Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis.

Heparan sulfate (HS) proteoglycans (HSPGs) bind to multiple growth factors/morphogens and regulate their signaling. 6-O-sulfation (6S) of glucosamine within HS chains is critical for many of these ligand interactions. Sulf-1 and Sulf-2, which are extracellular neutral-pH sulfatases, provide a novel post-synthetic mechanism for regulation of HSPG function by removing 6S from intact HS chains. The Sulfs can thereby modulate several signaling pathways, including the promotion of Wnt signaling. We found induction of SULF2 transcripts and Sulf-2 protein in human lung adenocarcinoma and squamous cell carcinoma, the two major classes of non-small-cell lung carcinomas (NSCLCs). We confirmed widespread Sulf-2 protein expression in tumor cells of 10/10 surgical specimens of human lung squamous carcinomas. We studied five Sulf-2(+) NSCLC cell lines, including two, which were derived by cigarette-smoke transformation of bronchial epithelial cells. shRNA-mediated Sulf-2 knockdown in these lines caused an increase in 6S on their cell surface and in parallel reversed their transformed phenotype in vitro, eliminated autocrine Wnt signaling and strongly blunted xenograft tumor formation in nude mice. Conversely, forced Sulf-2 expression in non-malignant bronchial epithelial cells produced a partially transformed phenotype. Our findings support an essential role for Sulf-2 in lung cancer, the leading cancer killer.

Endoscopic 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Endoscopic 13C-urea breath test may avoid contamination of oral urease and rapidly discriminate Helicobacter pylori-positive and Helicobacter pylori-negative patients. AIMS: To compare the accuracy of endoscopic 13C-urea breath test with conventional invasive methods in diagnosis of Helicobacter pylori infection. PATIENTS: One hundred patients who attended for routine upper gastrointestinal endoscopy were included. METHODS: 13C-urea was applied to the stomach through the working channel of endoscope at the end of endoscopic examination. Breath samples were collected before endoscopy and 2, 4, 6, 8, 10 min after consumption of 100 or 50 mg 13C-urea. Helicobacter pylori infection was defined as those with positive culture or positive results of both histology and CLO test. RESULTS: The accuracy of 100 mg endoscopic 13C-urea breath test was significantly higher than that of culture and CLO test (100% vs. 88% and 92%, p = 0.02 and 0.03, respectively). The accuracy of 50 mg endoscopic 13C-urea breath test was higher than that of histology and CLO test (98% vs. 90% and 96%, respectively), although the differences were not statistically significant. CONCLUSIONS: Endoscopic 13C-urea breath test has a higher accuracy compared with biopsy-based modalities. It may be a good choice to diagnose Helicobacter pylori infection if endoscopy is indicated for a dyspeptic patient.

Follow-up of Helicobacter pylori status by using 13C-urea breath test in nonulcer dyspeptic patients after eradication therapy.

BACKGROUND: The role of eradication therapy is still controversial in H. pylori-related nonulcer dyspepsia (NUD). The aim of this study was to follow up the H. pylori status after eradication therapy in patients with NUD by using l3C-urea breath test (UBT). METHODS: Patients with a clinical and endoscopic diagnosis of NUD were included. H. pylori infection was established by endoscopic biopsies and 13C-UBT. Patients with H. pylori infection then received a quadruple therapy with colloidal bismuth subcitrate, metronidazole, tetracycline and lansoprazole. Two months after completion of therapy, endoscopic biopsies and 13C-UBT were performed again to confirm eradication. A follow-up 13C-UBT was carried out again in one year to detect recurrence of H. pylori infection. RESULTS: Eighty-eight of the 148 patients (59.5%) were found to have H. pylori infection by both endoscopic biopsies and 13C-UBT. Anti-H. pylori therapy was given for 55 patients and proved successful in 33 of them two months after the end of therapy. However, recurrence was found one year later in three of these 33 cases, making a recurrence rate of 9.1% (3/33). Three of the 22 cases with unsuccessful eradication were found to have H. pylori eradication at one year by follow-up 13C-UBT. One of the 33 H. pylori-positive patients without anti-H. pylori therapy, who had negative 13C-UBT in one year follow-up, was found taking a high dose and long period of antibiotics. CONCLUSIONS: The recurrence rate of H. pylori infection in our study was higher than that in the Western population. Delayed eradication of H. pylori may occur after anti-H. pylori therapy. Spontaneous eradication is rare in patients not receiving anti-H. pylori eradication.

