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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 73 records · Page 4Linked to original sources
PubMed1991

A pilot study of sphincter-sparing management of adenocarcinoma of the rectum.

After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy.

Adenocarcinoma↗
PubMed1991

A 5-year study of cryosurgery in the treatment of liver tumors.

This report summarizes our 5-year experience with cryosurgery for in situ ablation of liver tumors. The liver was exposed with laparotomy, and the tumors were subjected to two freeze-thaw cycles using liquid nitrogen delivered by insulated probes; cryoablation was monitored with intraoperative ultrasonography. Tumor markers and computed tomography evaluated tumor response during long-term follow-up. From 1985 to 1990, 32 patients (19 men and 13 women) were entered into this study. The histologic characteristics of the tumors were as follows: colorectal, 24 patients; hepatoma, three patients; neuroendocrine, two patients; and others, three patients. After a follow-up period of 5 to 60 months (median follow-up, 24 months), nine patients (28%) remained disease free, 11 patients (34%) were alive with disease, and 12 patients (38%) died. The patterns of failure included liver and extrahepatic disease in 54% of cases, liver disease only in 32% of cases, and extrahepatic disease only in 14% of cases. In patients with "liver only" failure, recurrence at the treatment site occurred in three patients (9%). This study establishes the long-term effectiveness of cryosurgery in the treatment of primary and metastatic liver tumors.

Adult↗
PubMed1991

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584.

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

Adenocarcinoma↗
PubMed1991

Preneoplastic lesions induced by myc and src oncogenes in a heterotopic rat colon.

With the use of viral vectors harboring myc and src oncogenes, we have assessed the potential contribution of these different elements to colonic neoplasia using a transplantation technique resulting in the formation of a heterotopic colon in Wistar Furth rats. While myc alone induced atypia and some dysplasia, src induced focal dysplastic lesions throughout the colon mucosa with evidence of metaplasia. In contrast, lesions induced by myc and src acting cooperatively, were highly dysplastic with evidence of tumor formation after protracted periods. These results indicated the formation of histologically distinct preneoplastic lesions elicited by the action of a single oncogene in colon implants with the production of adenocarcinomas when such oncogenic elements act cooperatively. This model provides an opportunity for studies of the action of different oncogenes, acting singly or in combination, in the multi-step progression to colon tumor formation.

Animals↗
PubMed1991

Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications.

The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU.

Costs and Cost Analysis↗
PubMed1990

Induction of carcinoembryonic-antigen-gene expression in human colorectal carcinoma by sodium butyrate.

The effect of sodium butyrate on the expression of the carcinoembryonic-antigen (CEA) gene was studied in two poorly differentiated colorectal-carcinoma cell lines (Clone-A and MIP-101) and in one well-differentiated cell line (LS-174T); A.T.C.C. no. CCL 188). Northern-blot and dot-blot analyses indicated a steady increase in CEA mRNA from day 4 to a maximal level by day 14 after these cells were exposed to 2 mM-sodium butyrate. Studies using nuclear run-off assays followed by dot-blot hybridization to a partial CEA cDNA clone demonstrated that specific increases in gene transcription rates (3-fold in MIP-101, 4-fold in LS-174T and 6-fold in Clone-A) are not sufficient to account for the observed increases in CEA mRNA abundance. Further studies showed that CEA-specific transcripts have a half-life of about 60-80 min, and treatment with sodium butyrate increased the stability of CEA-specific transcripts to about 340 min in LS-174T cells and to about 500 min in Clone-A cells. We conclude that the induction of the CEA-gene expression by sodium butyrate in colorectal-cancer cells is mediated by both transcriptional and post-transcriptional mechanisms, with CEA mRNA stability as one of the major check-points.

Butyrates↗
PubMed1990

Expression of human alpha-actinin in human hepatocellular carcinoma.

Little is known regarding gene expression during hepatocyte transformation. We have isolated an alpha-actinin complementary DNA from a human hepatocellular carcinoma library. This partial 2.4-kilobase complementary DNA has high homology with human placental and chicken nonmuscle alpha-actinins; our isolate contains the entire 3' noncoding region and it is within these sequences where the major differences between the vertebrate alpha-actinin complementary DNAs arise. Northern analysis revealed a 3.5-kilobase transcript in nonmuscle and a smaller 3.0-kilobase species in muscle tissue. Levels of alpha-actinin expression were low in normal liver and we investigated its expression during both hepatocyte proliferation and transformation. We found no increase during rat hepatocyte regeneration up to 24 h following two-thirds hepatectomy. However, high levels of alpha-actinin transcripts were observed in human hepatocellular carcinoma compared to noninvolved adjacent liver. We conclude that the alpha-actinin gene is highly expressed when hepatocytes have assumed the malignant phenotype.

