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Biomedical subjects

C Watson

Publications and source records attributed to C Watson.

At least 91 records · Page 5Linked to original sources

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection.

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.

Adult↗

Multiple frequency bioimpedance: a bed-side technique for assessment of fluid shift patterns in a patient with severe dehydration.

This report describes the use of multiple frequency bioimpedance analysis (MFBIA) to monitor fluid changes in a patient who developed severe dehydration and recovered. Initially, the patient weighed 53.2 kg, his total body water (TBW; D(2)0 dilution) was 33.5 L, his extracellular water (ECW; Br dilution) was 19.5 L, and hydration of the fat-free mass (FFM; dual-energy X-ray absorptiometry) was normal (73%). The resistances at infinite and 0 frequency were R(inf) = 454 and R(0) = 580 ohm respectively, which predicted TBW = 33.1 L and ECW = 16.6 L. On day 7, when the weight loss was 7.2 kg, FFM had decreased by 7.4 kg, and R(inf) and R(0) had increased to 662 and 902 ohm respectively, predicting decreases of 5.8 L in TBW and 3.7 L in ECW. On recovery (day 14), all parameters had returned to baseline values. This study encourages the use of MFBIA as a bed-side technique for the serial assessment of body water compartments in patients with disturbances in fluid balance.

Journal Article↗

Isolation and characterization of phenoloxidase from egg masses of the gastropod mollusc, Biomphalaria glabrata.

Previous studies have shown that phenoloxidase activity is present in the albumen gland and egg masses of Biomphalaria glabrata, and its potential role in egg formation in this snail has been proposed. In the present study, a phenoloxidase enzyme has been isolated from the supernatant of egg mass homogenates using a combination of hydrophobic interaction chromatography and gel filtration high-performance liquid chromatography (GF-HPLC). The isolated phenoloxidase eluted as a single peak of activity upon GF-HPLC (representing a 132-fold purification) and subsequently was detected as a single band with an estimated molecular mass of 35 kDa by SDS-PAGE analysis. Phenylthiourea-inhibitable mono- and diphenoloxidase activities were demonstrated for the isolated enzyme suggesting that both enzyme activities are associated with a single, tyrosinase-type molecule.

Ammonium Sulfate↗

Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors.

Human breast cell carcinoma MCF-7 cells were found to bind 125I-labeled rat amylin (rAmylin) and the peptide amylin antagonist radioligand 125I-AC512 with high affinity. This high affinity binding possessed characteristics unique to the already defined high affinity binding site for amylin in the rat nucleus accumbens [Mol. Pharmacol. 44:493-497 (1993); J. Pharmacol. Exp. Ther. 270:779-787 (1994); Eur. J. Pharmacol. 262:133-141 (1994)]. To further define this receptor, we report results of expression cloning studies from an MCF-7 cell library. We isolated two variants of a seven-transmembrane receptor that were identical to two previously described human calcitonin receptors (hCTR1 and hCTR2). These receptors were characterized by expression in different surrogate host cell systems. Transient expression of hCTR1 in COS cells yielded membranes that bound 125I-AC512 and 125I-salmon calcitonin with high affinity, but no high affinity binding was observed with 125I-human calcitonin (hCAL) or 125I-rAmylin. Stable expression of hCTR1 in HEK 293 cells produced similar data. In contrast, expression of hCTR2 in COS cells yielded membranes that bound 125I-AC512, 125I-hCAL, and 125I-rAmylin with high affinity. The agonists 125I-hCAL and 125I-rAmylin bound 65% and 1.5%, respectively, of the sites bound by the antagonist radioligand 125I-AC512 in this expression system. This pattern of binding was repeated in HEK 293 cells stably transfected with hCTR2 (125I-hCAL = 24.8% Bmax, 125I-rAmylin = 8% Bmax). In both expression systems, the agonists hCAL and rAmylin were much more potent in displacing their radioligand counterparts than was the antagonist radioligand 125I-AC512. For example, the pKi value for displacement of 125I-AC512 by rAmylin was 7.2 in HEK 293 cells but rose to 9.1 when displacing 125I-rAmylin. Finally, hCTR2 was expressed in baculovirus-infected Ti ni cells. In this system, only specific binding to the antagonist 125I-AC512 and agonist 125I-hCAL was observed; no binding to 125I-rAmylin could be detected. These data are discussed in terms of two working hypotheses. The first is that amylin is a weak agonist for hCTR2 and that this receptor is unrelated to the amylin receptor found in this cell line. The second is that hCTR2 couples to different G proteins for calcitonin and amylin function in different cells. At present, these data cannot be used to disprove conclusively either hypothesis.

Amino Acid Sequence↗

Evaluation of a project to enhance knowledge of hereditary diseases and management.

