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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 145 records · Page 8Linked to original sources
PubMed2000

Sorting of tropomyosin isoforms in synchronised NIH 3T3 fibroblasts: evidence for distinct microfilament populations.

The nonmuscle actin cytoskeleton consists of multiple networks of actin microfilaments. Many of these filament systems are bound by the actin-binding protein tropomyosin (Tm). We investigated whether Tm isoforms could be cell cycle regulated during G0 and G1 phases of the cell cycle in synchronised NIH 3T3 fibroblasts. Using Tm isoform-specific antibodies, we investigated protein expression levels of specific Tms in G0 and G1 phases and whether co-expressed isoforms could be sorted into different compartments. Protein levels of Tms 1, 2, 5a, 6, from the alpha Tm(fast) and beta-Tm genes increased approximately 2-fold during mid-late G1. Tm 3 levels did not change appreciably during G1 progression. In contrast, Tm 5NM gene isoform levels (Tm 5NM-1-11) increased 2-fold at 5 h into G1 and this increase was maintained for the following 3 h. However, Tm 5NM-1 and -2 levels decreased by a factor of three during this time. Comparison of the staining of the antibodies CG3 (detects all Tm 5NM gene products), WS5/9d (detects only two Tms from the Tm 5NM gene, Tm 5NM-1 and -2) and alpha(f)9d (detects specific Tms from the alpha Tm(fast) and beta-Tm genes) antibodies revealed 3 spatially distinct microfilament systems. Tm isoforms detected by alpha(f)9d were dramatically sorted from isoforms from the Tm 5NM gene detected by CG3. Tm 5NM-1 and Tm 5NM-2 were not incorporated into stress fibres, unlike other Tm 5NM isoforms, and marked a discrete, punctate, and highly polarised compartment in NIH 3T3 fibroblasts. All microfilament systems, excluding that detected by the WS5/9d antibody, were observed to coalign into parallel stress fibres at 8 h into G1. However, Tms detected by the CG3 and alpha(f)9d antibodies were incorporated into filaments at different times indicating distinct temporal control mechanisms. Microfilaments in NIH 3T3 cells containing Tm 5NM isoforms were more resistant to cytochalasin D-mediated actin depolymerisation than filaments containing isoforms from the alpha Tm(fast) and beta-Tm genes. This suggests that Tm 5NM isoforms may be in different microfilaments to alpha Tm(fast) and beta-Tm isoforms even when present in the same stress fibre. Staining of primary mouse fibroblasts showed identical Tm sorting patterns to those seen in cultured NIH 3T3 cells. Furthermore, we demonstrate that sorting of Tms is not restricted to cultured cells and can be observed in human columnar epithelial cells in vivo. We conclude that the expression and localisation of Tm isoforms are differentially regulated in G0 and G1 phase of the cell cycle. Tms mark multiple microfilament compartments with restricted tropomyosin composition. The creation of distinct microfilament compartments by differential sorting of Tm isoforms is observable in primary fibroblasts, cultured 3T3 cells and epithelial cells in vivo.

3T3 Cells↗
PubMed2000

Investigation of different ontogenetic stages of Raillietiella sp. (Pentastomida: Cephalobaenida): suboral gland and frontal gland.

In Raillietiella sp. larvae we discovered a gland whose duct pores shed their secretion caudally of the mouth onto the integument. This gland type, which we call the suboral gland, seems to be characteristic of all pentastomid species. We discuss its possible function in the invasion of the larvae into the intermediate host. Furthermore, we identified frontal gland cells and their ducts in Raillietiella and differentiated them from buccal glands and their ducts. They appear to be a general feature of pentastomids and exist even in early ontogenetic stages.

Animals↗
PubMed2000

Outcome of group cognitive-behavior therapy for bulimia nervosa: the role of core beliefs.

