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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 55 records · Page 3Linked to original sources

Single nucleotide polymorphism of the MxA gene promoter influences the response to interferon monotherapy in patients with hepatitis C viral infection.

The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2'-5' oligoadenylate synthetase, dsRNA-activated protein kinase and MxA protein. Among these, MxA protein is assumed to be the most specific surrogate parameter for IFN action. This study was performed to elucidate whether a single nucleotide polymorphism (SNP) (G/T at nt-88) in the promoter region of the MxA gene influences the response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection. Polymorphisms of the MxA gene in 235 HCV patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequency of SNP was compared between sustained-responders (n = 78) and nonresponders (n = 157), as determined by biochemical and virological responses to IFN. Multivariate analysis showed that among all patients, HCV genotype, HCV RNA level and the SNP of the MxA gene were independent and significant determinants of the outcome of IFN therapy [odds ratio 3.8 (95% confidence interval 2.0-7.0), P < 0.0001; 0.27 (0.15-0.50), P < 0.0001; 1.8 (1.0-3.4), P = 0.0464, respectively]. Furthermore, among patients with a low viral load (< or =2.0 Meq/mL), MxA-T-positive patients were more likely to show a sustained response compared with MxA-T-negative patients [2.87 (1.3-6.3); 62%vs 36%; P = 0.0075]. Our findings suggested that the SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load.

Adult↗

Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects.

AIMS: Adipocytokines, products from adipose tissue, have biological activities on the vascular system, and may affect diabetic angiopathy. In this study, we assessed the relationship between adiposity and plasma adipocytokine levels, and investigated the clinical significance of adiposity and plasma adipocytokine levels on diabetic micro- and macroangiopathy in Type 2 diabetic subjects. METHODS: We studied 231 Japanese Type 2 diabetic subjects (135 men and 96 women, aged 60.4 +/- 12.3 years, body mass index 24.8 +/- 5.2 kg/m2). We measured adipocytokine [adiponectin, leptin, resistin, and tumour necrosis factor (TNF)-alpha] levels, lipid profiles and urine albumin excretion. We also performed optic fundus examination and measured carotid intramedia thickness (IMT) using B-mode ultrasonography, and the localization of fat with abdominal computed tomography. A group of 93 subjects with microalbuminuria or overt proteinuria was compared with the other 148 to assess the effect on nephropathy. A group of 191 eyes with simple retinopathy or more advanced changes was compared with 263 eyes without retinal changes to assess the effect on retinopathy. RESULTS: Plasma adiponectin level was negatively correlated with both visceral (r = -0.37, P < 0.01) and subcutaneous (r = -0.25, P < 0.01) fat areas. Resistin concentration was positively related with visceral fat area (r = 0.15, P < 0.05). Adiponectin concentration was positively correlated with age (r = 0.26, P < 0.01). TNF-alpha was correlated with IMT (r = 0.16, P < 0.05) after correction for age. Logistic regression analysis indicates a 4085 times greater chance of having retinopathy with a one unit increase in TNF-alpha (pmol/l) and a 30.64 times greater chance of having nephropathy with one unit increase in leptin (nmol/l). CONCLUSIONS: The present observations suggest that visceral and subcutaneous fat has an impact on microangiopathy as well as macroangiopathy, possibly through different adipocytokines.

Adipocytes↗

The effects of additional carbohydrate in the coiled-coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aalpha Arg141-->Ser with extra glycosylation).

Fibrinogen Lima is an abnormal fibrinogen with an Aalpha Arg141-->Ser substitution resulting in an extra N-glycosylation at Aalpha Asn139, which seems to be responsible for the impairment of fibrin polymerization. We have studied the polymerization and properties of clots made from both plasma and purified fibrinogen of both the homozygous and heterozygous forms. The clot permeation studies with both plasma and purified protein revealed a normal flux through the network for the heterozygous form but very decreased permeation in the homozygous form. Consistent with turbidity results, the clot network of the homozygous form, seen by scanning electron microscopy, was tight and composed of thin fibers, with many branch points, while the appearance of clots from the heterozygous form was similar to that of control clots, but in both cases the fibers were more curved than those of control clots. The rheological properties of clots from the homozygous form were also altered, with rigidity being increased in plasma clots, but decreased in the purified system, a consequence of the balance between numbers of branch points and fiber curvature. From these results it seems that the extra carbohydrate moiety, located in the alpha coiled-coil region close to the betaC domains, impairs the protofibril lateral association process, giving rise to thinner, more curved fibers, with the structural anomalies being most pronounced in the clots from the homozygous plasma. These studies support a model for fibrin polymerization in which the betaC-betaC interactions are involved in lateral aggregation.

