Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 19 recordsLinked to original sources

PubMed2006

Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells.

Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or beta-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signal-activated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear beta-catenin, ABI was significantly higher than in those without. These results collectively indicate that beta-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.

Adenoma↗

PubMed2006

The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors.

OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy using the Cyberknife are useful treatments for multiple or large metastases. Here we present our results of Cyberknife radiosurgery for 71 patients with 148 metastatic brain lesions. METHODS: There were 32 women and 39 men with a median age of 63 (range: 30-88) years. Radiographic follow-up was available for 60 patients with 104 lesions. The mean and median initial volumes of the tumor per lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time of the initial Cyberknife treatment. Forty patients (56%) had a single lesion, and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up, there were no permanent symptoms resulting from radiation necrosis. Overall 6-month and 1-year survival rates were 74% and 47%, respectively, and the median survival time was 56 weeks. The Karnofsky performance score and extracranial metastasis were significant prognostic factors at 6 months and 1 year, respectively, in both univariate and multivariate analyses. Age or multiple metastases did not influence prognosis at 6 months and 1 year. Local control was achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage, no patient died as a result of intracranial disease. Twenty-five patients developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4 weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of patients with large tumors, our results for survival and tumor control rates are comparable to those of published series. The Cyberknife provides the advantage of allowing for fractionated treatment to multiple or large-size tumors.

Adult↗

PubMed2006

Feasibility of left lobe living donor liver transplantation between adults: an 8-year, single-center experience of 107 cases.

Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.

Adult↗

PubMed2006

Reciprocal expression of 17alpha-hydroxylase-C17,20-lyase and aromatase cytochrome P450 during bovine trophoblast differentiation: a two-cell system drives placental oestrogen synthesis.

No definitive information is yet available on the steroidogenic capacity of the two morphologically distinct cell types forming the bovine trophoblast, the uninucleated trophoblast cells (UTCs) and the trophoblast giant cells (TGCs). Hence, in order to localise 17alpha-hydroxylase-C17,20-lyase (P450c17) on a cellular level and to monitor its expression as a function of gestational age, placentomes from pregnant (days 80-284; n = 19), prepartal (days 273-282; 24-36 h prior to the onset of labour; n = 3) and parturient cows (n = 5) were immunostained for P450c17 using an antiserum against the recombinant bovine enzyme. At all stages investigated, P450c17 was exclusively found in the UTCs of chorionic villi (CV), where staining was ubiquitous between days 80 and 160, but was largely restricted to primary CV and the branching sites of secondary CV between days 160 and 240. Thereafter, a distinct ubiquitous staining reoccurred in the UTCs of all CV in late pregnant, prepartal and parturient animals. Using an antiserum against human aromatase cytochrome P450 (P450arom), specific cytoplasmic staining was observed in TGCs. In placentomes from pregnant cows, staining intensity was higher in mature compared with immature TGCs and was more pronounced in the trophoblast covering big stem villi compared with the trophoblast at other sites of the villous tree. In placentomes of a parturient cow, specific staining was only found in mature TGCs that survived the normal, but substantial, prepartal decline in TGC numbers. These results clearly showed that bovine UTCs and TGCs exhibit different steroidogenic capacities, constituting a 'two-cell' organisation for oestrogen synthesis. P450c17 expression appears to be quickly down-regulated and P450arom is up-regulated when UTCs enter the TGC differentiation pathway.

Animals↗

PubMed2005

Assessment of room temperature influence on finger blood flow response induced by short-term grasping of vibrating handle.

