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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 19 recordsLinked to original sources

A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

Amino Acid Sequence

[Bronchial cancer associated with atheromatous arteriopathy. Prognostic and therapeutic consequences in pulmonary excision].

Between January 1980 and January 1985, 462 consecutive patients underwent lung resection for bronchogenic carcinoma. Eighty of these patients (17.3 percent) had atherosclerosis involving mainly the coronary arteries (40 percent). The mortality rate was significantly higher in patients with atherosclerosis (10 percent) than in those without it (4.7 percent), but the long-term survival was not affected with the presence of atherosclerosis. The lung carcinoma-atherosclerosis association raises two problems: what investigations should be carried out in this group of patients at risk, and what treatment should be given priority when vascular lesions are present and likely to become complicated by pulmonary surgery? However, the presence of atherosclerosis should not lead to a re-evaluation of the need for lung resection.

Adult

Calcitonin-like immunoreactivity in the blue crab: tissue distribution, variations in the molt cycle, and partial characterization.

Calcitonin-like immunoreactivity has been found in blood and tissues of the marine blue crab, Callinectes sapidus Rathbun. The activity in blood rises significantly during the immediate premolt (D4) stage, but tissue immunoreactivity does not vary significantly with molt stage. The immunoreactivity to antisalmon calcitonin serum is due to a 27.2 kDa protein that shows strong similarities in amino acid composition to a similar protein in a lobster and to human calcitonin precursor. The protein is most abundant in the midgut glands (hepatopancreas), but is also found in significant quantities in several other tissues. Immunoreactivity in the blood appears to be primarily due to the same molecular weight fraction, with secondary contributions from smaller molecules, closer in size to vertebrate calcitonin. A physiological function of the calcitonin-like substance in calcium transport during or after molt has yet to be demonstrated.

Amino Acid Sequence

[Exogenous photosensitizing agents].

The frequent use of remedies either in topical or systemic form has led to a rising number of photosensitizations. The different cutaneous manifestations of exogenous photosensitizers e.g. phototoxicity and photoallergy, are described. We treat the most important agents of these reactions and lay stress upon the patient's interview and the phototesting in order to find out the substance, that induced photodermatosis.

Humans

[Castleman's disease. An intrapulmonary isolated form with fissural exteriorization].

We report a well-documented case of Castleman's disease which embodied all the main features of its localized forms, those most frequently described in the literature. This case was particular by its unusual intrapulmonary location and its intra-fissural development, which explains why the diagnosis was not considered preoperatively. A review of the literature showed that beside the localized forms of Castleman's disease multifocal forms have recently been reported; these have a much poorer prognosis, and their treatment has not yet been established.

Adult

Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.

Animals

Glycosylation-inhibiting factor from human T cell hybridomas constructed from peripheral blood lymphocytes of a bee venom-sensitive allergic patient.

Human T cell hybridomas, which constitutively secrete glycosylation inhibiting factor (GIF), were constructed from PBL of an allergic individual who was sensitive to honey bee venom. PBMC of the patient were stimulated with either denatured or cyanogen bromide-treated bee venom phospholipase A2 (PLA2), and Ag-activated cells were propagated by IL-2 in the presence of human recombinant lipocortin I. T cells obtained in the cultures were fused with a HAT-sensitive mutant of the human lymphoblastoid cell line CEM. Approximately one-third of hybridoma clones constitutively secreted GIF. The GIF-producing hybridomas were CD3+ and bore TCR-alpha beta. GIF formed by unstimulated hybridomas lacked affinity for bee venom PLA2. Upon cross-linking of CD3, however, a majority of the GIF-producing hybridomas formed IgE-binding factors and GIF, the latter of which had affinity for bee venom PLA2. Both nonspecific GIF and Ag-binding GIF from the hybridomas bound to an immunosorbent coupled with the anti-lipomodulin mAb 141-B9. Using an affinity-purified GIF as an immunogen, we established mouse B cell hybridomas that secreted monoclonal anti-human GIF. In order to characterize human nonspecific GIF, one of the GIF-producing hybridomas was adapted to a serum-free medium, and culture supernatant was fractionated by DEAE-Sepharose column chromatography and by gel filtration. The majority of nonspecific GIF in the culture supernatant was recovered from DEAE-Sepharose by elution of the column with 10 mM Tris-HCl buffer, pH 8.0, containing 50 mM NaCl. Affinity-purification of GIF in the DEAE Sepharose fraction by using anti-GIF-coupled Affigel, and analysis of the purified GIF by SDS-PAGE revealed that human GIF is a single polypeptide chain of 14 to 15 kDa. Gel filtration of both crude and affinity-purified GIF preparations confirmed the molecular size of the cytokine.

