Automatic karyotype analysis.
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Centromere↗
Biomedical subjects
J Graham
Publications and source records attributed to J Graham.
Endogenous nitric oxide modulates vasopressor responses, but not depressor responses, to spinal sympathetic nerve stimulation in pithed rats.
The effects of N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase (1,5, and 10 mg/kg) on vasopressor and depressor responses to segmental sympathetic nerve stimulation were studied in the pithed rat preparation. Vasopressor responses were evoked by stimulation of the spinal sympathetic outflow at T6-T8 (30 V, 0.05 ms at 5 Hz with 10 pulses). This pressor response was biphasic: An initial transient response (to nerve stimulation) was followed by a later prolonged response (to adrenal catecholamine release). L-NAME 1, 5, and 10 mg/kg increased mean arterial blood pressure (MAP); this effect was maximal at 1 mg/kg L-NAME, but had no effect on heart rate (HR). L-NAME 1, 5, and 10 mg/kg potentiated both phases of the pressor response; the effect was maximal at 10 mg/kg. Vasodepressor responses were evoked by stimulation of the spinal sympathetic outflow at S2-L6 (30 V, 0.05 ms at 5 Hz with 10 pulses). L-NAME 1, 5, and 10 mg/kg did not inhibit these depressor responses. We conclude that inhibition of the synthesis of endogenous NO causes a hypertension in pithed rats that is associated with increased vasoconstriction in response to sympathetic nerve stimulation and adrenal catecholamine release. Systemic vascular depressor responses to segmental sympathetic nerve stimulation are not affected, however; therefore, NO cannot be the major mediator of these responses.
Animals↗
Salvage whole abdomen radiation therapy: its role in ovarian cancer.
PURPOSE: In spite of high initial response rates, many patients with epithelial ovarian carcinoma eventually fail their primary treatment. Further treatment with second-line regimens has been ineffective in producing durable responses. Thus, whole abdomen radiation therapy was evaluated as a salvage therapeutic modality as to its feasibility, efficacy, and toxicity. METHODS AND MATERIALS: Between June 1983 and June 1990, 44 patients who failed one or more chemotherapeutic regimens were treated with whole abdomen radiation therapy. Forty patients had epithelial carcinoma of the ovary and the remaining had primary adenocarcinoma of the peritoneal cavity. Radiation was delivered with an open-field technique and 2500 cGy were planned to the whole abdomen, with a boost when indicated. Prior to radiation, the amount of residual disease after debulking was noted to be microscopic in one-half of the patients and macroscopic in the other half. Pelvis alone was the site of residual disease in 14 patients, and upper abdominal involvement was found in 30. RESULTS: Five patients (11%) were unable to complete the planned therapy secondary to acute toxicity. The 4-year actuarial survival and recurrence-free survival rates for the entire group were 23% and 22%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease at 37% and 42% were significantly better than those for the patients with macroscopic residual disease at 9% and 5% (p < 0.005; p < 0.001) at 4 years, respectively. Patients with disease limited to pelvis only had a recurrence-free survival of 56% compared to 0% when the upper abdomen was involved (p < 0.005). The abdomino-pelvic cavity was the first site of recurrence in 28 of 31 patients in whom the site of recurrence could be determined. Eight patients (18%) experienced bowel complications, of whom five needed surgical intervention. CONCLUSIONS: Whole abdomen radiation therapy with a pelvic boost is feasible with acceptable acute and late toxicity. It is effective in patients with minimal residual disease.
Abdomen↗
Application of artificial neural networks to chromosome classification.
This work presents an approach to the automatic classification of metaphase chromosomes using a multilayer perceptron neural network. Representation of the banding patterns by intuitively defined features is avoided. The inputs to the network are the chromosome size and centromeric index and a coarsely quantized representation of the chromosome banding profile. We demonstrate that following a fairly mechanical training procedure, the classification performance of the network compares favourably with a well-developed parametric classifier. The sensitivity of the network performance to variation in network parameters is investigated, and we show that a gain in efficiency is obtainable by an appropriate decomposition of the network. We discuss the flexibility of the classifier developed, its potential for enhancement, and how it may be adapted to suit the needs of current trends in karyotyping.
Algorithms↗
Efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent gliomas (phase I/II study).
Twenty-two patients with recurrent glioma have been treated on a dose escalation protocol with fractionated stereotactic external beam radiotherapy (SRT). All had previously received radical radiotherapy (median dose 55 Gy) as part of the initial treatment. The dose of SRT was increased from 30 Gy in six fractions to 50 Gy in ten fractions. Median survival from the date of SRT was 9.8 months. There was no significant acute morbidity but five patients who received > or = 40 Gy developed steroid responsive neurological deterioration assumed to represent late radiation damage. The survival and toxicity in patients with recurrent glioma are comparable with interstitial therapy. Fractionated SRT is a noninvasive form of localised radiation which may be a suitable alternative to interstitial therapy in this group of patients.
