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B J Hoffman

Publications and source records attributed to B J Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed2000

CT or EUS for the initial staging of esophageal cancer? A cost minimization analysis.

BACKGROUND: Patients with advanced (T4 and/or M1) esophageal cancer are offered palliative therapy. Computed tomography (CT) is sensitive for distant metastases but is less sensitive than endosonography for T4 disease and celiac lymphadenopathy. The aim of this study was to determine whether initial CT or endosonography costs less to diagnose advanced esophageal cancer. METHODS: A decision model compared the costs of the 2 strategies. Sensitivity analysis and threshold analysis were used to identify the most important determinants of the overall cost of identifying advanced disease. RESULTS: Initial CT is the least costly strategy if the probability of finding advanced disease by initial CT is greater than 20%, if the probability of finding advanced disease by initial endoscopic ultrasound (EUS) is less than 30%, or if the cost of EUS is greater than 3.5 times the cost of CT. However, in our referral center population, endosonography found advanced disease more frequently than CT (44% vs. 13%; p < 0.0001) and the least costly strategy was initial endosonography (expected cost $804 vs. $844). CONCLUSION: CT remains as the initial staging test of choice in most clinical settings. However, in referral centers, initial EUS may be reasonable, but individualized model inputs must be obtained before reliable conclusions can be drawn.

Adult↗
PubMed1999

Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures.

Noradrenergic locus coeruleus (LC) efferents to the forebrain suppress seizures in several models of epilepsy. Using in situ hybridization, we demonstrate that tyrosine hydroxylase (TH) and norepinephrine transporter (NET) but not vesicular monoamine transporter 2 (VMAT2) mRNA levels are transiently elevated in LC neurons following kainic acid-induced status epilepticus. These increases of TH and NET mRNAs and presumably of the proteins themselves might enhance synthesis and reuptake of NE postictally.

Animals↗
PubMed1999

Esophageal cancer staging: improved accuracy by endoscopic ultrasound of celiac lymph nodes.

BACKGROUND: Clinical staging of esophageal cancer is required for optimal therapy but remains imprecise. Pathologic verification of involved lymph nodes could potentially direct treatment allocation. With the rising incidence of distal and gastroesophageal junction adenocarcinomas, assessment of the celiac axis lymph nodes (CLNs) becomes important because it is a common nodal drainage basin. Endoscopic ultrasound (EUS) permits evaluation of CLNs and biopsy by fine-needle aspiration. This study examined the usefulness of this staging tool. METHODS: A consecutive series of 62 patients with esophageal cancer considered resectable by computed tomographic scan underwent EUS for T and N staging and were retrospectively studied. A CLN visualized by EUS as greater than 5 mm was considered positive. Fine-needle aspiration of the CLN was performed routinely. Endoscopic ultrasound and computed tomographic staging were compared on the basis of pathologic verification of CLNs. RESULTS: It was possible to evaluate CLNs by EUS in 59 (95%) of 62 patients: positive in 19, negative in 40. In EUS-positive patients, fine-needle aspiration was positive in 15, falsely negative in 2, and not done in 2. By computed tomographic scan, CLNs were negative in 57 patients and positive in 2. The CLNs were positive in 23 of 54 patients eligible for CLN pathologic verification. All positive CLNs not identified by EUS (7 false-negative EUS) were microscopic foci in one or two nodes and were associated with T3 tumors. Sensitivity and specificity of EUS were 72% and 97%, respectively, compared with 8% and 100% for computed tomographic scan. When EUS identified CLNs, fine-needle aspiration confirmed positivity in 88% of cases. CONCLUSIONS: Endoscopic ultrasound with fine-needle aspiration is useful in the detection and confirmation of CLN metastasis. In T3 tumors of the distal esophagus, a negative EUS result does not substantiate absence of CLN disease. Endoscopic ultrasound with fine-needle aspiration may be important in guiding treatment for patients with distal adenocarcinoma and documenting disease before neoadjuvant therapy.

Adenocarcinoma↗
PubMed1999

Association of HLA-DR and -DQ alleles with idiopathic achalasia.

