A case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis

A 49-year-old man was admitted to our hospital with mild proteinuria. Prior to admission, he had been diagnosed as having Sjögren’s syndrome in association with primary biliary cirrhosis. Examination of a renal biopsy under light microscopy revealed diffuse and global mesangial cell proliferation and a spike and/or bubbling formation of the glomerular basement membrane (GBM), resembling membranoproliferative glomerulonephritis. In contrast, immunofluorescent studies showed marked immunoglobulin and complement depositions in the mesangial areas; however, only faint granular IgG and IgA deposition was observed along the GBM. Interestingly, electron microscopy revealed that a microtubular structure, derived from podocytes, was present in the GBM. We present a case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis.     

Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel fiber (PF)-terminals and climbing fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.     

Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood

Umbilical cord blood (UCB) has been used as a potential source of various kinds of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells (EPCs), for a variety of cell therapies. Recently, EPCs were introduced for restoring vascularization in ischemic tissues. An appropriate procedure for isolating EPCs from UCB is a key issue for improving therapeutic efficacy and eliminating the unexpected expansion of nonessential cells. Here we report a novel method for isolating EPCs from UCB by a combination of negative immunoselection and cell culture techniques. In addition, we divided EPCs into 2 subpopulations according to the aldehyde dehydrogenase (ALDH) activity. We found that EPCs with low ALDH activity (Alde-Low) possess a greater ability to proliferate and migrate compared to those with high ALDH activity (Alde-High). Moreover, hypoxia-inducible factor proteins are up-regulated and VEGF, CXCR4, and GLUT-1 mRNAs are increased in Alde-Low EPCs under hypoxic conditions, while the response was not significant in Alde-High EPCs. In fact, the introduction of Alde-Low EPCs significantly reduced tissue damage in ischemia in a mouse flap model. Thus, the introduction of Alde-Low EPCs may be a potential strategy for inducing rapid neovascularization and subsequent regeneration of ischemic tissues.     

Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants

To examine whether donor-derived cells could exist in nonhematopoietic tissues of recipients after allogeneic hematopoietic stem-cell transplantation, we examined the patterns of the short tandem repeat (STR) of DNA extracted from fingernail clippings of recipients so that the contamination of blood cells was excluded. All 21 patients reached donor-derived hematopoiesis after transplantation and 20 of them were in remission of the primary diseases at the time of sampling. Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from fingernail samples showed coexistence of the donor pattern of the STRs, sharing from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was from 305 to 2399 days among positive cases. These results demonstrate for the first time the existence of stable contribution of donor cells in fingernails among recipients of allogeneic hematopoietic stem cells.     

Two cases of gastrointestinal stromal tumor (GIST) of the stomach and a consideration of its malignancy potential and treatment strategy - report of two cases

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach both of which were assessed as highly malignant, but took different clinical courses. Case 1: A 72-year-old male. Case 2: A 63-year-old female. The tumor size of Case 1 was suggestive of high malignancy, but only a partial gastrectomy was selected because it did not show any invasive findings. This patient has been followed up for 3 years post-operatively and no recurrence or metastasis has been noted. Case 2 had liver and lymph node metastases, which was consistent with high malignancy. We performed a total gastrectomy with distal pancreatosplenectomy and segmental liver resection. But after surgery, liver metastasis recurred therefore, imatinib mesylate was administered as adjuvant chemotherapy and since then, the tumor has been diminishing in size. No definitive evidence for adjuvant therapy has been established so far, but we suggest that post-operative adjuvant therapy is effective for high-risk GIST.     

A case of advanced gastric cancer which has kept partial response with the fifth-line chemotherapy

We report a case of a 48-year-old male with advanced gastric cancer. A total gastrectomy was performed for cancer of remnant stomach. S-1 was administered for cytological cancer cells detected by abdominal cavity lavage as the first-line chemotherapy. After 2 cycles of S-1, cervical lymph nodes were enlarged, and the patient underwent paclitaxel monotherapy as the second-line chemotherapy. After 8 cycles, Virchow lymph nodes were enlarged. The regression of Virchow lymph nodes were observed with a S-1 /CPT-11 combination therapy as the third-line chemotherapy and DOC/CPT-11 as the fourth-line chemotherapy. We then used a combination chemotherapy of CPT-11 60 mg/m2 and CDDP 30 mg/m2 at day 1 and 15, every 4 weeks as the fifth-line chemotherapy. A partial response was achieved after 2 cycles, and has been continued for 7 months. The hematological toxicities and the non-hematological toxicities of grade 2 or higher were not observed. This regimen may be effective for patients with advanced gastric cancer resistant to prior chemotherapy with several agents.     

Five cases of pseudomyxoma peritonei underwent abdominal lavage and administering CDDP

We examined five cases of pseudomyxoma peritonei with treatments of cytoreduction surgery, abdominal lavage and intraperiotoneal administration of cisplatin (CDDP). These primary lesions contained one case of pancreas and four cases of appendix. Histological types contained one case of well differentiated adenocarcinoma and four cases of signet ring cell carcinoma. All cases underwent a resection of primary lesion and muconodule, abdominal lavage with saline and 5% glucose or low molecule dextran solution. CDDP was administered into the abdominal space during and after the surgery, a total amount of 100 to 400 mg/body. There were no cases of collected ascites within one year, except one case that we could not follow. There was a possibility that a short-term quality of life was improved by multidiciplinary therapy containing cytoreduction surgery and intraperiotoneal administration of CDDP.