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S Williams

Publications and source records attributed to S Williams.

At least 379 records · Page 21Linked to original sources

Rhythmic firing of medial septum non-cholinergic neurons.

The presence of theta rhythm (5-10 Hz) in the hippocampus has been shown to enable long-term potentiation, a synaptic mechanism which has been proposed to underlie learning and memory. Medial septum cholinergic and GABAergic neurons that project to the hippocampus have been hypothesized to play conjointly a major role in the genesis of this rhythm. Building upon previous studies that have established the electrophysiological criteria for distinguishing cholinergic and non-cholinergic neurons in this area, it is demonstrated here that medial septum non-cholinergic neurons, putatively GABAergic, have the ability to discharge in rhythmic clusters of action potentials occurring at frequencies ranging from 1 to 8 Hz. Within the clusters, the firing frequency of action potentials varied between 13 and 57 Hz in a voltage-dependent manner. In addition, small voltage-dependent subthreshold membrane potential oscillations (16-54 Hz) were observed between clusters. Both subthreshold oscillations and clusters were eliminated by tetrodotoxin at 1 microM. These results indicate that non-cholinergic medial septum neurons could convey to the hippocampus not only theta but also higher frequency rhythmicity in the beta-gamma range (20-60 Hz).

Animals↗

The role of tumor necrosis factor receptors in tumor necrosis factor-alpha-mediated cytolysis of ovarian cancer cell lines.

OBJECTIVE: Our purpose was to define the expression of tumor necrosis factor receptors on ovarian cancer cells and determine what role these receptors play in tumor necrosis factor-alpha-mediated cytolysis. STUDY DESIGN: Cell surface expression of tumor necrosis factor-alpha receptors was determined on ovarian cancer cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780 by a tumor necrosis factor-alpha-binding assay that used iodine 125-labeled tumor necrosis factor-alpha. Monoclonal antibodies specific for the 55 to 60 kd (TR60) and 75 to 80 kd (TR80) tumor necrosis factor receptors were used to determine the relative density of each receptor type. To elucidate which receptor(s) was responsible for mediating the signal for cytolysis, 24-hour MTT cytolytic assays that used tumor necrosis factor-alpha and emetine were performed in the presence or absence of receptor-specific monoclonal antibodies. RESULTS: The four ovarian cell lines expressed a similar number of surface receptors, 4500 to 7000 per cell, had similar dissociation constants, 0.3 to 0.6 nmol/L, and expressed predominately the TR60 receptor subtype. Receptor function studies showed that the presence of the monoclonal antibody to the TR60 receptor completely inhibited tumor necrosis factor-alpha-mediated cytolysis, whereas the monoclonal antibody to the TR80 receptor only partially blocked cytolysis. CONCLUSIONS: Ovarian cancer cell lines express both tumor necrosis factor receptors, with the TR60 receptor being the dominant subtype. Tumor necrosis factor-alpha-mediated cytolysis appears to be dependent on the presence of a functional TR60 receptor. The TR80 receptor does not appear requisite for cytolysis; however, a complementary role cannot be excluded. Manipulation of tumor necrosis factor receptor subtypes on ovarian cancer cells may enhance the cytotoxic effects, thus improving the therapeutic efficacy of tumor necrosis factor-alpha.

Antibodies, Monoclonal↗

Growth modulatory effects of granulocyte-macrophage colony-stimulating factor on human cell lines derived from gynecologic malignancies.

OBJECTIVE: In spite of increased expression of granulocyte-macrophage colony-stimulating factor surface receptors on solid tumors, the growth modulatory effects of granulocyte-macrophage colony-stimulating factor have not been well defined in gynecologic malignancies. We assessed the in vitro growth effects of granulocyte-macrophage colony-stimulating factor on such cell lines. STUDY DESIGN: By use of a chromium 51 incorporation assay the in vitro growth effects of granulocyte-macrophage colony-stimulating factor on 12 cell lines derived from human malignancies were measured. RESULTS: No growth stimulatory or inhibitory effect was mediated by granulocyte-macrophage colony-stimulating factor on six cell lines, whereas three lines showed consistent but not statistically significant dose-dependent growth stimulation. There was, however, a statistically significant increase in growth of short duration in three other cell lines at clinically relevant doses of granulocyte-macrophage colony-stimulating factor. Fluorometric cell cycle analysis demonstrated no change in cell-cycle distribution. CONCLUSION: Within this in vitro system, stimulation of gynecologic malignancies in patients receiving granulocyte-macrophage colony-stimulating factor for mitigation of the myelosuppressive effects of cytotoxic chemotherapy does not appear to be widespread nor sustained beyond 48 hours.

