Biomedical subjects
M Sato
Publications and source records attributed to M Sato.
Postoperative intussusception after incidental appendicectomy.
Postoperative intussusception of the appendiceal stump is a rare complication of appendicectomy. We report an infant who developed an intussusception of the appendiceal stump 2 days following an appendicectomy performed during a right inguinal herniotomy as a day case. The intussusception was diagnosed on ultrasonography and was to be treated laparoscopically, but spontaneous reduction occurred during induction of general anesthesia.
Effect of reduction of portal vein pressure on the outcome of extreme small size liver transplants.
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New strategy for liver transplantation from non-heart-beating donors.
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Serum lipid profiles in Japanese women and men during consumption of walnuts.
OBJECTIVE: To determine the serum cholesterol, apolipoproteins and LDL oxidizability in young Japanese women and men during walnut consumption and to evaluate its active principle. DESIGN: Experimental study with a randomized design. SUBJECTS: Twenty healthy women and 20 healthy men. INTERVENTIONS: Subjects were randomly assigned to consume each of two mixed natural diets for 4 weeks in a cross-over design. Reference and walnut diets were designed and the walnut diet had 12.5% of the energy derived from walnuts (44-58 g/day). RESULTS: The total cholesterol and serum apolipoprotein B concentrations, and the ratio of LDL cholesterol to HDL cholesterol was significantly lowered in women and men when fed on the walnut diet, than when on the reference diet (P<or=0.05). The LDL cholesterol concentration was significantly lowered in women on the walnut diet (0.22 mmol/l, P=0.0008), whereas this decrease was not significant in men (0.18 mmol/l, P=0.078). The most prominent change in the fatty acid composition of the cholesteryl esters from serum after the walnut diet was an elevation of alpha-linolenic acid in women (76%, P<0.001) and men (107%, P<0.001). This elevation was negatively correlated to the change in LDL cholesterol in women (r=0.496, P=0.019) and men (r=0.326, P=0.138). The LDL oxidizability in women was not influenced by the diets (P=0.19). CONCLUSIONS: alpha-Linolenic acid in the walnut diet appears to be responsible for the lowering of LDL cholesterol in women. SPONSORSHIP: Kyushu University (Fukuoka, Japan) and the California Walnut Commission (California, USA).
Association of HLA-A*3303-B*4403-DRB1*1302 haplotype, but not of TNFA promoter and NKp30 polymorphism, with postherpetic neuralgia (PHN) in the Japanese population.
Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P = 0.0007 for A*3303, P = 0.001 for B*4403 and P = 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P = 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.
Replication and packaging of helper-dependent adenoviral vectors.
A helper-dependent adenovirus vector (HD AdV) that lacks all the coding sequences of viral proteins from the vector backbone was developed to overcome the problem of host cellular immune responses against E1-deleted AdV. One of the limitations of the current HD AdV system is its relatively inefficient propagation compared with that of E1-deleted AdV, which deters application of the HD AdV, especially in large animal models. We hypothesized that the low titers might be due in part to defects in replication and packaging of the vector DNA. We propagated two HD AdVs with similar marker gene cassettes and stuffer sequences, using two different helper viruses, and determined the replication and packaging efficiencies of viral DNA. Our analysis indicated a difference in replication and packaging efficiencies between the two vectors, which resulted in different propagation efficiencies. Furthermore, dl309, which is similar to the wild-type virus, demonstrated superior helper function over that of the loxP-containing helper virus, AdLC8cluc. These findings may have significant implications for the design of improved production systems of HD AdVs.
Possible mechanism of gene transfer into early to mid-gestational mouse fetuses by tail vein injection.
Our aim is to develop a simple gene transfer method into egg cylinder and mid-gestational murine embryos. We examined whether plasmid/lipid complexes injected into the tail veins of pregnant transgenic mice can be transferred to fetuses at E 4.5-13.5. When pregnant CETZ-17 mice carrying a transgene consisting of a ubiquitous promoter, floxed EGFP/CAT and the LacZ gene, were injected with a Cre expression vector DNA/lipid complex, Cre-mediated excision of the transgenes, as evaluated by X-gal staining, occurred in 10-50% of fetuses treated at E 11.5-13.5. Although younger embryos remained unstained, PCR analysis revealed low levels of the Cre vector DNA and recombined transgene. To examine the fate of a solution given intravenously, we injected trypan blue or fluorescence-labeled plasmid DNA/lipid complexes into females at E 5.5-11.5 and E 6.5, respectively. Both collected in the visceral endoderm (VE) lineage, but were undetectable in the embryo proper. These findings suggest that substances in maternal blood are delivered to post-implantation embryos via cells of the VE lineage and placenta, but that most are trapped in the VE. If significantly improved, gene transfer to fetuses by injection into the maternal circulation may become a promising tool in fetal gene therapy and embryological studies.
