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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 343 records · Page 19Linked to original sources

Huntingtin protein colocalizes with lesions of neurodegenerative diseases: An investigation in Huntington's, Alzheimer's, and Pick's diseases.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease associated with a CAG trinucleotide repeat expansion in a large gene on chromosome 4. The gene encodes the protein huntingtin with a polyglutamine tract encoded by the CAG repeat at the N-terminus. The number of CAG repeats in HD are significantly increased (36 to 120+) compared with the normal population (8-39). The pathological mechanism associated with the expanded CAG repeat in HD is not clear but there is evidence that polyglutamine is directly neurotoxic. We have immunolocalized huntingtin with an in-house, well-characterised, polyclonal antibody in HD, Alzheimer's disease (AD), and Picks disease (PiD) brains. Control brain tissue sections were from head injured and cerebral ischaemia cases. In HD, huntingtin was immunopositive in the surviving but damaged neurons and reactive astrocytes of the caudate and putamen. However, in AD and PiD the immunostaining was largely restricted to the characteristic intracellular inclusion bodies associated with the disease process in each case. In AD, huntingtin was localized only in the intracellular neurofibrillary tangles and dystrophic neurites within the neuritic amyloid plaques but not with the amyloid. In PiD, strongly positive huntingtin immunostaining was present within cytoplasmic Pick bodies. Our findings suggest huntingtin selectively accumulates in association with abnormal intracytoplasmic and cytoskeletal filaments of neurons and glia in neurodegenerative diseases such as HD, AD, and PiD. Cells in the CNS appear sensitive to damage by the aggregated, toxic levels of huntingtin and evidence of its interaction with neurofilaments could provide information about its potential role in the aetiology of HD.

Adult↗

Endocrine profiles of female striped bass (Morone saxatilis) in captivity, during postvitellogenesis and induction of final oocyte maturation via controlled-release GnRHa-delivery systems.

Plasma levels of reproductive and thyroid hormones were measured in captive striped bass females during postvitellogenesis and the spawning period (March-June). Circulating gonadotropin II (GtH II), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta, 21-trihydroxy-4-pregnen-3-one (17,20beta,21-P) remained low and unchanged in nonmaturing females, while 17beta-estradiol (E2) and testosterone (T) declined throughout postvitellogenesis. Plasma thyroxine (T4) declined significantly in mid-April, while triiodothyronine (T3) increased in mid-May. The only female that ovulated spontaneously had markedly different E2, T, and T3 profiles during postvitellogenesis, and had a surge in plasma GtH II during final oocyte maturation (FOM). The lack of a GtH II surge is presumably responsible for the absence of FOM, but earlier, and as of yet unknown, endocrine disruptions during postvitellogenesis may determine the female's ability to undergo FOM. Treatment of females with a gonadotropin-releasing hormone agonist (GnRHa)-delivery system induced FOM and ovulation within 3 and 10 days, respectively, and resulted in the production of fertile eggs. Plasma GtH II increased continually after GnRHa implantation, even in the presence of declining GnRHa plasma levels. Plasma E2 increased first and peaked prior to FOM, whereas T peaked at the peripheral germinal vesicle (GV) stage. Plasma 17,20beta-P and 17,20beta,21-P increased dramatically at the GV breakdown (GVBD) stage. Plasma T4 was unaffected by the GnRHa treatment, whereas T3 decreased after GnRHa implantation and remained low throughout FOM. Based on the observed hormonal profiles, FOM can be separated into an early phase (lipid-droplet coalescence, GV migration) associated with E2 and T elevations, and a late phase (yolk-globule coalescence, GVBD) associated with 17,20beta-P and 17,20beta,21-P elevation.

Animals↗

Effects of light on plasma somatolactin levels in red drum (Sciaenops ocellatus).

