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E Roach

Publications and source records attributed to E Roach.

13 recordsLinked to original sources
PubMed1998

Staging of oesophageal carcinoma by endoscopic ultrasound: preliminary experience.

BACKGROUND: Endoscopic ultrasound (EUS) is a relatively recent imaging modality that is capable of visualizing oesophageal tissue layers and para-oesophageal structures. Current pre-operative staging of oesophageal cancer is less than satisfactory, and a modality which may improve pre-operative staging, thus allowing a more rational approach to choice of treatment, may be a welcome addition to current techniques. The purpose of the present study was to evaluate the accuracy of EUS in the staging of oesophageal carcinoma in a consecutive cohort of patients. METHODS: Forty-three patients with oesophageal cancer were prospectively staged with EUS using the radial scanning Olympus EUM-3 echo-endoscope. In the 28 patients who underwent surgery EUS staging was correlated with operative and histological findings to evaluate the EUS accuracy rate of assessing tumour depth (T stage), and the presence of nodal involvement (N stage) using internationally accepted TNM staging criteria. RESULTS: Endoscopic ultrasound accuracy rates for overall T-staging was 61% whereas that of N-staging was 75%. The overall TNM pathological staging was 75% accurate by EUS. CONCLUSIONS: Compared to published literature figures for oesophageal staging by computed tomography scanning (39-54%) these results demonstrate that EUS has a reasonable accuracy rate for staging. Endoscopic ultrasound may prove to be a useful additional modality in the management of oesophageal cancer.

Adenocarcinoma↗
PubMed1995

Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. Results of the first multicentre Australian trial. Australia Hepatitis C Study Group.

Two hundred and thirty patients with histologically proven chronic hepatitis C were randomized to receive one of the following treatment protocols: (a) 3 million units of interferon alfa-2b thrice weekly for 6 months, (b) 5 million units thrice weekly for 6 months, or (c) 3 million units thrice weekly for 2 years. The short-term response to treatment was defined by normal alanine aminotransferase for at least 3 months and until the end of treatment, and was confirmed by loss of hepatitis C viraemia in 42 (91%) of 46 cases as determined by reverse transcription-polymerase chain reaction. Short-term response to interferon alfa-2b was independent of the incremental dose, being 64% for 5 million units and 58% for 3 million units. Long-term response to interferon alfa-2b was defined by continued normality of alanine aminotransferase levels for at least 6 months after treatment withdrawal. The long-term response rates among responders treated for 6 months and those treated for 2 years were 29% and 54%, respectively (p < 0.001). Among all 18 patients tested, serum HCV-RNA was negative at both 6 and 12 months of follow-up in all long-term responders, and none have subsequently relapsed. Improvement in hepatic necroinflammatory changes was confirmed by quantitative histology (Scheuer score) in responders at the end of interferon alfa-2b treatment. The changes were significantly greater among those who had been treated for 2 years compared with those treated for 6 months (p < 0.05 and p < 0.02, respectively, for portal and lobular inflammation scores). Several pretreatment characteristics could be correlated with a favourable response to interferon alfa-2b. Thus, absence of cirrhosis was associated with a short-term response of 75%, while only 42% of patients with cirrhosis had a short-term response (p < 0.001). The frequency of short-term response to interferon alfa-2b also differed according to mode of disease acquisition, being best for injecting drug use (71%), less favourable for blood transfusion (56%) and worst for sporadic cases (43%) (p < 0.01). This observed difference, however, was not independent of histology on multivariate analysis. In summary, a 5 million unit dose of interferon alfa-2b failed to improve the short-term or long-term response to interferon alfa-2b treatment, but prolongation of interferon alfa-2b treatment to 2 years resulted in substantially improved long-term response rate.

Adolescent↗
PubMed1991

Localization of Y1 receptors for NPY and PYY on vascular smooth muscle cells in rat pancreas.

To localize binding sites for peptide YY (PYY) in the pancreas we utilized a slide-mount autoradiographic technique on frozen sections of rat pancreas incubated with 125I-Tyr36-PPY. Saturable autoradiographic labeling was located over pancreatic blood vessels, whereas islets, acinar cells, ducts, and neural elements did not appear to be specifically labeled. Isolated vascular fragments were prepared by collagenase digestion of rat pancreas. Binding experiments with 125I-Tyr36-PYY showed saturable binding to the fraction enriched in blood vessels but not to acini. Inhibition of 125I-Tyr36-PYY binding by nonradioactive neuropeptide Y (NPY) and PYY were similar, with half-maximal inhibition at 31.2 +/- 5 pM (n = 6); the potency of pancreatic polypeptide (PP) was 10,000 times lower. The binding site was classified as belonging to a Y1 type of NPY and/or PYY receptors, since [Leu31,Pro34]NPY, a specific Y1-receptor agonist, inhibited binding similar to NPY. To further localize the bound [125I-Tyr36]PYY within the blood vessels, light- and electron-microscopic autoradiographs were prepared and quantitated. Autoradiographic grains were located predominantly over vascular smooth muscle cells, although saturable localization was also seen over endothelial cells. It is concluded that in the pancreas Y1 receptors are predominantly located on vascular smooth muscle cells.