It is hypothesized that individuals who benefit less from CBT will be those who have more pathological core beliefs (unconditional beliefs, unrelated to food, shape and weight). Twenty bulimic women were treated using 12 sessions of conventional group CBT. Eating behavior and attitudes were assessed pre- and posttreatment. Core beliefs were assessed at the beginning of the programme, and were used as predictors of change across treatment (once any effect of pretreatment psychopathology was taken into account). Group CBT was effective, with reductions of over 50% in bulimic symptoms. Outcome on most indices was associated with pretreatment levels of pathological core beliefs. Possible reasons for these findings are discussed.

Adolescent↗
PubMed2000

Primary human bone cultures from older patients do not respond at continuum levels of in vivo strain magnitudes.

Osteoporosis is characterized by excessive loss of bone mass, while exercise is believed to maintain or enhance bone mass. Since exercise marginally affects osteoporosis, we wondered whether bone cells from osteoporotic patients would fail to respond to strain. Primary human bone-like cultures were obtained from females over age 60 with hip arthroplasty procedures performed for either osteoporotic fracture (n = 8) or non-osteoporotic osteoarthrosis (n = 5). Cultures (96,000 cell/cm2) were strained in rectangular optically clear silastic wells. Three periods of uniaxial substratum strain (1000 micro-strain, 1 Hz, 10,000 cycles, sine wave) were provided every 24 h using a four-point bending, computer-controlled device. Results at a frequency of 1 Hz were compared to cultures exposed to 20 Hz with bone cells derived from one osteoarthritic subject. Alterations in protein level expression of bone-related proteins were determined using a semi-quantitative confocal approach along with enzyme (alkaline phosphatase) activity and enzyme mRNA copy number using cRNA RT-PCR. Strain did not alter levels of bone-related protein levels, enzyme activity, or steady state copy number per cell in response to strain in either group. Strained cultures from osteoporotic patients exhibited little variation from unstrained controls, while individual cultures from osteoarthritic patients exhibited increases in one protein or the other. The results suggest that bone cells from older individuals may not be responsive to continuum levels of strain anticipated with vigorous activity.

Aged↗
PubMed2000

Mechanisms of the contractile effect of the hydroalcoholic extract of Cissampelos sympodialis Eichl. in the rat aorta.

In the present work the effect of the aqueous fraction of the ethanolic extract of the leaves (AFL) of Cissampelos sympodialis Eichl. was investigated in the rat aorta. In the presence of functional endothelium, AFL produced concentration-dependent contractions (EC50 value of 76.6 +/- 17.8 micrograms/ml). In the absence of functional endothelium, the concentration-response curves to AFL were significantly shifted to the left (EC50 values of 1.3 +/- 0.9 micrograms/ml) without modification of its maximal contractile effect. In the presence of L-NAME (300 microM) and of indomethacin (10 mM), the concentration-response curves produced by AFL were also shifted to the left (EC50 values of 21.8 +/- 6.2 and 24.3 +/- 13.2 micrograms/ml, respectively). The treatment of the aortas with L-NAME (300 microM) plus indomethacin (10 microM) produced a significant shift to the left of the concentration-dependent curves of AFL (EC50 value of 4.9 +/- 2.2 micrograms/ml), similar to that observed in the absence of the vascular endothelium. In addition, AFL-induced contraction was abolished in the presence of prazosin (1 microM), and significantly shifted to the right in the presence of yohimbine (EC50 value of 723.6 +/- 76.4 micrograms/ml). Thus, based on these results, it can be concluded that contractions induced by AFL in the rat aorta were due to activation of alpha-adrenoceptors. Furthermore, these results also showed that the AFL-induced contractions were modulated by the endothelium, via the release of NO and of a cyclooxygenase-derived relaxant product. Finally, it can be concluded that the contractile effects of AFL on vascular smooth muscle may play an important role in the hypertensive effects of this plant in vivo.

Adrenergic alpha-Antagonists↗
PubMed2000

Ideals, perceptions, and evaluations in early relationship development.

