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Biomedical subjects

J Harmon

Publications and source records attributed to J Harmon.

17 recordsLinked to original sources

Aggressive multimodality therapy for stage III esophageal cancer: a phase I/II study.

BACKGROUND: Stage III advanced locoregional esophageal carcinoma is frequently unresectable and inconsistently represented in therapeutic trials of esophageal cancer. METHODS: From 1992 to 1998, 34 of 131 total esophageal cancer patients were designated stage III (16 T3N1, 9 T4N0, 9 T4N1) and medically fit to enter a combined modality protocol with continuous infusion 5-fluorouracil (CIS-FU, 300 to 600 mg/m2/day), high-dose external beam irradiation (60 Gy), and interval esophagectomy. Staging before and after induction therapy included computed tomography; endoscopy, and endoscopic ultrasound. RESULTS: Significant toxicity from induction therapy included death (5/34; 14.7%), pneumonitis (5/34; 14.7%), mucositis (13/34; 38%), and hand-foot syndrome (3/34; 8.8%). In addition to the five deaths, 11 patients did not proceed to operation because of development of esophagorespiratory fistula in 3, distant disease in 2, persistence of T4 stage in 2, progression of comorbidities in 2, and patient refusal in 2. There was a discrepancy between clinical complete response (cCR) at restaging 56% (19/34) and pathologic CR (pCR) noted at the time of operation (8/34; 23.5%). Complete resections were possible in 16 of 18 patients explored. Complications in 4 patients included: death (1), airway injury (1), chylothorax requiring reoperation (1), anastomotic leak (1), recurrent nerve injury with vocal cord paresis (2), and ascaris infection (1). Actuarial survival analysis using the Kaplan-Meier method and log-rank testing showed a 36-month survival of 20% for the group as a whole and 27% for patients restaged cCR (cCR vs PR, p = 0.0046). Treatment failure is predominantly distant, with good local control in resected patients. N0 node status was strongly associated with survival (N0 vs N1 p = 0.0024). There is a trend towards improved survival in the resected group (resected 22% vs nonresected 10% at 3 years, p = 0.17). CONCLUSIONS: Response rates and survival are commensurate with multiple completed phase II and III trials. These are attained at a higher treatment-related mortality. T4 patients can be successfully resected in selected patients. Even in advanced disease, nodal status is a significant predictor of survival.

Adenocarcinoma↗

Benign enterogenous cyst of the pancreas.

A 26-year-old woman was evaluated for a mass found by computed tomography (CT). Radiographically, the mass resembled a pancreatic cystadenoma. The patient had had left upper quadrant abdominal pain for several years and low grade fevers and indigestion for 5 months. At surgery, a unilocular cystic mass was found anteriorly and caudally to the tail of the pancreas in the lesser sac. The cystic structure was connected to the pancreas by a tubular structure, which was suture ligated and divided. A review of the literature revealed this cyst to be the fifth reported case of enterogenous cyst of the pancreas. The case is unique, differing from previous reports in that ciliated respiratory epithelium, transitional epithelium, gastric mucosa, a bilayered smooth muscle wall, and a serosal surface were present in the cyst wall.

Adult↗

Insulin increases the processing efficiency of messenger ribonucleic acid-S14 nuclear precursor.

Feeding a lipogenic diet increases transcription and enhances processing of the rat hepatic messenger RNA (mRNA)-S14 gene. To determine the separate roles of insulin and increased glucose in these processes, we used the streptozotocin-induced diabetic rat model. Diabetes caused a reduction in mature mRNA-S14 in chow- and lipogenic diet-fed animals (P < 0.006 and P < 0.001, respectively). Insulin restored these levels to normal. Despite the known effects of insulin and carbohydrate on the transcription of this gene, we were unable to demonstrate significant changes in the nuclear proteins that bind to carbohydrate response regions. Yet, insulin restored the content of the mRNA by increasing the ratio of mature to precursor mRNA-S14. Insulin significantly increased this ratio (P < 0.0001) independent of diet and diabetes, further supporting the action of insulin on increasing processing from precursor to mature mRNA. The mechanism of the enhanced processing was studied by ribonuclease mapping and primer extension analysis. Ribonuclease mapping showed that lipogenic diet feeding increases the efficiency of processing at a step before formation of the branched form of the precursor mRNA. Taken together, our data demonstrate for the first time that insulin significantly enhances the efficiency of processing of a pre-mRNA.

