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Biomedical subjects

L Thomas

Publications and source records attributed to L Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1996

Phorbol ester and okadaic acid regulation of Na-2Cl-K cotransport in rabbit tracheal epithelial cells.

We evaluated a role for protein kinase C (PKC) in the regulation of rabbit tracheal epithelial Na-Cl(K) cotransport. Short-term treatment with phorbol 12-myristate 13-acetate (PMA) dose dependently increased bumetanide-sensitive Na and Cl efflux and elevated staurosporine- and bumetanide-sensitive Na, Cl, and K uptake. PMA and the alpha 2A-adrenergic agonist guanabenz both induced contransport with a stoichiometry of 2 Cl:1 Na and 2 Cl:1 Rb and elevated staurosporine-sensitive PKC activity in cytosolic and particulate fractions. Prolonged PMA treatment did not sustain bumetanide-sensitive 2 Cl:1 Na and 2 Cl:1 Rb transport but did block stimulation of bumetanide-sensitive transport by PMA or guanabenz and elevation of PKC activity by PMA and guanabenz in a particulate fraction. Cells treated with okadaic acid exhibited a staurosporine- and bumetanide-sensitive 2 Cl:1 Na and 2 Cl:1 Rb uptake. In cultured monolayers, basolateral perfusion with epinephrine, isoproterenol, or PMA increased short-circuit current (Isc). Basolateral application of bumetanide reduced elevated Isc to baseline levels, indicating a role for Cl secretory cells in a reconstituted tracheal epithelium. Pretreatment of transmonolayer cultures with PMA diminished the stimulatory response to epinephrine. These results indicate that, in rabbit tracheal epithelial cells, alpha-adrenergic stimulation activated Na-2Cl-K cotransport and that PKC is a critical effector in this process.

Animals↗
PubMed1996

Medullary sponge kidney associated with congenital hemihypertrophy.

Medullary sponge kidney is a developmental disorder characterized by ectatic and cystic malformation of the collecting ducts and tubules. Clinical manifestations include urinary tract infections, renal stones, and hematuria. It can be associated with other developmental disorders. A case of medullary sponge kidney associated with congenital hemihypertrophy, complicated by nephrocalcinosis and nephrolithiasis, is reported here.

Adult↗
PubMed1996

[Carboplatin and etoposide combination for the treatment of recurrent epithelial ovarian cancer].

UNLABELLED: The objective of this phase II study was to determine the efficacy and toxicity of a combination of carboplatin and etoposide as salvage treatment, in previously treated patients with persistent or recurrent ovarian cancer following first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: From July 1990 to August 1994, 58 patients were treated with 3-week cycles of chemotherapy consisting of carboplatin (200 mg/m2, D1) and etoposide (120 mg/m2, D1, D2). Criteria for evaluating previous response to cisplatin were strictly defined. RESULTS: The overall response rate was 36%, with five complete responses (CR, 9%), 16 partial responses (PR, 27%) and the median duration of response was 10 months (range: 4 to 38). In the group of patients who progressed during the first year following the diagnosis, the response was 1 CR and 2 PR (12%) and in the group of patients who progressed from the second year after diagnosis, 4 CR and 14 PR (56%), with a median survival of 8.5 and 21 months respectively (p = 0.0013). The response rate was 59% in the potentially platinum sensitive group versus 8.7% in the primary resistant group (0.02 < p < 0.05). Myelotoxicity was the main side-effect but did not appear to be cumulative. Grade 3 and grade 4 anemia were observed in 26% and 3% of the patients respectively, neutropenia in 14% and 2% and thrombocytopenia in 14% and 8.5%. One patient died of sepsis associated with neutropenia. CONCLUSION: Treatment was easily manageable and well tolerated. The advantage of carboplatin and etoposide combination in potentially responsive patients is represented by the reduced nephrotoxicity, neurotoxicity and ototoxicity as compared with cisplatin containing regimen, with durable feasibility in outpatients. This second-line chemotherapy for ovarian cancer is effective as salvage treatment in potentially responsive patients with late recurrent tumors, while paclitaxel is the drug of choice for patients who have developped primary or secondary resistance to platin therapy.

Actuarial Analysis↗
PubMed1996

[Locally developed sarcoma of the thoracic wall].

