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Biomedical subjects

R Wong

Publications and source records attributed to R Wong.

At least 109 records · Page 6Linked to original sources
PubMed1996

Bipedal lymphography in the management of carcinoma of the anal canal.

The purpose of this study was to determine the extent of metastatic pelvic lymph nodes evident on bipedal lymphography in a group of patients under consideration for combined radiation therapy and chemotherapy as definitive treatment for carcinoma of the anal canal. Lymphography was attempted in 32 patients and successful bilateral cannulation and opacification of nodes was achieved in 28 (88%). Seven patients had lymphographic evidence of external iliac node metastases (25%). When patients were categorized according to the extent of clinically evident disease at presentation, 0/15 patients with T1/T2 tumours had positive lymphograms whereas 7/13 patients with T3/T4 tumours and/or positive inguinal or peri-rectal nodes had positive lymphograms (Fisher's exact test p = 0.0015). All patients with a positive lymphogram had undergone CT scanning of the pelvis and in only one patient was external iliac node involvement detected. In none of these patients was visceral or more extensive nodal metastases discovered. Subsequently, the external iliac nodes with radiological evidence of metastases on lymphography were included in the treatment volume taken to radical dosage. The projected cause specific actuarial 5 year survival for this cohort of patients is 86% (median follow-up 4 years). Since the prognosis for patients who relapse in pelvic nodes is poor, bipedal lymphography is advocated as a staging procedure in patients with advanced primary tumours and in all patients with clinically positive inguinal or peri-rectal lymph nodes who are being considered for curative therapy.

Adult↗
PubMed1996

Automated HPLC screening of newborns for sickle cell anemia and other hemoglobinopathies.

Automated HPLC is used to test dried blood-spot specimens from newborns for hemoglobins (Hb) F, A, S, C, E, and D. We present the method and report on its performance determined during >4 years of testing 2.5 x 10(6) newborns. The method features automated derivation of presumptive phenotypes; quantitative quality control and proficiency testing; throughput of one specimen per minute; small sample volume; hemoglobin concentrations quantified with an interlaboratory CV of 14-18%; retention times with interlaboratory CV of <2% and matching, within +/- 0.03 min, of laboratories and reagent lots; control of peak resolution; 0.5% detection limit for Hb S and C, and 1.0% for Hb F, A, E, and D; few interferences; and negligible background and carryover. Shortcomings of the method are the absence of microplate barcode identification and the need for manually pipetting the sample eluate into the microplate.

Anemia, Sickle Cell↗
PubMed1996

The role of radiotherapy in the management of pelvic recurrence of rectal cancer.

Unresectable pelvic recurrence from carcinoma of the rectum becomes invariably symptomatic. While radiotherapy remains the most common antineoplastic modality used for palliation of symptoms, the optimal radiation dose and fractionation remains undefined. A systematic review of the literature was performed to determine the most effective dose fractionation schedule for the relief of symptoms in patients with pelvic recurrence. An expert panel reviewed and interpreted the data, with a special focus on indications, effectiveness, optimal dose fractionation, and toxicity of radiotherapy in this context. Only retrospective data (level V evidence) were available on this issue and were reviewed. Pain relief was the major indication for treatment, although bleeding and mucous discharge were also seen as indications for radiotherapy. Initial pain relief appeared to be achievable in 70-90% of patients. The median duration of pain relief was approximately three months, 23-50% of patients had symptom control at six months. The value of "local control" as a meaningful additional endpoint was discussed. There were no significant differences observable in initial symptom response and the proportion maintaining a response at six months, within the range of doses employed, comparing "lower" versus "higher" doses (using 45-50 Gy as the dividing dose). Toxicity was usually evaluated qualitatively and was deemed acceptable. The expert panel agreed that pelvic radiotherapy has a definite value in the relief of symptoms in patients with pelvic recurrence from rectal carcinoma. The optimal dose fractionation in this context could not be determined in view of the quality of the data available. Well designed, randomized studies with clinically relevant study arms and endpoints are necessary to define an optimal dose fractionation against which alternative strategies can be compared.

Humans↗
PubMed1995

Ultrastructural basis for synaptic transmission between jaw-muscle spindle afferents and trigeminothalamic neurons in the rostral trigeminal sensory nuclei of the rat.

