A comparison of two treatments for depression: the antidepressive program vs. traditional therapy.

This study compared a traditional therapy for depression with Antidepressive therapy, a regime of meaningless, boring work designed to provoke the patient to an assertive expression of anger. The Ss were 32 neurotic and 24 psychotic patients at the Tuscaloosa, Alabama Veterans Administration Hospital. Improvement was measured by scores on the Purpose-In-Life Test (PIL) and the Self-Rating Depression Scale. All patient groups improved significantly within a 1-week period. Neurotics treated on the Antidepressive program improved significantly more than neurotics treated on the Traditional program. However, the data failed to indicate that either program was significantly more effective than the other in the treatment of psychotics.     

Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.

Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.     

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.     

IL-4 and IL-10 modulate autoimmune haemolytic anaemia in NZB mice

New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia (AIHA). Here the effect of injecting NZB mice with plasmids encoding IL-4 (pIL-4) or IL-10 (pIL-10) on NZB disease was tested. Both constructs delayed the development of anaemia as judged by increased haematocrit values as compared with controls, but neither altered the IgG1 to IgG2 red blood cell (RBC) bound autoantibody levels. The increased haematocrit value was associated temporally with increased RBC bound IgG in NZB mice treated with pIL-10, but not pIL-4. By contrast, up-regulation of splenic macrophage FcgammaRIIb2 mRNA was associated temporally with increased haematocrit values in NZB mice given pIL-4. However, no such increase occurred in NZB mice that inhaled a peptide containing a dominant T-cell epitope, although this treatment is known to bias the autoimmune response towards Th2 and to reduce the severity of anaemia. It is considered that IL-4 treatment, in part, ameliorates NZB anaemia by increasing the expression of the inhibitory FcgammaRIIb2 and thereby reducing the capacity of splenic macrophages to phagocytose autoantibody coated RBC, but that this mechanism does not explain the beneficial effects of the inhaled peptide.     

Three-dimensional tissue engineering of hyaline cartilage: comparison of adult nasal and articular chondrocytes

Adult chondrocytes are less chondrogenic than immature cells, yet it is likely that autologous cells from adult patients will be used clinically for cartilage engineering. The aim of this study was to compare the postexpansion chondrogenic potential of adult nasal and articular chondrocytes. Bovine or human chondrocytes were expanded in monolayer culture, seeded onto polyglycolic acid (PGA) scaffolds, and cultured for 40 days. Engineered cartilage constructs were processed for histological and quantitative analysis of the extracellular matrix and mRNA. Some engineered constructs were implanted in athymic mice for up to six additional weeks before analysis. Using adult bovine tissues as a cell source, nasal chondrocytes generated a matrix with significantly higher fractions of collagen type II and glycosaminoglycans as compared with articular chondrocytes. Human adult nasal chondrocytes proliferated approximately four times faster than human articular chondrocytes in monolayer culture, and had a markedly higher chondrogenic capacity, as assessed by the mRNA and protein analysis of in vitro-engineered constructs. Cartilage engineered from human nasal cells survived and grew during 6 weeks of implantation in vivo whereas articular cartilage constructs failed to survive. In conclusion, for adult patients nasal septum chondrocytes are a better cell source than articular chondrocytes for the in vitro engineering of autologous cartilage grafts. It remains to be established whether cartilage engineered from nasal cells can function effectively when implanted at an articular site.     

T-cell specificity in murine autoimmune haemolytic anaemia induced by rat red blood cells

Autoimmune haemolytic anaemia (AIHA) can be induced in mice by repeated injections with rat red blood cells (RBC). Here we describe the identification of rat and murine RBC antigens recognized by T-cells from mice with this disease. Splenic T-cells from mice with AIHA proliferated in response to multiple murine RBC membrane components, each of which is recognized by rat RBC induced autoantibodies. Thus, there were responses to murine autoantigen fractions that correspond in apparent molecular mass with the anion channel Band 3, with spectrin from the membrane skeleton and with the high and low molecular mass glycophorins, and the equivalent fractions from rat RBC also stimulated proliferation by T-cells. It was confirmed that purified Band 3 from murine and rat RBC also elicited responses. In contrast with the results in AIHA, T-cells from healthy control mice failed to respond to the antigens from either species, with the exception of proliferation induced by murine spectrin in one experiment and weak responses elicited by rat Band 3. It is suggested that T-cells activated by multiple cross-reactions between rat and murine RBC proteins, and by epitope spreading, are necessary to drive autoantibody production in this model of AIHA.     

Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.

