Optic flow signals in extrastriate area MST: comparison of perceptual and neuronal sensitivity

The medial superior temporal area of extrastriate cortex (MST) contains signals selective for nonuniform patterns of motion often termed "optic flow." The presence of such tuning, however, does not necessarily imply involvement in perception. To quantify the relationship between these selective neuronal signals and the perception of optic flow, we designed a discrimination task that allowed us to simultaneously record neuronal and behavioral sensitivities to near-threshold optic flow stimuli tailored to MST cells' preferences. In this two-alternative forced-choice task, we controlled the salience of globally opposite patterns (e.g., expansion and contraction) by varying the coherence of the motion. Using these stimuli, we could both relate the sensitivity of neuronal signals in MST to the animal's behavioral sensitivity and also measure trial-by-trial correlation between neuronal signals and behavioral choices. Neurons in MST showed a wide range of sensitivities to these complex motion stimuli. Many neurons had sensitivities equal or superior to the monkey's threshold. On the other hand, trial-by-trial correlation between neuronal discharge and choice ("choice probability") was weak or nonexistent in our data. Together, these results lead us to conclude that MST contains sufficient information for threshold judgments of optic flow; however, the role of MST activity in optic flow discriminations may be less direct than in other visual motion tasks previously described by other laboratories.     

Inter- and intraspecific placentae in sheep, goats and sheep-goat chimaeras.

These studies compared inter- and intraspecific placentae during implantation and at full-term in sheep, goats and interspecific sheep-goat chimaeras. Histological sections prepared from intra- and interspecific day-26, 32 and 36 placentae in ewes and does indicated an altered ability of the trophoblast to invade the maternal caruncle in interspecific pregnancies. Two sheep-in-goat pregnancies were less, and two goat-in-sheep pregnancies were more, invasive than homologous pregnancies. Caprine pregnancies in chimaeras generally terminated before timed samples could be obtained, but biopsy samples collected at laparotomy between days 42 and 48 demonstrated both normal and abnormal placentation in chimaeras after breedings to rams. In six of 11 full-term fetal placentae from ovine pregnancies in chimaeras, there was abnormal retention of maternal caruncular tissue to the extent that macroscopic lesions were visible on the surface of the fetal cotyledons. Histological observations indicated that proliferation of maternal septa and hyalinization of maternal vessels had occurred at the expense of the fetal villi. Overall, the results suggested that the physiological events that regulate implantation are different in the two species, despite anatomical similarities between the ovine and caprine placenta. The caprine conceptus is likely to be rejected in the ovine or chimaeric uterus because of its over-invasiveness in the early stages of implantation, whereas the ovine conceptus can survive in the potentially chimaeric uterus.     

Identification and isolation of a common tumor-associated molecule using monoclonal antibody

A monoclonal antibody, 16B-13, derived from the immunization of BALB/c mice with a lung tumor line, immunoprecipitates a common tumor-associated molecule with an apparent mol. wt of 37,000 from lactoperoxidase-ionated lung carcinoma, colon carcinoma, gastric carcinoma, brest carcinoma, melanoma and lymphona cells, but not from normal fibroblasts. Analysis by two-dimensional gel electrophoresis of the cell surface-labeled 16B-13 antigen from a colorectal and a melanoma cell line reveals four components with similar mol. wts but with different isoelectric points. The antigen purified froma a colorectal carcinoma cell line by immunoaffinity chromatography was shown to be a 37,000 mol. wt polypeptide similar to that obtained by the lactoperoxidase-labeling procedure. However, the purified antigen from the melanoma cell line shows the presence of a 65,000 mol. wt polypeptide and the loss of the 37,000 mol. wt component as detected by Comassie blue staining and immunoprecipitation.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

Modulation of immune responses to Mycobacterium bovis in cattle depleted of WC1(+) gamma delta T cells

It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4(+) T cells produce Th1 cytokines, such as gamma interferon (IFN-gamma), in response to mycobacterial antigens and that the cytolytic activity of CD8(+) cells toward infected macrophages is important. However, the extent and manner in which gamma delta T cells participate in this response remain unclear. In ruminants, gamma delta T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1(+) gamma delta T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1(+) gamma delta T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1(+)-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1(+) gamma delta T cells, which become significantly activated (CD25(+)) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1(+)-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1(+) gamma delta TCR(+) cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis--a hypothesis supported by the decreased innate production of IFN-gamma, which was observed in WC1(+)-depleted calves.     

Cystadenoma with mesenchymal stroma (CMS) in the liver and bile ducts. A clinicopathologic study of 17 cases, 4 with malignant change

This study of 17 cases describes a homogeneous clinicopathologic group of tumors previously subsumed under the general term, hepatobiliary cystadenoma. This unique group of neoplasms that the authors have termed "cystadenoma with mesenchymal stroma" (CMS), occurred exclusively in women and showed two essential tumor components: a cyst lining of columnar to cuboidal, mucin secreting epithelium; and a moderately to densely cellular stroma composed of spindle (rarely oval) cells. The stromal element appeared similar to primitive mesenchyme, both on light and electron microscopic study, showing variable differentiation toward fibroblasts, smooth muscle, adipose tissue and capillaries. Cases of hepatobiliary "cystadenoma" in the literature with histology similar to CMS had similar sex and age incidences, while histologically dissimilar cases, lacking the mesenchymal stroma, had significantly different parameters. Four cases of CMS in this series showed malignant change that was manifested as papillary adenocarcinoma, suggesting the need for complete surgical removal of these premalignant neoplasms.     

The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Community care staff attitudes towards delivering a falls prevention exercise intervention to community care clients

Millions of older people world-wide receive community care services in their home to assist them to live independently. These services often include personal care, domestic assistance and social support which are delivered by non-university trained staff, and are frequently long term. Older people receiving community care services fall 50% more often than individuals of similar age not receiving services. Yet, few ongoing community care services include exercise programs to reduce falls in this population. We conducted an earlier study to examine the feasibility of community care staff delivering a falls prevention program. A critical finding was that while some of the assessment and support staff responsible for service delivery delivered the falls prevention exercise program to one or two clients, others delivered to none. Therefore, the aim of this qualitative sub-study was to understand reasons for this variation. Semi-structured interviews were conducted with 25 participating support staff and assessors from 10 community care organisations. Staff who had successfully delivered the intervention to their clients perceived themselves as capable and that it would benefit their clients. Older clients who were positive, motivated and wanted to improve were perceived to be more likely to participate. Staff who had worked at their organisation for at least 5 years were also more likely to deliver the program compared to those that had only worked up to 2 years. Staff that did not deliver the intervention to anyone were more risk averse, did not feel confident enough to deliver the program and perceived their clients as not suitable due to age and frailty. Experienced staff who are confident and have positive ageing attitudes are most likely to deliver falls prevention programs in a home care organisation.