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A Koterba

Publications and source records attributed to A Koterba.

8 recordsLinked to original sources
PubMed1998

Aberrant regulation of transforming growth factor-alpha during the establishment of growth arrest and quiescence of growth factor independent cells.

Autocrine transforming growth factor alpha (TGFalpha) is an important positive growth effector in malignant cells and plays a significant role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms by which TGFalpha confers a growth advantage in progression is poorly understood. The highly tumorigenic cell line HCT116 up-regulates TGFalpha mRNA expression during growth arrest, whereas the poorly tumorigenic growth factor-dependent FET cell line down-regulates TGFalpha mRNA expression as it becomes quiescent. We have identified a 25-bp sequence at -201 to -225 within the TGFalpha promoter which mediates the differential regulation of TGFalpha expression during quiescence establishment in these two cell lines. This same sequence confers TGFalpha promoter responsiveness to exogenous growth factor or autocrine TGFalpha. The abberant upregulation of TGFalpha mRNA in quiescent HCT116 cells may allow them to return to the dividing state under more stringent conditions (nutrient replenishment alone) then quiescent FET cells (requires nutrients and growth factors). Antisense TGFalpha approaches showed that the dysregulated TGFalpha expression in quiescent HCT116 cells is a function of the strong TGFalpha autocrine loop (not inhibited by blocking antibodies) in these cells.

Base Sequence↗
PubMed1998

Regulation of transforming growth factor alpha expression in a growth factor-independent cell line.

Aberrant transcriptional regulation of transforming growth factor alpha (TGF alpha) appears to be an important contributor to the malignant phenotype and the growth factor independence with which malignancy is frequently associated. However, little is known about the molecular mechanisms responsible for dysregulation of TGF alpha expression in the malignant phenotype. In this paper, we report on TGF alpha promoter regulation in the highly malignant growth factor-independent cell line HCT116. The HCT116 cell line expresses TGF alpha and the epidermal growth factor receptor (EGFR) but is not growth inhibited by antibodies to EGFR or TGF alpha. However, constitutive expression of TGF alpha antisense RNA in the HCT116 cell line resulted in the isolation of clones with markedly reduced TGF alpha mRNA and which were dependent on exogenous growth factors for proliferation. We hypothesized that if TGF alpha autocrine activation is the major stimulator of TGF alpha expression in this cell line, TGF alpha promoter activity should be reduced in the antisense TGF alpha clones in the absence of exogenous growth factor. This was the case. Moreover, transcriptional activation of the TGF alpha promoter was restored in an antisense-TGF alpha-mRNA-expressing clone which had reverted to a growth factor-independent phenotype. Using this model system, we were able to identify a 25-bp element within the TGF alpha promoter which conferred TGF alpha autoregulation to the TGF alpha promoter in the HCT116 cell line. In the TGF alpha-antisense-RNA-expressing clones, this element was activated by exogenous EGF. This 25-bp sequence contained no consensus sequences of known transcription factors so that the TGF alpha or EGF regulatory element within this 25-bp sequence represents a unique element. Further characterization of this 25-bp DNA sequence by deletion analysis revealed that regulation of TGF alpha promoter activity by this sequence is complex, as both repressors and activators bind in this region, but the overall expression of the activators is pivotal in determining the level of response to EGF or TGF alpha stimulation. The specific nuclear proteins binding to this region are also regulated in an autocrine-TGF alpha-dependent fashion and by exogenous EGF in EGF-deprived TGF alpha antisense clone 33. This regulation is identical to that seen in the growth factor-dependent cell line FET, which requires exogenous EGF for optimal growth. Moreover, the time response of the stimulation of trans-acting factor binding by EGF suggests that the effect is directly due to growth factor and not mediated by changes in growth state. We conclude that this element appears to represent the major positive regulator of TGF alpha expression in the growth factor-independent HCT116 cell line and may represent the major site of transcriptional dysregulation of TGF alpha promoter activity in the growth factor-independent phenotype.

Cell Division↗
PubMed1994

Acetaldehyde alters coagulation protein function.

Acetaldehyde is the first metabolite of ethanol and has the potential to react with proteins and alter their function. This study evaluated the function of clotting proteins that had been preincubated with acetaldehyde as compared to those incubated with buffer or ethanol as controls. Thrombin, fibrinogen, thromboplastin, or whole plasma were preincubated with 1.8-447 mM acetaldehyde, 1.7-429 mM ethanol, or buffer for varying time periods prior to use in a clotting assay. Clot formation was measured with an automatic fibrometer. Acetaldehyde prolonged the clotting time but ethanol did not. These experiments indicate that circulating acetaldehyde would have the potential to react with proteins of the clotting system and alter their function. Therefore, it is possible that not all of the abnormalities in coagulation in alcohol abusers result from inadequate hepatic synthesis. Perhaps some of the deranged coagulation may be the result of the interaction of acetaldehyde with coagulation proteins.

Acetaldehyde↗
PubMed1986

Nosocomial infections and bacterial antibiotic resistance in a university equine hospital.

A base-line study of bacteria isolated from horses admitted to the Veterinary Medical Teaching Hospital during a 6-month period was performed to determine the extent of multiresistant nosocomial infections caused by gram-negative aerobic bacteria other than Salmonella spp. Results of this study indicated that 21.9% of the 105 horses from which cultures and sensitivities were available had developed nosocomial gram-negative aerobic infections, with high rates of resistance to gentamicin, kanamycin, and trimethoprim sulfadiazine, three of the most often prescribed antibiotics in this hospital. In addition, a prospective study of antibiotic-resistant bacteria of fecal origin was performed to determine whether there was a change in the degree of antibiotic resistance of a horse's intestinal flora while the horse was hospitalized. Bacterial culturing for gram-negative lactose fermenting bacteria was done on fecal specimens collected directly from the rectum on day 1 and day 7 of a horse's hospitalization. Susceptibility testing was done on each isolant. Of the 24 paired fecal specimens obtained, Escherichia coli and Klebsiella sp isolated on day 7 were resistant to a significantly higher number of antibiotics than day 1 isolants (P = 0.003, P = 0.043, respectively).

Animals↗
PubMed1982

Acid-base and electrolyte alterations in horses with exertional rhabdomyolysis.

In examination of the acid-base and electrolyte status of 7 horses with acute exertional rhabdomyolysis, the most consistent abnormality was hypochloremia. Metabolic acidosis was not evident in any of the horses. Therefore, the use of sodium bicarbonate in treatment of such disorders may not be indicated in all cases.

Acid-Base Imbalance↗