The effects of illumination on circulating somatolactin (SL) levels were studied in red drum sampled at various times during a 24-h light-dark cycle (l2L:l2D) and during a 24-h period of constant light. Plasma SL concentrations were low in red drum sampled during the light phase (0.6 +/- 0.05-1.1 +/- 0.2 ng/ml). The levels were significantly elevated during the early-dark phase (5.8 +/- 1.0 ng/ml) and declined during the late-dark phase (0.39 +/- 0.05 ng/ml). In contrast, plasma SL levels remained low. (0.4 +/- 0.1-1.3 +/- 0.4 ng/ml) in fish sampled through a 24-h constant light period following a 1-week exposure to the light-dark cycle. Circulating SL levels were also significantly elevated during the early-dark phase in fish maintained under a reversed light-dark cycle. The role of the eyes in mediation the SL response to light was evaluated by comparing circulating SL levels in optic-tract sectioned and enucleated fish with those of intact (control) fish. Plasma SL concentrations were significantly higher in optic-tract sectioned and enucleated fish (6.5 +/- 0.9-13.8 +/- 1.5 ng/ml) than in control fish (0.6 +/- 0.05-3.9 +/- 0.7 ng/ml) during both the early-dark phase and the early-light phase of the 24-h light-dark cycle. The absence of significant changes in plasma SL levels between the light and dark phases in optic-tract sectioned and enucleated fish appears to be due to a loss of light perception in these fish. Moreover, intact and sham-operated red drum maintained in constant darkness had dramatically increased plasma SL levels (18.8 +/- 2.0-24.8 +/- 1.8 ng/ml). The present results are consistent with our earlier findings that plasma SL levels are elevated in fish kept in constant darkness and in a dark-background tank (reduction in overall light levels) during the light phase. Taken together, these results suggest that plasma SL levels are elevated in red drum in the absence of light and in response to low illumination. Interestingly, the integument of the fish became light during the dark phase of the light-dark cycle. In our earlier studies, the increase of plasma SL concentrations was associated with aggregation of melanophores, and direct effects of SL on melanophore aggregation were demonstrated. Overall, our studies with red drum suggest a possible role of elevated SL levels on melanophore aggregation during the dark phase of the 24-h day-night cycle.

Animals↗

Acinetobacter baumannii colonization in ventilated preterm infants.

The role of Acinetobacter baumannii in infections in ventilated preterm infants was evaluated in 15 colonized infants (11 male, 4 female) in a pediatric intensive care unit. These cases were randomly matched by birth weight and gestational age with ventilated non-colonized controls (8 male, 7 female). Case records were reviewed for signs and symptoms of infection. Colonized infants were ventilated significantly longer (p < 0.05) than controls, and had body temperatures of > 37 degrees C for a significantly longer period of time (p < 0.05). No other parameter of infection differed significantly between the groups. The duration of intensive care treatment did not differ between cases and controls, nor did the weight gain during intensive care treatment. No fatalities occurred in either group.

Acinetobacter↗

Magnetic resonance angiography of giant intracranial aneurysms.

3D time-of-flight magnetic resonance angiography (3D TOF MRA) and 2D MRA with presaturation were evaluated in 18 patients with 21 giant intracranial aneurysms. 3D TOF MRA gave optimal images of proximal unruptured and nonthrombosed aneurysms. 2D MRA with presaturation was more informative in cases of distal, haemorrhagic or thrombosed aneurysms and in assessment of their components (thrombus, haemorrhage, patent residual lumen).

Angiography, Digital Subtraction↗

Diversity of sexual dimorphism in electrocommunication signals and its androgen regulation in a genus of electric fish, Apteronotus.

Gymnotiform electric fish emit an electric organ discharge that, in several species, is sexually dimorphic and functions in gender recognition. In addition, some species produce frequency modulations of the electric organ discharge, known as chirps, that are displayed during aggression and courtship. We report that two congeneric species (Apteronotus leptorhynchus and A. albifrons) differ in the expression of sexual dimorphism in these signals. In A. leptorhynchus, males chirp more than females, but in A. albifrons chirping is monomorphic. The gonadosomatic index and plasma levels of 11-ketotestosterone were equivalent in both species, suggesting that they were in similar reproductive condition. Corresponding to this difference in dimorphism, A. leptorhynchus increases chirping in response to androgens, but chirping in A. albifrons is insensitive to implants of testosterone, dihydrotestosterone or 11-ketotestosterone. Species also differ in the sexual dimorphism and androgen sensitivity of electric organ discharge frequency. In A. leptorhynchus, male discharge at higher frequencies than females, and androgens increase electric organ discharge frequency. In A. albifrons, males discharge at lower frequencies than females, and androgens decrease electronic organ discharge frequency. Thus, in both chirping and electric organ discharge frequency, evolutionary changes in the presence or direction of sexual dimorphism have been accompanied and perhaps caused by changes in the androgen regulation of the electric organ discharge.

Androgens↗

Operative risk and prognostic factors of typical bronchial carcinoid tumors.

BACKGROUND: This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS: From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.

Adolescent↗

[Epilepsy and cancer].

