Can a bone marrow cell contribute to organ regeneration? In vivo analysis using transgenic rats with reporter genes

Although implantation of multipotent bone marrow-derived stem cells represents an attractive new cell therapy to repair damaged tissues, recent reports have raised serious concerns over the feasibility of using stem cells deriving from the bone marrow to promote cell transdifferentiation. We established transgenic (Tg) rats with reporter genes as specific molecular tags to examine the effect of bone marrow cells (BMCs) on transdifferentiation into tissues/organs. To monitor transdifferentiation events of locally transplanted BMCs into hepatocytes or capillary endothelial cells, a liver injury model and an ischemic hind-limb model were developed in rats. To test the ability of circulating bone marrow-derived cells to give rise to myocytes after skeletal muscle injury, we used a bone marrow cell transplantation model from Tg rats, which showed ubiquitous expression of beta-galactosidase (lacZ), into lethally irradiated non-Tg rats. Our results show that there was little transdifferentiation of BMCs into the targeted cells in these tissue injury models. However, in the ischemic hind-limb model, laser Doppler imaging and histologic analysis showed that both implantation of BMCs and treatment with microspheres incorporating basic fibroblast-like growth factor (bFGF), which enables the release of bFGF at the site of action over a period of time, effectively induced angiogenesis. In conclusion, rat BMCs with specific marker genes could be a useful tool for detecting transdifferentiation events in vivo.     

Controlled delivery of bFGF to recipient bed enhances the vascularization and viability of an ischemic skin flap

Therapeutic angiogenesis is a promising approach to treat ischemic skin flaps. We delivered basic fibroblast growth factor (bFGF) to the recipient bed of a rat dorsal skin flap by a drug delivery system with acidic gelatin hydrogel microspheres (AGHMs), and assessed augmentation of neovascularization and flap viability. An axial skin flap was elevated on the back of male Sprague–Dawley rats, and bFGF solution or bFGF-impregnated AGHMs were injected into the recipient bed. The dose of bFGF in the bFGF solution was set to 15 (Sol-15 group), 50 (Sol-50 group), or 150 μg (Sol-150 group). Correspondingly, 2 mg AGHMs were impregnated with 15 (AGHM-15 group), 50 (AGHM-50 group), or 150 μg (AGHM-150 group) bFGF. Other groups of animals received phosphate-buffered saline (Sol-Cont group) or phosphate-buffered saline-impregnated AGHMs (AGHM-Cont group) as controls. Seven days later, analyses of the area of necrosis, microangiographic findings, and histological findings in the flap were carried out. The area of necrosis in the AGHM-150 group was significantly smaller than that in the other groups. Microangiographic and histological analyses showed that neovascularization of the ischemic skin flap significantly increased in the AGHM-150 group as compared with the Sol-150 group and the AGHM-Cont group. These findings suggest that continuous delivery of bFGF to the recipient bed by bFGF-impregnated AGHMs enhances the viability of an ischemic skin flap.     

Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer

Objective: This study evaluates the risks of postoperative complications in 124 patients with non-small-cell lung cancer who received pre-operative induction chemoradiotherapy and surgery. Methods: All patients with non-small-cell lung cancer who underwent surgery after induction therapy between January 1990 and December 2003 were reviewed. We adopted univariate and multiple logistic regression models to identify predictors that increased the incidence of postoperative complications. Results: Of 124 patients, 59 received carboplatin and docetaxel, 53 received cisplatin and etoposide, and 12 received other platinum-based combinations. Pre-operative thoracic radiotherapy was performed concurrently with chemotherapy. The median dose to the primary tumor was 40 Gy, and 29 patients (23.4%) received radiotherapy of more than 45 Gy before surgery. There were 25 pneumonectomies (20.2%). The overall postoperative mortality was 9 of 124 patients (7.3%), and complications developed in 54 patients (43.5%). Multivariate analysis demonstrated that only thoracic radiotherapy of more than 45 Gy predicted postoperative complications (P = 0.021; odds ratio, 3.620; 95% confidence interval, 1.214–10.797). Conclusions: Thoracic radiotherapy of more than 45 Gy, in combination with chemotherapy, was a significant risk factor for postoperative complications.     