Length of the antral segment in pylorus-preserving gastrectomy.
BACKGROUND: Pylorus-preserving gastrectomy (PPG) has the advantages of preventing dumping syndrome and duodenogastric reflux. However, time was required to reduce symptoms of gastric fullness or to improve food intake after surgery. The aim of this study was to investigate whether the length of the retained antral segment influenced the postoperative symptoms in patients who underwent PPG. METHODS: Thirty patients with early gastric cancer who underwent PPG were divided into two groups according to the length of the retained antrum. In group 1 (n = 20) the transection was 1.5 cm and in group 2 (n = 10) it was 2.5 cm proximal to the oral edge of the pyloric ring. The subjects were interviewed and examined periodically to assess symptoms, food intake, body-weight and serum nutritional variables. Endoscopy and a radioisotope gastric emptying test were performed 1 year after the operation. RESULTS: In group 1 gastric fullness after meals was common, resulting in poor food intake and poor recovery of body-weight. A high incidence of food residue in the remnant stomach was found in group 1. With regard to gastric emptying, seven of 20 patients in group 1 and one of ten in group 2 had a delayed emptying curve 1 year after operation. CONCLUSION: Group 2 was superior to group 1 in terms of postprandial symptoms, food intake, recovery of body-weight and gastric emptying. The length of the retained antrum may play an important role in the motility of the pyloric ring following PPG.
Two novel strains of Wolbachia coexisting in both species of mulberry leafhoppers.
Wolbachia is an intracellular symbiont that causes reproductive disorders in many insects. Its presence in the leafhoppers Hishimonoides sellatiformis and Hishimonus sellatus, vectors of mulberry dwarf-Phytoplasma, was confirmed by the PCR analysis of 16S rDNA, ftsZ and wsp. Sequencing of cloned PCR products revealed that two Wolbachia strains coexist in both leafhoppers. The phylogenetic analysis of wsp revealed that these strains belong in novel positions in the B-group of Wolbachia. These strains were detected by PCR and/or PCR-RFLP in all of the tested non-genital organs including salivary glands, as well as in the tested genital organs of Hishimonoides sellatiformis. In addition, Wolbachia-like organisms were observed by electron microscopy in all PCR-positive organs. We discuss the possible horizontal transmission of Wolbachia via mulberry trees.
Antibacterial activity of isoflavonoids isolated from Erythrina variegata against methicillin-resistant Staphylococcus aureus.
AIMS: To screen 16 isoflavonoids isolated from Erythrina variegata (Leguminosae) for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: The roots of E. variegata were macerated with acetone. The chloroform-soluble fraction of the residue was subjected to repeated silica gel column chromatography followed by elution with various solvents. Structures of the isolated compounds were determined by extensive spectroscopic studies. Each compound was dissolved in dimethyl sulphoxide and added to agar plates (final concentration 1.56-100 microg ml(-1) and suspensions of MRSA spotted onto the agar plates to determine the minimum inhibitory concentration (MIC). Repeated silica gel chromatography yielded 16 compounds and spectroscopic studies revealed that all were isoflavonoids. Whilst 14 compounds showed antibacterial activity in this concentration range, the MIC values varied significantly among them. Of the active compounds, 3,9-dihydroxy-2,10-di(gamma,gamma-dimethylallyl)-6a,11a-dehydropterocarpan (erycristagallin) and 9-hydroxy-3-methoxy-2-gamma,gamma-dimethylallylpterocarpan (orientanol B) exhibited the highest activity with MIC values of 3.13-6.25 microg ml(-1). CONCLUSIONS: Erycristagallin and orientanol B showed the highest anti-MRSA activity (3.13-6.25 microg ml(-1). SIGNIFICANCE AND IMPACT OF THE STUDY: Erycristagallin and orientanol B could be leading compounds for phytotherapeutic agents against MRSA infections.
Histopathological grading does not affect survival after R0 surgery for gastric cancer.