During 1992 and 1993, in a designated suburban area of Perth, Western Australia, information on hereditary disease was provided for health professionals and the general community. This information was in the form of posters, pamphlets, postal flyers and return letter cards, a static display, newspaper articles, advertisements and radio broadcasts, and professional seminars. The aim of this project was to evaluate the effectiveness of combined strategies to convey practical information about hereditary disease to the community and health professionals. Multiple measures of response evaluation were used, which included structured questionnaire surveys of health professionals and members of the community before and after the project. In the community surveys, respondents who were female, married, middle aged, and parents, and had a higher level of education or were born in Australia, New Zealand, or the United Kingdom were generally better informed about hereditary diseases. This intervention resulted in only meagre changes in community knowledge about hereditary disease, even though promotional materials were shown to be appropriate. General Practitioners (GPs) and Child Health Nurses (CHNs) were supportive of clinical genetic services and recognised a need for continuation of education in this field. There is a rapidly increasing need for community and health professional comprehension of the applications of the new genetic technology. This project indicates that routine educational and health promotion strategies will not be enough to achieve desired levels of knowledge and attitude change.

Adult↗

Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

Adolescent↗

Gender, race and poverty: bringing the sociopolitical into psychotherapy.

OBJECTIVE: To explore the modification of traditional psychotherapy to provide a more relevant service for non-dominant groups including women, Maori and the poor. METHOD: The philosophy and practice of a psychotherapy service that made overt sociopolitical issues for women, Maori and the poor was analysed and linked with literature on psychotherapy for non-dominant groups. RESULTS: Traditional psychotherapy, with its focus on the intrapsychic, has not addressed the condition of marginalised groups such as the poor, ethnic minorities including Maori, and some women, whose mental health difficulties have major contributions from external sources. The service analysed, and much of the literature, used social analysis as a therapeutic tool to break the cycle of self-blame and doubt and to contextualise intrapsychic experience. As non-dominant groups lack power, power differences in the therapy relationship should be lessened to avoid retraumatising the patient. CONCLUSION: It is possible for psychotherapy to broaden its traditional base to include a sociopolitical viewpoint. This would make it more available and meaningful to a wider range of people, especially those with the double disadvantage of adverse intrapsychic and sociopolitical factors.

Adult↗

Regulation of aromatase activity within the breast.

Local oestrogen biosynthesis within the breast can be highly variable, in vitro aromatase activity both in breast cancers and mammary adipose tissue displaying over a 40-fold range between the highest and lowest levels. Evidence is presented to show that: (i) transcriptional activity may influence oestrogen biosynthesis within breast cancers in that both aromatase mRNA and STAT nuclear binding are correlated positively to in vitro aromatase activity; (ii) the local presence of cancer may enhance aromatase activity in particulate fractions and primary fibroblast cultures from mammary adipose tissue; (iii) tumour extracts and breast cyst fluids may induce aromatase in cultured fibroblasts, the active principles responsible for these effects being incompletely defined (although the combination of interleukin (IL)-6 and its soluble receptor dramatically enhances aromatase activity, it is unclear whether this particular cytokine system can account for the stimulatory effects of breast extracts and fluids); (iv) the aromatase activities in both breast cancer and adipose tissues are susceptible to classical aromatase inhibitors such as aminoglutethimide and 4-hydroxyandrostenedione (and to newer inhibitors such as CGS16949 and CGS20267 at low nanomolar concentrations) but reduced sensitivity to 4-hydroxyandrostenedione may be observed in certain breast cancers. These findings may have important implications for the development and progression of hormone-dependent cancers within the breast.

Adipose Tissue↗

Differential patterns of neutrophil adhesion molecules during cardiopulmonary bypass in humans.

BACKGROUND: Neutrophils are activated during cardiopulmonary bypass, and it is believed that they play an important role in the postoperative inflammatory response. The effects of neutrophils are mediated by the surface adhesion molecules L-selectin, beta 2-integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1), and it has been reported that beta 2-integrins are upregulated and L-selectin downregulated by cardiopulmonary bypass. However, the time course of these changes and their relative importance are unclear. METHODS AND RESULTS: To investigate the temporal changes in the expression of the neutrophil surface adhesion molecules L-selectin, beta 2-integrins, and PECAM-1 induced by cardiopulmonary bypass, we used immunofluorescent flow cytometry in blood samples obtained at various times (before anesthesia, before bypass, and 0.25, 0.5, 1, 2, 4, 24, and 48 hours after initiation of bypass) from patients undergoing routine coronary artery bypass graft surgery. Anesthesia had no effect on the expression of any of the study molecules. The expression of all beta 2-integrins was not significantly affected during the entire study period. The mean fluorescence (expressed as a percentage of control) of CD18 did not change significantly during the first 2 hours after the initiation of cardiopulmonary bypass, but then it declined by 4 hours (P = NS) and attained its lowest values after 24 and 48 hours. The mean fluorescence of CD11b and CD11c decreased by 2 and 4 hours and remained reduced after 24 hours and 48 hours. The expression of PECAM-I decreased rapidly after the initiation of cardiopulmonary bypass to achieve 60 +/- 8% of the preanesthesia control values (P < .05) after only 1 hour; it fell to its lowest after 4 hours (44 +/- 8%; P < .05); and then it recovered partially by 24 hours (60 +/- 11%; P < .05), with a further recovery toward control after 48 hours (77 +/- 8%; P = NS). The profile for the mean fluorescence of PECAM-I was identical to that observed with its expression. In contrast, the expression and mean fluorescence of L-selectin were not changed during the 48-hour period. CONCLUSIONS: This study has demonstrated that cardiopulmonary bypass in humans induces (1) a rapid reduction in the expression of PECAM-I of circulating neutrophils, (2) a later reduction of beta 2-intergrin activity without significant changes in their expression, and (3) no alterations in the expression and activity of L-selectin. Thus, although the mechanism for the absence of neutrophil upregulation of beta 2-integrins and downregulation of L-selectin (no activation) remains to be elucidated, the downregulation of PECAM-1 indicates an early neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response usually associated with cardiopulmonary bypass.