Animals↗

Direct evidence for a role of the "spot 14" protein in the regulation of lipid synthesis.

"Spot 14" is a nuclear protein that is rapidly induced by thyroid hormone (T3) and dietary carbohydrate in liver. We used an antisense oligonucleotide to inhibit induction of spot 14 protein by T3 and glucose in primary cultures of rat hepatocytes to test the hypothesis that the protein could function in the regulation of lipid synthesis. Spot 14 protein was undetectable in hepatocytes maintained in 5.5 mM glucose without T3, and was induced within 4 h after addition of 27.5 mM glucose and 50 nM T3 to the culture medium, reaching a maximal level within 24 h. Accumulation of spot 14 protein was markedly inhibited in hepatocytes transfected with a spot 14 antisense oligonucleotide, but not in those treated with a control oligonucleotide. Transfection of the antisense, but not control, oligonucleotide also abrogated the increase in lipogenesis induced by T3 and glucose. Reduced triglyceride formation accounted for the diminished net lipid synthesis. In contrast to lipogenesis, glucose uptake was not significantly affected by the transfections. Antisense transfection inhibited the induction of both ATP-citrate lyase and fatty acid synthase immunoreactivities, as well as malic enzyme activity, indicating that the observed reduction in lipogenesis could be explained by diminished cellular content of lipogenic enzymes. Reduced malic enzyme activity in antisense-transfected hepatocytes was accompanied by lowered relative abundance of malic enzyme mRNA, suggesting that the antisense effects on lipogenic enzymes were mediated at the pretranslational level. The oligonucleotides did not significantly affect lipogenesis in a rat hepatoma cell line that does not express detectable spot 14 mRNA or protein. These data directly implicate the spot 14 protein in the transduction of hormonal and dietary signals for increased lipid metabolism in hepatocytes.

Animals↗

Immunochemical study of subunit VI (Mr 13,400) of mitochondrial ubiquinol-cytochrome c reductase.

A preparation containing the Mr 13,400 protein (subunit VI), phospholipid, and ubiquinone was isolated from bovine heart mitochondrial ubiquinol-cytochrome c reductase by a procedure involving Triton X-100 and urea solubilization, calcium phosphate-cellulose column chromatography at different pHs, acetone precipitation, and decanoyl-N-methylglucamide-sodium cholate extraction. The protein in this preparation corresponds to subunit VI of ubiquinol-cytochrome c reductase resolved in the sodium dodecyl sulfate-polyacrylamidce gel electrophoresis system of Schägger et al. (1987, FEBS Lett. 21, 161-168) and has the same amino acid sequence as that of the Mr 13,400 protein reported by Wakabayashi et al. (1985, J. Biol. Chem. 260, 337-343). The phospholipid and ubiquinone present in the preparation copurify with but are not intrinsic components of, the Mr 13,400 protein. This preparation has a potency and behavior identical to that of a free phospholipid preparation in restoring activity to delipidated ubiquinol-cytochrome c reductase. Antibodies against Mr 13,400 react only with Mr 13,400 protein and complexes which contain it. They do not inhibit intact, lipid-sufficient ubiquinol-cytochrome c reductase. However, when delipidated ubiquinol-cytochrome c reductase is incubated with antibodies prior to reconstitution with phospholipid, a 55% decrease in the restoration activity is observed, indicating that the catalytic site-related epitopes of the Mr 13,400 protein are buried in the phospholipid environment. Antibodies against Mr 13,400 cause an increase of apparent Km for ubiquinol-2 in ubiquinol-cytochrome c reductase. When mitoplasts or submitochondrial particles are exposed to a horseradish peroxidase conjugate of the Fab' fragment of anti-Mr 13,400 antibodies, peroxidase activity is found mainly in the submitochondrial particles preparation; little activity is detected in mitoplasts. This suggests that the Mr 13,400 protein is extruded toward the matrix side of the membrane.

Amino Acid Sequence↗

Avoiding digester imbalance through real-time expert system control of dilution rate.

Process control of anaerobic digesters is a particularly challenging problem because of the diversity of possible causes that can lead to digester imbalance. Conventional control schemes can fail in consequence of a reversal in the sign of the steady-state gain caused by some type of disturbance. In this work we present an expert system approach that takes into account the particularity of this process. The developed algorithm is demonstrated to compensate successfully for changes in the digester feed medium when simulated against a model for a continuous anaerobic digester.

Anaerobiosis↗

Plasma apolipoprotein C-III levels in children with type I diabetes.