Antibodies, Monoclonal

Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.

The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.

Animals

Single photon emission computed tomography study of subclinical rhythmic electrographic discharge in adults.

Subclinical rhythmic electrographic discharge in adults (SREDA) is considered a benign EEG pattern of uncertain significance, although it may closely resemble an EEG seizure pattern. We investigated a 57-year-old man with a very lateralized epileptiform activity localized to the occipito-temporal areas of the right hemisphere. Neuropsychological tests, clonazepam injection and 99m Tc-HMPAO-SPECT were performed during the SREDA and compared to the interparoxysmal data, providing further evidence that SREDA cannot be considered as an epileptic pattern and that, in some instances, it may be related to chronic hypoxic/ischemic mechanisms.

Brain

Adrenal-kidney and gonadal steroidogenesis during sexual differentiation of a reptile with temperature-dependent sex determination.

Adrenal-kidney and gonadal steroidogenesis were studied during early development in the red-eared slider turtle, Trachemys scripta, which exhibits temperature-dependent sex determination. In vitro steroid secretion by adrenal-kidney-gonad complexes (AKGs) incubated for 6 hr was determined by radioimmunoassay (RIA). AKGs from presumptive males and females secreted progesterone at developmental stages before (stage 15), during (stages 17 and 19), and after (stage 21) the temperature-sensitive period for sex determination, and progesterone secretion increased significantly throughout the period from stage 15 to 21. Presumptive male AKGs secreted significantly more progesterone than female AKGs at stage 19. Corticosterone secretion by AKGs was observed at stage 17 in males only, but in both sexes at stages 19 and 21. Testosterone, estradiol, androstenedione, and dehydroepiandrosterone secretion by AKGs was detected only at stage 21. Of the steroids measured, progesterone and corticosterone were consistently secreted at the highest levels. Although some sex differences were observed, no obvious patterns of sexually dimorphic steroid secretion from AKGs were apparent. Gonads from stage 21, stage 24, and 10-day-old hatchlings from both presumptive sexes incubated with [7-3H]pregnenolone showed only weak precursor conversion, primarily to polar metabolites, in incubations as long as 24 hr. None of the steroids assessed by RIA of AKG incubates could be identified by TLC or HPLC analysis of the stage 21 and stage 24 gonadal incubates. However, progesterone was tentatively identified in incubates of 10-day post-hatch female gonads. For stage 21 females, AKGs were separated into gonadal and adrenal-kidney tissue (AK) components and incubated in vitro for 1, 3, and 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands

Isolation of maturational gonadotropin subunits from spotted seatrout (Cynoscion nebulosus) and development of a beta-subunit-directed radioimmunoassay for gonadotropin measurement in sciaenid fishes.

Maturational gonadotropin (GTH) subunits were isolated from pituitaries of the spotted seatrout (Cynoscion nebulosus), a marine perciform teleost, by ethanolic extraction and ion-exchange, gel-filtration, and reverse-phase chromatography. Partial amino acid sequencing of the N-terminal regions of the alpha and beta subunits indicated 60-80% identities with various carp and salmon GTH subunits. The spotted seatrout GTH beta-subunit was used as radioligand in a radioimmunoassay (RIA) with Atlantic croaker (Micropogonias undulatus) GTH antiserum. Pituitary extracts and plasmas from a variety of sciaenid fishes diluted parallel to the croaker GTH standard in the RIA. These data suggest that there is a high degree of immunological similarity among the GTH beta subunits of sciaenid fishes. The RIA measured increased levels of GTH in the plasmas of three species of sciaenid fishes, spotted seatrout, orangemouth corvina (Cynoscion xanthulus), and red drum (Sciaenops ocellatus), following injections of a luteinizing hormone-releasing hormone analog. The beta-subunit-directed GTH RIA increases considerably the number of species in which studies of GTH physiology can now be conducted.

Amino Acid Sequence

Stimulatory effects of serotonin on maturational gonadotropin release in the Atlantic croaker, Micropogonias undulatus.