Clinical significance of oral urease in diagnosis of Helicobacter pylori infection by [13C]urea breath test.

This study was performed to evaluate the effect of oral flora on [13C]urea breath test in detecting H. pylori infection and find an optimal method and timing for sample collection. Forty-five volunteers were included in this study. The [13C]urea breath test was performed using mouthwash, endoscopic administration, and conventional methods. According to the receiver-operating characteristic curves, the earliest optimal time for discriminating H. pylori-positive and H. pylori-negative patients was at 25 min with the mouthwash method with 78% sensitivity and 82% specificity, at 2 min with the endoscopic administration method with 100% sensitivity and 100% specificity, and at 6 min with the conventional method with 100% sensitivity and 95% specificity. The study shows a significant effect of oral urease on the results of the [13C]urea breath test. The timing of sampling collection can be shortened to 6 min with the conventional method or to 2 min through endoscopic administration.

Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes.

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.

Does inadequate exercise lower the accuracy of myocardial perfusion scintigraphy?

The predictive accuracy of exercise myocardial perfusion scintigraphy (EMPS) in detecting coronary artery disease (CAD) in patients who fail to achieve an adequate level of exercise is not clear. This investigation was carried out in order to compare the sensitivity, specificity and accuracy of EMPS in adequate exercise patients with those in inadequate exercise patients. We have retrospectively compared the results of EMPS with coronary angiography (CAG). One hundred and forty-eight patients with both tests within 6 weeks were included. Adequate exercise was defined as > or = 85% maximally predicted heart rate for age. The overall sensitivity and specificity of EMPS to detect CAD were 92.5% (74/80) and 75%, (51/68), respectively. The sensitivity and specificity in adequate exercise patients were 94.1% (32/34) and 67.6% (23/34), whereas those in inadequate exercise patients were 91.3% (42/46) and 82.4% (28/34). The accuracy was 80.9% (55/68) and 87.5% (70/80), respectively. Patients with inadequate exercise had lower sensitivity but higher specificity of EMPS for detecting CAD, and achieved a higher accuracy than those with adequate exercise.

99Tcm-dimercaptosuccinic acid renal scintigraphy for detection of renal cortical defects in acute pyelonephritis: posterior 180 degrees SPECT versus planar image and 360 degrees SPECT.

To evaluate the usefulness of the posterior 180 degrees acquisition technique for renal defects in acute pyelonephritis (APN), a prospective study was conducted using planar imaging, 360 degrees and posterior 180 degrees renal single photon emission computed tomography (SPECT) with 99Tcm-dimercaptosuccinic acid. Sixty subjects with the suspicion of APN were included. The kidneys were divided into three zones: each was graded as positive, equivocal or negative for renal defects. To evaluate inter-observer variation, each study was read in a double-blind fashion by two nuclear physicians. Renal defects were found in 24 patients (31 kidneys and 47 zones) with posterior 180 degrees SPECT, 23 patients (29 kidneys and 44 zones) with 360 degrees SPECT (McNemar's test, P = 0.375 for zones) and 15 patients (16 kidneys and 24 zones) with planar image (P = 0.001 for zones, vs 180 degrees and 360 degrees SPECT). The proportion of positive agreement for posterior 180 degrees and 360 degrees SPECT between readers for the presence of renal defects was 0.81 and 0.62, respectively, whereas the proportion of negative agreement was 0.92 and 0.87, respectively. Both posterior 180 degrees and 360 degrees SPECTs significantly detected more renal defects than planar imaging. The detectability of renal defects in APN by posterior 180 degrees renal SPECT was equal to 360 degrees SPECT but inter-observer agreement was better.