Cell Cycle↗

Implementation of a breast and cervical cancer screening program in a public hospital emergency department. Cancer Control Center of Harlem.

STUDY OBJECTIVE: To assess the feasibility and yields of screening for breast and cervical cancer in an urban public hospital emergency department. METHODS: Women who presented to the ED of a large, urban public hospital during the study period with nonurgent conditions were eligible for a Papanicolaou test (Pap smear) and a clinical breast examination (CBE) if they were 18 years of age or older and for a mammogram if they were 40 years of age or older, provided they had not had the screening examination within the past year. The Pap smear and CBE were performed by a nurse, and mammography was scheduled for a later date. Women with gynecologic complaints were excluded. RESULTS: On the basis of screening history, medical status, and age, 1,850 (32%) of the 5,830 women seen in the ER during the 23-month study period were eligible for both mammography and CBE, and 2,361 (41%) were eligible for Pap smears. Of these women, 116 (6%) completed mammography and CBE, and 644 (27%) received Pap smears. Among screened women, 10 (9%) and 20 (3%), respectively, had results that were suspicious or positive for breast or cervical cancer. Follow-up rates were low: 20% for breast screening and 50% for Pap smears. Among those receiving follow-up, 1 woman was found to have breast cancer and 8 were found to have cervical neoplasia. CONCLUSION: ED cancer screening was feasible and yielded a high rate of cancer detection. Program efficiency was hampered by low volume and high numbers of patients lost to follow-up after abnormal screening results. Greater integration into the acute care setting and more intensive recruitment and follow-up strategies are needed to maximize the potential yield and cost effectiveness of such programs.

Adolescent↗

Changing femoral geometry in growing girls: a cross-sectional DEXA study.

In elderly women, a long hip axis length has been shown to increase the risk of hip fracture. However, to date, few measurements of hip geometry have been reported in children and adolescents. The present cross-sectional dual-energy X-ray absorptiometry (DEXA) study of 200 girls aged 3-16 years was undertaken to determine at what age adult hip geometry is achieved and to examine possible influences of anthropometry and body composition on the development of femur axis length (FAL) and femur width (FW) during growth. Adult values for FAL and FW were achieved by age 15 years. Age, height, lean tissue mass, total body bone mineral content (BMC), weight, FW, neck of femur bone mineral density (BMD), and fat were each strongly associated with FAL (p < 0.001), the highest correlations being with age (r = 0.917) and height (r = 0.906). However, after adjusting for age and height, only lean tissue mass, weight, and fat mass remained significantly associated with FAL, suggesting that bone mineral accrual does not influence variance in FAL. Our results also suggested that fat mass and weight per se tended to have greater influence on FW than on FAL in age- and height-adjusted data. Twin studies indicate that 20% of adult hip axis length is associated with environmental factors. We therefore conclude that any environmental effects of physical activity or nutrition on hip geometry must occur before early teen-age years.

Absorptiometry, Photon↗

Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats.

In the current study, we examined the effects of minocycline, on the osteopenia of ovariectomized aged rats. Old female rats were randomly divided into five groups: sham, ovariectomized control and ovariectomized treated with minocycline, 17beta-estradiol, or both agents. Bone samples were collected 8 wk after the treatment. Ovariectomy reduced bone mineral density of the whole femur and at the condylar, distal metaphyseal and head-neck-trochanter regions 10%-19% and the loss of bone density was prevented by treatment with minocycline or 17beta-estradiol. Histomorphometric analysis of distal femur showed ovariectomy reduced the trabecular bone area, the trabecular bone number, trabecular bone thickness and increased the trabecular bone separation. The microanatomic structure of trabecular bone also showed that the number of nodes, node to node, cortical to node, node to free end was reduced by ovariectomy. Treatment with minocycline attenuated the effect of ovariectomy on trabecular bone in aged animals. In contrast, cortical bone was not affected by ovariectomy or minocycline treatment. The effect of minocycline on bone turnover was also examined. Minocycline increased osteoid surface, mineralizing surface, mineral apposition rate, bone formation rate and reduced eroded surface. We have therefore concluded that the modest increase in bone mineral density and the improvement in the trabecular bone status noted in minocycline treated ovariectomized aged rats is likely due to an increase in bone formation coupled with a decrease in bone resorption.

Absorptiometry, Photon↗

The New Zealand Rugby Injury and Performance Project: alcohol use patterns within a cohort of rugby players.