Trigeminothalamic neurons were retrogradely labeled by injection of horseradish peroxidase into the ventroposteromedial nucleus of the thalamus in rats. Jaw-muscle spindle afferent axons were then physiologically identified and intracellularly stained with biotinamide. The ultrastructure of labeled spindle afferent boutons was then studied in the caudolateral supratrigeminal region (Vsup) and dorsomedial trigeminal principal sensory nucleus (Vpdm). A total of 418 stained spindle afferent boutons were identified in Vsup and Vpdm; approximately 75% of these synapsed with dendrites, 10% synapsed with somata, and 15% synapsed with axons. Most jaw-muscle spindle afferent boutons were postsynaptic to unlabeled P-type boutons. Reciprocal synapses between spindle afferent boutons and unlabeled boutons were occasionally observed. A few dendrites in Vsup and Vpdm received synapses from multiple spindle afferent boutons. Conversely, some large (from 3 x 6 to 4 x 8 microns) and giant (from > 4 x 8 to 5 x 10 microns) spindle afferent boutons simultaneously contacted two to five dendrites and/or somata. Jaw-muscle spindle afferent boutons also formed synapses with retrogradely labeled trigeminothalamic neurons in Vsup and Vpdm. Numerous unlabeled S-and F-type boutons converged onto the same trigeminothalamic dendrite or soma contacted by a spindle afferent bouton. A small number of synaptic triads consisting of an unlabeled P-type bouton, a spindle afferent bouton, and either a dendrite or soma were also encountered. These data indicate that sensory feedback from the masticatory muscles is subject to presynaptic inhibition and integration prior to reaching the thalamus. This pathway is likely to be important in the relay of proprioceptive and kinesthetic information from the muscles of mastication to the thalamus.

Afferent Pathways↗
PubMed1995

Projection of jaw-muscle spindle afferents to the caudal brainstem in rats demonstrated using intracellular biotinamide.

Intracellular staining with biotinamide was used to study the axonal projection and synaptic morphology of rat jaw-muscle spindle afferents. Intracellular recordings in the mesencephalic trigeminal nucleus (Vme) were identified as spindle afferent responses by their increased firing during stretching of the jaw-elevator muscles. Biotinamide-stained axon collaterals with boutons were found in the trigeminal motor nucleus (Vmo), Vme, the region dorsal to Vmo including the supratrigeminal region, the dorsomedial portion of the trigeminal principal sensory nucleus, and the dorsomedial part of the rostral spinal trigeminal subnucleus oralis. Additional, previously undescribed projections of jaw-muscle spindle afferents were found to the dorsomedial portion of the caudal spinal trigeminal subnucleus oralis (Vodm), the dorsomedial part of the spinal trigeminal subnucleus interpolaris (Vidm), the caudal parvicellular reticular formation, laminae IV and V of the spinal trigeminal subnucleus caudalis (Vc), and the dorsal division of the medullary reticular field. Labeled spindle boutons in Vodm formed predominately axodendritic synapses. Some of these boutons received presynaptic inputs from unlabeled P-type boutons containing clear, spherical, or flattened vesicles. In Vidm, labeled collaterals and boutons were densely clustered into glomerular-like structures. Labeled boutons in Vidm made axodendritic, axosomatic, and axoaxonic synapses and received synaptic contacts from unlabeled boutons containing clear, spherical, or flat and pleomorphic vesicles. Unlabeled presynaptic boutons in Vidm occasionally contained dense core vesicles. Labeled boutons in Vc mainly formed synaptic contacts with large diameter dendrites. This projection of jaw-muscle spindle afferents to caudal brainstem regions may play a significant role in masticatory-muscle stretch reflexes and in the integration of trigeminal proprioceptive information and its transmission to higher centers.

Afferent Pathways↗
PubMed1995

Reduced inter- and intrasubject variability in cyclosporine pharmacokinetics in renal transplant recipients treated with a microemulsion formulation in conjunction with fasting, low-fat meals, or high-fat meals.

This cross-over study compared the pharmacokinetic parameters obtained from cyclosporine (CsA) concentration-time profiles after administration of the corn oil-based soft gel cap (CsA-GC) with those with the microemulsion (CsA-ME) gel cap. Neither the fasting state nor the coadministration of a low- or high-fat breakfast affected the pharmacokinetics of CsA presented in either formulation. Comparisons of the three sets of pharmacokinetic parameters--namely, after fasting or after low-fat or after high-fat diets--demonstrated the CsA-ME formulation to display greater intraindividual reproducibility of the C0 and C12 trough levels (TLs), Cmax, tmax, and area under the concentration-time curve (AUC) than the CsA-GC formulation. Although the degree of interindividual variation in AUC, Cmax and tmax after CsA-ME administration was slightly, but significantly, less than after CsA-GC administration, there was no difference between the two formulations in terms of the customarily monitored C0 or C12 TL values. CsA-ME showed higher correlation coefficients of drug exposure (AUC) with C12 than CsA-GC (0.910 versus 0.712). However, CsA-ME administration resulted in only modest improvement over CsA-GC administration in the relationships between drug dose and C0, C12, or AUC--namely, 0.645 versus 0.496, 0.611 versus 0.517, and 0.700 versus 0.501, respectively. Correlation analysis between individual timed samples and AUC determinations revealed that CsA-ME requires significantly less frequent blood monitoring for prediction of total drug exposure than does CsA-GC. Although the clinical utility of this reproducible pharmacokinetic behavior remains to be demonstrated in the de novo transplant setting, the markedly reduced intraindividual variation produced by administration of CsA-ME will likely improve the accuracy of pretransplant prediction of, and reduce the frequency of subsequent adjustments in, CsA doses.