Adolescent↗
Effects of genotype and cryopreservation of avian semen on fertility and number of perivitelline spermatozoa.
1. The fertility of freshly diluted and cryopreserved samples of semen obtained from a population of chickens selected for duration of fertility of cryopreserved spermatozoa (FS line) and its unselected control (FC line) were compared over a range of spermatozoa concentrations (10, 40, 80, and 160 x 10(6) sperm/50 microliters insemination). 2. The spermatozoa of the FS line had greater fertility than spermatozoa of the FC line, whether freshly diluted or cryopreserved. Cryopreservation resulted in a reduction in fertility, regardless of line. There were no significant line by genotype interactions. 3. There were fewer spermatozoa from the FC line than the FS line found in the perivitelline membrane (perivitelline spermatozoa). The increase in number of perivitelline spermatozoa with increasing sperm concentration was greater in the FS than FC line. However, the slope of the increase in sperm number in the perivitelline membrane with increasing concentrations of cryopreserved spermatozoa was zero. 4. A minimum of 10(3) perivitelline spermatozoa must be found on day 2 post-insemination for duration of fertility to exceed three days. The ability to produce spermatozoa capable of reaching the forming perivitelline membrane appears to be a quantitative, rather than a qualitative, trait and may be subject to genetic manipulation.
Animals↗
A neural network approach to automatic chromosome classification.
Classification of banded metaphase chromosomes is an important step in automated clinical chromosome analysis. We have conducted a preliminary investigation of the application of artificial neural networks to this process, making use of a natural representation of the banding pattern. Two different network architectures have been compared: the Kohonen self-organizing feature map and the multi-layer perception (MLP). For each of these a search of their respective parameter spaces over a limited range has resulted in configurations of modest dimension which achieve creditable classification rates. The MLP in particular shows promise of being a useful classifier. When size and shape features are supplied as inputs to the MLP in addition to a low-resolution banding profile, misclassification rates are obtained which are comparable with those of a well developed statistical classifier.
Chromosomes↗
Double firing of ECT machine.
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Electroconvulsive Therapy↗
Intraarticular ACL reconstruction using the patellar tendon: arthroscopic technique.
Endoscopic ACL reconstruction using the bone-patellar tendon-bone autograft has been shown to have good, reliable results. The procedure provides excellent reproducible fixation immediately and allows for early aggressive rehabilitation that includes range of motion, strengthening, and rapid return to sports.
Anterior Cruciate Ligament↗
Research review: pattern analysis for quality problems in medicine.
In conclusion, these results suggest that pattern analysis may provide a flexible and dynamic tool with which to sort cases prior to review, and evaluate changing medical practice patterns. Patterns analysis may also provide a way to avoid spending time and resources on cases with a low probability of quality problems. Lastly, pattern analysis promises to increase timely information and feedback to health care professionals and organizations.
Data Collection↗
BCG cell imaging using scanning probe microscopy.
Scanning tunneling microscopy (STM) and atomic force microscopy (AFM) were used to obtain images of the surface of whole, intact BCG (bacille Calmette Guerin, a mycobacterium) cells in air and under solution by immobilizing the cells onto glass slides (AFM only) or highly oriented pyrolytic graphite. The technique used for AFM imaging involved depositing a submonolayer of cells under a centrifugal force followed by fixation/dehydration using polar organic solvents. AFM images agree well with images from light and electron microscopy and showed large numbers of BCG cells in their distinctive cord arrangement. The AFM also proved useful for identifying extracellular microgranules which cannot be seen with light microscopy. For STM imaging, the hydrophobicity of BCG enabled strong adhesion from aqueous solution onto graphite. STM images of BCG could only be obtained while scanning in aqueous solution, and the cells showed a large variation in contrast when different samples were imaged. The STM provided greater detail of surface features than the AFM and was able to produce images of periodic layers corroborating observations made by transmission electron microscopy.
Microscopy↗
The effect of progestins on prolactin receptor gene transcription in human breast cancer cells.
The sex steroid hormone progesterone modulates the developmental and lactogenic activity of prolactin in the mammary gland. Regulation of the level of prolactin receptor (PRLR) provides one possible mechanism by which this may occur, prompting this investigation of the molecular mechanisms involved in progestin regulation of prolactin receptor levels. Treatment of T-47D and MCF-7 human breast cancer cells with 10 nM of the synthetic progestin ORG 2058 for 24 hr resulted in an increase in all four PRLR mRNA transcripts detected. The effect of ORG 2058 was shown in T-47D cells to be time- and concentration-dependent and resulted in an approximate two-fold increase in PRLR mRNA after 24 hr of treatment with 10 nM or 100 nM ORG 2058. Nuclear run-on assays indicated that ORG 2058 increased the rate of T-47D PRLR gene transcription at all times between 1 hr and 28 hr of treatment. The protein synthesis inhibitors cycloheximide and puromycin abrogated the induction of PRLR gene transcription at 1 hr and 2 hr, which demonstrated that on-going protein synthesis was required for the ORG 2058 effect and suggested that progestins may exert some transcriptional effects via the induction of an intermediary protein. These experiments demonstrated that progestin induced a transcriptionally based increase in PRLR gene expression and provided a mechanism by which progesterone may modulate the mitogenic activity of prolactin during mammary gland development.