Evaluation of the Effect of Radiation Therapy to Nasopharyngeal Carcinoma by Positron Emission Tomography with 2-

Purpose: This investigation evaluated the effectiveness of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose (PET-FDG) in assessing residual tumor or tumor recurrence in postradiation nasopharyngeal carcinoma (NPC) patients.Procedures: Forty-six patients with histologically proven NPC who received radiotherapy were included. PET-FDG images were analyzed by a semiquantitative method, metabolic ratio (tumor to cerebellum ratio).Results: The overall sensitivity and specificity of PET-FDG to detect residual tumors and recurrent lesions in the postradiation patients were 80% (12/15) and 87% (27/31), respectively. In patients with PET-FDG 6 months after radiation therapy, the sensitivity and specificity raised to 92% (11/12) and 100% (20/20), respectively.Conclusions: PET-FDG is effective in the evaluation of NPC treated with radiation. The optimal timing in assessing residual tumor or tumor recurrence in postradiation patients should be 6 months or later.

A 15-minute [13C]-urea breath test for the diagnosis of Helicobacter pylori infection in patients with non-ulcer dyspepsia.

BACKGROUND: Non-ulcer dyspepsia (NUD) accounts for the majority of dyspeptic patients and studies on the epidemiology of Helicobacter pylori infection in NUD depend on a non-invasive and rapid diagnostic test. This study was performed to determine the sensitivity and specificity of a 15-min simplified protocol of the [13C]-urea breath test ([13C]-UBT) for the diagnosis of H. pylori infection in patients with NUD. METHODS: One hundred and thirty-six patients with a clinical and endoscopic diagnosis of NUD were included. The [13C]-UBT was modified from the European standard protocol. The baseline breath sample was collected 5 min after the patient took a test meal and the 13CO2 was collected 15 min after the patient drank 100 mg [13C]-urea. The gold standard used for comparison was either a positive culture or positive histology + positive rapid urease test sampled on upper gastrointestinal endoscopy. RESULTS: The prevalence of H. pylori infection in NUD by the gold standard was 59.6%, whereas that calculated by the [13C]-UBT was 60.3%. The sensitivity and specificity of [13C]-UBT was 93.8 and 89.1% compared with the gold standard. The shortened collection time and simplification of the procedure may have led to a decline in specificity. CONCLUSION: The 15-min [13C]-UBT is a rapid but less specific protocol for detecting the presence of H. pylori infection in patients with NUD.

Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT.

We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid.

Posterior 180 degrees 99mTc-dimercaptosuccinic acid renal SPECT.

UNLABELLED: As a result of a high percentage of hypoactive upper poles of kidneys in traditional 99mTc-dimercaptosuccinic acid (DMSA) SPECT, a prospective study was conducted using 180 degrees acquisition technique compared with 360 degrees to minimize tissue attenuation. METHODS: Anterior 180 degrees, posterior 180 degrees and 360 degrees renal SPECT images were obtained simultaneously using a dual-head camera. Forty-one subjects without renal disease and 16 subjects with 21 cortical defects were included in this study. The total counts of the raw data in the anterior 180 degrees, posterior 180 degrees and full 360 degrees were calculated. Small regions of interest were drawn over the cortex of the kidney on coronal and reoriented sagittal slices. Quantitative evaluation of regional activity was performed on the same frames in all three acquisition methods. RESULTS: Comparison of the total renal counts between the anterior and posterior 180 degrees data showed reduced counts in the anterior 180 degrees data collection (P < 0.01). Visual evaluation of the reconstructed images from anterior 180 degrees, posterior 180 degrees and full 360 degrees data collection showed the best image uniformity in the posterior 180 degrees image. The upper/lower pole ratio in the posterior 180 degrees renal SPECT images increased significantly in comparison to full 360 degrees renal SPECT images (P < 0.01) and anterior 180 degrees SPECT images (P < 0.01). The renal defects were more clearly visualized in the posterior 180 degrees renal SPECT images than the full 360 degrees renal SPECT images. The defect/normal cortex ratios in the posterior 180 degrees renal SPECT images were much lower than those from the full 360 degrees SPECT images (P < 0.01) and those from the anterior 180 degrees SPECT images (P < 0.01). CONCLUSION: The posterior 180 degrees acquisition technique can avoid the problem of hypoactive upper pole and can be less time consuming in 99mTc-DMSA SPECT images. It also provides superior lesion contrast in the clinical evaluation of patients with renal scarring.