S4a + S5 With caudate lobe (SI) resection using the Taj Mahal liver parenchymal resection for carcinoma of the biliary tract

Recently we have been performing S4a + S5 with total resection of the caudate lobe (SI) by using a dome-like dissection along the root of the middle hepatic vein at the pinnacle, which we refer to as the Taj Mahal liver parenchymal resection, for carcinoma of the biliary tract. This procedure offers the following advantages: (1) It allows total resection of the caudate lobe, including the paracaval portion (S9), and (2) because the cut surface of the liver is large, it allows intrahepatic jejunostomy to be performed more easily with a good field of view. The indications for this procedure include hilar bile duct carcinoma, gallbladder carcinoma, and choledochal cyst (type IVA). Because of the high rate of hilar liver parenchyma and caudate lobe invasion associated with hilar bile duct carcinoma, the liver must be resected. The Taj Mahal procedure is indicated in cases where extended liver resection is impossible. The dissection limits of this procedure are, on the left side, the B2 + 3 bifurcation at the right margin of the umbilical portion of the portal vein and, on the right side, the B8 of the anterior branch and the B6+7 bifurcation of the right posterior branch. This procedure could also be described as a reduced form of extended right hepatectomy and extended left hepatectomy. For gallbladder carcinoma, this procedure is indicated to ensure an adequate surgical margin and eradicate transvenous liver metastasis, particularly in cases of pT2 lesions. Hilar and caudate lobe invasion also occurs in liver bed-type gallbladder carcinoma, and bile duct resection and caudate lobe resection are required for the surgery to be curative. We performed this procedure in four cases of hilar bile duct carcinoma, five cases of gallbladder carcinoma, and one case each of choledochal cyst (type IVA) with carcinoma of the bile duct and gallbladder adenomyomatosis. Curative resection was possible in all except the patient with adenomyomatosis, and all of the patients are alive and recurrence free 10 to 37 months postoperatively. This procedure, in addition to preserving liver function, provides a wide field of view and facilitates reconstruction of multiple intrahepatic bile ducts. Thus it can be said to be a curative operation not only in patients considered high risk but also in those whose hilar bile duct carcinoma is limited to the bifurcation area (Bismuth type IIIa and IIIb) and in gallbladder carcinoma up to pT2 with slight extension on the hepatic side. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998 (poster presentation).     

Twelve microsatellite markers in the invasive tunicate, Didemnum vexillum, isolated from low genome coverage 454 pyrosequencing reads

454 pyrosequencing reads were used to isolate microsatellites in the global marine ascidian invader, Didemnum vexillum. This method allows simple and cost-effective isolation of new markers from organisms without existing genomic information and, to our knowledge, has not been used before to develop a polymorphic microsatellite marker set. Loci had between two and eleven alleles and overall mean observed and expected heterozygosities of 0.57 and 0.62, respectively. These markers will greatly facilitate research required to develop control and mitigation strategies for D. vexillum.     

Local administration trials of interleukin-2 for head and neck cancer.

Recombinant interleukin-2 (rIL-2) has been administered locally in 20 patients with head and neck cancer. Two complete responses in lower lip cancer and 1 partial response in lingual cancer have been obtained. Immunohistological study reveals that tumor infiltrating lymphocytes (TILs), including activated T lymphocytes and natural killer cells, are increased after rIL-2 use. Intraarterial chemotherapy, performed subsequently to the local use of rIL-2 results in a dramatic decrease in tumor size within a short time, and a high frequency of CR cases is observed. Local use of rIL-2 is beneficial for treatment of head and neck cancers, and induction immunochemotherapy combining locally used rIL-2 and arterially infused anticancer drugs plays an important role in a multidisciplinary treatment for these cancers.     

Correction note on "The demand for health with uncertainty and insurance"

This paper proves the non-existence of an optimal solution under the Liljas [Liljas, B. (1998). The demand for health with uncertainty and insurance. J. Health Econ., 17, 153-170] type of insurance. The reason for the non-existence is that the insurance induces the individual to increase his time input, relative to medical expenditure in the household production of health investment. Hence, it distorts the balance of inputs in the production of health investment. Moreover, it also distorts the household production for consumption goods through time constraints. Therefore, this paper proposes an alternative insurance that covers the time loss due to illness and has an optimal solution.     

Three-dimensional reconstruction of biliary tract using spiral computed tomography for laparoscopic cholecystectomy

To increase the safety of laparoscopic cholecystectomy, we have analyzed the biliary tract in a three-dimensional fashion. The union of the biliary ducts was studied in 50 patients using spiral computed tomography (CT) after intravenous infusion cholangiography. Depending on the union and course of the cystic duct to the common bile duct, cystic duct anatomy was classified into six categories: ipsilateral gallbladder side (type I) and contralateral side with anterior course (type II); contralateral side with posterior course (type III); intrahepatic side (type IV); intrapancreatic side (type V); and unclassified (type VI). The length of the cystic duct was also determined. The cystic duct was identified in 42 cases (84%); 30 cases (60%) were type I, 9 cases (18%) type III, and a single case (2%) of types II, IV and V, respectively. The length of the cystic duct was < or =2 cm in 30 cases that had a shorter operating time compared to 12 cases with a cystic duct <2 cm (p <0.01). In conclusion, three-dimensional reconstruction of the cystic duct anatomy using spiral CT provides simple classification of bile duct anatomy, and this preoperative information may increase the safety of laparoscopic cholecystectomy.