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K S Thompson

Publications and source records attributed to K S Thompson.

At least 19 recordsLinked to original sources
PubMed2001

Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of human fibroblasts.

We have investigated the expression of AP-1 transcription factor proteins during the in-vitro ageing of human fibroblasts. The numbers of these cells that are in the cell cycle gradually decreases up to 45 cumulative population doublings (cPD), thereafter the decline is steeper, until almost all cells enter a post-mitotic state by 60 cPD. We observed that a 34 kd junB species began to replace the 44 kd junB species after 41 cPD. This was followed, after 44 cPD, by a loss of fra1 and both junD species. After 49 cPD there was a gradual decline in the levels of fos and jun proteins, but disproportionately, so that the fos/jun protein ratio also declined. Although fos and jun proteins were still clearly present at 60 cPD, utilisation of the AP-1 DNA consensus sequence could not be demonstrated after 54 cPD. These data indicate that significant changes occur in the composition of the AP-1 transcription factor during ageing, but also that alterations in its DNA binding activity may involve other factors.

Cell Line↗
PubMed2001

BTS 72664-- a novel CNS drug with potential anticonvulsant, neuroprotective, and antimigraine properties.

BTS 72664, (R)-7-[1-(4-chlorophenoxy)]ethyl]-1,2,4-triazolo(1,5-alpha)pyrimidine, was identified as a drug development candidate from a research program designed to discover novel, broad-spectrum, non-sedative anticonvulsant drugs. BTS 72664 antagonized bicuculline (BIC)- and maximal electroshock (MES)-induced convulsions with ED(50) values of 1.9 and 47.5 mg/kg p.o., respectively. In rodents, it has a wide spectrum of activity preventing seizures induced by picrotoxin, pentylenetetrazol, i.c.v. 4-aminopyridine or NMDA, and audiogenic seizures in DBA-2 mice and GEPR-9 rats. BTS 72664 was also effective in preventing convulsions in amygdala-kindled rats The lack of sedative potential was predicted on the basis of wide separation between ED(50) in anticonvulsant models and TD(50) for motor impairment in mice in rotating rod and inverted horizontal grid tests. BTS 72664 is likely to produce its anticonvulsant effect by enhancing chloride currents through picrotoxin-sensitive chloride channels, and by weak inhibition of Na(+) and NMDA channels. It does not act, however, at the benzodiazepine binding site. In addition to its potential use in the treatment of epilepsy BTS 72664 may be useful in the treatment of stroke. At 50 mg/kg p.o. x 4, given to rats at 12 hourly intervals, starting at 15 min after permanent occlusion of middle cerebral artery (MCA), it reduced cerebral infarct size by 31% (measured at 2 days after insult) and accelerated recovery in a functional behavioral model. BTS 72664 prevented increases in extraneuronal concentrations of glutamate, glycine and serine brain levels induced by a cortical insult to rats (cf. cortical spreading depression). It may, therefore, have also antimigraine activity.

Animals↗
PubMed2000

Hepatoid carcinoma of the pancreas.

BACKGROUND: The majority of primary extrahepatic neoplasms exhibiting features of hepatocellular carcinoma in terms of morphology, immunohistochemistry, and behavior have been described in the stomach. To the authors' knowledge only a few cases have involved other organ sites. They frequently are associated with other histologic type tumors such as adenocarcinoma, and portend an aggressive behavior. METHODS: Two examples of hepatoid carcinoma arising from the pancreas are reported in the current study. RESULTS: One case was a malignant islet cell tumor with a full-blown clinical syndrome of glucagon overproduction, histologic evidence of hepatocytic differentiation, bile production, and alpha-fetoprotein (AFP) positivity. The second tumor was a ductal carcinoma showing periodic acid-Schiff positive and diastase-resistant hyaline globules, AFP production, and ultrastructural resemblance to hepatocytic cells. CONCLUSIONS: The rare observation of cellular phenotypic transformation that corresponds with the process of hepatocytic transdifferentiation of pancreatic cells demonstrated in animal models and the common embryologic foregut derivation of the pancreas and liver also may explain the phenomenon of pancreatic hepatoid carcinoma.