INTRODUCTION: Seizures are common in patients presenting with intracranial tumors. Nevertheless, the incidence of cancer is not higher in patients with seizures. We attempted to summarize situations that can lead to the diagnosis or treatment of seizures in patients presenting with cancer. CURRENT KNOWLEDGE AND KEY POINTS: Focal neurological signs on clinical examination when seizures occur for the first time in patients with cancer lead to brain imaging. As a result of recent advances in neuro-imaging techniques, the presence of a tumor is now more frequently observed in patients with seizures. PERSPECTIVES AND FUTURE PROJECTS: As it may have irritating effects on the cerebral cortex, chemotherapy is able to either increase or induce seizures in patients presenting with cancer. Potential pharmacological interactions between antiepileptic and cytotoxic drugs thus require close surveillance in patients with cancer.

Anticonvulsants↗

Clinical patterns and trends of outcome of elderly patients with bronchogenic carcinoma.

OBJECTIVE: To investigate the clinical characteristics and determinants of operative mortality and long-term survival of elderly patients submitted to pulmonary resection for intended cure of lung cancer. METHODS: Retrospective analysis of 500 consecutive pulmonary resections performed in patients aged over 70 years from 1975 to 1996. Predictors of in-hospital mortality were identified by univariate and multivariate analyses. Determinants of long-term outcome were investigated in all survivors, with no patient being lost to follow-up. RESULTS: Mean age was 74 +/- 3 years (maximum: 90), and 36 patients were octogenarians. The sex-ratio M:F was 5:3. History of combined cardiovascular or previous neoplastic disease was noted in 193 and 63 patients, respectively. The predominant histology was squamous cell carcinoma (n = 243), with a significantly higher incidence in male than in female. Most patients received standard procedures, while 103 patients underwent extended resections for tumors involving the mediastinum (n = 44), the chest wall (n = 33), the carina (n = 2) or had a sleeve resection of the main bronchus (n = 24). Procedures were considered to be complete and curative in 459 patients, among whom 294 had a stage I disease. There were 37 (7.4%) in-hospital deaths. Mortality rates following pneumonectomy, bilobectomy, lobectomy and lesser resection were 11:136, 4:34, 22:291, and 0:39, respectively. Age, male gender, hypertension, low FEV1 and extended procedure were identified as independent predictors of early mortality. Overall survival rates were 33.7 and 12% at 5 and 10 years, respectively. Multivariate analysis demonstrated that the disease stage was the main prognosticator. During the follow-up period, cancer recurrence (n = 183; 39.5%) or second primary lung cancer (n = 20; 4.3%) occurred in 203 patients, among whom 18 (9%) had a second lung resection. Carcinoma in other systems occurred in 25 patients (5.3%), and major cardiovascular event in 51 (11%). CONCLUSIONS: Male and squamous cell carcinoma are characteristic of elderly patients with resected lung cancer. Operative mortality is acceptable for standard resection, and survival figures are concordant with those reported in other series which include younger patients.

Aged↗

Adhesion of colorectal carcinoma cells to the endothelium is mediated by cytokines from CEA stimulated Kupffer cells.

We hypothesize that a major factor regulating hepatic metastasis is the ability of CEA (carcinoembryonic antigen) producing colorectal carcinomas to activate Kupffer cells. CEA and NCA (nonspecific cross-reacting antigen) bind to an 80 kDa Kupffer cell receptor by the peptide sequence PELPK and stimulate cytokine production. Cytokines induce sinusoidal endothelial cells to express intercellular adhesion molecules and increase adhesion of the tumor cells and retention in the liver. In this study human Kupffer cells were activated in vitro with CEA, NCA, and the peptide PELPK. This resulted in release of IL-1beta, TNF-alpha and IL-6. CEA non-producing MIP-101 colon carcinoma cells labeled with 51Cr were incubated on monolayers of ECV-304 human umbilical vein endothelial cells treated with these Kupffer cell derived cytokines or with comparable recombinant human (rH) cytokines. Specific antibodies to the adhesion molecules ICAM-1, VCAM-1, E-selectin and beta2integrin were used to block their functions. A significant enhancement in the adhesion of colorectal carcinoma cells occurred when endothelial cells were stimulated with a very low concentration of Kupffer-cell derived cytokines. Activated endothelium demonstrated significant up-regulation primarily of ICAM-1. The adhesion was blocked by an antibody to ICAM-1. A combination of Kupffer-cell derived cytokines was more effective than IL-1beta or TNF-alpha alone. IL-6 alone did not influence adhesion under our conditions. Our results suggest a mechanism for CEA in the modulation of colorectal carcinoma adhesion to the hepatic endothelium and its enhancement of metastatic potential.

Carcinoembryonic Antigen↗

Radiation inactivation of some food-borne pathogens in fish as influenced by fat levels.

