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Biomedical subjects

L A Jones

Publications and source records attributed to L A Jones.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Prognostic differentiation of ovarian carcinomas by immunohistochemical analysis of estrogen receptor expression].

Analogous to breast cancer, the expression of estrogen receptors (ER) by human ovarian cancers is thought to be of prognostic significance. This prospective study was designed to evaluate the ability of immunohistochemistry (IHC) for ER to define prognostic subgroups in this disease and to possible characterize the group of patients that would benefit from ER analysis. The IHC technique for localising ER was published by Press and Green (1984). In IHC the percentage of cells stained was determined as well as the staining intensity that was graded on a 4 step scale. Tissue from the primary focus of 61 ovarian cancers was sampled during surgery and frozen immediately. FIGO Stage 1 disease was observed in 7 patients, stage 2 in 2, stage 3 in 36 and stage 4 in 16 women. Tumours of histological grade 1 were found in 3 cases, grade 2 in 20 and grade 3 in 38 specimen. Serous carcinoma was diagnosed in 43 lesions, mixed cell types in 10, mucinous and endometrioid each in 4. Minimal follow-up was 8 years. Statistical analysis was performed using the Wilcoxon Rank and Log-Rank test of Kaplan Meier curves. The median survival was 10.62 +/- 1.83 years for stage 1, 5.83 +/- 0.39 years for stage 2, 2.38 +/- 0.39 years for stage 3, and 3.71 +/- 0.76 years for stage 4. Tumour stage (p < 0.05), grade (p < 0.05) and cell type (p < 0.01) were predictors of survival. Age was of borderline significance (p = 0.058). The relative amount of stained cells was no predictor of prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Abnormal radiosensitivity of lymphocytes from breast cancer patients with excessive normal tissue damage after radiotherapy: chromosome aberrations after low dose-rate irradiation.

There is a need for a simple, rapid assay for predicting normal tissue reactions in radiotherapy patients to reduce morbidity in sensitive patients and to allow dose escalation in resistant cases. Towards this goal we have investigated the gamma-ray sensitivity of lymphocytes from 16 breast cancer patients who had shown an exaggerated acute or late radiation reaction ('overreaction') of normal tissues after radiotherapy, using chromosome damage (dicentrics) as the endpoint because of its close relationship with cell killing. The use of a low dose-rate (LDR; 0.31 cGy min-1) was found to be better than a high dose-rate (170 cGy min-1) in discriminating between over-reactors and controls, as predicted (and here confirmed) from previous studies on ataxia-telangiectasia (A-T) homozygotes and heterozygotes. Five of seven patients with excessive early skin reactions (e.g. erythema, moist desquamation) showed abnormal radiosensitivity, manifested either as aberration yields above the control range after LDR exposure or as less sparing than controls. The average LDR yield for early over-reactions was significantly higher than for controls (p = 0.009) and average sparing was less (p = 0.0002). Two of 10 patients with late complications (fibrosis, telangiectasia) had LDR yields above the control range, but the average yield for late over-reactors was not significantly above that of controls. Unexpectedly, two patients (one early, one late reaction) had LDR aberration yields below the control range. Quantitatively our results are consistent with the notion that over-reacting breast cancer patients are carriers of the A-T gene. Pilot studies on controls showed that the sparing effect of LDR irradiation was increased by lowering the dose-rate to 0.13 cGy min-1 and by using micronuclei rather than metaphase damage as the endpoint. These modifications to the protocol will be used in a large-scale prospective study.

Adult↗
PubMed1995

Analysis of short-latency reflexes in human elbow flexor muscles.