CD18 Antigens↗

IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes.

Using a quantitative monolayer adhesion assay, the current report shows that treatment of human umbilical vein endothelial cells (HUVEC) with IL-6 increases their adhesiveness for blood lymphocytes, particularly CD4+ cells, but not for polymorphonuclear cells and monocytes. This effect, which was most pronounced when using low concentrations of the cytokine (0.1-1.0 U/ml) and a short incubation period (4h), was also apparent with microvascular endothelial cells and a hybrid endothelial cell line. Skin lesions from patients with mycosis fungoides contain high levels of IL-6, and blood lymphocytes from patients with this disorder also exhibited an enhanced adhesion to IL-6-treated HUVEC. The cytokine enhanced intercellular adhesion molecule-1 (ICAM-1) expression and induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on endothelial cells. Antibody blocking studies demonstrated that the vascular adhesion molecules ICAM-1, VCAM-1 and E-selectin and the leucocyte integrin LFA-1 all contributed to lymphocyte binding to endothelium activated by IL-6. It is proposed that IL-6 may be involved in the recruitment of lymphocytes into non-lymphoid tissue.

Adjuvants, Immunologic↗

Medial temporal lobe heterotopia as a cause of increased hippocampal and amygdaloid MRI volumes.

Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampus and amygdala are useful in detecting hippocampal and amygdaloid sclerosis in patients with temporal lobe epilepsy. In these pathological entities, volumetric MRI analysis shows the epileptogenic structures to be atrophic when compared to the normal, nonepileptogenic side. Described are 2 patients with increased hippocampal and amygdaloid volumes on the side of seizure onset due to medial temporal lobe heteroto pias. Care must be taken in the interpretation of volumetric MRI data to make certain that asymmetries in hippocampal and amygdaloid measurements are due to atrophy and sclerosis of the abnormal side and not to increased tissue such as heterotopic gray matter.

Adult↗

Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production.

Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (TH2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (TH1) cells express distinctive protection against infection with different pathogens. Interleukin-4 promotes the differentiation of naïve CD4+ T cells into IL-4 producers and suppresses their development into IFN-gamma producers. CD1-specific splenic CD4+NK1.1+ T cells, a numerically minor population, produced IL-4 promptly on in vivo stimulation. This T cell population was essential for the induction of IL-4-producing cells and for switching to immunoglobulin E, an IL-4-dependent event, in response to injection of antibodies to immunoglobulin D.

Animals↗

The sympathetic innervation of the eyes and face: a clinicoanatomic review.

Most of the details regarding the course of the sympathetic fibers to human ocular structures are based on anatomical and physiological studies in lower animals. While studying a clinical problem involving pericarotid sympathetic fibers, it became obvious that these animal observations cannot adequately explain the findings in human diseases affecting these pathways. An attempt was made, therefore, to clarify this situation. We were able to gather enough information from human clinical and experimental studies, from our own clinical observations, and from our cadaver dissections to conclude that these pathways are somewhat different from those which are usually described in the literature. Based on this information, we conclude that 1) the oculosympathetic fibers in man do not course through the tympanic plexus and/or trigeminal ganglion, and 2) the sweat glands of the face receive their innervation from both internal and external carotid sympathetic plexuses. We also have suggestive, but inconclusive, evidence regarding the final mode of distribution of these fibers to the dilator of the pupil and the smooth muscle portion (deep layer) of the levator palpebrae superioris muscle (superior tarsal muscle).

Animals↗

The Bradford and Airedale baby hearing project. An assessment of the impact of screening on the earlier detection of infant hearing loss.

An infant screening programme based on auditory brain stem response testing (ABR) to detect hearing loss in high-risk babies has been introduced in West Yorkshire. In the 3 year period prior to the introduction of the screen hearing loss was diagnosed by the age of 9 months in only 12%. This increased to 85% for children screened by a high-risk register and ABR.

Evoked Potentials, Auditory, Brain Stem↗