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Biomedical subjects

B J Hoffman

Publications and source records attributed to B J Hoffman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Endoscopic ultrasound guided fine needle aspiration of malignant pancreatic lesions.

PURPOSE: To evaluate the accuracy, safety, and clinical utility of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of pancreatic masses. METHODS: Forty-seven patients were referred for EUS with a pancreatic mass and suspicion of pancreatic cancer based upon painless obstructive jaundice, epigastric abdominal pain plus weight loss/anorexia, or idiopathic pancreatitis. All patients underwent EUS with both radial (Olympus UM20) and linear array (Pentax FG32-UA) systems. After TNM staging by EUS, ultrasound directed FNA of the pancreatic mass was performed using a 23 gauge, 4 cm long needle. RESULTS: EUS-guided FNA was performed in all 47 patients. Results: successful targeting = 100%, adequate cellularity = 100%, FINDINGS: adeno Ca = 25, squamous cell Ca = 1, lymphoma = 1, poorly differentiated Ca= 1, atypical cytology or suspicious for carcinoma = 9, no malignant cells = 10. The sensitivity, specificity, positive predictive value and negative predictive value of EUS-guided pancreatic FNA for the diagnosis of malignancy was 64%, 100%, 100% and 16% respectively. CONCLUSIONS: EUS with FNA is useful for detection of malignancy in a pancreatic mass. The procedure appears to have a complication rate of 2%. Impact of this technique on clinical management of patients needs further evaluation.

Adenocarcinoma↗
PubMed1996

A novel nonneuronal catecholaminergic system: exocrine pancreas synthesizes and releases dopamine.

Cells of the exocrine pancreas produce digestive enzymes potentially harmful to the intestinal mucosa. Dopamine has been reported to protect against mucosal injury. In looking for the source of dopamine in the small intestine, we found that the duodenal juice contains high levels of dopamine and that the pancreas itself has a high dopamine [and dihydroxyphenylalanine (dopa)] content that does not change significantly after chemical sympathectomy. Furthermore, we were able to demonstrate tyrosine hydroxylase (TH) activity in control pancreas as well as in pancreas from rats after chemical sympathectomy. Immunostaining and in situ hybridization histochemistry confirmed both the presence of TH, dopamine, and the dopamine transporter, and the mRNAs encoding TH and dopamine transporter, and the presence of both types of vesicular monoamine transporters in the exocrine cells of the pancreas. Since there are no catecholaminergic enteric ganglia in the pancreas, the above results indicate that pancreatic cells have all the characteristics of dopamine-producing cells. We suggest that the pancreas is an important source of nonneuronal dopamine in the body, and that this dopamine has a role in protecting the intestinal mucosa and suggests that dopamine D1b receptor agonists might be used to help mucosal healing in the gastrointestinal tract.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer.

BACKGROUND: Esophageal endoscopic ultrasonographic (EUS) guidance for fine-needle aspiration (FNA) of mediastinal lymph nodes has been introduced only recently. The utility of EUS/FNA in diagnosing and staging bronchogenic carcinoma is unknown. METHODS: After a thoracic computed tomographic scan, 27 patients with known or suspected lung cancer underwent EUS. Accessible abnormal mediastinal lymph nodes were aspirated under EUS guidance. Patients with positive cytologic studies did not undergo further testing, whereas the remaining patients underwent mediastinal exploration. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for both chest computed tomography and EUS/FNA: RESULTS: Twenty-two of 27 patients had mediastinal adenopathy by computed tomography scan. Sixteen patients had positive findings on EUS, 15 with positive FNA (10 non-small cell lung cancer; 5 small cell lung cancer) and 1 with T4 status. Fourteen patients with positive FNA had lymph nodes sampled at level 5, level 7, or both. Of 11 patients with negative EUS/FNA, 2 had positive findings at operation (sensitivity 89%). The diagnosis of lung cancer was established in 7 patients. CONCLUSIONS: The results showed that EUS/FNA improves the accuracy of computed tomographic scan in the staging of lung cancer. By accessing lymph nodes at levels 5 and 7, EUS/FNA complements mediastinoscopy and is considered the staging modality of choice in these regions. Positive EUS/FNA can obviate the need for further invasive staging.