The effects of serotonin (5-HT) injection alone, and in combination with des Gly10 [D-Trp6]-luteinizing hormone-releasing hormone ethylamide (LHRHa), on plasma maturational gonadotropin (GtH) levels in the Atlantic croaker, Micropogonias undulatus, were examined. An injection of 5-HT (20 micrograms/g body wt) alone did not significantly elevate GtH levels, whereas simulatneous administration of LHRHa (20 ng/g body wt) and 5-HT elicited a greater elevation of plasma GtH levels than that induced by LHRHa alone. Pretreatment of 1-year-old fish with fluoxetine (10 micrograms/g), a 5-HT reuptake inhibitor, only slightly augmented the effect of 5-HT on GtH levels, whereas pretreatment with ketanserin (10 micrograms/g), a 5-HT receptor antagonist, completely inhibited the potentiating effect of 5-HT on the GtH response to LHRHa. Administration of LHRHa (20 ng/g) or 5-HT (20 micrograms/g) significantly elevated GtH levels in the 2- and 3-year-old croaker, but the combined treatment failed to increase GtH levels above those induced by LHRHa alone. However, with a lower dose of LHRHa (5 ng/g), the combination produced an additive effect. Serotonin (20 micrograms/ml media) alone, and in combination with LHRHa (10 ng/ml media), significantly stimulated GtH release from the pituitaries of gonadally mature 2- and 3-year-old female croaker during an 18-hr incubation in vitro, but not from pituitaries of gonadally regressed fish. The combined treatment of LHRHa with 5-HT also significantly stimulated in vitro GtH release during 6- and 12-hr pituitary incubations, whereas these treatments alone were ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Torso injury patterns and mechanisms in car crashes: an additional diagnostic tool.

Torso injuries among car occupants involved in sever collisions are often life threatening. This study considers whether knowledge of the type of impact and associated trends of torso injuries would assist the rapid diagnosis of injuries by emergency personnel. For the purpose of this analysis the pelvis was included in the torso. The data source was the Cooperative Crash Injury Study which holds detailed injury information on over 6200 car crash occupants. Restrained front seat occupants with an ISS of 16+ who were involved in frontal or side collisions were selected. A total of 286 occupants fell into these selection criteria. The frequency of injury to each torso part was determined to give an approximate likelihood of injury in each impact configuration. The injury data were further analysed to look for patterns of injury in frontal or side impacts. The likelihood of all torso injuries, except sternal and lumbar spinal injuries, increased in side impacts, particular examples being the spleen and pelvis. There were statistically significant associations between injuries to different torso parts. In frontal impacts rib fracture indicates the distinct possibility of underlying organ injury. Vehicle damage data coupled with readily diagnosed injuries can suggest the possibility of less easily detectable injuries.

Abdominal Injuries

Self-repair in dialogues of schizophrenics: effects of hallucinations and negative symptoms.

This paper concerns the discourse features of verbal hallucinations and negative symptoms of schizophrenia. A total of 46 schizophrenics, varying in verbal hallucination and in negative symptoms status, and 22 controls were tested on the Reporter Test. The frequency with which they issued inadequate instructions, attempted to repair the inadequacies, and the success of repairs were compared. We observed that schizophrenics, on the whole, issued more wrong and incomplete instructions. This was in part related to their worse working memory, but it was not affected by verbal hallucinations or negative symptoms. We observed, further, that schizophrenics had no particular problems monitoring messages for inadequacies. We did find, however, that schizophrenics with verbal hallucinations had a specific problem with self-repairing wrong instructions. We interpret these results in the framework of Hoffman's (1986b) plan disruption-based model of verbal hallucinations; the Frith (1987) and Frith and Done (1988) internal monitoring model of positive and negative symptoms; and finally Frith and Frith's (1990) model of negative and positive schizophrenia and we use the results to specify the models.

Adult

Comparison of the efficacy and adverse effect profile of cefotaxime and ceftriaxone in ICU patients with susceptible infections.

In a prospective randomized double-blind trial, the efficacy and safety of cefotaxime and ceftriaxone were compared in intensive care unit (ICU) patients with serious infections requiring systemic antimicrobial therapy. Patients were randomly assigned to receive either cefotaxime 1 g i.v. t.i.d. or ceftriaxone 2 g every 24 hr. Clinical and bacteriologic assessments were made before treatment, at 48 hr and 5 days during treatment, and 48 hr after treatment. At the time of reporting, a total of 34 patients had been entered into the trial, 27 of whom were evaluable; 23 patients (85%) completed a minimum of 5 days antibiotic treatment. At the end of treatment, using current statistics 67% of cefotaxime and ceftriaxone patients demonstrated clinical cure or improvement. Bacteriologic responses appeared greater in the cefotaxime group (55% vs 42%). The incidence of adverse effects, which were usually minor, was similar in each group. From these preliminary results, it would appear that at the doses used in this study, cefotaxime and ceftriaxone are equally effective in the treatment of infections in the ICU.

Adolescent