Actinin↗
PubMed1990

A carcinoembryonic antigen (CEA) binding protein from ascites influences CEA uptake by macrophages.

A variant of CEA which is less readily endocytosed by macrophages has been isolated from malignant ascites. In vivo, CEA is cleared more slowly by the liver (t1/2 = 15.1 minutes) than CEAs isolated from hepatic metastases (t1/2 = 3.1 minutes). In vitro, rat and human Kupffer cells and rat alveolar macrophages endocytose this CEA less effectively. This slow clearing form of CEA is associated with a smaller (45kD) acidic glycoprotein (CORA) with which it forms a stable complex. CORA can be visualized on reducing gels but not on non reducing gels or by HPLC run under non reducing conditions. This suggests a non-covalent complex between the two glycoproteins. Analysis of protein conformation by circular dichroism revealed changes in the ascites CEA consistent with binding of CORA to the molecule. Western blot showed that CORA crossreacts with antisera to alpha 1-acid glycoprotein and double immunodiffusion demonstrated cross-reactivity but not identify. Sequencing of CNBr peptides showed sequence homology with alpha 1-acid glycoprotein but areas of unique sequence were also found. It is suggested that binding of CORA to CEA blocks the macrophage receptor binding of CEA.

Amino Acid Sequence↗
PubMed1990

Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy.

Albright's hereditary osteodystrophy is an autosomal dominant disorder characterized by a short stature, brachydactyly, subcutaneous ossifications, and reduced expression or function of the alpha subunit of the stimulatory G protein (Gs alpha) of adenylate cyclase, which is necessary for the action of parathyroid and other hormones that use cyclic AMP as an intracellular second messenger. We identified a unique Gs alpha protein in erythrocytes from two related patients with Albright's hereditary osteodystrophy and reduced Gs alpha bioactivity. The Gs alpha variant was recognized by a carboxyl terminal-specific Gs alpha antiserum but not by polyclonal antiserums specific for the amino terminus of Gs alpha. To investigate the molecular basis for this structurally abnormal Gs alpha protein, we studied the Gs alpha gene by restriction-endonuclease analysis. DNA from the two patients had an abnormal restriction-fragment pattern when digested with Ncol, which was consistent with loss of an Ncol restriction site in exon 1 of one Gs alpha allele. Amplification of a 260-base-pair region that includes exon 1 of the Gs alpha gene and direct sequencing of the amplified DNA revealed an A-to-G transition at position +1 in one Gs alpha allele from each of the two patients. This mutation converts the initiator ATG (methionine) codon to GTG (valine), blocking initiation of translation at the normal site. Translation of the abnormal Gs alpha messenger RNA would result in the synthesis of a truncated Gs alpha molecule lacking the amino terminus. We conclude that in at least some patients with Albright's hereditary osteodystrophy, the disease is caused by a single-base substitution in the Gs alpha gene and is thus due to an inherited mutation in a human G protein.

Adenylyl Cyclases↗
PubMed1990

New surgical treatments for recurrent colorectal cancer.

Currently, only two areas of recurrence in patients with colorectal cancer are potentially surgically curable: isolated liver and isolated lung metastases. Regional recurrence from rectal cancer, although probably not resectable for cure, offers an appropriate palliative goal because symptoms in such patients are intolerable. We review several new diagnostic and therapeutic techniques that have allowed wider application of surgical approaches for cure or palliation in patients with recurrent colorectal cancer.

Adenocarcinoma↗
PubMed1990

Inhibition of sialic acid incorporation prevents hepatic metastases.

It has been hypothesized that the metastatic capacity of tumors may be correlated with hypersialylation of the cell surface. We used a novel inhibitor of sialic acid incorporation, KI-8110, to determine the effect of depletion of cell surface sialic acid on the metastatic behavior of three human colorectal cancer cell lines, in which hepatic seeding was related to tumor cell differentiation. Treatment of tumor cells with KI-8110 prior to intrasplenic injection prevented liver colonization. Total cellular sialic acid was reduced, as was that of the cell surface. Secreted forms of carcinoembryonic antigen also were depleted of sialic acid by this treatment. These data show that depletion of sialic acid from cell surface glycoconjugates reduces the incidence of hepatic metastases from human colorectal primary tumors and adds to the mounting evidence of the importance of sialic acid in determining the biological behavior of tumor cells.