This research examined partner and relationship perceptions and ideal standards in 100 individuals over time, from the 1st to the 12th month of their dating relationships. As expected, the results revealed that (a) individuals evaluated their relationships on both distinct evaluative components and global evaluative dimensions, (b) higher ideal-perception consistency was associated with higher perceived quality of relationships and partners, (c) more positive perceptions of partners and relationships at earlier points in time were associated with more importance being placed on relevant ideals over time but not vice versa, and (d) higher levels of ideal-perception consistency predicted lower rates of relationship dissolution but were mediated through perceptions of relationship quality. These results support the ideal standards model (Fletcher & Simpson, in press).

Adolescent↗
PubMed2000

HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes.

Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.

Animals↗
PubMed2000

An encore for ribosome biogenesis in the control of cell proliferation.

Although the importance of cell growth for cell-cycle progression has been recognized for thirty years, the molecular basis of this relationship is poorly understood. However, researchers have begun to tease apart these two processes in model systems. This commentary focuses on one potential mechanism by which ribosome biogenesis antagonizes cell-cycle progression until the cell has grown to an adequate size.

Animals↗
PubMed2000

Transcription inhibitors stimulate translation of 5' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway.

We have analysed the effect of transcription inhibitors on the polysomal localization of 5' terminal oligopyrimidine (TOP-) mRNAs. It is known that, in vertebrates, the translation of this group of mRNAs is regulated according to the growth status of the cell. Mitogenic stimulation of quiescent cells induces a rapid recruitment of TOP mRNAs from translationally inactive light messenger ribonucleoprotein particles to polysomes. It was found that administration of transcription inhibitors to resting cells causes a similar collective translational activation of TOP mRNAs, without affecting global translation. A number of transcription inhibitors were tested in amphibian and mammalian cultured cells. Actinomycin D (act D), cordycepin, and 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole caused a similar activation whereas alpha-amanitin or low doses of act D did not induce the translational response. Concentrations of act D sufficient to induce TOP mRNA translation also induce 40S ribosomal protein S6 kinases 1 (S6K1) activation. Moreover at these concentrations of act D increased phosphorylation of 4E-BP1 was also observed, indicating the involvement of FRAP/mTOR. Consistent with this observation, pretreatment of resting cells with rapamycin suppresses the activation of TOP mRNA translation induced by act D. These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR.

Amanitins↗
PubMed2000

Successful medical treatment of acute bilateral emphysematous pyelonephritis.

Emphysematous pyelonephritis most often presents as an acute medical emergency, typically in a septic diabetic patient with acute renal failure. The management of this condition has traditionally been surgical, with nephrectomy. However, some recent reports have described successful medical interventions. We describe a case of acute bilateral emphysematous pyelonephritis in a frail patient not suitable for bilateral nephrectomy and long-term dialysis. This condition was managed medically, not surgically, with intensive antibiotic and circulatory support. The outcome was complete recovery after months of hospital-based treatment. We discuss the management of this rare but important condition in detail.

Acute Kidney Injury↗
PubMed2000

Primary intraosseous carcinoma of the mandible--a case report and review of the literature.

BACKGROUND: Squamous cell carcinoma arising within bone is a rare lesion and is only seen essentially in the jaw bones. METHODS: A case of primary intraosseous carcinoma arising in the mandible is reported in a 60-year-old female patient. Twenty-eight cases of primary intraosseous carcinoma published in the literature, till date, are reviewed. RESULTS: The mean age of the patients at the time of diagnosis was 53 years and the male: female ratio was 2.2:1. The posterior mandible was the predominant site. Fourteen of 28 patients presented with routine dental disorders, while eight patients complained of swelling, four of severe pain and three had sensory disturbances. The incidence of lymphadenopathy was 10 (34.481%) out of the 29 cases reviewed here. Wide surgical excision is accepted as the treatment of choice. CONCLUSION: The most common presenting symptom of these tumours is swelling and persistent pain in the jaw. Hence, in making a diagnosis one is likely to consider benign dental conditions. The importance of considering intraosseous carcinoma as a possibility in all cases of persistent pain and swelling in the jaw is emphasized so that suitable treatment can be instituted early.