1. A motor and digital controller have been developed to apply rapid stretches to the human elbow joint. The digital controller returns the forearm to the initial position before the reflex contraction. Thus short-latency reflex responses can be cleanly separated in time from the mechanical effects of the stretch under a wide variety of loading conditions. 2. The reflex force varies linearly with the velocity of stretch over nearly 2 orders of magnitude. The reflex force also varies linearly with the tonic level of force over the entire range of forces studied (0-100 N). This contrasts sharply with, for example, the human ankle joint, which shows a very limited linear range. 3. As the digital controller is made more compliant (less stiff), reflex shortening increases dramatically and becomes more prolonged, whereas the reflex force becomes somewhat smaller and shorter. With compliant loads and the brief stretches we applied, the reflex shortening is approximately equal to the stretch that generated it. 4. Simulations of the results confirm that the dependence of reflex shortening and force on the stiffness of the load is mainly determined by the mechanics of the limb and muscles. The simulations also indicate that 1) the gain of the reflex is as high as it can be without causing instability and 2) the presence of a rectification nonlinearity (e.g., lengthening the muscle produces a reflex, but shortening the muscle does not) is mainly responsible for preserving the stability of the elbow system.

Adult↗
PubMed1995

Effects of estrogenic chemicals on development.

The sum of the evidence supports the necessity to continue to investigate the developmental effects of estrogenic and antiestrogenic compounds when exposure occurs early in life. Additional studies will answer questions relevant to the molecular definition of the developmental or carcinogenic effects of estrogens such as hormone-induced gene alterations. These studies also support the need to use the neonatal mouse model to demonstrate the consequences of reproductive and nonreproductive stem-cell exposure to estrogenic compounds.

Animals↗
PubMed1994

A molecule expressed on accessory cells, activated T cells, and thymic epithelium is a marker and promoter of T cell activation.

T cell maturation results in part from direct cell-cell interactions between developing thymocytes and thymic stromal cells. Identification of the cell surface molecules involved in these interactions has been approached by production of mAbs reactive to thymic stromal cell surface Ags. A mAb against one such Ag, mouse thymic stroma (MTS) mAb MTS 23, stains a subset of thymic medullary epithelium by immunohistology. In addition, it was found to detect, by flow cytometry, an Ag constitutively expressed on peripheral B cells and macrophages as well as thymic and splenic dendritic cells. This Ag was also up-regulated on T cells and thymocytes within 24 to 48 h after activation. We then investigated whether the Ag identified by MTS 23 may represent a functional accessory molecule. MTS 23 was able to block up to 75% of T cell proliferation in soluble anti-CD3 and Ag-induced responses in a dose-dependent manner, but not under conditions in which no APCs were required. The molecule detected by this mAb has an apparent molecular mass of 120 kDa under reducing and nonreducing conditions. On the basis of these molecular properties and expression pattern, it is therefore postulated that MTS 23 may detect a novel accessory molecule important for T cell activation. Its expression on thymic epithelium is consistent with the notion that T cell development is not solely a consequence of unique molecular interactions, but also of signals arising from combinations of interactions involving molecules also expressed extrathymically.

Animals↗
PubMed1994

Tactile sensory impairments and prehensile function in subjects with left-hemisphere cerebral lesions.

The relation between tactile sensory impairments and functional activity of the hand was studied in a group of 10 subjects with cerebrovascular accidents (CVAs) that involved the left hemisphere. Pressure sensitivity and static and moving two-point discrimination thresholds were measured on the thumbs and index fingers of both hands of these subjects and on a group of 14 control subjects. Functional use of the hand was assessed using object and material recognition tests and the Jebsen test of hand function. Prehensile capacity was evaluated with a pinch-force test that examined the influence of load force and surface texture on the forces used to grasp an object. For this group of subjects with left-hemisphere CVAs, elevated sensory thresholds were associated with slower performance on the recognition tests, but not with the Jebsen test. The ability to control the forces used to grasp an object was also found to be deficient in these subjects, although the forces were still adapted to the loads being supported and the surface properties of the object being held.

Adult↗
PubMed1994

Relationship between chromosome aberrations, micronuclei and cell kill in two human tumour cell lines of widely differing radiosensitivity.

