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Biomedical subjects

R A Knight

Publications and source records attributed to R A Knight.

At least 19 recordsLinked to original sources
PubMed1992

IGF-II mRNA expression in LI human glioblastoma cell line parallels cell growth.

A human glioblastoma cell line was found to express in vitro mRNA transcripts specific for insulin-like growth factor-II (IGF-II) and growth-hormone releasing-hormone (GHRH). In the absence of gross morphological changes, retinoic acid reduced the growth rate without major change of IGF-II mRNA expression, while alpha-difluoromethylornithine produced a complete growth arrest and a sharp decrease of IGF-II mRNA expression. Both reagents increased the expression of GHRH mRNA. Also in this glioblastoma cell line, like other neuroectodermal tumours, IGF-II mRNA is expressed independently from GHRH and seems to be parallel to growth rate.

Blotting, Northern↗
PubMed1992

Measurements of potential differences in human subjects induced by motion in a superconducting magnetic field.

We have attempted to measure the electromotive forces (emfs) induced in human beings moving at a constant speed in a highly dense magnetic field. Experiments were initially conducted on a set of models, and then directly on human subjects. The models consisted of single circular loops of Tygon tubing (I.D., 0.635 cm; O.D., 0.9525 cm) filled with normal saline solution, with circumferences of 20, 40, 60, 80, and 100 cm. The models were connected to an amplifier via silver/silver-chloride electrodes. Each saline loop was mounted on a movable platform, with the plane of the loop perpendicular to the platform's axis; the platform was enabled to move at known constant speeds into and out of the bore of a 1.89-T magnet. The human subjects were then substituted for the saline loops, with the long axis parallel to the direction of motion, and with standard EKG electrodes placed at 180 degrees successively on the ankle, calf, lower thigh, upper thigh, chest, and head. In all cases, for human subjects and models, the peak induced voltage was directly proportional to the speed of movement and the square of the circumference of the bounded cross-sectional areas. Thus, for the saline loops, the correlation coefficient between induced voltage and circumference was .998, and for human subjects, .947. Under the loose assumption that for equal circumferences the bounded areas in human subjects were equal to those in the circular loops, the induced emfs in human subjects were consistently about 13% greater than those in the loops. At a mean speed of 1.18 m/s, the chest had a peak induced voltage of 260 mV, while the voltage at the ankle had a peak of 19.8 mV. The experimental data were used to estimate the corresponding induced-current density at the pericardium, 17 mA/m2. We conclude for a human subject moving at constant speed along the body's long axis into a magnetic field that Faraday's law is closely followed for various cross-sections of the body. Further, in those cases in which the magnetic field and its gradient are not well-established, one can use saline-filled loops to estimate approximate values of voltages induced in human subjects.

Electric Conductivity↗
PubMed1992

Analysis of the evolution of focal cerebral ischemia in the rat using the eigenimage filter.

The eigenimage filter was used to evaluate the results of a MRI study of cerebral ischemia in a rat model. This linear filter segments a desired feature in an image sequence from other features which may interfere with its observation. The animals were imaged temporally, after occlusion of the middle cerebral artery, to investigate the evolution of the ischemic process. The temporal evolution of ischemia was evaluated by analysis of the "eigenimages," calculated T2 and T1 map images, and images for the angles between signature vectors defined in the eigenimage technique. The eigenimages and angle map images demonstrated an improved visibility of the lesion at all time points, as compared to the original images and T2 and T1 map images. The eigenimages also demonstrated signal intensity changes within the area of ischemia. These changes are speculated to be related to variations in local cerebral blood flow resulting in varying degrees of tissue damage. The eigenimage intensities and the angles between signature vectors demonstrated time-related changes similar to the T2 and T1 values. Since the eigenimage filter and angle calculations are not dependent upon physical models (like T2 and T1), and the errors associated with these models, they may be preferable as methods for tissue characterization.

Animals↗
PubMed1992

Characterisation of a human glioblastoma cell line (LI) expressing hypothalamic and pituitary hormones.

