Immune responses of graft mesenteric lymph node in small bowel transplantation

BACKGROUND: The high proportions of lymphoid tissues are thought to be one of the underlying factors inducing severe allograft rejection following small bowel transplantation. Mesenteric lymph nodes (MLN) contained in the intestinal graft are not only a source of donor-derived professional antigen-presenting cells, but also offer a field for immune interaction between donor and host cells. We investigated immune responses in graft MLNs with or without FK506 to develop a novel strategy to control small bowel allograft rejection. MATERIALS AND METHODS: Heterotopic small bowel transplantations were performed from Brown Norway donors to Lewis recipients. Changes in population of lymphocytes, expressions of costimulatory molecules, apoptosis, and cytokine profiles in graft MLNs were evaluated. RESULTS: The increase in apoptotic cells and cytokine responses relating to rejection in the graft MLNs developed prior to those in graft jejunum. While donor lymphocytes in graft MLNs were rapidly replaced to host-derived lymphocytes independent of FK treatment, increase in CD8(+) T cells in host population was seen only in recipients without FK506 treatment. The expressions of B7 molecules on donor cells in graft MLNs were significantly lower in the recipients with FK treatment. CONCLUSIONS: Immune responses in graft MLNs have significant impact on the outcome of the small bowel allograft. Apoptosis of graft MLN cells was well correlated with and ahead of progression of acute rejection. Modulation of costimulatory molecules on donor-derived MLN cells in the allograft and specific suppression of host CD8(+) T cells are possible ways to control severe rejection after allogeneic small bowel transplantation.     

Cervical myelopathy due to OPLL: clinical evaluation by MRI and intraoperative spinal sonography

BACKGROUND: Concerning the relationship between morphology and clinical outcome, there have been many reports using computed tomography/myelography but not so many using axial magnetic resonance imaging (MRI) of the spinal cord. This is the first report to correlate axial cord image, intensity changes in MRI, and cord expansion pattern using intraoperative ultrasonography. OBJECTIVE: The objectives were to correlate MRI studies, axial cord images/expansion, and changes in MRI intensity to see if there is a direct prognostic significance to these changes and to determine whether preoperative axial MRI images of the spinal cord predict recovery from compressive myelopathy. METHODS: Posterior cervical decompressions with laminoplasty were performed in 44 patients with cervical myelopathy due to ossification of the posterior longitudinal ligament. On T2-weighted MR images, the cross-sectional shape of the cord at the level of maximal compression was categorized as boomerang, teardrop, or triangle. Additionally, with use of intraoperative ultrasonography, the expansion pattern of the cord that occurred intraoperatively was contrasted with that seen on postoperative MR images. RESULTS: Clinical recovery rates were the worst for those with triangular, intermediate for those with boomerang, and the best for those with teardrop shape. Preoperative low T1 and high T2 signals were found in most cases with triangular cord configurations. Triangular cord configurations showed the least expansion among the three categorized spinal cords. CONCLUSION: Patients with triangular deformity of the cord have atrophy as confirmed on MR studies where there is a low T1 and high T2 signal in the cord. Poor postoperative clinical recovery correlates with the lack of postoperative cord expansion on either MR or ultrasound evaluations. Those with either teardrop or boomerang deformities demonstrate a relatively good recovery rate.     

Comparison of surgical outcomes between macro discectomy and micro discectomy for lumbar disc herniation: a prospective randomized study with surgery performed by the same spine surgeon

STUDY DESIGN: A prospective study was conducted on the surgical procedures for lumbar disc herniation. OBJECTIVE: The objective of this study is to investigate the surgical outcomes of different methods when performed by the same surgeon, using a prospective study. BACKGROUND: Macro discectomy is widely known as a common surgical procedure for lumbar disc herniation, while microdiscectomy in place of Caspar technique (the Caspar method) and microendoscopic discectomy by a posterior approach are reported as less invasive surgical methods for this condition. However, there have not been a significant number of prospective studies conducted to compare different surgical procedures for lumbar disc herniation. MATERIALS AND METHODS: The target of our study was a group of 62 patients (male: 43, female: 19) who underwent surgery by macro discectomy (A group) and 57 patients (male: 33, female: 24) who underwent surgery by microdiscectomy in place of Caspar technique (B group). The mean ages at surgery were 34 (14 to 62) years and 41 (18 to 65) years respectively, and the mean duration of follow-up was 2 years and 8 months (12 months to 4 years). For all patients, the surgery was performed by 1 of the authors. The items investigated were the operation time, amount of bleeding, duration of hospitalization, amount of analgesic agent used after surgery, pre- and postoperative scores based on judgment criteria for treatment of lumbar spine disorders established by the Japanese Orthopaedic Association score, visual analog scales (VAS, 0 to 10) for lumbago before surgery and at discharge, VAS for sciatica before surgery and at discharge, perioperative complications, and cases requiring further surgery. RESULTS: There were no significant differences between the 2 surgical procedures in the frequency of use of an analgesic agent after surgery, the pre- and postoperative Japanese Orthopaedic Association scores or postoperative VAS for sciatica. Statistically significant differences were observed in the operation time, amount of bleeding, duration of hospitalization, and postoperative VAS for lumbar pain, but the differences were not large, and may not have been clinically significant. CONCLUSIONS: For herniotomy for lumbar disc herniation, both macro discectomy and microdiscectomy are appropriate, as long as surgeons have mastery of the procedures.     

