Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor-secreting cells in a model of middle cerebral artery occlusion in rats

OBJECT: This study was conducted to evaluate the effects of grafting encapsulated basic fibroblast growth factor (bFGF)-secreting cells in rat brains subjected to ischemic injury. METHODS: Two cell lines were used for encapsulated grafting in this experiment, namely, a bFGF-secreting cell line established by genetic manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty-seven Sprague-Dawley rats were used in this experiment. The animals were divided into the following three groups: those receiving grafts of encapsulated bFGF-secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK cells (naive BHK group); and those with no grafts (control group). The authors implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF and naive BHK groups. Six days after grafting, the host and control animals underwent permanent right middle cerebral artery occlusion (MCAO) with an intraluminal suture procedure. The infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride staining and computerized image analysis 24 hours after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling 12 hours after MCAO. The authors found that the infarct volume in the BHK-bFGF group was reduced by approximately 30% compared with that in the naive BHK and control groups. In the ischemic penumbral area, the number of apoptotic cells in the BHK-bFGF group was significantly decreased compared with that in the other groups. CONCLUSIONS: The grafting of encapsulated BHK bFGF-secreting cells protected the brain from ischemic injury. Encapsulation and grafting of genetically engineered cells such as bFGF-secreting cells is thus thought to be a useful method for protection against cerebral ischemia.     

Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen

BACKGROUND: Early growth response factor-1 (Egr-1) plays an important role in regulating multiple factors involved in the progression of vascular lesions. This study examined our hypothesis that Egr-1 plays a critical role in the early stage of chronic cardiac allograft rejection and in the proliferation of the smooth muscle cell response to alloantigen. MATERIALS AND METHODS: Antisense Egr-1 oligodeoxynucleotide (ODN) was ex vivo gene transfected into the donor hearts from DBA/2 mice, followed by heterotopic allografting into B10.D2 recipients. The allografts were harvested on day 30. Egr-1 and its target molecules, such as platelet-derived growth factor (PDGF)-A, basic fibroblastic growth factor (bFGF), vascular cell adhesion molecule (VCAM)-1, transforming growth factor (TGF)-beta and nonmuscle myosin heavy chain B (SMemb), were identified immunohistochemically, and the percentage of the lumen occluded by the intima was calculated. For the cell proliferation assay, sensitized T cells were harvested from B10.D2 recipients as stimulator and then added to the SMCs, which were harvested from DBA/2 mouse aorta. Cellular proliferation was measured and Egr-1 and its target gene expression were examined by real-time RT-PCR. RESULTS: Egr-1 and its target genes were expressed in the thickened intima from untreated recipients. Egr-1 antisense ODN inhibited not only Egr-1 expression but also its target genes and significantly suppressed intimal thickening of coronary arteries. Egr-1 antisense ODN also significantly inhibited cell proliferation and expressions of Egr-1 and Egr-1 target genes in a mixed cell culture model. CONCLUSION: We conclude that Egr-1 plays an important role in the formation of the cardiac allograft vasculopathy responding to alloantigens.     

Changes in the surgical health care system and future aspect of surgery

Since universal coverage of health insurance of Japan was introduced in 1961. Japan's health care system has become one of the few comprehensive systems from the perspective of national welfare. In 2002, as the gross national medical expenditure (GNME) increased to 30 trillion yen, the Japanese Government employed a policy of medical cost containment. In Japan, the ratio of GNME to the gross national product (GNP) is not so high in the world, and it ranks 6th among developed countries (OECD-Health Data, 2002). During the past 38 years from the scientific viewpoint the Joint Committee of Social Insurance established by the Multidisciplinary Group of Surgical Associations has evaluated the rationalization of surgical fee (include doctor's fee). If our system is employed, more fair surgical care may be provided in the future.     