The influence of low (0.39-1.1%), medium (4.25%) and high (7.1-32.5%) fat levels in fish on radiation inactivation of four food-borne pathogens was investigated. Cells of Listeria monocytogenes 036, Yersinia enterocolitica F5692, Bacillus cereus and Salmonella typhimurium at logarithmic phase were inoculated in 10% fish homogenates and subjected to gamma irradiation at ice temperature (0-1 degree C) with doses ranging from 0.05 to 0.8 kGy. The radiation survival curves of L. monocytogenes and B. cereus were characterized by shoulders, while a tailing effect was depicted by cells of Y. enterocolitica and B. cereus. The D10 values in kGy calculated on the exponential part of the curve ranged from 0.2 to 0.3, 0.15 to 0.25, 0.1 to 0.15 and 0.09 to 0.1 for L. monocytogenes 036, B. cereus, Salm. typhimurium and Y. enterocolitica F5692, respectively. This order (D10) of radiation resistance of each organism was not affected by the fat content of the fish. Inoculated pack studies carried out separately with each pathogen in fatty (Indian sardine, 7.1%) and lean (Golden anchovy, 0.39%) fish showed no difference in their survival after exposure to 1 kGy and 3 kGy doses, which corroborated the above observation. The practical significance of these results in the application of the technology is discussed.

Adipose Tissue↗

Shared tumor antigens in colorectal carcinoma and neuroendocrine tumors.

ND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated colorectal cancer. We demonstrate its expression in 25% of gastrointestinal neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly differentiated colorectal cancer cell line that does not express CEA or other tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors is detected in only five of seven patients with the carcinoid syndrome and two of four of those without evidence of the syndrome. However, the reactivity was less in the patients with localized disease, and this test is unlikely to be of diagnostic utility in this group of patients. The sharing of this antigen in colorectal cancer and neuroendocrine tumors is not universal, but does support the common-cell progenitor theory for the origin of these tumors.

Animals↗

Perinuclear anti-neutrophil cytoplasmic antibodies in ulcerative colitis after restorative proctocolectomy do not correlate with the presence of pouchitis.

BACKGROUND: Although perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) expression is strongly associated with ulcerative colitis, its relationship with the occurrence of pouchitis after restorative proctocolectomy is uncertain. METHODS: Serum p-ANCA was assayed using both indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) in 49 patients, of whom 25 had, and 24 had not, developed pouchitis. Control sera were obtained from 15 healthy volunteers. RESULTS: By means of indirect immunofluorescence, p-ANCA was detected in 45.8% of patients without and in 48% with pouchitis (NS). Twenty-three (46.9%) of the 49 colitis patients were p-ANCA-positive, compared with none of the 15 controls (P < 0.01). By means of ELISA, p-ANCA positivity was present in 50% of patients without and in 68% with pouchitis (NS). CONCLUSION: Whereas p-ANCA was associated with ulcerative colitis as compared with normal individuals, it was not associated with pouchitis. Thus it is unlikely to be a suitable pre-operative marker to identify those patients who will develop pouchitis.

Adult↗

Differential expression of alpha2,6-sialyltransferase in colon tumors recognized by a monoclonal antibody.

It has been reported that alpha2,6-sialyltransferase (alpha2,6-ST; E.C. 2.4.99.1) activity is associated with cellular differentiation. To define its role in colon carcinoma differentiation, we have generated murine monoclonal antibodies (MAb) against alpha2,6-sialyltransferase. The MAb, designated 6B9 of IgM isotype, showed strong reactivity with the purified and crude alpha2,6-ST by ELISA and dot blot assays. Western blotting with MAb 6B9 identified purified alpha2,6-ST of MW 47 kDa and the same MW protein from rat and human liver extracts. The MAb also reacted with two other liver proteins of approximate MW 65 and 100 kDa. Immunoperoxidase studies with formalin-fixed paraffin-embedded tissues showed that MAb 6B9 reacts with liver tissues, the staining of hepatocytes was granular and cytoplasmic. There was a distinct pattern of zonal distribution of this enzyme in hepatocytes located particularly in the portal areas of the liver corresponding to zone 1. Normal colon (100%) and hyperplastic polyps (100%) showed very weak to no reactivity. Adenomas (100%) demonstrated moderate reactivity, while the poor (33%), moderate (100%) and well-differentiated (80%) colon adenocarcinomas showed strong reactivity. Results suggest that alpha2,6-ST is associated with the differentiation state of colon tumors.

Animals↗