The relationship between chromosome aberration frequency, micronucleus (MN) formation and cell kill was investigated in two human tumour cell lines, RT112, a radioresistant bladder carcinoma cell line, and HX142, a radiosensitive neuroblastoma cell line. As MN are generally accepted to result from acentric chromosome fragments that are lost at nuclear division and all unstable aberrations result in an acentric fragment, a 1:1 correlation between aberrations and MN might be expected. There was a good correlation between cell kill and aberration frequency in the two cell lines, however the relationship between cell kill and MN formation in the lines was very different. RT112 showed 0.22 aberrations and 0.21 MN per Gy whilst HX142 showed 0.61 aberrations and 0.078 MN per Gy. Possible reasons for the discrepancy observed in HX142 are discussed.

Cell Survival↗
PubMed1994

Two transthyretin mutations (glu42gly, his90asn) in an Italian family with amyloidosis.

A family with familial amyloidotic polyneuropathy (FAP) was previously found to have a substitution of asparagine for histidine at position 90 of transthyretin. Members with his90asn developed FAP. However, close examination of the transthyretin gene revealed that glu42gly is coinherited with his90asn in this family. Since glu42gly has already been seen in Japanese FAP patients, and his90asn has been found in Portuguese and German individuals without FAP, we conclude that his90asn is a nonpathogenic variant.

Adult↗
PubMed1994

Peripheral mechanisms of touch and proprioception.

The basic sensory mechanisms involved in transducing information concerning the spatial properties of objects and the movements and forces generated by the hand are briefly reviewed. The contribution of different cutaneous mechanoreceptors to the processing of spatial information is discussed in the context of psychophysical and neurophysiological studies of the tactile sensory system. The specialization of the hand with respect to the sensory mechanisms that contribute to our awareness of finger position, movement, and force is reviewed, and experimental evidence indicating the critical role played by muscle spindle receptors in proprioception is described.

Hand↗
PubMed1994

Orthotopic liver transplantation for familial amyloidotic polyneuropathy.

Orthotopic liver transplantation for inborn errors of metabolism has become a standard indication for transplantation in pediatric and adult patients with alpha-1 antitrypsin deficiency, Wilson's disease and tyrosinemia, amongst several less common diseases. Familial amyloidotic polyneuropathy (FAP) is a rare autosomal dominant disease whose metabolic origin lies in an abnormal protein synthesized primarily in the liver. FAP, also discussed as the autosomal dominant form of amyloidosis, is characterized as a hereditary form of amyloidosis. It is the rarest form of amyloidosis affecting kindreds of specific ethnic backgrounds. The true incidence of this disease in the United States is not known. The mutant protein, called transthyretin or prealbumin, forms amyloid fibrils which accumulate in vital tissues ultimately leading to the patient's death. Liver transplantation for this inherited disease leads to the production of normal transthyretin protein. This theoretically should arrest the disease process. The first 5 patients in the United States with FAP who have undergone transplantation are presented.

Adult↗
PubMed1993

Improved prediction of survival in advanced adenocarcinoma of the ovary by immunocytochemical analysis and the composition adjusted receptor level of the estrogen receptor.