Animals↗
PubMed1990

An observation of polymorphism in pentamidine isethionate.

Two forms of pentamidine isethionate have been identified from two commercial samples of the compound. The lower melting form was produced by freeze drying and has a melting point of 133.4 degrees C whilst the higher melting form has a melting point of 192 degrees C. Powder x-ray diffraction studies showed that each modification was crystalline and the infra-red spectra showed differences that could be attributed to polymorphism. It was noted that when the freeze dried material was exposed to the atmosphere it converted to the higher melting form and was hygroscopic. Examination of this compound in a formal polymorphism screen was advocated.

Calorimetry, Differential Scanning↗
PubMed1990

Expectancy effects in caffeine research.

The impact of expectancy on the experience of caffeine-related symptoms was investigated by randomly assigning subjects to an expectancy or nonexpectancy instructional condition. Subjects were administered the State-Trait Anxiety Inventory and a Symptom Questionnaire prior to and 45 minutes after receiving their designated instructional set and ingesting a cellulose-filled gelatin capsule which ostensibly was filled with caffeine. Results revealed that a significant expectancy effect existed on five Symptom Questionnaire items.

Adult↗
PubMed1990

Preneoplastic lesions induced by myc and src oncogenes in reconstituted mouse bladder.

To define a role for different oncogenes in bladder neoplastic progression we have introduced viral myc and src oncogenes, singly or in combination, into intact normal urothelium. After incubation with virus, infected mucosa was heterotransplanted under the renal capsule of syngeneic animals and monitored for progression toward malignancy by use of histologic and immunofluorescence techniques. Although v-myc alone induced focal hyperplastic change, more dysplastic lesions were observed after expression of the src oncogene product in urothelial implants. In contrast, lesions induced by myc and src acting cooperatively were highly proliferative, displaying evidence of tumor formation within the 6-week study period. The presence and expression of myc and src oncogenic proteins, associated with preneoplastic and neoplastic lesions, was confirmed by use of Southern blot analysis and an immune complex kinase assay, respectively. These results indicate the formation of histologically distinct preneoplastic change elicited by the action of a single oncogene with induction of neoplastic changes when such oncogenic elements act cooperatively. This model provides an opportunity to study the action of different oncogenes throughout bladder neoplastic progression in vivo.

Animals↗
PubMed1989

Experimental liver metastasis. Implications of clonal proclivity and organ specificity.

"Spontaneous" lung metastases develop in over 50% of the animals bearing subcutaneous isografts of WB-2054, a rat colon carcinoma. A metastatic variant has been developed by "Fidler" type in vivo selection, yielding 100% lung metastasis. In a five-week assay to test the organ specificity of this lung metastatic variant, however, "experimental" liver and lung metastases could be induced in 100% and 60% of animals on portal venous and intravenous injections, respectively. The results demonstrate selection of a metastatic variant from heterogeneous primary tumor, and suggest at least two interacting mechanisms: (1) mechanical (the anatomy of the blood-borne metastatic pathways) and (2) biologic (factors intrinsic to primary tumor subpopulations that can be selected for metastatic proclivity). In addition, liver metastases were successfully established from colon tumors induced by cecal wall injection of tumor cells. Such a spontaneous liver metastasis model will be useful to study the specific mechanisms involved during metastasis of colon cancer to the liver.

1,2-Dimethylhydrazine↗
PubMed1989

Primary cancer of the liver. Evaluation, treatment, and prognosis.

Between 1970 and 1985, a diagnosis of primary hepatocellular carcinoma was established in 98 patients. Sixty-one cases developed in the presence of chronic liver disease, and only six of these were considered resectable. Of these, the median survival was 19 months. There was one perioperative death. Of the 98 tumors, 37 arose in normal livers. Of the 16 patients with tumors in normal livers that were resected, all survived operation. The long-term median survival was 32 months. Two subsets of the fibrolamellar and clear-cell variants appeared to carry a more favorable prognosis.

Adult↗