Loss of claudin-1 expression correlates with malignancy of hepatocellular carcinoma

BACKGROUND: The prognosis for the hepatocellular carcinoma (HCC) patient is affected by invasion and metastases. The attenuated expression of adherens junction protein epithelial-cadherin (E-cad) correlates with a more malignant potential in HCC. However, the potential of the claudin (CL) family of tight junctional proteins for HCC prognosis has remained unrecognized. MATERIALS AND METHODS: We immunohistochemically examined the expression of CL-1 and E-cad in resected specimens from 55 HCC cases. The percentage of CL-1- or E-cad-positive cells was counted in HCC cells and the surrounding hepatocytes and scored as 0 (0%), 1 (1-33%), 2 (34-66%), and 3 (67-100%). The expression of CL-1 or E-cad was considered "preserved" if the score in HCC was equal to or more than that in the surrounding hepatocytes, and "attenuated" if not so. RESULTS: In nontumorous tissue, CL-1 and E-cad were observed at the lateral surface of hepatocytes and biliary epithelial cells. In well-differentiated HCCs, the expression of CL-1 and E-cad was preserved in 12 of 14 cases. In poorly differentiated HCCs, E-cad expression was preserved in 9 of 18 cases, while CL-1 expression was preserved in only 4 cases (P<0.01 versus well-differentiated HCCs). HCCs with portal invasion showed significantly attenuated CL-1 expression than those without portal invasion (P<0.05). The survival rate after hepatectomy for HCC with attenuated CL-1 expression was significantly lower than that for HCC with preserved CL-1 expression. CONCLUSIONS: Attenuated expression of CL-1 closely correlates with the dedifferentiation and portal invasion of HCC. Down-regulated CL-1 expression may serve as a potential marker for a poor prognosis in HCC.     

Pancreatic insulinoma combined with glucagon positive cell: A case report

We present a 70-year-old man who was referred for surgery with uncontrollable hypoglycemia. Ultrasonography and abdominal contrast computed tomography revealed a hypervascular tumor of 1 cm in diameter in the pancreatic tail. With a diagnosis of insulinoma, we performed a distal pancreatectomy. The patient showed a good postoperative course without any complications. The patient’s early morning fasting hypoglycemia disappeared. The respective levels of C-peptide and insulin dropped from 14.9 ng/mL and 4860 μIU/mL preoperatively to 5.3 ng/mL and 553 μIU/mL after surgery. A histopathological examination demonstrated that the tumor was a pancreatic neuroendocrine tumor, grade 1. Immunostaining was negative for insulin and positive for CD56, chromogranin A, synaptophysin and glucagon. These findings suggested that the tumor was clinically an insulinoma but histopathologically a glucagonoma. Among all insulinoma cases reported between 1985 and 2010, only 5 cases were associated with independent glucagonoma. In this report, we characterize and discuss this rare type of insulinoma by describing the case we experienced in detail.     

Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.

BACKGROUND: Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats. METHODS: We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method. RESULTS: Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes. CONCLUSIONS: Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.     

Expression of type IV collagen in the developing human kidney

The distribution of α1–6 chains of type IV collagen (α1–6(IV)) in human fetal kidneys was examined by indirect immunofluorescence. By 11 weeks of gestation, α1, 2, 3, 4, and 6(IV) were already present, but α5(IV) appeared relatively late, at 21 weeks. α1(IV) and α2(IV) were present in all basement membranes, α3(IV) and α4(IV) were restricted to the glomerular basement membrane and parts of the tubular basement membrane. α5(IV) was distributed in the glomerular basement membrane, Bowman’s capsule, and parts of the tubular basement membrane. α6(IV) was present in the Bowman’s capsule, parts of the tubular basement membrane, and occurred in parts of the glomerular basement membrane at the early capillary loop stage, but disappeared during the later capillary loop stage. Received October 23, 1997; received in revised form and accepted February 6, 1998     

Human Skin Xenograft Rejection in CD45 Exon-6 Knockout Mice: The Implication of Involvement of a Direct Pathway

The results of previous studies indicate that only CD4⁺ T cells generated via the indirect pathway play an essential role in causing discordant skin xenograft rejection. The present study was conducted in an attempt to clarify further the roles of effector T cells generated via direct pathways on discordant xenograft rejection using CD45 exon-6 knockout (CD45−/−; C57BL/6 (B6): H-2^b) mice. It has been strongly suggested that CD45 exon-6 knockout mice have profound impairment in T-cell functions via an indirect pathway. When human skin was grafted onto untreated normal C57BL/6 (B6; H-2^b) mice, rejection occurred within 12 days; however, in the CD45 exon-6 knockout mice, the grafts lasted for slightly longer as in fully allogeneic C3H (H-2^k) skin rejection, with a mean survival time ± SD of 19.4 ± 1.5 days and median survival times of 19 days. The difference in survival periods between the human and C3H skin grafts in the CD45 knockout mice was not statistically significant. Both CD4⁺ and CD8⁺ T cells seemed activated in the spleens of these CD45 exon-6 knockout mice 10 days after the human skin grafting. These results suggest that effector T cells generated via a direct pathway can cause discordant skin xenograft rejection, and that CD45 exon-6 knockout mice can generate effector T cells via a direct pathway to reject discordant skin xenografts, similarly to fully allogeneic skin allografts. Received: June 24, 1999 / Accepted: May 30, 2000     

Dermatomyositis accompanied by rectal cancer: Report of a case

(Received for publication on Jan. 5, 1999; accepted on Sept. 17, 1999)