Adult↗
PubMed2000

Studies on uptake, sub-cellular trafficking and efflux of antisense oligodeoxynucleotides in glioma cells using self-assembling cationic lipoplexes as delivery systems.

The cellular uptake of antisense oligodeoxynucleotides (ODNs) may be enhanced by the use of carriers such as cationic liposomes or lipoplexes, but little is known about the intracellular fate and subcellular trafficking of these systems in target cells. In this study, we report on the cellular uptake and biodistribution of ODNs in the presence and absence of optimised self-assembled cationic lipoplexes using the C6 glioma cell line as an in vitro model. Biotin or radiolabelled 15-mer phosphorothioate (PS) ODNs were synthesised and their cellular uptake and subcellular biodistribution characterised in the presence and absence of an optimised cationic lipoplex delivery system using studies ranging from cellular association, cellular efflux and transmission electron microscopy (TEM). Ultrastructural studies clearly showed PS ODNs in the absence of liposomal delivery to be sequestered within endosomal and lysosomal vesicular bodies indicative of endocytic uptake. ODNs were also visible, to a lesser extent, in the nucleus and cytoplasm. By employing DOSPA (2'-(1",2"-dioleoyloxypropyldimethyl-ammonium bromide)-N-ethyl-6-amidospermine tetra trifluoroacetic acid) and DOPE (dioleoylphosphatidylethanolamine) complex in a 3 : 1 ratio, as a delivery system for ODNs at a optimal lipid/DNA charge ratio of 1 : 1, the level of ODN cellular association was significantly increased by approximately 10-12 fold with a concomitant change in subcellular distribution of PS ODN. TEM studies indicated enhanced penetration of ODN within the cytosol and the cell nucleus with reduced presence in vesicular compartments. Efflux studies confirmed that cationic lipoplexes promoted entry of ODNs into 'deeper' cellular compartments, consistent with endosomal release. Optimised cationic lipoplexes improved cellular delivery of ODNs by enhancing cell association, uptake and by favourably modulating the intracellular trafficking and distribution of ODNs into non-vesicular compartments including the cytosol and nucleus.

Animals↗
PubMed1999

Cytopathologic evaluation of lung carcinomas presenting as brain metastasis.

Brain metastasis is an uncommon initial presentation of lung carcinoma. One arm of this analysis is a retrospective review of 137 cases of surgically diagnosed solitary brain metastasis, which were eventually found to be of lung origin, encountered at Hines VA Hospital during the period 1958 to 1996. The second arm is composed of fine-needle aspiration biopsy specimens of primary lung tumor in 23 patients with an initial clinical diagnosis of brain metastasis and without the benefit of surgery, seen from 1981 through 1996. Our results in both analyses indicate that pulmonary adenocarcinoma is the predominant primary tumor that initially manifests as a brain metastasis, approaching 76% (107 and 17 cases, respectively), followed by small-cell carcinoma at 20% (24 and five cases, respectively) and large-cell undifferentiated carcinoma and squamous-cell carcinoma at 2% each. The predominance of adenocarcinoma as a source of brain metastasis in lung cancer patients probably reflects its rising incidence overall of late. Collateral findings also suggest that surgical resection of a solitary and small brain metastasis as well as of a discrete lung primary, whenever feasible, as the most effective procedure to improve survival and quality of life of patients.

Adenocarcinoma↗
PubMed1999

Successful reversal of Barrett's esophagus with multipolar electrocoagulation despite inadequate acid suppression.