Important advances have been obtained in the care of soft tissue sarcoma in adults, mainly in the field of locoregional treatment. Surgery or combination of surgery and radiotherapy allow adequate tumor control with preservation of function for the majority of patients. However, the management of locally advanced primaries remains problematic. Moreover, although patients survival mainly depends on the metastatic risk of the disease, controversies remain in definition of pronostic factors as well as in the evaluation of the role of chemotherapy in curative therapeutical strategies. The case reported here allows a discussion of the different modalities of treatment for adults with soft tissue sarcomas and stresses the necessity of a multimodal approach in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Functional outcome of laparoscopically transposed ovaries in the multidisciplinary treatment of cervical cancers. Analysis of risk factors].

OBJECTIVES: To evaluate the place of ovarian transposition by laparoscopy in the treatment of cervical cancers. METHODS: From March 1992 to November 1994 at Institut Bergonié, 11 patients (mean age: 40 years; 36-44 years) with invasive squamous cell carcinoma of the uterine cervix stages Ib (4 cases) and IIb (7 cases) underwent lateral high ovarian transposition by laparoscopy performed during a staging inter-iliacal lymphadenectomy. There was no complication during surgery but one phlebitis occurred postoperatively. The treatment for the cervical cancer included: brachytherapy (11 cases), external beam radiotherapy (EBRT) (9 cases), surgery (6 cases), chemotherapy (2 cases). Ovarian radiation dosis was calculated and hormonal status assessed. RESULTS: Ovarian preservation was achieved in 30% of the cases. The mean lowest cumulative dosis to the ovaries was 1.78 Gy. Age was the most predictive factor for ovarian preservation. CONCLUSION: With ovarian laparoscopic transposition, ovarian function can be preserved in selected patients requiring first line radiotherapy for cancer of the cervix. After the age of 40 years, transposition should be restricted to small T1 tumors treated by brachytherapy. When EBRT is required for larger lesions, transposition should be reserved to younger patients.

Adult↗
PubMed1996

Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists.

The release in 1993 of a new reference material for serum proteins, CRM 470/RPPHS 5 has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. Conversion to the new reference material results in significant changes in reference values for some proteins. The establishment of new reference ranges will take a considerable time, and in the interim several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies already undertaken.

Blood Proteins↗
PubMed1996

[A Q-fever pneumonia epidemic in Dusseldorf].

There was an unusually high incidence of atypical pneumonias in the catchment area of the Rhine river near the university of Düsseldorf in July 1994 during a long period of hot and dry weather. The 18 patients described in this paper (5 women and 13 men) complained of sudden onset of fever up to over 40 degrees C, often associated with severe headache and dry cough. Almost all of these patients had previously been healthy and active and of young to middle age (average 38 years) without any bronchopulmonary anamnesis. Radiology revealed that all the patients had in most cases defined pulmonary infiltrates without any specific preference for a particular site. Serology was initially negative, but four weeks later the complement fixation reaction titre was positive for Coxiella burnetii antibodies in 14 patients (78%). All patients became symptom-free within a few days'time when treated with a combination of antibiotics which included doxycycline, whereas the infiltrates receded completely only after several weeks. The occurrence of pulmonary Q-fever in a large northern German conurbation had been rare at that time. Such epidemics, however, were also noted in Berlin (1992) and in Dortmund (1993). The epidemic reported in this article probably originated from one of the frequent flocks of sheep grazing along the banks of the Rhine river near Düsseldorf. The infections were probably acquired by inhalation of airborne organisms in infected aerosols derived from infected sheep, promoted by the long-term very hot and dry weather which was at the same time very windy, leading to an unusually extensive spreading of the pathogens throughout a very large infected aerosol area.

Adult↗
PubMed1996

[Localized bilateral and symmetrical neurofibromatosis].

INTRODUCTION: We report the first case of bilateral neurofibromatosis localized distally on the lower limbs. CASE REPORT: A 36-year-old woman presented about 20 nodular lesions of the plantar and both lateral aspects of both feet which developed progressively after age 30. Histology examination evidenced neurofibromas. Clinical features and laboratory results enabled us to eliminate von Recklinghausen disease in this mother of 3 children. DISCUSSION: This observation allowed us to situate symmetrical and bilateral neurofibromatosis in the Riccardi classification for genetic counselling. We conclude that the case was a type V neurofibromatosis in a sporadic bilateral form, rarely reported in the literature.

Adult↗
PubMed1995

Intracellular trafficking of furin is modulated by the phosphorylation state of a casein kinase II site in its cytoplasmic tail.