Carcinoma, Squamous Cell↗
PubMed2000

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Adolescent↗
PubMed2000

Osteosarcoma of the jaws: a 30-year retrospective review.

OBJECTIVE: This article reviews osteosarcomas of the jaws referred to the Department of Oral Pathology, Eastman Dental Institute, for histologic diagnosis during the 30 years from 1968 to 1998, to compare the clinical behavior of the tumors, to assess how they differ from the reported characteristics of tumors from other sites, and to report on observations of clinical and diagnostic significance. STUDY DESIGN: The clinical, radiographic, and histopathologic records of 25 patients were obtained for retrospective review. Supportive and follow-up clinical and histopathologic material was obtained from the referring clinicians. RESULTS: The mean age of presentation of the primary lesions was 36. 9 years (range, 10-87 years) with a slight female predilection. The most common presenting features were swelling, pain, ulceration, or a neurologic deficit. The radiographic appearance of the lesions was mixed with areas of radiopacity and radiolucency. Histologically, the lesions ranged from those dominated by immature bony trabeculae separated by a cytologically bland stroma to high-grade, cellular lesions with regions of marked atypia and mitotic activity. Most had areas of chondroid formation, in addition to neoplastic osteoid. The main complication was local recurrence. Metastasis was rare and occurred as a solitary process or at a late stage in the disease progression. This was in contrast to lesions metastatic to the jaws, which were higher grade in appearance and had metastasized widely, early in the disease process. Primary osteosarcoma occurring in patients with a history of radiotherapy was typically more aggressive. CONCLUSION: Primary osteosarcomas of the jaws are a group of lesions distinct from those occurring in the long bones. Osteosarcomas of the jaw arising in a former radiation field may be a discrete group of lesions with a more aggressive behavior pattern.

Adolescent↗
PubMed2000

Motivation for treatment in a prison-based therapeutic community.

Current research concludes that participation in postprison aftercare is critical to the effectiveness of prison-based therapeutic community (TC) treatment. This conclusion makes it imperative to understand the client determinants of retention in prison treatment, particularly continuance in postprison aftercare. Currently, however, little data exist as to client predictors of seeking and remaining in prison-based TCs or entering postrelease aftercare. In the present study, significant relationships were obtained between initial motivation (i.e., Circumstances, Motivation, Readiness [CMR] scores), retention, aftercare, and outcomes in a sample of substance abusers treated in a prison-based TC program. Implications are discussed for theory, research, and treatment policy.

Adult↗
PubMed2000

The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments.

The mammalian proprotein convertases (PCs) are a family of secretory pathway enzymes that catalyze the endoproteolytic maturation of peptide hormones and many bioactive proteins. Two PCs, furin and PC6B, are broadly expressed and share very similar cleavage site specificities, suggesting that they may be functionally redundant. However, germline knockout studies show that they are not. Here we report the distinct subcellular localization of PC6B and identify the sorting information within its cytoplasmic domain (cd). We show that in neuroendocrine cells, PC6B is localized to a paranuclear, brefeldin A-dispersible, BaCl(2)-responsive post-Golgi network (TGN) compartment distinct from furin and TGN38. The 88-amino acid PC6B-cd contains sorting information sufficient to direct reporter proteins to the same compartment as full-length PC6B. Mutational analysis indicates that endocytosis is predominantly directed by a canonical tyrosine-based motif (Tyr(1802)GluLysLeu). Truncation and sufficiency studies reveal that two clusters of acidic amino acids (ACs) within the PC6B-cd contain differential sorting information. The membrane-proximal AC (AC1) directs TGN localization and interacts with the TGN sorting protein PACS-1. The membrane-distal AC (AC2) promotes a localization characteristic of the full-length PC6B-cd. Our results demonstrate that AC motifs can target proteins to distinct TGN/endosomal compartments and indicate that the AC-mediated localization of PC6B and furin contribute to their distinct roles in vivo.

Amino Acid Motifs↗