Conventional cytosol estrogen receptor analysis is not a significant prognostic variable in serous ovarian carcinoma. Although the use of immunocytochemical receptor analysis for estrogen does provide prognostically useful information in enhanced accuracy of predicting survival in patients with ovarian cancer, its usefulness can still be improved. Surgical samples from ovarian carcinomas are heterogeneous in tissue composition. Immunocytochemical receptor analysis allows for the specific assessment of the tumorous portions of a histological specimen. However, it is limited by its dependence on staining intensity as the determining factor. Biochemical receptor analysis does provide objective information concerning the number of receptor molecules present in a given sample, but the value is not adjusted for histological composition of the tumor section. Therefore, we have attempted to combine the advantages of both methods. By adjusting the conventional receptor analysis for the percentage of tumor present in the specimen, we have eliminated the tissue heterogeneity as a confounding variable. The resulting value is named Composition Adjusted Receptor Level or CARL. A prospective study was performed on the estrogen receptor concentrations in 61 ovarian cancers. Minimum follow-up was 8 years. For the percentage of tumor in the specimen, a highly significant correlation of the assessment of the two pathologists was observed. Stage (P < 0.05) and grade (P < 0.05) as well as cell type (P < 0.05) were found to be significant prognostic variables. In an attempt to eliminate the confounding influences of these variables, the CARL of the estrogen receptor was assessed with regard to its prognostic significance in 32 grade 2 and 3 serous carcinomas of the ovary, stage III and IV. A linear correlation between CARL and survival was found above a threshold estrogen receptor concentration of 15 fmol/mg cytosol protein using a correlation of the Cox proportional hazards model (P < 0.02). Our data suggest that (a) the assessment of the percentage of tumor in a given sample is not significantly observer dependent, (b) CARL is a significant predictor of survival in serous ovarian carcinoma, and (c) a CARL should be determined for the analysis of any cytosol receptor in solid tumors.

Adenocarcinoma↗
PubMed1993

Chicken ovalbumin upstream promoter transcription factor (COUP-TF): an orphan steroid receptor with a specific pattern of differential expression in human ovarian cancer cell lines.

The possible role of a novel steroid receptor in ovarian malignancy was investigated. The evolutionarily conserved orphan steroid receptor COUP-TF (chicken ovalbumin upstream promoter transcription factor) was originally identified as a protein interacting with an upstream promoter element of the chicken ovalbumin gene. The human receptor protein was purified from a cervical cancer cell line. An immunocytochemical technique for the visualization of COUP-TF was developed using a specific polyclonal rabbit antibody. Four established ovarian cancer cell lines were evaluated. The patterns of COUP-TF expression were compared to the staining intensities of immunocytochemical assays for estrogen receptor (ER), androgen receptor (AR), aromatase, and HER2/neu. A comparison of the ovarian cancer cell lines showed differential expression of COUP-TF in the nucleus. The pattern of COUP-TF expression did not follow the profile of any of the other four variables. In agreement with transfection experiments showing reduction of activity of other steroid receptors by elevated COUP-TF levels, high COUP-TF expression correlated with low ER activity also in native ovarian cancer cells. These data represent the first reported evidence that COUP-TF-like proteins may play a role in the metabolism and possibly in the process of dedifferentiation of human ovarian cancer.

Aromatase↗
PubMed1993

T cell tolerance and antigen presenting cell function in the thymus.

B7 expression appears much more extensive than previously recognized with anti-human B7 reagents on human leucocyte populations: it is extremely high on splenic and thymic DC, moderate on macrophages and activated B cells, and low on resting B cells. Additionally, B7 is entirely undetectable on any thymic epithelial cells belonging to a panel of transformed cell lines and T cells, but its expression on epithelial cells in situ is still under investigation. This expression pattern is consistent with the hierarchy of costimulatory signal activity among these cell types, with DC being the most effective, and epithelial cells (like other cells of non-hemopoietic origin) not at all. Future studies will investigate to which extent B7 is involved in clonal deletion, i.e., the selection process dependent on self-antigen presentation by DC and B cells.

Animals↗
PubMed1993

Influence of the mechanical properties of a manipulandum on human operator dynamics. II. Viscosity.

