority of the cancer samples but in no sample of normal cervix; it appeared to be partly due to ageing of the sample, and is not phenotypically related to the malignant process. Analysis of genetic variance for phosphoglucomutase at the PGM1 locus revealed a highly significant excess of the PGM1-1 phenotype in patients with cancer of the endometrium, which may reflect susceptibility to endometrial cancer in patients with this phenotype. At the PGM2 locus, samples of malignant cervix were deficient in "Band f" compared with normal cervix samples, all of which showed this band. Conversely, gene products of the PGM3 locus were found in most samples of malignant cervix and a small minority of normal cervix samples. Compared with the isomorphic distribution of lactate dehydrogenase enzymes in normal uterine tissue, cancers showed a shift towards either a more anodal or a more cathodal pattern. The former may be associated with tumours enjoying a good oxygen supply, and the latter with tumours which, because of their depth or poor blood supply have to function under less aerobic conditions.
A new technique for the quantitation of isoenzymes was applied to assess the proportions of red cells in the circulation of parabiosed mice. Two parent-F1 hybrid combinations showing phosphoglucose isomerase polymorphism were examined at successive stages of parabiosis and after separation. Once red cell populations became mixed, 3 days after union, the ratio of red cell phenotypes was never significantly different from one partner to the other, although parental red cells became predominant after about 20 days. However, F1 hybrid red cells could always be detected. After separation of parabiosed mice there was a return to the original composition although this took longer than would be expected on the basis of reported red cell life span. Packed cell volume measurements indicated that a parental polycythaemia and F1 hybrid anaemia developed in one strain combination but not in the other. Evidence was adduced to support the hypothesis of a difference in red cell flux being responsible for the generation of this polycythaemia-anaemia.
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