BACKGROUND: Barrett's epithelium is a risk factor for esophageal cancer. In this study we attempted to reverse Barrett's epithelium in an acid-reduced environment by using multipolar electrocoagulation. METHODS: All patients had specialized columnar epithelium of at least 2 cm in length. Patients with dysplasia on successive screening examinations were excluded. Esophageal motility and 24-hour pH studies were performed before therapy and at 9 and 18 weeks. All patients received lansoprazole 30 mg twice a day regardless of pH study results. Multipolar electrocoagulation was applied to one side of the esophagus (2 to 3 cm per session) with the contralateral side serving as control. Biopsies were obtained from each 2 cm length at each endoscopy and reviewed by a single, blinded pathologist. At the 9-week evaluation of the treatment side, all patients elected to undergo multipolar electrocoagulation therapy for the control side. RESULTS: Twenty-seven patients completed the study: 21 men and 6 women, ages 33 to 81 years, length of specialized columnar epithelium 2 to 10 cm. Endoscopy at the 18-week follow-up showed normal mucosa (n = 16), residual small (< 3 mm) islands or tongue-shaped extensions of apparent specialized columnar epithelium (n = 7), untreated distal strips (< 5 mm) of apparent specialized columnar epithelium at the gastroesophageal junction (n = 3), and persistent specialized columnar epithelium (n = 1). Histologically, only 5 of 27 patients had residual specialized columnar epithelium at week 18. Of 16 patients with a normal endoscopic appearance, one still had specialized columnar epithelium on biopsy. While on lansoprazole, pH studies were normal in 15 of 26 patients at 9 weeks. Of 22 patients with histologic evidence of specialized columnar epithelium reversal, 10 had persistently abnormal 24-hour pH studies (pH < 4, 6.1% to 33.7% of total time). Four of five patients with residual specialized columnar epithelium on biopsy had persistent reflux. Side effects of multipolar electrocoagulation were transient, and treatment did not adversely alter motility patterns. CONCLUSIONS: Multipolar electrocoagulation therapy can induce re-epithelialization with normal squamous mucosa in most patients with specialized columnar epithelium and does not adversely affect esophageal motility. Adequate acid suppression is not mandatory for therapy to be effective in the short term.

Adult↗
PubMed1999

Relationship between a self-reported health questionnaire and laboratory tests at initial office visits.

BACKGROUND: Dental patients routinely complete a medical questionnaire and have an oral interview during their initial visit, but may have undiagnosed systemic problems which can affect their dental treatment. METHODS: Thirty-nine consecutive patients referred for a periodontal evaluation completed a medical questionnaire and an oral interview. They were referred to a hospital laboratory for an urinalysis, complete blood count, and a standard blood chemistry panel. RESULTS: The self-reported medical history responses were compared with the laboratory data and several abnormalities were noted. Abnormal levels were found with cholesterol, (26/39 patients, 67%); triglycerides, (13/39, 33%); glucose, (6/39, 15%); eosinophils, (18/39, 46%); and monocytes, (10/39, 26%). Smokers (17/39, 44%) had a higher number of abnormal levels or percentages of cholesterol, triglycerides, basophils, lymphocytes, eosinophils, and monocytes. Gender differences were seen in elevated triglyceride levels, abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and self-reported cardiovascular disease. CONCLUSIONS: This study demonstrated that many patients are unaware of their current medical status and a significant number had undiagnosed abnormalities.

Adult↗
PubMed1998

GABA-evoked depolarisations in the rat cortical wedge: involvement of GABAA receptors and HCO3- ions.

The effect of gamma-aminobutyric acid (GABA) was investigated on cortical wedges prepared from male Sprague-Dawley rats. GABA evoked concentration-dependent depolarisations (EC50: 0.8 mM), which were attenuated by up to 60% when bicarbonate-buffered aCSF was replaced with HEPES-buffered aCSF. Responses to 1 mM GABA were attenuated by (-)-bicuculline and picrotoxin and were potentiated by chlordiazepoxide and pentobarbitone. Ionotropic glutamate receptor antagonists had no effect. We conclude that GABA-evoked depolarisations are mediated via GABAA receptors, arising in part from HCO3- efflux from cells.

Animals↗
PubMed1998

Metastasis of unknown origin: the role of fine-needle aspiration cytology.