Growth hormone-secreting pituitary adenoma associated with primary moyamoya disease--case report

A 40-year-old female presented with growth hormone (GH)-secreting pituitary adenoma associated with primary moyamoya disease manifesting as amenorrhea, acromegaly, and transient ischemic attack. Magnetic resonance (MR) imaging revealed a tumor mass extending from the sella turcica to the suprasellar cistern, and MR angiography demonstrated stenoses in the bilateral internal carotid arteries with basal moyamoya vessels. Her blood GH and insulin-like growth factor (IGF-1) levels were elevated to 78.94 and 923.0 ng/ml, respectively. The patient underwent removal of the pituitary adenoma because her ischemic symptoms disappeared after oral aspirin medication. Subtotal resection resulted in persistence of the high blood GH and IGF-1 levels. Postoperative MR angiography showed progression of the stenoses in the bilateral internal carotid arteries. Excess systemic GH and IGF-1 may participate in the progression of vascular disease and so could have caused the deterioration of the moyamoya disease.     

Ring-enhanced mass in the brain of a woman with systemic lupus erythematosus and elevated serum CA19-9 level: brain abscess or metastatic tumor?--case report

A 70-year-old woman with systemic lupus erythematosus presented with a brain abscess manifesting as progressive monoparesis of the right lower extremity over 4 days. She had had no episodes of fever, and did not complain of headache or exhibit any signs of meningeal irritability. Computed tomography of the brain showed a round, low-density mass with strong ring enhancement in the left frontal lobe. Laboratory examination found a moderately elevated serum level of CA19-9, a marker of some digestive organ cancers. Together with the absence of febrile episodes, headache, and a rise in leukocyte count, the initial suspicion was metastatic brain tumor rather than brain abscess. However, diffusion-weighted magnetic resonance imaging depicted the mass as a very hyperintense area. The neuroimaging diagnosis was brain abscess. After conservative treatment with intravenous antibiotics for 6 weeks, the brain abscess completely resolved, and the patient was discharged without neurological deficits.     

Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients

 The thiazolidinedione (TZD) class of antidiabetic drugs has been shown to inhibit the formation of bone-resorbing osteoclasts in vitro and to decrease bone resorption markers in vivo. These drugs also inhibit the expression of leptin in adipocytes. Less leptin can be associated with higher bone mass, based on analyses of mice deficient in leptin action. Effects of 1-year treatment with troglitazone, a member of the TZDs, on bone mineral density (BMD) and bone metabolism were examined in 25 Japanese type 2 diabetic patients. Glucose metabolism was improved, whereas body mass index and percent body fat did not change throughout the study. The percent change of BMD was negatively correlated with that of serum leptin, whereas it was not associated with changes of bone metabolic markers, type I collagen N-telopeptide (NTx), bone alkaline phosphatase (ALP), body mass index, or HbA1c. Serum leptin decreased in 68% of subjects (responders) after 1-month treatment and was consistently lower than the basal level throughout the treatment. Percent changes of BMD were significantly higher in the responders than in the nonresponders and in nondiabetic subjects at 6 and 12 months. NTx and bone ALP decreased at 1 month but increased thereafter in either group of patients. Thus, it is suggested that the decrease in serum leptin with no reduction in body fat mass by troglitazone is associated with preventing bone loss in type 2 diabetic patients. Hence, TZDs may have an advantage for diabetic patients who have risk factors for osteoporosis. Received: July 7, 2002 / Accepted: November 19, 2002 Offprint requests to: Y. Takeuchi     

Nucleotide sequences of putative cDNAs for guinea-pig monoamine oxidase

To study the molecular structure of guinea pig monoamine oxidase (MAO) and its phylogenetic relationship with other mammalian MAOs, we determined nucleotide sequences of putative MAO cDNAs isolated from guinea pig tissues. Both the 5- and 3-ends of the cDNAs were amplified using the RACE (rapid amplification of cDNA ends) method. The sequence (1924 bp) of a putative guinea-pig MAO-B cDNA covers a complete coding region that corresponds to 521 amino acids. We also analyzed a partial sequence of a putative guinea-pig MAO-A cDNA, which corresponds to 506 amino acids, but have left the region of 66 bp at the 3-end undetermined. The nucleotide and deduced amino-acid sequences of the putative guinea-pig MAO cDNAs showed the highest homology with that of human MAO cDNAs among the known mammalian MAO sequences. These results suggest that guinea-pig MAOs are structurally similar to human MAOs. Our molecular phylogenetic data support the idea that guinea pigs and rodents diverged before the separation between rodents and other lineage leading to Primates and Artiodactyla.