AIM: It is unclear whether Histopathological Grading (UICC, TNM Classification) affects survival after resection for gastric cancer. METHODS: To investigate the prognostic significance of Histopathological Grading after gastrectomy, 1455 patients who underwent gastric resection for gastric adenocarcinoma were reviewed. RESULTS: The R0 (UICC, R Classification) resection rate was inversely correlated with the grade (86.5% for Grade 1, 79.7% for Grade 2 and 69.2% for Grade 3) and the R1 and R2 resection rates increased with the grade. The Histopathological Grading did not influence survival in the 1119 patients who underwent R0 resection (71.0% for Grade 1, 65.7% for Grade 2 and 66.7% for Grade 3). When multivariate analysis was performed for the 1119 cases undergoing R0 resection, the Histopathological Grading was not a determinant prognostic factor. CONCLUSION: We conclude that the UICC Histopathological Grading affects R0 resection rates, but does not affect survival independently.
Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase.
Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient diet for 4 weeks, we examined whether Zn deficiency affects systemic blood pressure (BP) levels in a genetically hypertensive state through a fall in the activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet had a progressive increase in systolic BP during the dietary conditioning. Consequently, SHR fed a Zn-deficient diet exhibited significantly increased levels of systolic BP by 2 weeks after the start of dietary treatment when compared with SHR fed a standard diet. Similarly, levels of basal mean arterial pressure (MAP) observed at the end of dietary treatment were SHR fed a Zn-deficient diet > SHR fed a standard diet. Administration of the nitric oxide synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in the two groups of rats, demonstrating the involvement of the vasodilator, nitric oxide (NO), in the regulation of systemic BP in a genetically hypertensive state. The expression of endothelial (e) NOS mRNA and protein in the thoracic aorta paralleled basal MAP levels in the two groups of rats, suggesting the counter-regulation of eNOS against the developed hypertensive state in SHR fed a Zn-deficient diet. On the other hand, administration of the superoxide scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in an increase in systemic BP in a genetically hypertensive state. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO, based on the formation of peroxynitrite coming from the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment completely restored MAP levels in SHR fed a Zn-deficient diet to levels comparable to those observed in SHR fed a standard diet, indicating that a further increase in systemic BP levels seen in SHR fed a Zn-deficient vs. a standard diet is presumably brought by a reduction in the action of the vasodilator, NO, resulting from an increase in the action of superoxide. The activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta was significantly decreased in SHR fed a Zn-deficient diet relative to SHR fed a standard diet. It appears that a decrease in the activity of Cu/Zn-SOD observed in the thoracic aorta of SHR fed a Zn-deficient diet at least in part plays a role in an increase in the action of superoxide in this model. Thus, Zn deficiency may be a factor to develop genetic hypertension presumably through the oxidative stress caused by superoxide.
Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis.
OBJECTIVE: To test the hypothesis that dynamic load at baseline can predict radiographic disease progression in patients with medial compartment knee osteoarthritis (OA). METHODS: During 1991-93 baseline data were collected by assessment of pain, radiography, and gait analysis in 106 patients referred to hospital with medial compartment knee OA. At the six year follow up, 74 patients were again examined to assess radiographic changes. Radiographic disease progression was defined as more than one grade narrowing of minimum joint space of the medial compartment. RESULTS: In the 32 patients showing disease progression, pain was more severe and adduction moment was higher at baseline than in those without disease progression (n=42). Joint space narrowing of the medial compartment during the six year period correlated significantly with the adduction moment at entry. Adduction moment correlated significantly with mechanical axis (varus alignment) and negatively with joint space width and pain score. Logistic regression analysis showed that the risk of progression of knee OA increased 6.46 times with a 1% increase in adduction moment. CONCLUSIONS: The results suggest that the baseline adduction moment of the knee, which reflects the dynamic load on the medial compartment, can predict radiographic OA progression at the six year follow up in patients with medial compartment knee OA.
Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH.