Metastasis of unknown origin (MUO) manifests either as a tumor deposit in an organ, often cervical lymphadenopathy, or as a multiorgan carcinomatosis. As a diagnostic and therapeutic challenge, the definition of its cell type and possibly its origin is imperative, although a limited diagnostic investigation is usually recommended. At Hines VA Hospital from 1986 to 1994, there were 116 cases with admitting clinical diagnosis of MUO, evaluated by fine-needle aspiration cytology (FNAC). The ages of patients ranged from 29 to 82 years (mean 56 years). All were male; Caucasians predominated. The FNAC examination with Diff-Quik and Papanicolaou smears were complemented with special and immunostains in 48 cases (41%) and electron microscopy in 93 cases (80%). The FNAC involved lymph nodes in 57 cases (49%), liver in 27 cases (23%), skin in 22 cases (19%), bone in six cases (5%), lung in three cases (3%), and pleura in one case (1%). The neoplasm was generally cell typed, and there were 60 adenocarcinomas/poorly differentiated carcinomas, 26 small-cell carcinomas (SCC), 23 squamous-cell carcinomas (SQCC), and six undifferentiated large-cell carcinomas. The primary source was defined in 30 cases (26%), consisting of lung in 11 cases, prostate in nine, kidney in four, colon in four, pleura in one, and peritoneum in one. Clinical correlation also supported a lung origin for the SCC, while the majority of the SQCC in upper and middle cervical lymph nodes were considered head-and-neck tumors. Our results affirm that FNAC is a viable and simple procedure in MUO investigations.

Adult↗
PubMed1998

Utilization of fine-needle aspiration cytology in the diagnosis of neoplastic superior vena caval syndrome.

Superior vena caval syndrome often presents as an acute or subacute oncologic emergency that requires immediate action, usually with high-dose radiotherapy. With improved chemotherapeutic regimens for various malignancies, prompt and appropriate treatment of the syndrome is possible. Tissue diagnosis, therefore, is pursued, but invasive procedures are commonly associated with technical difficulties and complications. We find fine-needle aspiration biopsy a rapid, highly reliable, and well-tolerated procedure in selected situations and herein report 17 patients with initial presentation of superior vena caval syndrome efficaciously diagnosed with fine-needle aspiration cytology. The cell types were eight lung small-cell carcinomas, four poorly differentiated adenocarcinomas, two undifferentiated large-cell carcinomas, and one each of malignant large-cell lymphoma, myxoid liposarcoma, and thymic large-cell neuroendocrine carcinoma. Further experience, however, is warranted with this widely available procedure.

Aged↗
PubMed1998

Multivesiculated macrophages: their implication in fine-needle aspiration cytology of lung mass lesions.

Alveolar macrophages are almost invariably present in percutaneous fine-needle aspiration cytology of the lung. They may predominate, appear foamy and finely vesiculated, or may reflect the cellular composition of the lung mass lesion. In a review of 172 cases of "negative for malignant cells" from the percutaneous lung fine-needle aspiration cytology file in an 8-year period at Hines VA Hospital, the vacuolated macrophages were evaluated qualitatively and quantitatively. Among the 53 cases (34%) showing vacuolated macrophages, only 5-25% of the cells were multivesiculated, the cytoplasmic vacuoles were few, focal, and occasionally global, and the majority of the vacuolated macrophages contained anthracotic or hemosiderin pigments. One case exhibited striking multivesiculation in at least 95% of macrophages and also in bronchial and alveolar cells, fibroblasts, and endothelial and inflammatory cells, a finding consistent with amiodarone toxicity (index case 1). The diagnosis was confirmed on subsequent transbronchial lung biopsy. In another patient with clinical HIV infection, the multivesiculation was also seen in 95% of the macrophages with associated acute inflammatory exudate, coccobacilli, and a positive culture for Rhodococcus equi (index case 2). In most cases, the vacuolated macrophages are reactive and inflammatory. Occasionally, as in our index cases they may actually indicate a specific diagnosis.

Actinomycetales Infections↗
PubMed1997

Weak blockade of AMPA receptor-mediated depolarisations in the rat cortical wedge by phenytoin but not lamotrigine or carbamazepine.

The effects of the anticonvulsants, lamotrigine, phenytoin and carbamazepine, were investigated on NMDA and non-NMDA receptor agonist-evoked responses and against spontaneous epileptiform discharges, in the in vitro rat cortical wedge. Lamotrigine weakly attenuated responses to (RS)-alpha-amino-3-hydroxy-5-methoxy-4-isoxazole propionic acid (AMPA) and quisqualate (IC50 values >> 100 microM), but was without effect on responses to NMDA. Phenytoin weakly, but concentration-dependently, attenuated responses to AMPA and quisqualate, but much less potently attenuated responses to NMDA (IC50 values 163, 248 and >> 300 microM, respectively). Carbamazepine (3-100 microM) significantly attenuated responses to NMDA and at 100 microM attenuated responses to AMPA and quisqualate. These effects were not concentration dependent, with the IC50 values >> 100 microM. Lamotrigine and phenytoin weakly, but concentration-dependently, reduced the frequency (IC50 values 254 and > 300 microM, respectively) and amplitude (IC50 values 141 and > 300 microM, respectively) of spontaneous epileptiform discharges, whereas carbamazepine had no effect. The results show that the anticonvulsant effects of these antiepileptics are unlikely to involve antagonism of ionotropic glutamate receptors, although blockade of non-NMDA responses may play a role in the anticonvulsant profile of phenytoin. Furthermore, the data show that clinically effective anticonvulsants do not necessarily attenuate spontaneous epileptiform discharges in the rat cortical wedge.