BACKGROUND & AIMS: Idiopathic achalasia is a motility disorder of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter and a loss of normal peristaltic activity in the body of the esophagus. The loss of inhibitory neurons in the distal esophagus, as well as abnormalities in the vagus nerve, dorsal motor nucleus of the vagus nerve, and autonomic nervous system, have been described in achalasia. Although the underlying cause of idiopathic achalasia is unknown, the diffuse neuronal effects found suggest a possible viral or neurodegenerative mechanism. By use of serological methods, a significant association between the HLA-DQ1 phenotype and idiopathic achalasia has been found, suggesting a possible immunogenetic mechanism. To further define immunogenetics in the pathogenesis of idiopathic achalasia, we performed tissue typing in patients with achalasia to determine their specific HLA phenotypes. METHODS: We prospectively studied 32 patients (23 white and 9 black) with idiopathic achalasia. Peripheral blood was collected, and HLA-DR and -DQ typing by polymerase chain reaction with sequence-specific primers was performed. Results were compared with those from 268 racially matched local controls. RESULTS: Idiopathic achalasia and the broad HLA-DQ1 allele were not significantly associated in either population, although a trend was found in white subjects (odds ratio [OR], 2.16; chi2 = 5.36, P corrected [Pc] = 0.0824). Further subtyping in white subjects revealed a significant association between idiopathic achalasia and the DQB1*0602 allele (OR, 3.10; chi2 = 7.32, Pc = 0.0408). A strong trend was also found with the DRB1*15 allele (OR, 2.83; chi2 = 8.11, Pc = 0.0572). In the black population, there was no association between idiopathic achalasia and DQB1*0602 or DRB1*15, but a trend was found with DRB1*12 (OR, 6. 19; chi2 = 5.19, P = 0.0227 uncorrected, Pc = 0.295). CONCLUSIONS: Idiopathic achalasia is associated with HLA alleles in a race-specific manner. These results support an immunogenetic mechanism in the pathogenesis of idiopathic achalasia.

Adult↗
PubMed1999

Bile duct stones and laparoscopic cholecystectomy: a decision analysis to assess the roles of intraoperative cholangiography, EUS, and ERCP.

BACKGROUND: The least costly management strategy for patients undergoing laparoscopic cholecystectomy is unclear. METHODS: A decision model incorporating cost ratios, test accuracy, complication, and failure rates was used to determine the costs of 4 peri-laparoscopic cholecystectomy strategies: endoscopic retrograde cholangiopancreatography (ERCP), intraoperative cholangiography (IOCG), endoscopic ultrasound (EUS), and expectant management. RESULTS: Expert IOCG is least costly for intermediate-risk patients when the risk of stones is between 17% and 34%. If expert EUS is available, 0% to 10% ("low" risk) merits expectant management; 11% to 55% ("intermediate" risk) merits EUS; and greater than 55% ("high" risk) merits ERCP. Thresholds were most sensitive to changes in the risks of symptoms and complications due to retained stones; and to procedural costs, sensitivity, and success rates. Neither IOCG nor EUS appears likely to reduce overall costs unless their accuracy and success rates are greater than 90% and their procedural cost is less than 60% to 70% that of ERCP. When neither are available, ERCP is preferable when the risk of stones is greater than 22%. Thresholds were relatively insensitive to changes in the risk and severity of ERCP-induced pancreatitis. CONCLUSIONS: The least costly strategy for laparoscopic cholecystectomy patients depends primarily on the risk of stones and stone-related symptoms, but procedural costs and operator expertise are also critical.

Cholangiography↗
PubMed1999

Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo.

A growing body of evidence suggests that serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive serotonin transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate serotonin transporter messenger RNA expression during rat embryonic development. Serotonin transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, serotonin transporter messenger RNA was detected in neural crest cells, some of which respond to serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were serotonin transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained serotonin transporter messenger RNA by late gestation. The expression of serotonin transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of serotonin transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a serotonin concentration gradient across epithelia, either from serotonin in the amniotic fluid or from neuronal enteric serotonin, as a developmental cue. Our results demonstrating serotonin transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the transporter most likely responsible for the previously identified accumulation of serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of serotonin transporter messenger RNA in early development supports the hypothesis that serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of serotonin may be regulated by transport. The striking pattern of serotonin transporter messenger RNA throughout developing sensory pathways suggests that serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of serotonin transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of serotonin transporter messenger RNA during ontogeny suggests a previously unappreciated role of serotonin in diverse physiological systems during embryonic development.