OBJECTIVE: To investigate the influence of room temperature on finger blood flow (FBF) change in healthy subjects exposed to short-term grasping of a vibrating handle under different room temperatures. METHODS: FBF was measured using a blood flowmeter in six male subjects on the dorsum of the middle phalanx of third finger in both hands once at the end of every minute for an equal duration of 5 min at pre-exposure, during exposure to grasping of vibrating handle with sinusoidal vibration and after exposure. Vibration was generated with a frequency of 125 Hz and an rms acceleration of 40 m/s(2). Measurements were conducted in four room temperatures of 15+/-1, 20+/-1, 25+/-1 and 30+/-1 degrees C. RESULTS: Compared with the baseline measurements in the exposed hand during grasping of vibrating handle most significant increase in FBF was observed at 15+/-1 degrees C (P<0.001) and least at 30+/-1 degrees C (P<0.05), and after vibration least significant FBF was found at 25+/-1 degrees C (P<0.05). In case of the unexposed hand significant increase in FBF was exhibited at 20+/-1 degrees C (P<0.01) and 30+/-1 degrees C (P<0.01) during vibration, and only at 15+/-1 degrees C (P<0.05) after vibration. CONCLUSIONS: Response in FBF due to grasping of vibrating handle was of different patterns from the baseline measurement under different room temperature conditions in both exposed and unexposed hands and it was influenced by room temperature. Overall, the influence was greater at lower test room temperature, inducing more significant increase in FBF.

Adult↗

PubMed2005

Effect of room temperature on percentage finger systolic blood pressure response to finger cooling.

Percentage finger systolic blood pressure (%FSBP) in response to finger cooling is used to assess vascular components of the hand-arm vibration syndrome and the measurement method is under discussion for standardization. It has been suggested that measurement circumstances including room temperature may affect %FSBP. We investigated the effect of room temperature on %FSBP response to finger cooling in healthy subjects. Six healthy male subjects who were medical students volunteered for the study. Multi-channel plethysmograph was used for simultaneous multi-finger FSBP measurements. The examination room was kept at 21 +/- 1 degrees C and 25 +/- 1 degrees C, and the subjects were randomly assigned. Percentage finger systolic blood pressures for the index, middle, ring and little fingers at 15 degrees C and 10 degrees C cuff-water temperatures were calculated. Four-way analysis of variance was performed to determine the independent effect of subject, room temperature, finger and cuff-water temperature factors on %FSBP. The room temperature as an independent factor affecting %FSBP was statistically significant (P < 0.01). From the results, it can be concluded that %FSBP response to finger cooling in healthy subjects may be affected by room temperature. Therefore, room temperature is expected to be controlled when assessing peripheral vascular components of the upper extremities using %FSBP response to finger cooling.

Adult↗

PubMed2005

Effects of waterproof covering on hand immersion tests using water at 10 degrees C, 12 degrees C and 15 degrees C for diagnosis of hand-arm vibration syndrome.

OBJECTIVES: To compare effects of waterproof covering on finger skin temperature (FST) and subjective hand pain during immersion tests using cold water at 10 degrees C, 12 degrees C and 15 degrees C. In the (Draft International Standard) of the International Organization for Standardization (ISO/DIS 14835-1), a water temperature of 12 degrees C and use of water covering are proposed. METHODS: Six healthy male subjects took part in the immersion tests and immersed both hands into water at 10 degrees C, 12 degrees C and 15 degrees C for 5 min, repeatedly, with waterproof covering (polyethylene gloves) or without (bare hands). The FST data from middle fingers and subjective pain scores for hand pain were analyzed. Furthermore, the test with water at 12 degrees C was repeated to assess the repeatability of the test. RESULTS: The glove and water temperature factors for FST were significant at every minute from 1 min during immersion up to 2 min after recovery, showing higher values for waterproof covering than for bare hands and showing lowest values for water temperature of 10 degrees C and highest for 15 degrees C. The glove and water temperature factors for subjective pain score were significant at the 1-min and 2-min points during immersion, showing lower scores for waterproof covering than for bare hands and showing highest scores for water temperature of 10 degrees C and lowest for 15 degrees C. The results of the first and second tests using water of 12 degrees C showed no systematic difference in FST and hand pain between the tests, with a few exceptions. CONCLUSIONS: Subjective pain during the cold immersion test with polyethylene gloves and water at 12 degrees C can be reduced, while the differences in FST between water temperatures of 10 degrees C and 12 degrees C were small or not apparent at some points during immersion and recovery. The test also seems to be suitable for repeatability. Further investigation on hand-arm vibration syndrome (HAVS) patients to validate the use of the immersion test with gloves to obtain sufficient data for diagnostic value is required.