The human glioblastoma cell line LI showed morphological features typical of its neuroectodermal origin. Cells were positive by immunofluorescence to GFAP, MHC class II, and L1 determinants. Cytogenetic analysis showed the presence of a modal chromosome number of 63, ranging from 58 to 69 chromosomes (DNA index was 1.6). Northern blot analysis demonstrated the presence of mRNA transcripts specific for transglutaminase C (type II or "tissue"), growth-hormone releasing-hormone (GHRH), insulin-like growth factor II (IGF-II), and proopiomelanocortin (POMC). The GHRH mRNA was present in two different sizes, one similar to the normal hypothalamic species of 0.75 kb, whilst the second species was a large transcript of approximately 10 kb size. Treatment with 5 microM retinoic acid or 5 mM alpha-difluoromethylornithine for 5 days sharply reduced the growth rate and also induced modulation of the ultrastructure and antigenic profile. This cell line may be useful to study glial differentiation and the relationship of GHRH, IGF-II and POMC expression with differentiation in neuroectodermal tumours.

Blotting, Northern↗
PubMed1992

Interleukin-6 and corticotrophin-releasing hormone mRNA are modulated during differentiation of human neuroblastoma cells.

Two cell clones [BE(2)-C and BE(2)-M17] derived from the human neuroblastoma cell line SK-N-BE(2) express corticotrophin-releasing hormone as well as interleukin-6 mRNA. Both genes are overexpressed, although with a different time course, following exposure to 5 microM retinoic acid, in parallel to the induction of neuroblastic differentiation. On the contrary, we are unable to detect interleukin-1 beta mRNA in these cell lines. Both cytokines are known to increase hypothalamic CRH mRNA. The production of cytokines and neuropeptides by neuroblastoma cells indicate a complex dialogue between tumour cells and anti-tumour immunity.

Blotting, Northern↗
PubMed1992

Effects of cyclosporine A on the hypothalamic-pituitary-adrenal axis and anterior pituitary interleukin-6 mRNA expression during chronic inflammatory stress in the rat.

In the rat, adjuvant arthritis (AA) is an inflammatory joint disease associated with chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have investigated the effects of the immunosuppressive agent cyclosporine A (CsA) on plasma levels of adrenocorticotropin (ACTH) and corticosterone (B), as well as on anterior pituitary proopiomelanocortin (POMC) and interleukin (IL)-6 mRNA accumulation in control and adjuvant-injected animals. In control animals, CsA reduced basal anterior pituitary POMC and IL-6 mRNA and decreased plasma levels of ACTH and B. Adjuvant-injected animals that were treated with CsA showed no clinical signs of AA. Moreover, CsA inhibited the arthritis-induced increases in pituitary POMC and IL-6 mRNA levels and in circulating ACTH and B. In vitro, CsA reduced the POMC mRNA content of cultured anterior pituitary cells and diminished the stimulatory effects of corticotropin-releasing hormone (CRH) on POMC mRNA expression and ACTH secretion from these cells. These data indicate that CsA has a direct action on the HPA axis and also reduces the activation of the HPA axis seen in chronic inflammatory arthritis.

Adrenocorticotropic Hormone↗
PubMed1992

Response of pituitary and spleen pro-opiomelanocortin mRNA, and spleen and thymus interleukin-1 beta mRNA to adjuvant arthritis in the rat.

During development of adjuvant-induced arthritis (AA) in the rat, pituitary pro-opiomelanocortin (POMC) mRNA expression was increased. Pituitary POMC mRNA was much higher following adrenalectomy and AA. Spleen POMC mRNA also increased with a similar time kinetics, although the levels in the spleen were much lower than those in the pituitary. In control animals, spleen interleukin-1 beta (IL-1 beta mRNA) was undetectable, whereas AA led to the accumulation of IL-1 beta mRNA and the highest levels were seen in the adrenalectomised AA group. Thymic IL-1 beta expression was also increased in AA animals. These results suggest that AA leads to the activation of both the neuroendocrine and the immune systems and the interaction between these systems may play a role in this disease state.

Adrenalectomy↗
PubMed1992

Action of interleukin-2 and interleukin-4 on CRF mRNA in the hypothalamus and POMC mRNA in the anterior pituitary.

We have used the technique of in situ hybridization histochemistry to determine corticotropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary of rats given a single ip injection of either interleukin (IL)-2 or IL-4. IL-2 increased POMC mRNA in the anterior pituitary in a dose-dependent manner. The effect was apparent both at 4 and 24 h after injection. No effect of IL-2 on CRF mRNA in the PVN was detected in these animals, suggesting that the increase in POMC mRNA was not driven by an increase in CRF. IL-4 was without effect at the hypothalamic level although this cytokine did result in a decrease in POMC mRNA in the anterior pituitary.