Animals↗
PubMed1997

Pleural effusion cytology of embryonal rhabdomyosarcoma.

This case report concerns an embryonal rhabdomyosarcoma of the testis in a 31-yr-old white male patient who underwent radical left orchiectomy, followed by combined irradiation and chemotherapy, and who 2 yr later presented with dyspnea at rest, nonproductive cough, and lower back pain for 1 wk. Chest radiographs demonstrated a bilateral pleural effusion and diffuse infiltrating lesion of the pleurae, mimicking a mesothelioma. The pleural fluid displayed noncohesive, malignant, small, round cells about 2-5 times larger than mature lymphocytes. They had large, darkly stained, pleomorphic nuclei and bubbly cytoplasm with poorly defined borders. The diagnosis of embryonal rhabdomyosarcoma was supported by a positive myosin immunostaining and ultrastructural findings of intracytoplasmic actin and myosin-type microfilaments. Our case is also notable in that the tumor was a pure rhabdomyosarcoma involving a testicular origin, and the patient is the oldest reported in the literature.

Adult↗
PubMed1997

Breast and cutaneous mycobacteriosis: diagnosis by fine-needle aspiration biopsy.

The breast and skin are considered to be rare sites of extrapulmonary mycobacterial infection, comprising 0.1% to 0.5% of all tuberculosis cases, respectively. Fine-needle aspiration biopsy (FNAB) is a rapid and minimally invasive approach to diagnose extrapulmonary tuberculosis, and has been used successfully in identifying tuberculous lesions in the lymph nodes, thyroid, kidney, pancreas, vertebrae, and testis. Two cases of extrapulmonary mycobacteriosis diagnosed by FNAB are described: a 59-year-old Hispanic male with cutaneous mycobacterial infection of the head and neck region, and a 58-year-old white male with a unilateral tuberculous mastitis. In both instances, the FNAB material demonstrated acute neutrophilic exudate, few isolated aggregates of epithelioid histiocytes and lymphocytes, and on Fite-Farraco stain mycobacteria. Reported cases of tuberculosis diagnosed by FNAB have been few; this is the first case of cutaneous tuberculosis diagnosed by FNAB.

Biopsy, Needle↗
PubMed1996

Synovial metastasis: diagnosis by fine-needle aspiration cytologic investigation.

Synovial metastases are a rare occurrence. Only 28 cases have been reported in the literature, 10 of which were diagnosed by fluid cytologic evaluation. We discuss 2 additional cases in which the diagnosis was made by fine-needle aspiration cytologic investigation. The first case is of a 47-yr-old man with small-cell carcinoma of the lung metastatic to the right knee joint; the second is of a 71-yr-old man with non-Hodgkin's mixed-cell nodular lymphoma also involving the right knee joint. The clinical features of these cases are similar to previously published instances of secondary synovial tumor, namely in regard to sex distribution (14 male and 16 female patients), age range (13-96 yr, mean 59 yr), and histologic types (adenocarcinoma, 13 cases; squamous-cell carcinoma, 4; lymphoma, 3; renal clear-cell carcinoma, 3; unknown origin, 2; rhabdomyosarcoma, 1; melanoma, 1; chordoma, 1; pulmonary clear-cell carcinoma, 1; and Ewing's sarcoma, 1). The condition usually has poor prognosis, with average patient survival of < 5 mo.

Aged↗
PubMed1995

High fat diet-induced hyperglycemia: prevention by low level expression of a glucose transporter (GLUT4) minigene in transgenic mice.

High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity. To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.

Animals↗