Animals↗
PubMed1988

Temperature dependence of high-affinity CCK receptor binding and CCK internalization in rat pancreatic acini.

125I-labeled cholecystokinin (CCK) binding and internalization were studied as a function of temperature in isolated rat pancreatic acini. At 37 degrees C, acini readily bound and degraded 125I-CCK. When labeled hormone binding was inhibited by increasing amounts of unlabeled CCK, competition-inhibition curves were biphasic, consistent with both high- (Kd, 18 pM) and low-affinity (Kd, 13 nM) binding sites. At 4 degrees C, acini bound only one-third as much 125I-CCK and degradation was essentially abolished. At 4 degrees C, CCK competition curves were consistent with a single class of low-affinity binding sites (Kd, 19 nM). Internalization of 125I-CCK was evaluated by three washing procedures utilizing acid, base, and trypsin. All were shown to remove membrane-bound 125I-CCK, and this finding was validated for trypsin by electron microscope autoradiography. After 1 h at 37 degrees C, washing showed 67% of bound 125I-CCK to be internalized and autoradiography showed 54% to be internalized. At 4 degrees C, internalization of bound CCK was greatly reduced but not abolished. When internalization of 125I-CCK was evaluated as a function of the medium concentration of CCK, both high- and low-affinity components were observed. These results suggest that high-affinity CCK binding and CCK internalization are separate temperature-sensitive processes. Moreover, internalization is not uniquely associated with high-affinity binding.

Animals↗
PubMed1986

Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini.

The internalization and intracellular distribution of 125I-insulin-like growth factor II (125I-IGF II) in mouse isolated pancreatic acini was studied by electron microscope autoradiography. 125I-IGF II was rapidly internalized; after 30 min over 70% of silver grains derived from the bound hormone were localized over the interior of the cells. The grain distribution from 125I-IGF II differed significantly from both a random grain distribution and that derived from bound 125I-insulin. The majority of intracellular 125I-IGF II grains were over the endoplasmic reticulum and Golgi; the Golgi showed the highest density of intracellular grains. Pretreatment of acini with 10 nM cholecystokinin octapeptide (CCK 8) reduced both the amount of acinar-associated IGF II and the density of intracellular 125I-IGF II grains. Moreover, CCK 8 altered the relative distribution of grains from 125I-IGF II between organelles. These studies indicate, therefore, that 125I-IGF II is internalized by pancreatic acini, and that this internalization is regulated by CCK 8.

Animals↗
PubMed1985

Localization of saturable CCK binding sites in rat pancreatic islets by light and electron microscope autoradiography.

Cholecystokinin (CCK) is a known stimulus for the release of insulin and other islet hormones. To localize islet cell CCK binding sites, we measured the uptake of 125I-CCK by the isolated, perfused rat pancreas. Light microscope autoradiographs revealed uptake of label over both the endocrine islets of Langerhans and the exocrine acini. This uptake of 125I-CCK was saturable, as it decreased markedly when a large excess of unlabeled CCK8 was included in the perfusion solution. To define which cells in the islets bound CCK, electron microscope autoradiographs were prepared. The majority of silver grains in islets were localized over beta cells (69%), although saturable uptake was also observed over alpha (12%) and other islet cells. When grain densities were analyzed (grains/micron 2), the highest density was observed over islet blood vessel cells. In contrast to islet blood vessels, there was no localization of 125I-CCK over acinar blood vessels. This study supports the concept, therefore, that there is a direct regulation of islet endocrine cells by CCK, and also raises the possibility that CCK influences islet hormone release via an indirect effect on the islet vascular endothelium.

Animals↗
PubMed1984

Methylamine and monensin do not block insulin internalization but do influence the intracellular distribution and action of insulin in pancreatic acini from diabetic mice.

Methylamine and monensin are two agents known to interfere with the recycling of membrane receptors. In the present investigation, we studied their effects on the binding, intracellular distribution, and action of insulin in isolated pancreatic acini prepared from diabetic mice. These drugs had several similar effects on these cells. In a dose-dependent fashion, both increased the amount of [125I]insulin associated with acini. Methylamine approximately doubled and monensin tripled the amount of insulin associated with cells. Employing electron microscope autoradiographs, we observed the accumulation of hormone in large vacuoles in the Golgi-lysosomal area after treatment with methylamine and in smaller swollen Golgi vesicles after treatment with monensin. The influences of both agents on the biological effects of insulin in acini were then investigated. Both agents blocked insulin stimulation of [3H]2-deoxy-D-glucose uptake in acini. The effect of methylamine was also studied on [3H]leucine incorporation into protein and was found to only partially block the effect of insulin. Since insulin and its receptor are internalized, it is likely that the accumulation of insulin in acini induced by these two agents was due to their inhibition of the cellular processing of insulin and its receptor. Moreover, the effects of these two agents to inhibit insulin-stimulated glucose transport may have resulted from either the inhibition of the recruitment of glucose carriers from the Golgi to the plasma membrane or an abnormal interaction of internalized insulin with the Golgi.