Blood Coagulation↗

Magnetic resonance spectroscopic determination of a neuronal and axonal marker in white matter predicts reversibility of deficits in secondary normal pressure hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. OBJECTIVE: To investigate whether 1H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting. METHODS: Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. RESULTS: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. CONCLUSIONS: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage.

Adult↗

Serum amyloid A, C-reactive protein and remnant-like lipoprotein particle cholesterol in type 2 diabetic patients with coronary heart disease.

BACKGROUND: Serum amyloid A (SAA) and C-reactive protein (CRP) have been suggested to be involved in the process of coronary heart disease (CHD) and to be potential markers and/or predictors of CHD. Remnant-like lipoprotein particles (RLPs), which are regarded as atherogenic remnant lipoprotein, are reported to be increased in type 2 diabetic patients. We assessed the association of CHD with SAA, CRP and RLP-cholesterol in type 2 diabetic patients. METHODS: One hundred and twenty-six diabetic patients without CHD and 41 patients with CHD were recruited from our hospital. Plasma SAA was measured by the latex agglutination nephelometric immunoassay. Plasma high-sensitivity CRP was measured by a latex immunoturbidity method. Plasma RLP-cholesterol was measured by an immunoabsorption enzyme method. RESULTS: The mean standard deviation values of RLP-cholesterol in patients with and without CHD were 0.22 (0.26) mmol/L and 0.15 (0.10) mmol/L, respectively (P <0.05). Median (interquartile ranges) for SAA in patients with and without CHD were 7.4 (4.2-11.2) mg/L and 3.9 (2.2-5.9) mg/L, respectively (P <0.001). Median (interquartile ranges) for CRP in patients with and without CHD was 1.14 (0.45-2.08) mg/L and 0.43 (0.19-1.25) mg/L, respectively (P <0.001). For all patients, the Spearman rank correlation statistics for RLP-cholesterol compared with SAA and with CRP were 0.213 (P <0.05) and 0.301 (P <0.01), respectively. CONCLUSION: These data suggest that SAA, CRP and RLP-cholesterol are increased in type 2 diabetic patients with CHD, and that the inflammatory proteins correlate with remnant lipoprotein.

Aged↗

Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study.

Several epidemiological studies suggested an inverse relation between serum cholesterol level and cancer mortality. We analyzed the relation between gastrointestinal cancers and serum cholesterol levels. A total of 631 patients were recruited as cancer-bearing cases, comprising 181 esophageal cancers, 251 gastric cancers and 199 colorectal cancers. A case-control analysis was conducted on the serum TC, HDL-C, LDL-C and TG levels. TC and LDL-C were significantly lower in cancer-bearers by approximately 15 mg/dl. Furthermore, analyses by cancer site also showed significantly lower TC and LDL-C levels in cancer-bearers than in controls for all three sites. In this analysis, early stage cancer-bearers showed a significant decrease in TC levels by approximately 11 mg/dl compared with controls, and also a similar decrease in LDL-C levels. These results suggest that low TC levels are not related to cancer stage. Furthermore, findings of no significant differences in HDL-C and TG between cancer-bearing cases and controls in addition to a specific decrease in LDL-C in cancer-bearers suggest that hypocholesterolemia observed in these cases stems from low LDL-C. However, cancer-bearers and controls showed a similar distribution of TC and LDL-C levels. We should be aware that latent cancer bearers may be present among subjects with hypocholesterolemia.

Case-Control Studies↗

Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study.