Adult↗

PubMed2005

Brain aromatase expression after experimental stroke: topography and time course.

Brain aromatase has been shown to be increased in expression after neurotoxic damage and to exert neuroprotection via generation of local oestrogens. The present study investigates the topography and time course of brain aromatase expression after experimental stroke (middle cerebral artery occlusion (MCAO)). Ovariectomised stroke prone spontaneously hypertensive rats underwent distal MCAO by electrocoagulation. Immunohistochemistry revealed increased brain aromatase expression at 24h and 8 days in the cortical penumbra/peri-infarct zones with no increase evident at 2h or 30 days post-MCAO. Double label studies indicate that some of the increased aromatase expression is associated with astrocytic processes. Thus, this is the first evidence that aromatase protein is increased after MCAO and the location (peri-infarct), time course (within 24h) and cellular localisation (astrocytic) indicate the potential for aromatase to promote the survival of cells in the penumbra after experimental stroke by local synthesis of oestrogens.

Animals↗

PubMed2005

Acute effects of glucocorticoids on ATP-induced Ca2+ mobilization and nitric oxide production in cochlear spiral ganglion neurons.

Rapid, non-genomic effects of glucocorticoids on extracellular adenosine 5'-triphosphate (ATP)-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) changes and nitric oxide (NO) production were investigated in type I spiral ganglion neurons (SGNs) of the guinea-pig cochlea using the Ca(2+)-sensitive dye fura-2 and the NO-sensitive dye 4,5-diaminofluorescein (DAF-2). Pretreatment of SGNs with 1 microM dexamethasone for 10 min, a synthetic glucocorticoid hormone, enhanced the ATP-induced [Ca(2+)](i) increase in SGNs. RU 38486, a competitive glucocorticoid receptor antagonist eliminated the effects of dexamethasone on the ATP-induced [Ca(2+)](i) increase in SGNs. These acute effects of dexamethasone were dependent on the presence of extracellular Ca(2+), thereby suggesting that dexamethasone may rapidly enhance the Ca(2+) influx through the activation of ionotropic P2X receptors which may interact with glucocorticoid-mediated membrane receptors. Extracellular ATP increased the intensity of DAF-2 fluorescence, indicating NO production in SGNs. The ATP-induced NO production was mainly due to the Ca(2+) influx through the activation of P2 receptors. S-nitroso-N-acetylpenicillamine, a NO donor, enhanced the ATP-induced [Ca(2+)](i) increase in SGNs while L-N(G)-nitroarginine methyl ester (L-NAME), a NO synthesis inhibitor, inhibited it. Dexamethasone enhanced the ATP-induced NO production in SGNs. The augmentation of dexamethasone on ATP-induced NO production was abolished in the presence of l-NAME. It is concluded that the ATP-induced [Ca(2+)](i) increase induces NO production which enhances a [Ca(2+)](i) increase in SGNs by a positive-feedback mechanism. Dexamethasone enhances the ATP-induced [Ca(2+)](i) increase in SGNs which results in the augmentation of NO production. The present study suggests that NO may play an important role in auditory signal transduction. Our results also indicate that glucocorticoids may rapidly affect auditory neurotransmission due to a novel non-genomic mechanism.

Adenosine Triphosphate↗

PubMed2005

Trends and regional variations in infant mortality rates in Japan, 1973-1998.

OBJECTIVE: The purpose of the study was to investigate the trends and regional variations in infant mortality rates in Japan. METHOD: The data from 1973 to 1998 analysed in this paper were from the Vital Statistics Division, Ministry of Health, Labor and Welfare of Japan. RESULTS: Infant mortality rates declined significantly between 1973 and 1998 in all regions. Statistically significant differences in infant mortality rates among the regions were observed in 1973, 1974, 1976, 1977 and 1978. However, the regional differences in infant mortality rates were insignificant thereafter, indicating elimination of regional variations in infant mortality in Japan. CONCLUSION: The results of this study indicated declines in infant mortality rates in all regions, with elimination of regional variations in infant mortality in Japan in the last two decades. This may be attributable to both qualitative and quantitative improvements in health and medical services in Japan.