Tc-99m MDP uptake in cerebral infarction: comparison with Tc-99m DTPA brain scan and Tc-99m HMPAO brain SPECT.

Intracerebral uptake of methylene diphosphonate (MDP) was unexpectedly found in metastatic work-up of lung cancer. The history of the 52-year-old patient revealed a sudden onset of weakness of right limbs 10 days ago. Technetium-99m diethylenetriamine pentaacetate (Tc-99m DTPA) brain scan and Tc-99m hexamethyl propylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) were done, and both showed abnormality in the left temporoparietooccipital region corresponding to the territory of left middle cerebral artery. A repeated bone scan four months later showed complete resolution of the intracerebral Tc-99m MDP uptake. We present this case to emphasize the importance of complementary and enhanced radionuclide images.

Efficacy of quantitative cholescintigraphy in the diagnosis of sphincter of Oddi dysfunction.

The diagnostic efficacy of time-activity curves (TAC) and common bile duct dynamics (CBDD) derived from quantitative cholescintigraphy (QC) was assessed in patients with suspected sphincter of Oddi dysfunction (SOD). Quantitative cholescintigraphy was performed on 34 cholecystectomized individuals with suspected SOD and 26 asymptomatic controls. Each patient with suspected SOD underwent endoscopic retrograde cholangiography and sphincter of Oddi manometry (SOM). After exclusion of eight patients because of failure of manometry, the final diagnoses of the remaining 26 patients were taken as the gold standard by which to determine the detectability of TAC and CBDD. The sensitivity of TAC reached 68.8%. Common bile duct dynamics showed equal sensitivity but was more specific than TAC. The sensitivity improved to 87.5% when TAC and CBDD were combined. We conclude that non-invasive QC provides good sensitivity and specificity in evaluating cholecystectomized patients with suspected SOD.

[Tc-99m MIBI myocardial scintigraphy in evaluation of the effect of percutaneous transluminal coronary angioplasty on coronary artery stenosis].

Tc-99m 2-Methoxy-Isobutyl-Isonitrile, a newly developed myocardial perfusion radiopharmaceutical for myocardial perfusion imaging, provides an accurate, noninvasive detection of coronary artery disease. The potential advantages of Tc-99m MIBI over T1-201 have been reported extensively. The purpose of this study is to evaluate the detectability of the diseased vessels and the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) on Tc-99m MIBI myocardial perfusion scan. Twenty cases of coronary artery disease were included. Single photon emission computed tomographic (SPECT) imagings were used. Forty myocardial imagings were done before and after PTCA. Twenty nine segments of perfusion defect were found preoperatively. The sensitivity and specificity for the images to detect the individual coronary arteries were 88% and 94%, respectively. After PTCA, 25 out of 29 perfusion defects (86%) resolved. Among these, 14 were transient defects (93%) and 11 were persistent defects (79%). Persistent defects on serial thallium and Tc-99m MIBI scans are commonly thought to represent fibrosis or scar. Some investigators suggest that the recovered persistent defects on thallium scan represent hypoperfusion of viable myocardium. In our study, we found that regions of persistent defects on Tc-99m MIBI scan often revert to normal-state after PTCA (79%), indicating the similar results on thallium scans. In conclusion, Tc-99m MIBI myocardial imaging is useful in detecting coronary artery disease and monitoring success of PTCA.