Autoradiography↗
A neural network chromosome classifier.
We present a chromosome classifier for automated karyotyping of banded chromosomes which uses a multi-layer perception neural network. Two network configurations have been investigated. The resulting classifiers have been trained and tested on data from three different data sets covering a range of data quality. Classification results compare very favourably with those obtained using a highly optimised parametric classifier.
Chromosomes↗
Results of the multicenter evaluation of the CEDIA Phenytoin assay.
Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay.
Dose-Response Relationship, Drug↗
Direct transcriptional regulation of the progesterone receptor by retinoic acid diminishes progestin responsiveness in the breast cancer cell line T-47D.
Retinoic acid (RA) treatment of T-47D human breast cancer cells results in a rapid decrease in the concentration of progesterone receptor (PR) mRNA which causes a slow loss of cellular PR protein (Clarke, C. L., Roman, S. D., Graham, J., Koga, M., Sutherland, R. L. (1990) J. Biol. Chem. 265, 12694-12700). The mechanisms involved are unknown and this study was undertaken to determine whether the decline in PR mRNA was due to transcriptional inhibition and to evaluate the functional consequences of the RA-mediated decrease in PR. The transcription rate of the PR gene was decreased by RA, and the effect was maximal 2-3 h after treatment. Cycloheximide cotreatment was unable to relieve the inhibitory effect of RA and PR transcription suggesting that the effect was not dependent on ongoing protein synthesis. There was no effect of RA on PR mRNA half-life at the times examined (0-6 h of RA treatment). To determine the functional consequence of PR down-regulation the progestin-responsive plasmid pMSG-CAT was expressed transiently in T-47D cells which were then exposed to RA for 24 h. RA-pretreated cells were then treated with the synthetic progestin ORG 2058 and the extent of progestin stimulation of chloramphenicol acetyltransferase (CAT) activity measured. ORG 2058 treatment resulted in an induction of CAT activity which was maximal at a progestin concentration of 1 nM. Interestingly, the ability of ORG 2058 to induce CAT activity was decreased in RA-pretreated cells. The diminished progestin responsiveness of RA-pretreated cells was confirmed in separate experiments which showed that the progestin inducibility of TGF-alpha mRNA was also decreased in cells treated with ORG 2058 following pretreatment with RA for 24 h. These data demonstrate that RA decreases PR mRNA concentrations by direct transcriptional inhibition, leading to decreased cellular PR concentrations. The decreased levels of PR result in impaired responsiveness to progestins and this suggests that RA derived from dietary vitamin A may have a role in modulating cellular sensitivity to progestins.
Breast Neoplasms↗
Ten years of living with AIDS.
Everyone who has been involved in AIDS work over the past decade has lost a loved one to the disease. The crisis, unfortunately, is far from over; the loss of life will continue for many years. This tenth anniversary provides an opportunity both for reflection and for garnering strength for the tasks that lie ahead.
Acquired Immunodeficiency Syndrome↗
A new, rapid, one-step method for the isolation of platelets from human blood.
We describe a new, rapid method for the isolation of platelets from human blood using a single centrifugation step through Nycodenz, an inert, nontoxic, nonionic medium. As judged by aggregation and nucleotide release studies, the platelets are recovered in high yield and in excellent functional condition.
Adenosine Diphosphate↗
Evidence for a role of glycine in area tempestas for triggering convulsive seizures.
An epileptogenic region of the deep prepiriform cortex, area tempestas (AT), triggers convulsive seizures in response to the focal application of GABA antagonists, muscarinic agonists and excitatory amino acid agonists. In all cases, activation of N-methyl-D-aspartate (NMDA)-sensitive receptors in AT is required for triggering convulsions from this site. To determine whether glycine is involved in the activation of NMDA-sensitive receptors in AT, we evaluated the effects of 7-chlorokynurenic acid (7-CLKYN); kynurenic acid (KYN) and 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on convulsions evoked by focal application of bicuculline methiodide (118 pmol) into AT. Significant anticonvulsant effects were obtained with 1.25 nmol of 7-CLKYN, 6.25 nmol of KYN and 60 nmol of HA-966 in AT. 7-CLKYN in AT also blocked the convulsant effects of carbachol (273 pmol) and kainic acid (117 pmol) injected into AT. When injected into the lateral ventricle, high doses (50-100 nmol) of 7-CLKYN were required in order to attenuate AT-evoked convulsions and these doses produced marked ataxia. In contrast, no ataxia was observed following 7-CLKYN application into AT at anticonvulsant doses. Our results implicate glycine antagonism as a mechanism for preventing convulsions triggered via NMDA receptor activation in AT and demonstrate that a different anatomical site of action is responsible for the motor impairment produced by glycine antagonism.
Animals↗