A giant retention cyst of the pancreas (cystic dilatation of dorsal pancreatic duct) associated with pancreas divisum

We describe a rare case of pancreas divisum associated with a giant retention cyst (cystic dilatation of the dorsal pancreatic duct), presumably formed following obstruction of the minor papilla. The patient was treated by pancreatico(cysto)jejunostomy. A 50-year-old man was admitted with complaints of increasing upper abdominal distension and body weight loss. There was no previous history of pancreatitis, gallstones, drinking, or abdominal injury. An elastic-hard tumor-like resistance was palpable in the upper abdomen. Computed tomography and ultrasound (US) examinations revealed a giant cystic lesion expanding from the pancreas head to the tail. Endoscopic retrograde cholangiopancreatography findings showed a looping pancreatic duct which drained only the head and uncinate process of the pancreas to the main papilla. A US-guided puncture to the cystic lesion revealed that the lesion continued to the main pancreatic duct in the tail of pancreas. The lesion was connected to a small cystic lesion, which was located inside the minor papilla, and ended there. The amylase level in liquid aspirated from the cyst was 37 869 IU/l, and the result of cytological examination of the liquid showed class II. A pancreatico(cysto)jejunostomy was performed, with the diagnosis being pancreas divisum associated with a retention cyst following obstruction of the minor papilla. The histological findings of a specimen from the cyst wall revealed that the wall was a pancreatic duct covered with mildly inflammatory duct epithelium; there was no evidence of neoplasm. The patient is currently well, and a CT examination 2 years after the operation showed disappearance of the cyst and normal appearance of the whole pancreas. Received: April 24, 2001 / Accepted: September 14, 2001     

Familial Crohn's disease with systemic lupus erythematosus

We describe a young Japanese woman who was diagnosed with Crohn's disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohn's disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohn's disease with SLE), patients with Crohn's disease who develop such clinical findings might need evaluation for SLE.     

Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management

AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps.METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations.RESULTS: NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8.CONCLUSION: We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.     

Polymorphism of CYP2C19 and gastric emptying in patients with proton pump inhibitor-resistant gastric ulcers

The aim of the present study was to investigate whether CYP2C19 polymorphism status and gastric emptying are related to healing in patients with gastric ulcers. We studied the CYP2C19 status in seven patients with proton pump inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy volunteers using polymerase chain reaction restriction fragment length polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The frequency of phenotypes, indicated by genotypes, did not differ significantly between the three patient groups. The peak time of 13C excretion in patients with PPI-resistant ulcers was significantly longer than that of patients with PPI-sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric emptying, but not CYP2C19 polymorphism, is likely to be an important factor in the delayed healing of patients with PPI-resistant gastric ulcer.     

The critical role of type-1 innate and acquired immunity in tumor immunotherapy

The discovery of a large array of tumor antigens has demonstrated that host lymphocytes can indeed recognize and destroy tumor cells as originally proposed in the cancer immunosurveillance hypothesis. Recent reports that led to the cancer immunoediting concept also strongly support the immunosurveillance hypothesis, and they further indicate that the host immune system plays a critical role not only in promoting host protection against cancer but also in selecting tumors that can better escape from immune attack. Thus, it is now clear that T cells have the ability to recognize and destroy spontaneously arising tumors. However, the generation of antitumor immunity is often difficult in the tumor-bearing host because of various negative regulatory mechanisms. Here, we review our recent work on tumor immunotherapy, which utilizes the activation of type-1 innate and/or acquired immunity as a potent strategy to overcome immunosup-pression in the tumor-bearing host. We have established a variety of tumor therapeutic protocols that aim to activate type-1 immunity, such as tumor-vaccine therapy with CpG encapsulat-ed in liposomes, cell therapy using tumor-specific Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG encapsulated in liposomes stimulated IL-12-producing DC and induced IFN-gamma-producing NK cells, NKT cells, and tumor-specific CTL. Th1 cell therapy was also shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the DLN, which was critical for inducing tumor-specific CTL at the tumor site. Therefore, we conclude that the activation of type-1 innate and acquired immunity is crucial for tumor immunotherapy in order to overcome strong immunosuppression in the tumor-bearing host.     

Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor

The precise function of ryanodine receptors (RyRs) in synaptic transmission is unknown, but three of their subtypes are expressed in the brain. We examined the roleof RyRs in excitatory synaptic transmission in hippocampal slices, using type 3 RyR (RyR3)-deficient mice. The alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid (AMPA) receptor-mediated basal synaptic responses in the CA1 region of mutant mice were smaller than those of wild-type mice, while there was no difference in N-methyl-d-aspartate receptor-mediated responses, suggesting selective postsynaptic modification of AMPA receptors by RyR3. The expression of synaptic AMPA receptor subunits examined by Western blotting or immunohistochemistry was indistinguishable, suggesting that the smaller AMPA synaptic responses in mutant mice were not due to the reduced number of synaptic AMPA receptors. Although the initial potentiation following tetanic stimulation of afferent fibers was similar, long-term potentiation (LTP) was smaller in mutant mice. There were no differences in presynaptic electrophysiological properties. We thus conclude that RyR3 postsynaptically regulates the properties of AMPA receptors and LTP.     