AIMS/HYPOTHESIS: Both insulin resistance and beta-cell dysfunction play a role in the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM) through impaired glucose tolerance (IGT). The aim of the study was to define the level of glycaemia at which beta-cell dysfunction becomes evident in the context of existing insulin resistance. METHODS: Insulin response (OGTT) and insulin sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects the insulin secretion/insulin resistance index (DeltaI/DeltaG/IR) was calculated as the ratio of the increment in plasma insulin to the increment in plasma glucose during the OGTT divided by insulin resistance, as measured during the clamp. RESULTS: In lean NGTs with a 2-h plasma glucose concentration (2-h PG) between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive decline in DeltaI/DeltaG/IR compared with NGTs with a 2-h PG less than 5.6 mmol/l. There was a further decline in DeltaI/DeltaG/IR in IGTs with a 2-h PG between 7.8 and 9.3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed coincident patterns of relation of 2-h PG to DeltaI/DeltaG/IR. CONCLUSION/INTERPRETATION: When the plasma insulin response to oral glucose is related to the glycaemic stimulus and severity of insulin resistance, there is a progressive decline in beta-cell function that begins in "normal" glucose tolerant individuals.

Adult↗

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance.

AIMS/HYPOTHESIS: Impaired glucose tolerance (IGT) is an insulin-resistant state and a risk factor for Type 2 diabetes. The relative roles of insulin resistance and insulin deficiency in IGT have been disputed. METHODS: In 40 IGT subjects and 63 sex-, age-, and weight-matched controls with normal glucose tolerance (NGT), we measured (i) indices of insulin sensitivity of fasting glucose production (by tracer glucose) and glucose disposal (M value on a 240 pmol x min(-1) x m(-2) insulin clamp) and (ii) indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) derived from model analysis (Am J Physiol 283:E1159-E1166, 2002) of the insulin secretory response (by C-peptide deconvolution) to oral glucose. RESULTS: In comparison with NGT, IGT were modestly insulin resistant (M=29+/-2 vs 35+/-2 micromol x min(-1) x kg(FFM)(-1), p=0.01); insulin sensitivity of glucose production also was reduced, in approximate proportion to M. Despite higher baseline insulin secretion rates, IGT was characterized by a 50% reduction in glucose sensitivity [53 (36) vs 102 (123) pmol x min(-1) x m(-2) x mM(-1), median (interquartile range), p=0.001] and impaired potentiation [1.6 (0.8) vs 2.0 (1.5) units, p<0.04] of insulin release, whereas rate sensitivity [1.15 (1.15) vs 1.38 (1.28) nmol x m(-2) x mM(-1)] was not significantly reduced. Glucose sensitivity made the single largest contribution (approximately 50%) to the observed variability of glucose tolerance. CONCLUSION/INTERPRETATION: In IGT the defect in glucose sensitivity of insulin release quantitatively predominates over insulin resistance in the genesis of the reduced tolerance to oral glucose.

Adult↗

Development of a new membrane-type heated humidifier for laparoscopic surgery.

BACKGROUND: Recently, several animal studies showed that the core body temperature falls during pneumoperitoneum, and this hypothermia could be prevented by using heated and humidified gas insufflation. However, there are no satisfactory heated humidifiers to meet this purpose. Therefore, we developed a new membrane-type heated humidifier. MATERIALS AND METHODS: The newly developed heated humidifier employs an ion-exchange membrane (Nafion: Du Pont Co. Ltd) tube that passes water selectively in molecular form and a gas compartment is completely separated from distilled water to prevent infection. This humidifier consists of a Nafion tube assembly and a case that includes the heater. A perforated protecting tube is located outside the Nafion tube to prevent direct contact with the Nafion tube when it is assembled. The Nafion tube assembly is inserted in the case, and dry gas flows inside of the Nafion tube. The space between the case and the Nafion tube assembly is filled with distilled water. A heater raises the temperature of the distilled water, and heat and water vapor are transferred to cold and dry gas through the Nafion membrane. Four different types of insufflators were involved in this performance comparison study: a Nafion-based heated and humidified insufflator, a conventional heated insufflator, a conventional heated and humidified insufflator, and a conventional cold and dry insufflator. Temperature and relative humidity were measured once each minute for 15 min, which was repeated four times. Each insufflator was operated at two rates of flow: 5 L/min and 10 L/min. RESULTS: Temperature and humidity of the conventional cold and dry insufflator, the Nafion membrane-type heated and humidified insufflator, the conventional heated insufflator, and the conventional heated and humidified insufflator measured at the distal end of circuit reached 22.0 +/- 0.2 degrees C and 0%, 36.7 +/- 1.1 degrees C and 100%, 29.0 +/- 0.4 degrees C and 0%, and 31.3 +/- 0.4 degrees C and 70.5 +/- 5.3% in 15 min at 5 L/min flow rates. At 10 L/min flow rates, temperature and humidity were almost the same as those at 5 L/min. The membrane-type heated humidifier demonstrated statistically significant improvement in both the temperature ( p < 0.0001) and relative humidity ( p < 0.0001) parameters in comparison to the conventional normal, heated, or heated and humidified insufflators at 5 L/min and 10 L/min continuous flow rate in statistics using repeated-measure ANOVA. CONCLUSION: This newly developed heated humidifier offers the great advantages of maintaining intraabdominal temperature and humidity in comparison to conventional insufflators for laparoscopic surgery.