Biopsy, Needle↗
PubMed1996

Endosonographic diagnosis of an esophageal duplication cyst.

A patient with an esophageal duplication cyst who presented with dysphagia is described here. The diagnosis was accurately made preoperatively by endosonography due to the demonstration of contiguity of the muscularis propria of the esophagus with the muscle layer of the cyst wall. Endoscopic ultrasound is the most reliable nonsurgical method for the diagnosis of this lesion, assisting in surgical planning in symptomatic patients and observation in asymptomatic ones.

Adult↗
PubMed1995

Lactose fed-batch overexpression of recombinant metalloproteins in Escherichia coli BL21 (DE3): process control yielding high levels of metal-incorporated, soluble protein.

A method for producing recombinant proteins in pilot scale fermentation equipment using a glucose fed-batch initial growth, followed by a midlog phase feeding of a glucose and lactose mixture is described. Using the host strain Escherichia coli BL21(DE3), the diiron protein stearoyl-acyl carrier protein delta 9 desaturase has been overexpressed at a biomass level of up to 12 g x liter-1 dry cell weight, representing a 12-fold increase in volumetric productivity relative to that obtained from batch fermentations. Under these conditions, a maximum of 36% of the total cellular protein accumulates as the desaturase polypeptide. A correlation between the slowed growth rate of the fed-batch culture, a continued, albeit slower, exponential growth under inducing conditions, and a favorable partitioning between formation of the soluble holoprotein and inclusion bodies is reported. This correlation suggests that fed-batch techniques can be used to beneficially influence rate-limiting processes in the maturation of overexpressed proteins, such as metal uptake and incorporation proposed here. By using cells produced from the fed-batch method, the iron-containing, soluble desaturase can be purified in a yield of up to 66 mg x g-1 dry cell weight (approximately 500 mg x liter-1 culture), representing a three to fivefold increase in the yield relative to that obtained from batch fermentations. In addition, these methods are suitable for the production of the Anabena 7120 vegetative [2Fe 2S] ferredoxin in E. coli BL21(DE3) pLysS, a host strain used for the overexpression of toxic proteins.

Cell Division↗
PubMed1995

Localization of serotonin subtype 6 receptor messenger RNA in the rat brain by in situ hybridization histochemistry.

The serotonin receptor subtype 6, which raises intracellular cyclic AMP via stimulatory G-proteins, has recently been cloned and characterized. To determine the distribution of serotonin subtype 6 messenger RNA, in situ hybridization was performed in coronal sections of rat brain. 35S-labeled riboprobe, complementary to the 5' non-coding region of the serotonin subtype 6 messenger RNA, and a 33P-labeled riboprobe complementary to its 3' non-coding region, were used for hybridization. Serotonin subtype 6 receptor message was found in serotonin projection fields, rather than regions of serotonin-containing cell bodies, suggesting that the receptor is mainly postsynaptic. Hybridization signal was highest in olfactory tubercle, as well as prominent in the striatum, nucleus accumbens, dentate gyrus, and CA1, CA2 and CA3 of the hippocampus. Less intense hybridization was observed in cerebellum, some diencephalic nuclei, the amygdala, and layers 2, 3, 4 and 6 of the cortex. This pattern of hybridization was observed with both probes, but not when sense transcripts were used. Because the serotonin subtype 6 receptor has a high affinity for the atypical antipsychotic clozapine, and because striatum and nucleus accumbens are proposed sites of antipsychotic drug effects, the possibility is raised that this receptor may play an important role in mediating the effects of the atypical antipsychotic agents.

Animals↗
PubMed1995

Serotonin 5-HT2C receptor stimulates cyclic GMP formation in choroid plexus.