Animals↗
PubMed1999

Diagnosis of pancreas divisum by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: During pancreatobiliary imaging by endoscopic ultrasound (EUS) at the authors' institution, it is customary to attempt to obtain the "stack sign", where the bile duct and the pancreatic duct can be seen to run in parallel through the pancreatic head. We suspected that such a view may not be attainable in patients with pancreas divisum because of the short ventral pancreatic duct. The aim of the study was to investigate whether the presence of pancreas divisum could be suspected on the basis of EUS findings. PATIENTS AND METHODS: The stack sign is obtained by positioning the echo endoscope in the long scope position with the transducer in the duodenal bulb. The balloon is then inflated and advanced snugly into the apex of the bulb. From this position, the bile duct (closest to the transducer) and the pancreatic duct can be seen to run in parallel through the pancreatic head. We attempted to obtain a stack sign during EUS examinations of six patients with pancreas divisum. EUS was done in these patients to look for evidence of chronic pancreatitis and the pancreas divisum was confirmed by endoscopic retrograde pancreatography. An attempt to obtain the stack sign was also made in 30 patients who had EUS for pancreatobiliary indications but did not have pancreas divisum. RESULTS: In only two out of six patients with pancreas divisum (33 %) were we able to obtain a stack sign. This was significantly different from the rate of observation of a stack sign in 83.3 % (25/30) of patients who did not have pancreas divisum (P=0.04). Of the two patients with pancreas divisum in whom a stack sign was seen, the ventral duct was markedly dilated (6.6 mm) in one, and the other patient had an unusually large ventral pancreas. CONCLUSIONS: The absence of a stack sign during pancreatobiliary imaging by EUS may suggest the diagnosis of pancreas divisum.

Congenital Abnormalities↗
PubMed1999

Endoscopic ultrasonography with fine-needle aspiration: an accurate and simple diagnostic modality for sarcoidosis.

BACKGROUND AND STUDY AIMS: Sarcoidosis is a chronic multisystem granulomatous disease that is often diagnosed after a finding of hilar and mediastinal lymphadenopathy on a chest radiograph. This often requires further evaluation by transbronchial biopsy or other clinical parameters. The present study is a descriptive, retrospective one using endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of mediastinal lymph nodes in seven patients with sarcoidosis. PATIENTS AND METHODS: Among 108 consecutive patients who underwent EUS-FNA of mediastinal lymph nodes for various clinical indications between July 1994 and October 1997, seven patients were found to have sarcoidosis on EUS-FNA, and the EUS morphology was studied in these patients. RESULTS: Sarcoidosis was diagnosed in seven patients using endosonographic characteristics and clinical follow-up. EUS with FNA showed cytological evidence of sarcoidosis in six patients. Seven patients were found to have subcarinal lymph nodes, and six patients had abnormally enlarged aortopulmonary (AP) window lymph nodes. The nodes in all patients had three endosonographic criteria for malignancy. The long axis of the largest mediastinal lymph nodes measured 3.44+/-1.42 cm (range 1.8-6.0 cm). The short axis measured 2.50+/-0.69 (range 1.0-4.0 cm). The average number of nodes seen in each patient was 2.80+/-0.75 (range 2-4). The nodes in all seven patients were discrete and well demarcated. A central hyperechoic strand was evident in these nodes in four patients (57%). There were no complications. CONCLUSIONS: Mediastinal lymph nodes in patients with sarcoidosis appear to have specific echo characteristics, and EUS-FNA can be used for confirmatory tissue diagnosis.

Adult↗
PubMed1999

Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience.

BACKGROUND: Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) is a recent innovation in the evaluation of gastrointestinal and pulmonary malignancies. AIMS: To review the experience with EUS-FNA of a large single centre. METHODS: 333 consecutive patients underwent EUS-FNA. Follow up data were available on 327 lesions in 317 patients, including 160 lymph nodes, 144 pancreatic lesions, 15 extraintestinal masses, and eight intramural tumours. RESULTS: A primary diagnosis of malignancy was obtained by EUS-FNA in 62% of patients with clinically suspicious lesions. The overall accuracy of EUS-FNA for the diagnosis of malignancy was 86%, with sensitivity of 84% and specificity of 96%. With respect to lesion types, the sensitivity, specificity, and accuracy were 85%, 100%, and 89% for lymph nodes; 82%, 100%, and 85% for pancreatic lesions; 88%, 100%, and 90% for perirectal masses; and 50%, 25%, and 38% for intramural lesions, respectively. Compared with size and sonographic criteria, EUS-FNA in the evaluation of lymph nodes provided superior accuracy and specificity, without compromising sensitivity. Inadequate specimens were obtained from only six patients, including 3/5 with stromal tumors. Only one complication occurred. CONCLUSIONS: EUS-FNA is safe and can readily obtain tissue specimens adequate for cytopathological diagnoses. Compared with size and sonographic criteria, it is a superior modality for the detection of nodal metastases. While providing accurate diagnosis of pancreatic and perirectal malignancies, results suggest the technique is less useful for intramural lesions.