Glomerular diseases in human renal allograft.

A total of 64 renal graft biopsies performed on 44 transplant patients from among 116 transplants (12 from living donors, 104 from cadavers) were analyzed during the period from July 1983 to December 1990. The frequency of allograft glomerular disease was 22.7% (10/44). Membranous glomerulonephritis (MGN) was detected in five patients; focal segmental glomerulosclerosis (FSGS), in two; transplant glomerulopathy, in two; and IgA nephropathy, in one. Nephrotic syndrome occurred in nine of the ten patients. Progressive deterioration of graft function developed in four patients associated with chronic rejection, and two of them later lost the graft. The remaining six patients had no chronic rejection and retained a stable renal condition with one exception, a patient who suffered from acute total occlusion of the right internal iliac artery and who eventually lost the graft. It is concluded that MGN is the most common allograft glomerular disease, but the outcome of the graft is probably related to the coexistent chronic rejection.

Experimental acute pancreatitis. In vitro magnetic resonance characteristics.

The effect of pancreatitis on magnetic resonance T1 and T2 relaxation times was evaluated in two different models of acute pancreatitis in the rat. Acute edematous pancreatitis was induced by repetitive intraperitoneal injections of the cholecystokinin-analogue caerulein; acute hemorrhage pancreatitis was induced by retrograde infusion of the bile salt sodium taurocholate into the pancreatic duct. T1 and T2 relaxation times were obtained in vitro from fresh pancreatic specimens at 37 degrees C with a 0.25 resistive spectrometer. In both edematous and hemorrhagic pancreatitis, significant prolongation of T1 and T2 was noted as early as 1.5 hours after the initiation of pancreatitis when compared with normal rat pancreas. Maximal prolongation occurred at 7 hours in the caerulein model with T1 of 966 +/- 46 msec (mean +/- SEM) (normal + 278 +/- 12 msec) and T2 of 75.9 +/- 2.9 msec (normal = 32.8 +/- 3.3 msec), and after 6 hours in the bile salt model with T1 of 798 +/- 40 msec and T2 of 92.5 +/- 3.3 msec. After the time point of maximal prolongation, T1 and T2 gradually decreased toward the normal values. The prolongation of T1 and T2 paralleled each other throughout the time course of pancreatitis in both models. The prolongation of both relaxation times correlated closely with pancreatic weight, water content, and amylase concentration in serum and ascites. The present determination of T1 and T2 relaxation times by in vitro spectrometry suggests that magnetic resonance imaging has the potential for detecting early pathologic changes in acute pancreatitis and thus may be helpful for an early clinical diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary edema: an MR study of permeability and hydrostatic types in animals.

Permeability pulmonary edema was induced in ten rats by intravenous injection of oleic acid. Hydrostatic pulmonary edema was induced in another ten rats by continuous infusion of saline. Permeability pulmonary edema was detected as increased signal intensity in all animals on images obtained with repetition times (TR) of 2.0 sec and echo times (TE) of 28 and 56 msec. Hydrostatic pulmonary edema was perceivable only in seven of ten rats. It was best seen on spin-echo TR = 2.0 sec, TE = 28 msec images as increased intensity either throughout the whole lung or in a predominant central distribution. The slopes of the relationships between the mean signal intensity and water content of both lungs were lower for hydrostatic pulmonary edema than for permeability pulmonary edema. Hydrostatic pulmonary edema demonstrated similar T1 but markedly shorter T2 relaxation times than permeability edema. Magnetic resonance imaging can be used to estimate severity of hydrostatic and permeability pulmonary edemas.