The serotonin 5-HT2C receptor (formerly designated the 5-HT1C receptor) of the choroid plexus triggers phosphoinositide turnover. In the present study, we demonstrate that receptor activation also triggers the formation of cyclic GMP (cGMP). Application of 1 microM 5-HT to porcine choroid plexus tissue slices resulted in stimulation of cGMP formation to a maximum of five-fold basal level, with an EC50 of 11 nM. This response was not inhibited by muscarinic or beta-adrenergic receptor antagonists. Serotonin receptor antagonists inhibited cGMP formation with apparent Ki values of 1.3 (mianserin), 200 (ketanserin), and 5,500 (spiperone) nM, respectively. Neither serotonin-stimulated cGMP formation nor PI turnover was inhibited by pertussis toxin pretreatment. Preliminary biochemical studies suggested that serotonin-stimulated cGMP formation was calcium, phospholipase A2, and lipoxygenase dependent, as incubation in low calcium buffers or inclusion of the phospholipase A2 or lipoxygenase inhibitors p-bromophenacylbromide or BW 755c resulted in significant reduction of cGMP formation. The present results suggest that in addition to triggering phosphoinositide turnover, choroid plexus serotonin 5-HT2C receptors trigger cGMP formation in a calcium-sensitive manner.

Animals↗
PubMed1995

Endoscopic retrograde cholangiopancreatography in pregnancy.

BACKGROUND: Pancreaticobiliary disease in pregnancy is relatively uncommon. The frequency of choledocholithiasis in pregnancy requiring intervention has been reported to be as low as one in 1200 deliveries. Traditionally, intervention in these patients has been surgical. Although surgery has an overall low morbidity and mortality for the expectant mother, it carries with it a 4- to 6-wk recovery period and a possibly increased risk of fetal wastage. Published information regarding the role and safety of ERCP in pregnancy is limited. This series of 23 pregnant patients undergoing ERCP was collected from six different medical centers. METHODS: Twenty-three pregnant patients with symptomatic pancreaticobiliary disease underwent a total of 29 ERCPs (three patients had diagnostic ERCP, and 20 had therapeutic ERCP). Fifteen, eight, and six procedures were performed in the first, second, and third trimesters, respectively. The only ERCP complication was pancreatitis in one patient. There was one spontaneous abortion (3 months after ERCP) and one neonatal death; however, casual relationship to ERCP was not apparent. CONCLUSION: Diagnostic and therapeutic ERCP appears reasonably safe and effective in pregnancy. Cautious and selective use of this procedure offers a viable alternative to surgery or observation in patients with emergent pancreaticobiliary problems.

Adult↗
PubMed1995

Predicting survival in fulminant hepatic failure using serum Gc protein concentrations.

Plasma Ge protein sequesters actin released into the circulation after massive hepatocyte necrosis, but is greatly depleted in the process. In fulminant hepatic failure (FHF), Gc is present in serum both as a complex with actin and as unbound protein, the latter becoming completely exhausted in those patients with the most severe FHF. In the present study, 47 consecutive patients with FHF, 39 of whom were the result of acetaminophen (AC) overdose, were evaluated to determine whether measurement of Gc protein levels could be used to predict survival. Using serum samples obtained shortly after admission as well as later samples, levels for total Gc protein, percentage of Gc complexed with actin, and calculated unbound Gc remaining in serum were compared for survivors and those who died of their illness. The most marked changes were present in unbound Gc levels in nonsurvivors, the mean of which for follow-up samples was 10% of normal mean values, as compared with 23% of normal mean values in those who survived (P < .01). Using a cutoff value for unbound Gc protein of > or = 34 micrograms/mL to predict survival, outcome was correctly predicted in 32 of 47 (68%) patients using early samples, and in 24 of 27 (89%) patients using later sera. No differences were observed between values and/or outcome in AC and non-AC cases. Measurement of Gc protein level correctly predicted all patients dying of hepatic failure. This single measurement compares favorably with multifactorial predictive models, such as the King's College model, and might be a useful test for patients being considered for transplantation.

Forecasting↗