Animals↗
PubMed1992

Glucocorticoid-mediated responses of plasma ACTH and anterior pituitary pro-opiomelanocortin, growth hormone and prolactin mRNAs during adjuvant-induced arthritis in the rat.

Adjuvant arthritis (AA) in the rat leads to chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the loss of its diurnal rhythmicity. We have investigated the effects of adrenalectomy (ADX) and different levels of corticosterone replacement upon plasma ACTH levels and anterior pituitary pro-opiomelanocortin (POMC), GH and prolactin mRNAs during the development of AA. In control ADX animals, we observed the negative feedback effects of exogenous corticosterone on plasma ACTH and anterior pituitary POMC mRNA. In the ADX animal with AA, however, the increased POMC mRNA which was observed was not reduced by exogenous corticosterone on day 7 of AA, although the negative feedback effect of corticosterone on plasma ACTH was intact. On day 14, however, even high dose corticosterone replacement failed to have a significant feedback effect on the raised levels of plasma ACTH. In control ADX animals, corticosterone replacement resulted in increased anterior pituitary GH mRNA and reduced prolactin mRNA. In contrast, in ADX animals with AA, GH mRNA was reduced and there was a further decrease in prolactin mRNA. In these animals, corticosterone replacement did not affect GH or prolactin mRNA expression. These data demonstrate a disruption of the normal mechanisms underlying feedback inhibition of the HPA axis by glucocorticoids during AA. Similarly, the glucocorticoid-dependent regulation of GH and prolactin mRNA expression is altered in AA.

Adrenalectomy↗
PubMed1991

Magnetization transfer contrast (MTC) in flash MR imaging.

Magnetization transfer between bound and free protons was used as a source of contrast in high speed MR imaging using the FLASH technique. Contrast in FLASH MR images was found to depend upon the reduced magnetization and the spin lattice relaxation rate of free protons in the presence of bound proton radio-frequency saturation. MTC FLASH imaging was thus used to estimate the variation with saturation frequency of free proton spin-lattice relaxation during magnetization transfer.

Animals↗
PubMed1991

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging.

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spin-spin relaxation time (T2), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T2 value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between "free" and "bound" water protons as measured by MTC imaging is at least partially responsible for the elevation in T2 values observed during ischemia, and may accompany breakdown of cellular structure.

Animals↗
PubMed1991

Characteristics and kinetics of proopiomelanocortin mRNA expression by human leucocytes.

Northern blot analysis of total and poly(A)+ RNA demonstrated that human leucocytes contain several proopiomelanocortin (POMC) mRNA species, including 0.8-, 1.2-, 1.5-, and 9.5-kb transcripts. Peripheral blood lymphocytes (PBL) were found to express all four species. The other cell types had either the 0.8-kb species alone or both 0.8- and 9.5-kb species. Neutrophils were the only cells to express the 9.5-kb transcript alone. In T cell clones, both interleukin (IL)-2 alone or the antigen for which the clone was specific induced POMC accumulation within 18-24 h. Cytoplasmic dot blot analysis of PBL RNA demonstrated that POMC expression could be induced by corticotrophin releasing factor, rIL-1, and phorbol ester, but not by calcium ionophore (A23187). In PBL activated in a mixed lymphocyte culture there was increased expression, particularly of the smaller species (0.8, 1.2, and 1.5 kb), within 1-3 days of activation. The intensity of the bands began to decline thereafter. The 9.5-kb POMC transcript essentially disappeared by Day 3.

Blotting, Northern↗
PubMed1991

Identifying critical dimensions for discriminating among rapists.

Considerable evidence has amassed in studies of both nonoffender and offender samples that demonstrates both that sexual aggression is determined by a multiplicity of variables and that convicted sexual offenders are markedly heterogeneous (Knight, Rosenberg, & Schneider, 1985; Malamuth, 1986). Attempts both to identify sexually coercive men in normal samples and to assess etiology, concurrent adaptation, treatment efficacy, and recidivism for convicted sexually aggressive offenders have also suggested that the critical determining components of sexual aggression interact in complex ways. The purpose of this article is to survey both the offender and nonoffender sexual aggression research for evidence about which dimensions should be included in multivariate models that attempt to discriminate rapists from nonrapists, to identify subgroups among rapists, or to enhance the efficiency of dispositional decisions about these offenders.