Adolescent↗
PubMed1999

Non-neuronal dopamine in the gastrointestinal system.

1. Dopamine (DA) is a protective agent in the gastrointestinal (GI) tract in both rats and humans. Therefore, we have studied the site of DA production in rat and human GI tract using a variety of techniques, including immunocytochemistry (ICC), in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, HPLC, western blotting and immunoelectron microscopy. 2. We found very high concentrations of DA that persisted after chemical sympathectomy (CS) in the gastric juice, the stomach mucosa and in the pancreas. Both the stomach mucosa and the pancreas also had tyrosine hydroxylase (TH) activity, most of which remained after CS. Double-labelling ICC showed that acid-producing parietal cells and the exocrine pancreas must also be capable of producing DA. 3. We isolated rat stomach parietal cells by cell fractionation and found that both DA and TH activity are present in isolated (denervated) parietal cells. These cells also have other features of aminergic cells: they are immuno- (and mRNA) positive for the DA plasma membrane transporter and vesicular monoamine transporter(s). In both gastric and duodenal mucosa, we demonstrated the presence of significant amounts of the D5 receptor that could serve as a target for locally produced DA. 4. Because DA, its biosynthetic enzymes and its transporters are also found in parietal cells in the human stomach, a mucosal protective system involving DA could be important clinically.

Animals↗
PubMed1998

Infraorbital nerve transection alters serotonin transporter expression in sensory pathways in early postnatal rat development.

The serotonin transporter MRNA has been found throughout the trigeminal sensory system late in gestation and during early postnatal development, a period known to be critical for maturation of the sensory circuitry. The purpose of the present study was to determine whether sensory denervation in newborn rat pups would alter either the density or pattern of expression of the 5-HT transporter (5-HTT) within the trigeminal system. We combined autoradiographic localization of 5-HT transporters and in situ hybridization techniques to visualize both the transporter protein and mRNA in thalamic sensory neurons and in the somatosensory cortex following unilateral infraorbital nerve transection at postnatal day 1. For comparative purposes, similar measurements were conducted in thalamic visual neurons as well as in the visual cortex. Lesion of the infraorbital nerve decreased the [3H]citalopram labelling of 5-HT transporters in the ventral basal and ventral medial areas of the thalamus contralateral to the lesion, while labelling of 5-HT transporters was decreased in both contralateral and ipsilateral sides of the lateral genicuate (visual thalamus). Citalopram labelling of 5-HT transporters was not significantly altered in somatosensory or in cingulate cortex, however a significant decrease was observed in the visual cortex. In contrast, there were no obvious changes in the intensity of the 5-HT mRNA hybridization signal in sensory or visual thalamic areas. Given that the serotonin transporter regulates extracellular concentrations of 5-HT, the present data suggest that altered peripheral innervation and thereby altered sensory inputs to the thalamus during fetal development can potentially influence 5-HT transporter densities and thus, may influence extracellular levels of 5-HT in thalamus and cortex during a critical period of synapse formation. In turn, modulation of 5-HT transporter levels may influence extracellular concentrations of 5-HT in thalamus and cortex during a critical period of synapse formation.

Animals↗
PubMed1998

Analysis of a gene encoding two glycine transporter variants reveals alternative promoter usage and a novel gene structure.

The rat GLYT-1 gene encodes two glycine transporter variants, GLYT-1a and GLYT-1b, that differ in NH2 termini and 5'-noncoding regions as well as in tissue distribution. The GLYT-1 gene contains 15 exons, with the first two specific for GLYT-1a and the third specific for GLYT-1b. By combining RNase protection and rapid amplification of cDNA ends analysis, we have determined transcription start sites for GLYT-1a and GLYT-1b. By using a functional luciferase reporter assay, we demonstrate that distinct promoters regulate the expression of these transporters in several cell lines. Serially truncated GLYT-1b promoter constructs reveal a basal promoter within 304 base pairs of the transcription start site, possible negative regulatory elements between -304 and -1310, and additional positive regulatory elements between -1310 and -5264. The GLYT-1 gene contains three sets of dinucleotide repeats, two AC repeats, and one TG repeat which may form stem-loop structures to either facilitate or interfere with transcription of one of the transporter isoforms. The potential use of dinucleotide repeats in this manner would represent a novel mechanism for gene splicing. The use of distinct promoters for GLYT-1a and GLYT-1b suggests that these transporters have unique regulatory requirements that may reflect the differential tissue-specific expression patterns in white matter (GLYT-1b) and gray matter (GLYT-1a).