The serum concentrations of apolipoproteins C-III, B, and A-I were determined in children with type I diabetes mellitus to establish whether they correlated with the level of glycosylated hemoglobin (Hb A1) and to determine whether these values differ between diabetic children and a population of normal children. Triglyceride (TG), total cholesterol (TC), and apolipoprotein (Apo) levels were studied in 95 children with type I diabetes; 51 of the children were attending a diabetes clinic and 44 were attending a diabetes summer camp. The level of Hb A1 correlated with Apo C-III (P less than .001) and TC (P less than .001) values in the clinic group, but not with Apo A-I or TG levels in either group. The Apo C-III level was higher in both groups of diabetic children (8.0 +/- 0.5 and 9.5 +/- 0.4 mg/dl) (P less than .01) than in normal subjects (6.1 +/- 0.2 mg/dl). We conclude that the Apo C-III level tends to be higher in diabetics than in normal subjects, even in the normotriglyceridemic camp group. The Apo C-III level correlated with both the TC level and Hb A1, suggesting that Apo C-III determinations in type I diabetic patients may permit early identification of atherosclerotic risk.

Adolescent↗

A sensitive and specific assay for plasminogen activators.

A simple, sensitive and specific assay for plasminogen activators is described. The assay utilizes fluorescein-labeled fibrinogen or fibrin at low concentrations, and enables simultaneous evaluation of the plasminogen and fibrin dependence of the reaction, that is, discrimination of tissue-type and urokinase-type plasminogen activators, and non-specific proteolysis. Addition of antisera verify identification of the activator species. The assay reagent contains plasminogen and fluorescein-labeled fibrinogen, to which is added the specimen and then then thrombin, either at the initiation or the termination of the reaction. Supernatant fluorescence is proportional to plasminogen activator concentration. With a four-hour incubation, 1 milliunit (14 pg) of tissue (melanoma) plasminogen activator (TPA) or 2 milliunit (36 pg) of urokinase (UK) may be detected.

Animals↗

Premature labor.

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Female↗

Comparative effect of x-ray and ultrasound (inducing hyperthermia) on the testes of rats--a rationale for male castration by ultrasound.

The testes of rats were treated by x rays, or ultrasound. 2000 rads single dose of x ray led to tubular atrophy, which was defined as destruction of all spermatogenic cells but Sertoli cells. Ultrasound of 1 W/cm2 for 15 min led to tubular necrosis, which was designated as complete disorganization of the seminiferous tubules with disappearance of spermatogenic as well as sertoli cells. The possibility of male castration by ultrasound is raised.

Animals↗

Test of an information-processing model of humor: physiological response changes during problem- and riddle-solving.

Heart rate and skin conductance were monitored continuously while subjects heard and responded to seven riddles and seven problems which were structurally similar. Hypotheses based on cognitive problem-solving models of humor were tested by comparing changes occurring during problem solving with those that occurred during "riddle solving". While heart rate tended to accelerate once a riddle or problem was presented and decelerate once the answer or punch line was given, there were significant differences in skin conductance between riddle- and problem-solving responses, suggesting that a purely problem-solving model of humor may be untenable. A test of Berlyne's hypothesis of arousal change and humor appreciation was also made. As predicted, humor appreciation was greatest for those who showed a moderate amount of change.

Arousal↗

Listeriosis in renal transplant recipients: report of an outbreak and review of 102 cases.

We observed six renal transplant recipients with listeriosis during a 10-week period in the autumn of 1979. Investigation of this outbreak established that the first four cases wer close contacts, all infected by Listeria monocytogenes serotype 1b. The source of infection and route of spread were not identified. A total of 102 renal transplant recipients with listeriosis have now been reported. The major manifestation of disease was meningitis in 50% of the patients, parenchymal disease of the central nervous system in 10%, both meningitis and parenchymal disease of the central nervous system in 9%, and primary bacteremia in 30%. The overall mortality rate was 26%. Pneumonia due to L. monocytogenes, a previously neglected finding, was present in seven patients (7%); five of the seven died. The route of transmission may sometimes be respiratory. Special techniques for isolation of L. monocytogenes from sputum are usually required but not complicated. We recommend that individual renal transplant patients with listeriosis be cared for with secretion and excretion precautions and that they be treated with ampicillin and gentamicin. We advocate the serotyping of all isolates and a careful case-control analysis of all epidemics, but we do not support the use of serologic testing or surveillance cultures.

Adult↗