Cause of Death↗

PubMed2005

Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.

Adult↗

PubMed2005

Nuclear factor {kappa}B inactivation in the rat liver ameliorates short term total warm ischaemia/reperfusion injury.

BACKGROUND: In hepatic ischaemia/reperfusion injury, activated liver macrophages (Kupffer cells) are dominantly regulated by a transcription factor, nuclear factor kappaB (NFkappaB), with respect to expression of inflammatory cytokines, acute phase response proteins, and cell adhesion molecules. AIMS: We assessed whether inactivation of NFkappaB in the liver could attenuate total hepatic warm ischaemia/reperfusion injury. METHODS: We studied rats with hepatic overexpression of inhibitor kappaBalpha super-repressor (IkappaBalpha SR) caused by a transgene introduced using an adenoviral vector. Hepatic ischaemia/reperfusion injury was induced under warm conditions by total occlusion of hepatoduodenal ligament structures for 20 minutes, followed by reperfusion. Controls included uninfected and control virus (AdLacZ) infected rats. RESULTS: IkappaBalpha SR was overexpressed in Kupffer cells as well as in hepatocytes, blocking nuclear translocation of NFkappaB (p65) into the nucleus after reperfusion. Gene transfection with IkappaBalpha SR, but not with LacZ, markedly attenuated ischaemia/reperfusion injury, suppressing inducible nitric oxide synthase and nitrotyrosine expression in the liver. Moreover, no remarkable hepatocyte apoptosis was detected under IkappaBalpha SR overexpression. CONCLUSIONS: Adenoviral transfer of the IkappaBalpha SR gene in the liver ameliorates short term warm ischaemia/reperfusion injury, possibly through attenuation of hepatic macrophage activation.

Adenoviridae↗

PubMed2005

Non-hotspot-related breakpoints of common deletions in Sotos syndrome are located within destabilised DNA regions.

BACKGROUND: Sotos syndrome (SoS) is a disorder characterised by excessive growth, typical craniofacial features, and developmental retardation. It is caused by haploinsuffiency of NSD1 at 5q35. There is a 3.0 kb recombination hotspot in which the breakpoints of around 80% of SoS patients with a common deletion can be mapped. OBJECTIVE: To identify deletion breakpoints located outside the SoS recombination hotspot. METHODS: A screening system for the directly orientated segments of the SoS LCRs was developed for 10 SoS patients with a common deletion who were negative for the SoS hotspot. Deletion-junction fragments were analysed for DNA duplex stability and their relation to scaffold/matrix attachment regions (S/MARs). These features were compared with the SoS hotspot and recombination hotspots of other genomic disorders. RESULTS: The breakpoint was mapped in four SoS patients, two with a deletion in the maternally derived chromosome. These breakpoint regions were located approximately 2.5 kb, approximately 9.6 kb, approximately 27.2, and approximately 27.7 kb telomeric to the SoS hotspot and were confined to 164 bp, 46 bp, 256 bp, and 124 bp, respectively. Two of the regions were mapped within Alu elements. All crossover events were found to have occurred within or adjacent to a highly destabilised DNA duplex with a high S/MAR probability. In contrast, the SoS hotspot and other genomic disorders' recombination hotspots were mapped to stabilised DNA helix regions, flanked by destabilised regions with high probability of containing S/MAR elements. CONCLUSIONS: The data suggest that a specific chromatin structure may increase susceptibility for recurrent crossover events and thus predispose to recombination hotspots in genomic disorders.

Abnormalities, Multiple↗

PubMed2004

Effect of word familiarity on visually evoked magnetic fields.