Corn Oil↗
PubMed1995

Gangliosides and spinal cord ischemia secondary to aortic cross-clamping in the rat model.

Gangliosides, complex glycolipids of the nervous system cell membranes, have been found effective both in reducing the degree of ischemic injury and in stimulating neuronal regeneration during the recovery period. In order to investigate their neuroprotective effect during spinal cord ischemia, 60 male Sprague-Dawley rats underwent occlusion of the thoracic aorta and both subclavian arteries for 13 min. In the postoperative period, function of hindlimbs was appraised, daily for 30 days, by a deficit score (0-15). The animals were then killed and spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. The rats received intraperitoneal injection of placebo (n = 29) or GM-1 30 mg/kg (n = 31) daily, from 2 days prior to surgery to 15 days after. The scores of each group for each day were analyzed by repeated measures analysis of variance. The rate of recovery was better for GM-1 (P < 0.001) from the 15th to the 30th day. A trend was seen toward lower scores in the GM-1 group (P = 0.056). Mean histologic scores (placebo = 1.14 +/- 0.23 SE, GM-1 = 1.58 +/- 0.22 SE) did not differ (Wilcoxon, P = 0.17). The present data support the hypothesis that functional improvement after spinal cord ischemia due to aortic occlusion is enhanced by the administration of gangliosides. Optical microscopy could document only irreversible injury and might not be sensitive enough to detect subtle changes during recovery of neural elements.

Animals↗
PubMed1995

Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy.

Patients with cardiac infarction show a decrease in glutathione peroxidase and superoxide dismutase activities, which are beginners in the scavenger processes of lipid peroxide and superoxide radicals, respectively. In this study, we investigate the effects of endovenous ozone therapy on serum lipid pattern and on antioxidant defense system, such as te glutathione redox one, in the blood of patients with myocardial infarct. Twenty-two patients who had an infarction, between 3 months and 1 year before the study, were treated with ozone by autohemotherapy during 15 sessions. A statistically significant decrease in plasma total cholesterol and low density lipoprotein was observed. High biologically significant increases on erythrocyte glutathione peroxidase and glucose 6-phosphate dehydrogenase activities were found. There was no change in plasma lipid peroxidation level. It was concluded that endovenous ozone therapy in patients with myocardial infarction has a beneficial effect on blood lipid metabolism, provoking the activation of antioxidant protection system.

Aged↗
PubMed1995

Role of gastroesophageal reflux disease in patients with cervical symptoms.

Otolaryngologists commonly see patients with various nonspecific upper aerodigestive or "cervical" symptoms. The relationship between gastroesophageal reflux disease and these symptoms has been studied but remains unclear. We reviewed the records of 216 patients with various cervical symptoms. Each patient underwent a uniform investigation that included barium swallow, esophageal manometry, acid stimulation testing, and esophagoscopy with distal biopsy. Patients were treated with a combination of a histamine H2 blocker or omeprazole and a prokinetic agent. Follow-up was obtained in 194 patients. Overall, evidence of gastroesophageal reflux disease was detected in 73% of patients. Complete resolution or improvement of symptoms was seen in 84% of patients with treatment. We believe gastroesophageal reflux disease is an important factor in the cause of cervical problems.

Adolescent↗
PubMed1995

Degeneration of axons in the corticospinal tract secondary to spinal cord ischemia in rats.