Alternative Splicing↗
PubMed1998

Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2. II. Expression in neural crest derivatives and their target sites in the rat.

We used in situ hybridization histochemistry to study the expression of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic development in the rat. In the adult rat VMAT2 is present exclusively in neuronal tissues and VMAT1 is present in the adrenal medulla and in certain intestinal endocrine cells. We found that both transporter molecules are more widely expressed during development. We demonstrate a complete overlap of the two VMAT mRNAs in the sympathetic nervous system between E13 and E21 days. In addition, VMAT2 (and to some extent VMAT1) mRNA is expressed in ganglionic cells of the parasympathetic nervous system and in cranial ganglia (trigeminal, vestibular and spiral ganglia) between E12 and E21. The sensory neurons of the dorsal root ganglia, which are also neural crest derivatives, express VMAT2 mRNA (E11-E21), exclusively. Both VMAT mRNAs are found in the developing GI system, but in different cells. VMAT1 mRNA was detected in organs of the endocrine system (pituitary gland, adrenal gland, testis, seminal vesicle), some connective tissue cells, and the thymus. We observed expression of both VMAT mRNAs in two separate cell groups in the placenta (E8-E10). Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect migration and differentiation of neural crest derivatives.

Adrenal Medulla↗
PubMed1998

Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2. I. The developing rat central nervous system.

We used in situ hybridization histochemistry to study the expression of the mRNA of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic and postnatal development of the central nervous system (CNS) in the rat. In the adult rat, VMAT2 mRNA is present exclusively in monoaminergic cell groups of the CNS and VMAT1 mRNA was reported to be present in the adrenal medulla and certain intestinal epithelial cells. In contrast to the above, the expression of VMAT1 mRNA has previously never been detected in the central nervous system. This study shows the first evidence that both transporter molecules are expressed in CNS during ontogenesis. We here demonstrate four main expression patterns detected during development: 1. VMAT2 mRNA expression in monoaminergic neurons of the brainstem beginning as early as embryonic day E13. 2. Expression of VMAT2 mRNA in all major sensory relay nuclei of central nervous system. 3. Co-expression of VMAT1 and VMAT2 mRNA in most limbic structures, basal ganglia, as well as in some hypothalamic nuclei. 4. Exclusive expression of VMAT1 mRNA in the neocortical subventricular zone, in the amygdala at early (E15-18) and late (P1-P28) timepoints, the granular cell layer of cerebellum, and in several brainstem motor nuclei. Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect wiring of sensory and also motor circuits. VMAT1 mRNA expression may reflect a specific effect of monoamines in glial differentiation and cerebellar granule cell migration and/or differentiation.

Aging↗
PubMed1998

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system.

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.

Amino Acid Sequence↗
PubMed1998

Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Our aim was to verify endoscopic ultrasound (EUS) accuracy to diagnose, rule out, and establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing ERCP for unexplained abdominal pain and/or suspected chronic pancreatitis underwent EUS. EUS was performed by experienced operators who were aware of the history but blinded to ERCP results. Chronic pancreatitis was defined using the Cambridge classification: 0 to 1 = "normal," 2 to 4 = "all chronic pancreatitis," 3 to 4 = "moderate to severe chronic pancreatitis." The number of EUS criteria required to obtain sensitivity, specificity, positive and negative predictive values > or = 85% was determined. EUS criteria for chronic pancreatitis are hyperechoic foci, hyperechoic strands, lobularity, hyperechoic duct, irregular duct, visible side-branches, ductal dilation, calcification, and cysts. RESULTS: One hundred twenty-six patients underwent EUS and ERCP. EUS was highly sensitive and specific (> 85%) depending on the number of criteria present. Chronic pancreatitis is likely (PPV > 85%) when more than two criteria (for "all chronic pancreatitis") and more than six criteria (for "moderate to severe chronic pancreatitis") are present. "Moderate to severe chronic pancreatitis" is unlikely (NPV > 85%) when fewer than three criteria are present. Independent predictors of chronic pancreatitis were "calcification" (p = 0.000001), history of alcohol abuse (p = 0.002), and the total number of EUS criteria (p = 0.008). CONCLUSIONS: EUS can accurately diagnose, rule out, and establish the severity of chronic pancreatitis found by ERCP.

Adult↗