We have examined the effects of 1,25(OH)2D3 on T-cell populations isolated by buoyant density and E rosetting from human tonsils. Cell proliferation was assessed by measuring the incorporation of 125iododeoxyuridine; interleukin-2 (IL-2) production was measured using an IL-2-dependent cell line, and the number of 1,25(OH)2D3 receptors was measured by whole-cell nuclear association assay. At a concentration of 10(-7) M, 1,25(OH)2D3 inhibited mitogen-induced T-cell proliferation in all E+ T-cell populations. This effect was more pronounced in the cells from the intermediate and high density layers and was reflected both in cell proliferative responses and in relative IL-2 synthesis. By adding the 1,25(OH)2D3 during the course of the mitogen assay, we demonstrated that activation of the T cell precedes the 1,25(OH)2D3-mediated inhibition. Cells that had been preincubated with mitogen in the presence of the 1,25(OH)2D3 were refractory to further stimulation by mitogens. Receptors for 1,25(OH)2D3 could not be detected in unstimulated T cells. However, activation led to the expression of high-affinity receptors for 1,25(OH)2D3. Co-incubation of the cells with mitogen and 1,25(OH)2D3 increased the number of receptors compared with mitogen alone. The effects provide further evidence for the hypothesis that 1,25(OH)2D3 is an important potential modulator of the immune system through its action on T cells. Taking our observations in conjunction with the known capacity of monocytes to hydroxylate the precursor metabolite (and thus synthesize the active form of cholecalciferol), the results support the suggestion that 1,25(OH)2D3 plays a role as a local mediator of mononuclear phagocyte-T cell interaction in human lymphomedullary tissues.     

The partnership between breast cancer advocates and scientists

The National Breast Cancer Coalition (NBCC) is a grassroots organization that represents breast cancer advocates and is committed to eradicating breast cancer. NBCC defines a breast cancer advocate as someone who has been personally affected by the disease (e.g., a breast cancer survivor, family member, or friend), represents a constituency, and is motivated to join the fight against the disease. One of the organization's goals is to ensure that breast cancer advocates have a seat at the table when decisions are made about breast cancer research and policy. To accomplish this goal, NBCC educates advocates so that they can participate in and make meaningful contributions to legislative, scientific, and regulatory decision-making bodies. In addition to creating educational opportunities for advocates, NBCC has spearheaded several initiatives designed to directly increase the quality and quantity of breast cancer research. NBCC has also played a major role in making funding available to breast cancer researchers. Two of NBCC's most notable programs include Project LEAD, an intensive science-training course for breast cancer advocates, and the Environmental Initiative, a collection of activities designed to improve research into the relationship between breast cancer and the environment. Breast cancer advocates trained by NBCC have partnered with the scientific community and individual scientists to improve the peer review, design, and implementation of breast cancer research.     

Distribution of fusimotor axons to intrafusal muscle fibres in cat tenuissimus spindles as determined by the glycogen-depletion method.

1. The distribution of fusimotor axons to bag1, bag2 and chain muscle fibres in cat tenuissimus spindles has been studied using a modification of the glycogen-depletion technique of Edstrrom & Kugelberg (1968). Single fusimotor axons were stimulated intermittently at 40-100/sec for long periods (30-90 sec) during blood occlusion. Portions of muscle containing the activated spindles were quick-frozen, fixed in absolute ethanol during freeze-substitution, and then embedded in paraffin wax. Serial transverse sections were stained for glycogen using the periodic acid-Schiff method, and examined for depletion. 2. Dynamic gamma axons (i.e. those that increase the dynamic index of primary-ending responses to ramp stretches of large amplitude) depleted bag1 fibres almost exclusively. 3. Static gamma axons (i.e. those that reduce or abolish the dynamic index) depleted both bag and chain fibres. Bag1 and bag2 fibres were depleted about equally. 4. A single static gamma axon may activate both bag and chain fibres in one spindle (the most common pattern), chain fibres only in another, and bag fibres only in a third spindle. 5. Static gamma axons with conduction velocities less than 25 m/sec also had a non-selective distribution, but no depletion was observed in bag2 fibres. 6. The zones of depletion produced by dynamic gamma axons were distributed more or less equally in the intra- and extracapsular parts of spindle poles, whereas those produced by static gamma axons were mainly intracapsular. 7. The results are compared with the glycogen-depletion studies of Brown & Butler (1973, 1975) and our own study of the distribution of static gamma axons to spindles in which all other motor axons had degenerated (Barker, Emonet-Dénand, Laporte, Proske & Stacey, 1973). The implications of the finding that both static gamma and dynamic gamma axons activate bag1 fibres are discussed.     

Quantification of the morphological features of a full microvascular network

Investigations into the changes that occur in microvasculature following the surgical procedure called delay have brought about the need for a computer system capable of quantifying the morphological features of a full microvascular network in terms of average vessel length, diameter, and tortuosity. Both the formulaic conventions that have been developed to measure these quantities as well as their implementation in the form of a HP-9000/UNIX based computer software system that we developed specifically for this purpose are discussed. Reliability studies performed using the final system to measure the microcirculatory network of a mouse latissmus dorsi muscle (LDM) showed 95% confidence intervals within 5% of means and coefficients of variability within 7% of means for all quantities measured in large (150–300 μm), medium (50–150 μm), and small (<50 μm) diameter vessels. These variations were significantly smaller than the changes that were observed in a preliminary study comparing these microvascular network parameters before and after delay in the hairless mouse LDM, showing the proposed quantification methods to be well suited to the study of the microvascular changes following delay. It is hoped that the formulaic conventions, implementation process and reliability data will provide a useful comparison for other researchers interested in measuring similar features of microcirculatory networks.