Although heavy drinking has traditionally been associated with rugby, the drinking patterns of New Zealand rugby players have not been examined. Three hundred and forty-eight rugby players (257 males and 91 females), completed the Alcohol Use Disorders Identification Test (AUDIT) at the beginning of the 1993 rugby season. The mean AUDIT scores were 11.2 (SD = 5.1) for the males and 8.7 (4.1) for the females: a cut-off of 8.0 has been recommended by the developers of the instrument for identifying alcohol use disorders. The consumption of large quantities of alcohol, and a high frequency of heavy drinking sessions were the norm for this group. Sixty-one per cent of males and 38% of females consumed six or more drinks in a session at least weekly: typically, men drank 10 or more drinks in a session and women 5-6 drinks. The patterns of drinking exhibited by the cohort give cause for concern regarding the health risks associated with such behaviour.

Adolescent↗

Entry to care: positive choice or fait accompli? developing a more proactive nursing response to the needs of older people and their carers.

A range of issues surrounding admission to either residential or nursing home care are considered from the perspectives of older people and their family carers. Drawing on the literature and a number of studies conducted by the authors, the processes and perceptions that shape and influence admission to care are identified. On the basis of the interaction of these factors a four-stage typology of admission is suggested: the positive choice, the rationalized alternative, the discredited option, and the fait accompli. The characteristics of each admission type are discussed and the implications for professionals, particularly nurses, working with older people and their carers are addressed.

Aged↗

Cab45, a novel (Ca2+)-binding protein localized to the Golgi lumen.

We have identified and characterized Cab45, a novel 45-kD protein from mouse 3T3-L1 adipocytes. Cab45 is ubiquitously expressed, contains an NH2-terminal signal sequence but no membrane-anchor sequences, and binds Ca2+ due to the presence of six EF-hand motifs. Within the superfamily of calcium-binding proteins, it belongs to a recently identified group of proteins consisting of Reticulocalbin (Ozawa, M., and T. Muramatsu. 1993. J. Biol. Chem. 268:699-705) and ERC 55 (Weis, K., G. Griffiths, and A.I. Lamond. 1994. J. Biol Chem. 269:19142-19150), both of which share significant sequence homology with Cab45 outside the EF-hand motifs. In contrast to reticulocalbin and ERC-55 which are soluble components of the endoplasmic reticulum, Cab45 is a soluble protein localized to the Golgi. Cab45 is the first calcium-binding protein localized to the lumenal portion of a post-ER compartment; Cab45 is also the first known soluble protein resident in the Golgi lumen. Cab45 can serve as a model protein to determine the mechanism of retention of soluble proteins in the Golgi compartment.

3T3 Cells↗

Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor.

Connective tissue growth factor (CTGF) is a 36-to 38-kDa peptide that is selectively induced by transforming growth factor-beta (TGF-beta) in fibroblastic cell types. We compared the biologic activities of CTGF with TGF-beta on fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a mitogen in monolayer cultures of normal rat kidney fibroblasts. CTGF did not stimulate anchorage-independent growth of NRK fibroblasts, however, or inhibit the growth of mink lung epithelial cells, distinguishing CTGF's growth-regulatory activities from those of TGF-beta. In NRK fibroblasts, both TGF-beta and CTGF significantly increased the transcripts encoding alpha 1 type I collagen, alpha 5 integrin, and fibronectin. Stimulation of type I collagen and fibronectin protein synthesis by TGF-beta and CTGF was confirmed by pulse labeling of cells with [35S]methionine. Subcutaneous injection of TGF-beta and CTGF into neonatal NIH Swiss mice resulted in a large stimulation of granulation tissue and fibrosis at the site of injection. In situ hybridization studies revealed that TGF-beta injection induced high levels of CTGF mRNA in the dermal fibroblasts at the injection site, demonstrating that TGF-beta can induce the expression of CTGF in connective tissue cells in vivo. No CTGF transcripts were detected in the epidermal cells in either control or TGF-beta-injected skin or in fibroblasts in control (saline-injected) skin. These results demonstrate that, like TGF-beta, CTGF can induce connective tissue cell proliferation and extracellular matrix synthesis.

Animals↗

Validation of the combined olfactory test.

A new test of olfactory function, the combined olfactory test, has been designed to assess odours easily recognizable by the test population. The test consists of an odour recognition test of nine odours, where an odour in a bottle is chosen from a list of four possible odours in a forced choice manner. This is followed by a threshold test using a series of three-fold dilutions of 1-butanol. The mean of the two scores is the combined olfactory score. The test was subjected to a validation study. It was performed on 133 participants with a normal sense of smell and a normal rhinological examination and on 94 participants who said that they did not have a sense of smell. There was a highly significant difference between the combined olfactory score in the normal and 'anosmic' groups (P < 0.001). This significant difference was the same between the two groups for the threshold and odour recognition arms of the test. There was a highly significant difference (P < 0.001) between the two subgroups of 'completely anosmic' and 'almost anosmic' participants, indicating that the test could grade the degree of olfactory dysfunction.

Adult↗