The influence of the viscosity of a manipulandum used by a human operator in a position-control pursuit-tracking task was examined. An active servo-system was used to set the viscosity of a manipulandum (motor) connected to the forearm to one of seven levels ranging in a geometric series from 12 to 800 N.s/m. During each condition the viscosity of the motor was held constant by a computer while subjects tracked, by moving their forearm in the sagittal plane, a visually presented target whose position changed randomly every 1.5 s for 255 s. Nonparametric and parametric impulse response functions were calculated between the input (target) and output (position) in each tracking condition. Nonparametric analyses revealed that subjects became sluggish at higher viscosities (above 200 N.s/m) and took longer to reach the target. A second-order low-pass transfer function was found to provide a very good description of tracking performance at each viscous level. The gain and damping parameter of this transfer function were not affected by the manipulandum's viscosity, whereas both the pure delay and natural frequency of the human operator system decreased systematically with increasing manipulandum viscosity. These findings suggest that over the range of viscosities studied, there is no speed-accuracy trade-off in terms of determining an optimal level of manipulandum viscosity for a human operator, and that a less viscous interface will result in faster performance.

Adult↗
PubMed1993

A perceptual analysis of viscosity.

The perception of viscosity was studied using the contralateral limb-matching procedure in which subjects adjusted the viscosity of a motor connected to the wrist of one (matching) arm until it was perceived to be the same as that of the motor attached to the other (reference) arm. Two servo-controlled electromagnetic linear motors with computer-controlled viscosity were used to present viscosities ranging in amplitude from 2 to 1024 N.s/m to 11 subjects. Ten different viscosities were matched by subjects, and there were ten repetitions of each stimulus amplitude. The psychophysical function relating the reference to matching viscosity was linear (99% variance accounted for), and the accuracy with which the viscosities were matched (slope of 0.88) paralleled that reported previously for force, limb position and stiffness. The Weber fraction for viscosity was 0.34, which is 50% larger than that measured for stiffness and over twice that reported for force. An analysis of the movements and forces generated to perceive the reference viscosity revealed that subjects did not vary the amplitude of the movements and typically made very small excursions of the forearm, but that both the velocity of the movements and force changed significantly as a function of the reference viscosity. These findings were interpreted as indicating that the human proprioceptive system is capable of integrating information regarding force and movement velocity so as to perceive the viscosity of a mechanical system connected to the limbs, but that its sensitivity to changes in viscosity is much less than would be predicted from its capacity to detect variations in muscle force and limb movement.

Adult↗
PubMed1993

Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: validation in humans.

OBJECTIVES: The aim of this study was to validate the use of myocardial contrast echocardiography to determine coronary blood flow reserve in humans. BACKGROUND: Although myocardial contrast echocardiography has been used to accurately quantify coronary flow reserve in animals, validation for its use in humans to measure flow reserve is lacking. METHODS: We analyzed the time-intensity curve from the anteroseptal region of the left ventricular short axis produced after a left main coronary artery injection of sonicated albumin before and after intracoronary administration of papaverine in 16 patients without angiographically significant coronary artery disease. The ratio of half-time of video intensity disappearance from peak intensity, variable of curve width, area under the time-intensity curve and corrected peak contrast intensity after papaverine compared with baseline were correlated with coronary flow reserve measured simultaneously with an intracoronary Doppler probe in the left anterior descending coronary artery. RESULTS: There was a strong inverse correlation with half-time of contrast washout and coronary flow reserve (r = -0.76, p = 0.0007) and a strong positive correlation between the variable of curve width (which is inversely proportional to curve width) and coronary flow reserve (r = 0.71, p = 0.002). There was a weak but significant inverse correlation between area under the time-intensity curve and coronary flow reserve (r = -0.54, p = 0.03) but no correlation between corrected peak contrast intensity and coronary flow reserve (r = -0.36, p = NS). Despite the strong correlation for the ratios for half-time of contrast washout and variable of curve width and actual coronary flow reserve measured with intracoronary Doppler probe, the transit time ratios consistently underestimated coronary flow reserve. CONCLUSIONS: Myocardial contrast echocardiography performed with left main coronary artery injections of sonicated albumin can be utilized to measure coronary flow reserve in humans. Transit time variable ratios (half-time of contrast washout and variable of curve width) derived from the time-intensity curve correlate most strongly with coronary flow reserve.

Adult↗