This study investigated the effect of word familiarity of visual stimuli on the word recognizing function of the human brain. Word familiarity is an index of the relative ease of word perception, and is characterized by facilitation and accuracy on word recognition. We studied the effect of word familiarity, using "Hiragana" (phonetic characters in Japanese orthography) characters as visual stimuli, on the elicitation of visually evoked magnetic fields with a word-naming task. The words were selected from a database of lexical properties of Japanese. The four "Hiragana" characters used were grouped and presented in 4 classes of degree of familiarity. The three components were observed in averaged waveforms of the root mean square (RMS) value on latencies at about 100 ms, 150 ms and 220 ms. The RMS value of the 220 ms component showed a significant positive correlation (F=(3/36); 5.501; p=0.035) with the value of familiarity. ECDs of the 220 ms component were observed in the intraparietal sulcus (IPS). Increments in the RMS value of the 220 ms component, which might reflect ideographical word recognition, retrieving "as a whole" were enhanced with increments of the value of familiarity. The interaction of characters, which increased with the value of familiarity, might function "as a large symbol"; and enhance a "pop-out" function with an escaping character inhibiting other characters and enhancing the segmentation of the character (as a figure) from the ground.

Adult↗

PubMed2004

Is graft size a major risk factor in living-donor adult liver transplantation?

Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (> or =40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a "small-for-size" graft for adult recipients, remains a feasible option in LDALT.

Adolescent↗

PubMed2004

The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury.

BACKGROUND: Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury. METHODS: After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate. RESULTS: Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P<0.050), hepatic enzyme release into the perfusate (P=0.038), total bile production (P=0.029) and malondialdehyde concentration (P=0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P=0.032). TNF-alpha levels were not affected. CONCLUSIONS: MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.

Animals↗

PubMed2004

Evaluation of [18F]fluorinated sigma receptor ligands in the conscious monkey brain.

PET-imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)-diseases in which the sigma receptors are involved. The [(18)F]fluoroethylated analogs of SA4503 and SA5845 ([(18)F]FE-SA4503 and [(18)F]FE-SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [(18)F]FE-SA4503 or [(18)F]FE-SA5845 (n = 3 for both groups, 220-802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [(18)F]FE-SA4503 for 120 min and "cold" SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120-min PET-scan with [(18)F]FE-SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [(18)F]FE-SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [(18)F]FE-SA5845 binding to give PET-images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [(18)F]FE-SA5845 and [(18)F]FE-SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [(18)F]FE-SA5845 was higher in all brain regions than that of [(18)F]FE-SA4503 (4.75-8.79 vs. 1.65-4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [(18)F]FE-SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain.

Animals↗

PubMed2004

Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater.

Cancer of the papilla or the ampulla of Vater appears, from a clinical point of view, to be an intraduodenal or ampullary cancer. An adenoma-dysplasia-carcinoma sequence has been established. In 20%-40% of the patients with an adenoma of the papilla, a cancerous lesion in the adenoma is additionally observed. Oncological resection using a Kausch-Whipple technique or a pylorus-preserving partial pancreatico-duodenectomy (PPPD) offers a 5-year survival probability of between 45% and 65%. The hospital mortality after oncological resection at experienced centers is below 5%. The most frequent treatment-related complication is pancreatic fistula, which occurs in around 20% of the patients. In about 10% of the patients with a pT1 cancer and in 25% to 67% with pT2 and pT3 cancer, lymph node involvement has been observed. Lymph nodes in front of and behind the head of the pancreas are the primary targets for cancer cell disseminations. In more than one-third of the patients, lymph nodes in the inter-aortocaval space and the lymph nodes around the superior mesenteric artery and the nodes in the pancreatic segment of the hepatoduodenal ligament are involved. Therefore, tissue dissection, including, selectively, the N2 lymph nodes, is an essential component of radical surgery for cancer of the papilla. A standard Kausch-Whipple resection or PPPD without a selective extended lymph node dissection, including the interaortocaval and superior mesenteric artery nodes, results in about 30% of the patients having an R2-resection, i.e., with cancer left behind. The long-term survival is determined by the tumor biological factors: (1) absence of lymph node involvement and (2) absence of infiltration into the pancreas. The surgeon's contribution to the cure of cancer of the papilla is to perform an R0-resection with low hospital mortality and low postoperative morbidity. Patients without lymph node involvement, and with absence of infiltration into the pancreas, no lymph vessel invasion, and tumor-negative margins have major benefits from oncological resection in regard to curability of the cancer.

Ampulla of Vater↗