Clinical study of varicocele: Statistical analysis and the results of long-term follow-up

BACKGROUND: The results of clinical examinations of varicocele and the clinical outcome of varicocelectomy conducted at Tsukuba University Hospital, Tsukuba City, Japan were analyzed. METHODS: The subjects of the present study were sixty-four infertile male patients with varicocele who visited our hospital from 1991 to 1999. A physical examination, semen analysis and hormonal evaluation were performed for each patient. Patients selected their preferred type of treatment (varicocelectomy or conservative treatment) after providing their informed consent. RESULTS: The age of the patients was 34.1 +/- 5.1(mean +/- standard deviation [s.d.]) years, and the infertile duration was 4.2 +/- 3.0 (mean +/- s.d.) years. Fifty-one cases were left-sided; 13 were bilateral. Mean sperm density ( yen 106/mL) was 37.2 for Grade I, 21.3 for Grade II and 9.4 for Grade III. Sperm density was significantly lower in the higher-graded patients (P = 0.008). Varicocelectomy was performed in 31 cases; the postoperative/preoperative ratio of sperm density was significantly higher in the higher-graded varicocele (P = 0.04), and the peak/base ratio of follicle-stimulating hormone (FSH) after luteinizing hormone-releasing hormone (LH-RH) stimulation was significantly decreased after varicocelectomy (P = 0.007). The pregnancy rate in the partners of the varicocelectomized group (60%) was significantly higher than in the conservatively treated group (28%) P = 0.04; the mean follow-up duration was 76.2 months. CONCLUSION: These results show that varicocele should influence spermatogenesis, therefore altered spermatogenesis could be effectively treated by varicocelectomy, and varicocelectomy should induce a higher probability of pregnancy.     

Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibition of leukocyte function by administration of monoclonal antibody 60.3 (MoAb 60.3) improves electrophysiological recovery and decreases injury volume following transient focal cerebral ischemia in cats. METHODS: Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive either 2 mg/kg MoAb 60.3 (n = 8) directed at the CDw18 leukocyte antigen complex or an equal volume of diluent (sterile saline; n = 10) at 45 minutes of ischemia in a blinded fashion. RESULTS: Blood flow to the left temporoparietal cortex decreased to less than 5 ml/min/100 g with ischemia, but was minimally affected on the right side. Postischemic hyperemia occurred in the left caudate nucleus, whereas blood flow in other brain regions returned to control. No region demonstrated delayed hypoperfusion, and there were no differences between groups. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 10% of baseline amplitude at 180 minutes of reperfusion in both groups. Left hemispheric injury volume, as assessed by 2,3,5-triphenyltetrazolium chloride staining, was not affected by drug treatment (mean +/- SE values: MoAb 60.3, 37 +/- 5%; placebo, 38 +/- 7% of hemisphere). CONCLUSIONS: Inhibition of leukocyte function with MoAb 60.3 does not afford protection from severe focal ischemia and reperfusion in cats.     

Pronociceptive effects of nociceptin/orphanin FQ (13-17) at peripheral and spinal level in mice

The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is reported to be metabolized by aminopeptidase N and endopeptidase 24.15. In the present study, N/OFQ C-terminal fragments elicited nociceptive responses in the peripheral nociceptors and in the spinal cord, whereas N-terminal fragments had no significant nociception. The nociceptive effect of N/OFQ (13-17) was most potent and remained unchanged in N/OFQ peptide receptor (NOPR) gene knockout mice, indicating that N/OFQ (13-17)-induced nociception is mediated through a novel mechanism independent of the activation of NOPR. This finding was further confirmed by in vitro guanosine 5'-O-(3-[35S]thio)triphosphate binding experiments, in which N/OFQ (13-17) showed no significant binding activity in baculovirus/sf21 cells expressing NOPR together with G protein alpha(i)1-, beta1-, and gamma2-subunits, whereas N/OFQ showed stimulation in a concentration-dependent manner. On the other hand, although a typical bell-shaped dose-response relationship was observed with a wide range of N/OFQ doses in both peripheral and central nociception tests, N/OFQ (13-17) did not show bell-shaped dose-response relationship in the central nociception test. This finding indicates that N/OFQ (13-17), in contrast to N/OFQ, lacks the postsynaptic antinociceptive actions modulating substance P signaling in the spinal cord. Together, our results suggest that C-terminal fragments of N/OFQ have potent nociceptive actions, and N/OFQ (13-17) could have the potential to mediate its actions through a novel mechanism independent of the activation of NOPR in the nociceptors and in spinal synapses.     

Plasma Lactic Acid and Pyruvic Acid Levels in Migraine and Tension-Type Headache

We examined the lactic and pyruvic acid levels in the plasma of 14 patients with migraine, 17 patients with tension-type headache, and 12 normal controls. The lactic and pyruvic acid levels in the plasma of the migraine patients were significantly higher than those of the normal controls (9.6 ± 5.0 mg/dL and 0.51 ± 0.30 mg/dL versus 3.3 ± 1.9 mg/dL and 0.26 ± 0.20 mg/dL, respectively). There were no significant differences in the levels between the patients with tension-type headache and normal controls. Our results suggest that migraine patients may have functional abnormalities in mitochondrial energy metabolism.