Occlusion of the thoracic aorta and both subclavian arteries (XC) in the rat model produces spastic paraplegia. In order to characterize the lesion of white matter, 14 male Sprague-Dawley rats underwent XC for 10.5 to 12 min, were observed for 32 days and assessed with a lesion score. A sham group of eight underwent surgical manipulations without XC. The spinal cords were studied by optical microscopy and electron microscopy. An additional group of normal animals (n = 8) underwent spinal cord blood flow measurement with the autoradiographic technique. Optical microscopy showed normal histology in sham operated rats and rats with aortic cross-clamp and lesion score = 2-4 (n = 5), rare changes in the white matter of rats with lesion score = 8 (n = 2), and demyelination of the anterior and lateral tracts of the white matter and motor neuron loss in the gray matter of rats with lesion score = 13-15 (n = 7) and spastic paraplegia. In this last group, electron microscopy disclosed severe axonal degeneration of corticospinal tracts. In the same region spinal cord blood flow was higher than the remaining white matter. This study confirms that spastic paraplegia observed in the rat model after XC is due to degeneration of the pyramidal tracts, perhaps more susceptible to injury due to the high spinal cord blood flow.

Animals↗
PubMed1995

Expression of GTPase-deficient Ras inhibits vasopressin signaling in cultured cortical collecting duct cells.

Cross-talk between signaling pathways is increasingly recognized as integral to cellular function. We investigated whether the mitogen-activated protein kinase (MAPK) pathway alters vasopressin (AVP) stimulation of protein kinase A (PKA) by specifically studying the role of Ras. Mouse cortical collecting duct cells (M-1) were transfected with a cDNA encoding oncogenic Ras. Transfection was confirmed by Western blot analysis and functionally by enhanced basal MAPK activity. When compared with basal MAPK activity of 26.4 +/- 6.6 pmol/mg/min in controls, basal MAPK activity varied widely in Ras-transfected clones from 29.0 +/- 6.6 to 96.6 +/- 13.4 pmol/mg/min. Clones that functionally expressed activated Ras displayed complete abolition of AVP-stimulated PKA activity, whereas those that failed to express elevated basal MAPK activity showed intact AVP-stimulated PKA. The correlation between expression of high basal MAPK activity and inhibition of AVP-induced PKA yielded a correlation coefficient of -0.92 (P = 0.009). Exposure to 10 microM forskolin or 1 microgram/ml cholera toxin resulted in comparable activation of PKA in all clones. We found no correlation between PKC activity of the clones and PKA inhibition. To assess whether the observed effect was due to one known Ras target, cells were transfected with constitutively activated Raf. M-1 cells expressing activated Raf exhibited elevated MAPK activity. The Raf clones showed no impairment of AVP-stimulated PKA activity. We conclude that expression of activated Ras is inhibitory of AVP-induced PKA activation in the M-1 cortical collecting duct cell line at a site proximal to G alpha s protein. The failure of Raf to influence AVP signaling indicates that the action of Ras is through a pathway independent of this Ras target.

Amino Acid Sequence↗
PubMed1995

Methods for the quantification of DNA double-strand breaks determined from the distribution of DNA fragment sizes measured by pulsed-field gel electrophoresis.

Different methods were used for evaluating data for DNA double-strand breaks (DSBs), as obtained by pulsed-field gel electrophoresis (PFGE) after X irradiation of Chinese hamster ovary cells. A total of 60 data points in the dose range of 0 to 116 Gy, along with repair data for 30 and 60 Gy, were analyzed by four methods: (1) percentage of DNA released from the plug, (2) specific size markers (percentage of DNA less than specific sizes, (3) fragment size distributions and (4) shape of the molecular weight (M) distributions. With the last method, both the slope and the intercept of the logarithm of the amount of radioactive DNA/delta M/M plotted as a function of M were used for calculating DSBs/100 Mbp. The slope and the intercept analyses differ in that the former is relatively independent of DNA trapped in the agarose plugs, i.e. cannot be released by doses of 100-150 Gy, whereas the intercept is dependent on the percentage of DNA trapped. Also, calculations of DSBs/100 Mbp for methods 1, 2 and 3 depend on the amount of DNA trapped in the plug. However, the slope method is unreliable for doses below about 20 Gy, and the scatter of data points is much greater than that obtained by the intercept method and by methods 1, 2 and 3. Therefore, the fragment size distribution and the specific size marker methods give the most consistent results, with 0.49 +/- 0.03 (95% CI) (DSBs/100 Mbp)/Gy. With the specific size marker method, however, care must be taken in selection of size markers in relation to the levels of DSBs of interest. Assuming randomly distributed DSBs, all four methods gave essentially the same results; i.e., the dose response was linear with a calculated level of 0.5-0.6 (DSBs/100 Mbp)/Gy, which is the same as 0.47-0.62 determined previously by calibrating with 125IdU.

Animals↗
PubMed1995

Cell type-dependent modulation of the dominant negative action of human mutant thyroid hormone beta 1 receptors.