Human furin catalyzes the proteolytic maturation of many proproteins in the exocytic and endocytic secretory pathways by cleavage at the C-terminal side of the consensus sequence-ArgXaaLys/ArgArg decreases -. Both the trans-Golgi network (TGN) concentration and intracellular routing of furin require sequences in its 56 amino acid cytoplasmic tail. Here, we show that the furin cytoplasmic tail contains multiple trafficking signals. Localization to the TGN requires a cluster of acidic amino acids that, together with a pair of serine residues, forms a casein kinase II (CK II) phosphorylation site. We show that CK II efficiently phosphorylates these serines in vitro, and using a permeabilized cell system we provide evidence that CK II is the in vivo furin kinase. Analysis by mass spectrometry shows that, in vivo, furin exists as di-, mono- and non-phosphorylated forms. Finally, employing (i) furin constructs that mimic either non-phosphorylated or phosphorylated furin and (ii) the phosphatase inhibitor tautomycin, we show that the phosphorylation state of the furin cytoplasmic tail modulates retrieval of the endoprotease to the TGN. Thus, routing of furin is a two-tiered process combining a set of trafficking signals comprised of the primary amino acid sequence of the tail with its phosphorylation state.

Amino Acid Sequence↗
PubMed1995

An Alu VpA marker on chromosome I demonstrates that replication errors manifest at the adenoma-carcinoma transition in sporadic colorectal tumors.

Widespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. This aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: one Alu VpA polymorphism (MYCLI), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (AP delta 3 delta). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in the Alu VpA sequence at the MYCLI locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tumors.

Adenoma↗
PubMed1995

Oriented channel insertion reveals the motion of a transmembrane beta strand during voltage gating of VDAC.

Yeast VDAC channels (isolated from the mitochondrial outer membrane) form large aqueous pores whose walls are believed to consist of 1 alpha helix and 12 beta strands. Each channel has two voltage-gating processes: one closes the channels at positive potentials, the other at negative. When VDAC is reconstituted into phospholipid (soybean) membranes, the two gating processes have virtually the same steepness of voltage dependence and the same midpoint voltage. Substituting lysine for glutamate at either end of one putative beta strand (E145K or E152K) made the channels behave asymmetrically, increasing the voltage dependence of one gating process but not the other. The asymmetry was the same whether 1 or 100 channels were in the membrane, indicating oriented channel insertion. However, the direction of insertion varied from membrane to membrane, indicating that the insertion of the first channel was random and subsequent insertions were directed by the previously inserted channel(s). This raises the prospect of an auto-directed insertion with possible implications to protein targeting in cells. Each of the mutations affected a different gating process because the double mutant increased voltage dependence of both processes. Thus this strand may slide through the membrane in one direction or the other depending on the gating process. We propose that the model of folding for VDAC be altered to move this strand into the sensor region of the protein where it may act as a tether and guide/restrict the motion of the sensor.

Amino Acid Sequence↗
PubMed1995

Reduction of lipoprotein(a) following treatment with lovastatin in patients with unremitting nephrotic syndrome.

Pharmocologic treatment of the hyperlipidemia associated with the nephrotic syndrome with lovastatin has been previously shown to be safe and effective. However, there is no information on the effect of lovastatin treatment on plasma lipoprotein(a) [Lp(a)] levels in patients with the nephrotic syndrome. We administered lovastatin (40 to 80 mg/day) to 20 adult patients with unremitting nephrotic syndrome for 8 weeks to assess its effect on plasma Lp(a) and other plasma lipid concentrations. Apoprotein(a) (apo(a)) phenotype was determined in all patients. Patients were grouped according to their plasma Lp(a) levels. Those with elevated plasma Lp(a) (> or = 30 mg/dL) were placed in group I and those with normal Lp(a) levels (< 30 mg/dL) were placed in group II. Mean total cholesterol and LDL cholesterol were similarly and significantly reduced in groups I and II (-35.9% and -43.3%, P < 0.0005, P < 0.0005 group I, and -31.0% and -42.0%, P < 0.02, P < 0.03 group II, respectively). The median reduction in plasma Lp(a) was -32% (P < 0.003) in nephrotic patients in group I, whereas the median decline in plasma Lp(a) levels in nephrotic patients in group II was only -8.0% (P = 0.052). The overall frequency of the high molecular weight (M(r)) apo(a) phenotype S4 was 70% in nephrotic patients. There was no correlation between plasma Lp(a) and apo(a) phenotype. Treatment with lovastatin results in a favorable response in terms of total and low-density lipoprotein cholesterol lowering in patients with the nephrotic syndrome; however, plasma Lp(a) levels are uniformly and significantly reduced only in nephrotic patients with elevated baseline plasma Lp(a) concentrations. There was no correlation between plasma Lp(a) concentration and other lipid and biochemical parameters.

Adult↗