Skeletal effects are described for near-lifetime treatment of young, female rats with recombinant human PTH (1-34) (PTH). Rats (5-8 wk of age) were administered 0, 5, 30, or 75 microg/kg x d sc PTH for up to 2 yr, as part of an oncogenicity evaluation, which is required by regulatory agencies for potential chronic therapies. Proliferative lesions were observed in the skeleton as described in Vahle et al. (1 ); in this paper, we describe the quantitative bone data for this study. In the appendicular skeleton, PTH stimulated trabecular and endocortical mineral apposition to the near exclusion of marrow spaces at 5 microg/kg, with some periosteal apposition at 30 microg/kg, followed by considerable periosteal apposition and altered geometry at 75 microg/kg. Increased bone mass was observed for all treatment groups that substantially exceeded normal levels attained by vehicle controls and exceeded skeletal efficacy reported previously for similar doses in shorter-term studies. Dose-dependent increases in osteocalcin levels and a linear increase in wet weight of femora were observed for the entire treatment duration, suggesting nearly continuous PTH stimulation of osteoblasts and skeletal growth throughout life. Histology showed many osteocytes and prominent osteoblasts, but a conspicuous absence of osteoclasts. Morphometry showed a lack of distinction between trabecular and cortical bone. Biomechanics of vehicle controls showed that optimal mechanical integrity for the normal skeleton is observed at about 11 months of age. PTH greatly strengthened and stiffened vertebra and femora; however, the midshaft showed reduced toughness and increased brittleness with treatment, which was not the case for vertebra. Related studies of 6 and 9 months duration showed that the optimal duration for PTH skeletal efficacy was about 6 months in rats, based on toughness, strength, ultimate displacement, and architecture, especially for cortical bone. Therefore, treatment duration is an under appreciated aspect of PTH pharmacology; and PTH skeletal effects are a complex function of dose and duration. Comparative analyses showed that short-term treatment (6 months or less) is more advantageous than near-lifetime treatment, because PTH stimulates skeletal growth throughout life, resulting in abnormal architecture and untoward biomechanical properties in rats.
The multiple endocrine neoplasia type 1 gene product, menin, inhibits the human prolactin promoter activity.
Menin is a protein encoded by the gene mutated in multiple endocrine neoplasia type 1 (MEN1) characterized by multiple endocrine tumors of the parathyroid glands, pancreatic islets and the anterior pituitary, especially prolactinoma. In this study, we examined the effects of menin on human prolactin (hPRL) expression. In rat pituitary GH3 cells stably expressing menin, both PRL gene expression/secretion and thymidine incorporation into DNA were inhibited as compared with mock-transfected cells. The transcriptional activity of PRL promoter in GH3 cells co-transfected with menin was significantly decreased. A deletion mutation (569 delC), which we identified in a Japanese MEN1 family, was introduced into menin. When GH3 cells were transfected with a mutant menin expression vector, inhibition of hPRL promoter activity was partially reversed. These observations suggest that menin inhibits hPRL promoter activity and cell proliferation, raising the possibility that menin might play an important role in the tumorigenesis of prolactinoma.
[Metachronous lung cancer: indication and outcome].
Although lobectomy is the standard surgical treatment for primary lung cancer, it is unclear whether lobectomy will be benefit for patients with metachronous lung cancer. The purpose of this study is to evaluate the difference of benefit between lobectomy and limited resection at second lung resection. Forty-eight patients, who had already undergone lobectomy due to primary lung cancer, undergoing second lobectomy (n = 30) or limited resection (n = 18) for metachronous lung cancer were investigated. The over-all 5-year survival rate of second operation was 51.9%. Although there was no significant difference of 5-year survival rates between lobectomy and limited resection, 50.4% and 49.4%, respectively, lobectomy for T1N0 subset prolonged the survival compared to limited resection, 5-year survival rates, 69.6% and 31.7%, respectively. However, lobectomy resulted in more postoperative complications and less preservation of lung function. Lobectomy should be considered the surgical procedure of choice for patients with metachronous T1N0 lung cancer when lung function is preserved.
[Clinical study of double primary cancer involving the lung in resected cases].
Among all cases of surgically resected lung cancer, there were 56 cases (16.1%) of double primary cancer. The common sites of the other primary cancer was the stomach (19 cases), followed by large intestine (9 cases), urinary bladder (7 cases) and pharinx-larynx (7 cases). One patient had triple cancers. In all cases of double primary cancer, 46 cases were metachronous, 10 of which were cases of initial lung cancer. The 5-year survival rate of double primary cancer was 39.7%. Good result was obtained in metachronous cases with initial lung cancer. Most of prognosis of double primary cancer was determined by that of lung cancer. In more than half of initial cancer, the second primary cancer was detected by symptoms. So, special attention to the possibility of double primary cancer in patients with resected lung cancer is necessary for improvement of prognosis.