Animals↗
PubMed1984

In vivo localization of insulin binding to cells of the rat pancreas.

The uptake of 125I-insulin by rat pancreas was studied in vivo. Following fixation and light microscope autoradiography, saturable uptake of 125I-insulin was quantitatively demonstrated on acinar and duct cells but not on blood vessels and islets of Langerhans. Electron microscopy revealed the localization of 125I-insulin to the basolateral cell membranes of acinar and duct cells.

Animals↗
PubMed1983

The effect of chloroquine on the binding, intracellular distribution, and action of insulin on isolated mouse pancreatic acini.

The effects of chloroquine on the binding, intracellular distribution, and action of insulin were studied in isolated pancreatic acini prepared from diabetic mice. Chloroquine had three effects on these cells. First, chloroquine altered cellular morphology by inducing an increase in the number and size of autophagic vacuoles and vesicles in the Golgi-lysosomal region. Second, chloroquine, in a dose-dependent fashion, increased the amount of 125I-insulin associated with acini. A detectable effect of chloroquine was seen at 10 microM, and a maximal effect was seen at 30-100 microM where cell-associated insulin was more than doubled. Employing electron microscope autoradiographs, this accumulation of hormone was observed in the Golgi-lysosome area of the pancreatic acinar cell. Third, chloroquine had selective effects on the action of insulin. Preincubation with chloroquine had no effect on basal [3H]2-deoxy-D-glucose uptake, but in a dose-dependent fashion it decreased the stimulatory effect of insulin on this function; at 100 microM chloroquine, the effect of insulin was abolished. In contrast, chloroquine had negligible effects on the stimulation of 2-deoxy-D-glucose uptake into acini by cholecystokinin. Chloroquine in dose-dependent fashion partially inhibited basal [3H]leucine incorporation into acinar cell protein, but in contrast to its effects on 2-deoxy-D-glucose uptake, the drug had no effects on the stimulation of this function by insulin.+2

Animals↗
PubMed1982

Quantitative electron microscope autoradiographs of 125I-cholecystokinin in pancreatic acini.

To morphologically evaluate the interaction of cholecystokinin (CCK) with its receptors on pancreatic acinar cells, we incubated isolated mouse acini at 37 degrees C with radioiodinated CCK and then prepared quantitative electron microscope autoradiographs. Specific binding of CCK to acini was one-half maximal at 2 min of incubation and maximal after 10 min. The cell-associated radioactivity was extracted and analyzed on Sephadex G-50. After 2 min, 90% of the total cellular radioactivity remained as intact CCK; after 30 min, the intact radioactivity decreased to 65% of total. At 2 min, the fraction of bound hormone that fixed to acini was 84% of total; this amount decreased to 78% after 30 min. Thus, the majority of radioactivity in the autoradiographs at both time points was intact CCK; however, at 30 min, a small amount was also degraded hormone. After both 2 and 30 min of incubation, silver grains were highly concentrated over the basolateral plasma membrane. A significant number of grains were in the cell interior at both time points, increasing from 13% of total grains at 2 min to 42% at 30 min. At both times, the largest fraction of internalized grains was localized over the endoplasmic reticulum. At 30 min, a significant concentration of CCK grains was observed over multivesicular bodies. The present study demonstrates, therefore, that CCK binds to specific receptors on the basolateral surface of pancreatic acinar cells. After binding, the hormone is internalized, locates predominantly on the endoplasmic reticulum, and is then degraded.

Animals↗
PubMed1975

Holoprosencephaly: birth data, benetic and demographic analyses of 30 families.

Thirty families were studied to determine genetic and evnironmental factors involved in holoprosencephaly. Those with chromosomal abnormalities were excluded. Many factors appear to cluster in proband families, such as mental retardation, mental illness, endocrine disorders, increased twinning and poverty level socioeconomic status. The empiric recurrence risk was 6%. Among 7 with lobar holoprosencephaly, there were 3 females and 4 males, while there were 19 females and 6 males with alobar holoprosencephaly.

Abnormalities, Severe Teratoid↗
PubMedDate not supplied

Verrucous carcinoma of the oesophagus and achalasia.

A 67 year old male caucasian clerical worker with a background of long-standing gastro-oesophageal reflux-like dyspepsia and bronchiectasis presented to a tertiary hospital gastroenterology unit with a recent onset of dysphagia. An initial diagnosis of achalasia was made and within 1 year an established verrucous carcinoma of the upper oesophagus had developed. The tumour was inoperable due to tracheal invasion and therefore palliative treatment was given. The patient developed a tracheo-oesophageal fistula and died of pneumonia. Thus, verrucous squamous cell carcinoma of the oesophagus can occur with achalasia.

Aged↗