BACKGROUND: Mutations in the ligand-binding domain of the thyroid hormone receptor beta (TR beta) gene cause the syndrome of resistance to thyroid hormone (RTH). The clinical phenotype results from the antagonism of the normal TR alpha and the non-mutated TR beta alleles by the TR beta 1 mutants, via a dominant negative effect. There is, however, marked heterogeneity of organ resistance within and among kindreds with RTH. This study examines the potential role of cell type in modulating the dominant negative potency of human TR beta 1 (h-TR beta 1) mutants. MATERIALS AND METHODS: Transient transfections were performed in HeLa and NIH3T3 cells, using a wild type (WT) and three naturally occurring mutant h-TR beta 1 constructs, and three natural thyroid hormone response elements (TREs). Immunocytochemistry was performed to detect levels of TR beta 1 expression in these two cell types. In order to determine how TR beta 1 interacts with other cellular partners, gel-shift analyses using HeLa and NIH3T3 nuclear extracts were performed. RESULTS: Transfection studies using WT h-TR beta 1 in HeLa and NIH3T3 cells, showed that the 3,3',5-triiodothyronine (T3)-induced transactivation of the different TREs varied between cell types. Unlike the non-T3-binding h-TR beta 1 mutant, PV, mutants ED and OK displayed the expected T3-induced dose responsiveness in these two cell types. For each TRE examined, the magnitude of the dominant negative effect varied between the cell types. The levels of receptor expression in HeLa and NIH3T3 cells were identical, as determined by immunocytochemistry. Gel-shift analyses showed differences in the formation of hetero- and homodimers depending on both the cell type and TRE motif. CONCLUSIONS: The cell type in which a mutant receptor operates affects the relative amounts of hetero- and homodimers. Together with the nature of the mutation and the TRE-motif, this could modulate the dominant negative action of mutant receptors in different tissues, which, in turn, could contribute to the variable phenotypic characteristics of RTH.

3T3 Cells↗
PubMed1994

Automated HLA-B27 testing using the FACSPrep/FACScan system.

Tissue typing can help in the diagnosis of the seronegative arthropathy ankylosing spondylitis. Using an automatic sample preparation system and flow cytometry (FACSPrep/FACScan) we have developed a test for HLA-B27 screening using whole blood which is both rapid, reproducible, and permits simultaneous screening of large numbers of samples. We have used both indirect (248 cases) and direct (126 cases) monoclonal antibody staining techniques. Results were assessed using median channel shift (CS) from the negative control and relative fluorescence intensity. There is known cross-reactivity between HLA-B27 and HLA-B7 with the monoclonal antibody (MoAb) HLA-ABC-m3. Using this antibody and indirect staining, HLA-B7 samples had a significantly lower CS value than HLA-B27 samples. In 60% of these cases there was a clear distinction between HLA-B27 and HLA-B7. All HLA-B27 and HLA-B7 negative samples had a CS of 0 (P < 0.001). Using direct dual staining with CD3 and HLA-B27, all HLA-B27 and HLA-B7 negative samples had a low CS value (15 maximum), HLA-B7 samples had an intermediate CS value (20-85), and HLA-B27 samples had the highest CS values (70 upward). This system permits large scale rapid negative screening of samples with the elimination of over 60% as negatives (CS < 15). Limitations as a definitive test for HLA-B27 are due to MoAb cross-reactivity with HLA-B7 which necessitates other confirmatory techniques. The substitution of the HLA-ABC-m3 with the recently available HLA-B27 specific MoAb FD705 would substantially increase the value of this technique for routine HLA-B27 typing.

Antibodies, Monoclonal↗
PubMed1994

Detection of T-cell receptor beta chain mRNA in frozen and paraffin-embedded biopsy tissue using digoxigenin-labelled oligonucleotide probes in situ.

In situ hybridization techniques using a cocktail of digoxigenin-labelled T-cell receptor (TcR) constant (C) region beta oligonucleotide probes were used to detect TcR beta mRNA in frozen and paraffin-embedded tissue sections. The specificity of the C beta cocktail was confirmed by Northern blot analysis. The TcR C beta cocktail successfully hybridized to T cells in frozen and paraffin-embedded tissue obtained from patients with inflammatory arthropathies, B- and T-cell non-Hodgkin's lymphoma (NHL), and reactive tonsillitis, and showed staining patterns comparable to those obtained by conventional immunohistological detection of T cells. This is the first report of in situ studies using labelled TcR C beta oligonucleotide probes and may indicate the feasibility of investigating clonal T-cell populations using digoxigenin-labelled clonospecific probes in clinical samples in situ.

Biopsy↗