Aggression↗
PubMed1991

A multivariate model for predicting rape and physical injury outcomes during sexual assaults.

The relation of situational factors, offender aggression, and victim resistance to women's sexual abuse and physical injury during sexual assaults was analyzed using police reports and court testimonies of 274 women who either avoided rape or were raped. Hierarchical multiple regression showed that after situational factors were partialed out, (a) women's screaming/yelling was related to less severe sexual abuse, and (b) offender physical aggression was related to increased physical injury. An a priori model of the interrelations among offense components and injury outcomes was tested with path analysis. More forceful victim resistance was directly related to less severe sexual abuse even when partialing level of situational danger and the level of offender aggression. In contrast, more forceful victim resistance was not related to the level of physical injury when both the level of situational danger and the level of offender aggression in the assault were controlled.

Adult↗
PubMed1991

1H magnetic resonance imaging of normal brain tissue response to photodynamic therapy.

1H Magnetic resonance imaging (MRI) was used to study the effects of photodynamic therapy (PDT) on normal rat brain (n = 5) using T1-, T2-, diffusion-, and proton density (rho)-weighted images. Rats received intraperitoneal injections of 12.5 mg/kg of Photofrin II, and 48 hours later the dural area over the frontal cortex was treated with 35 J/cm2 of light (632 +/- 1 nm). The T1-, T2-, and diffusion-weighted images revealed an evolving high contrast region of brain that corresponded to the PDT-treated area. Lesioned brain exhibited significant increases in T1 and T2 relaxation times at 1 day (P less than 0.01) and 3 days (T1, P = 0.018; T2, P less than 0.01) after treatment, compared with the contralateral equivalent volume of nonlesioned brain. Water proton diffusion coefficient (DW) in the lesioned area decreased at 1 day (P = 0.026) and increased at 3 days (P = 0.012) compared with nonlesioned brain. An increase in the proton density ratio (rho D/rho O) from PDT (rho D) versus nonlesioned side (rho O) was found 3 days after PDT treatment (P = 0.03). The data indicate that the biophysical parameters obtained from magnetic resonance imaging scans, T1, T2, DW, and proton density, can be used to monitor changes in an evolving photochemically induced lesion.

Animals↗
PubMed1991

Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging.

We studied the effect of focal cerebral ischemia on the "state" of brain water using proton nuclear magnetic resonance imaging. Focal cerebral ischemia was induced in five halothane-anesthetized rats via tandem occlusion of the left common carotid artery and the left middle cerebral artery. The proton transverse relaxation time, the proton density, and the water diffusion coefficient were measured at various times from the same region of brain tissue from 1.5 to 168 hours after occlusion. Early measurements indicated significant changes in the transverse relaxation time (p = 0.004) and water diffusion coefficient (p = 0.002) of ischemic brain tissue compared with a homologous region from the contralateral hemisphere. However, the transverse relaxation time, proton density, and water diffusion coefficient in ischemic brain tissue showed different temporal evolutions over the study period. Diffusion coefficient weighting was superior to relaxation time and proton density weighting for the visualization of early cerebral ischemia. Our data suggest that nuclear magnetic resonance imaging is sensitive in detecting changes in proton-associated parameters during early cerebral ischemia and confirm significant changes (p less than or equal to 0.01) in the temporal evolution of transverse relaxation times, proton densities, and diffusion coefficients following middle cerebral artery occlusion.

Animals↗
PubMed1991

Child molesters who abduct.

This study examined the differences between 97 abducting and 60 nonabducting child molesters on selected typological and antisocial/criminal variables. Although the results supported one a priori hypothesis, they disconfirmed two others and yielded an unpredicted but theoretically interesting abductor covariate. Our hypothesis that child abductors would more likely be classified as "low" in their contact with children (i.e., have little or no contact with children outside of their offenses) than the nonabductors was supported. In contrast, our hypotheses that the abductors were more likely to be characterized by a history of antisocial and criminal behavior as well as a greater degree of aggression were not supported. Abductors were found to be lower in social competence than the child molesters who never abducted their victims. The results were discussed in terms of abduction as in victim control strategy that is more likely employed by offenders with poor social and interpersonal skills. The complex interrelation among social competence, weapons, and sadism for abductors and nonabductors was explored.

Child↗