Equipment Design↗

Studies on the genomic heterogeneity of Micrococcus luteus strains by macro-restriction analysis using pulsed-field gel electrophoresis.

Macro-restriction analysis by means of double digestion using DraI and VspI demonstrated that they cleaved the genomic DNAs from Micrococcus luteus JCM1464(T), JCM3347, and JCM3348 into four to five fragments in a distinguishable manner by pulsed-field gel electrophoresis (PFGE). Separate digestion with DraI and VspI cleaved the genomic DNA from M. luteus ATCC9341 into a relatively limited number of restriction fragments (six pieces). SspI and XbaI cleaved the genomic DNA from each of the four strains into restriction fragments in a distinctly different and distinguishable manner.Thus, PFGE profiles after digestion with these four restriction enzymes that recognize six specific base sequences demonstrated the heterogeneity at the whole genomic DNA level among the four strains of M. luteus. The size of the genomic DNA of M. luteus ATCC9341 was estimated to be approximately 2.3 Mb by the summing the lengths of the restriction fragments generated by each three restriction enzymes (DraI, SspI, and VspI) and averaging the results.

Base Sequence↗

Non-invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method.

AIMS: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three-element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non-invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. METHODS: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi-stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. RESULTS AND CONCLUSION: The Modelflow-estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min-1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non-invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.

Adult↗

Exercise training improves ageing-induced decrease in eNOS expression of the aorta.

AIMS: Ageing impairs endothelial function such as the regulation of vascular tone. The release of nitric oxide (NO), which has a potent vasodilator effect and antiatherosclerotic property, is decreased in the aorta of aged rats. Exercise training, however, has been reported to increase the expression of endothelial NO synthase (eNOS) in the aorta of young rats. In aged rats, it is not known whether the expression of eNOS is altered by exercise training. We hypothesized that exercise training would improve the ageing-induced decrease in eNOS expression in vessels, and examined the messenger RNA (mRNA) and protein expression of eNOS in the aorta of sedentary-young rats (sedentary-young group; 4 months old), sedentary-aged rats (sedentary-aged group; 23 months old), and swim-trained aged rats (training-aged group; 23 months old, swimming training for 8 weeks, 5 days week(-1), 90 min day(-1)). RESULTS: Body weight was significantly lower, and citrate synthase activity in the epitrochlearis muscle was significantly higher in the training-aged group compared with the sedentary-aged group. The mRNA expression of eNOS in the aorta was significantly higher in the training-aged group than in the sedentary-aged group, while it was significantly lower in both the sedentary-aged and training-aged groups than in the sedentary-young group. The expression of eNOS protein in the aorta was also significantly higher in the training-aged group than in the sedentary-aged group, while it was also significantly lower in the sedentary-aged group, but not in the training-aged group, than in the sedentary-young group. CONCLUSION: The present results revealed that the production of eNOS in the aorta decreases with ageing, and that the decreased production is increased by exercise training in aged rats, which may produce beneficial effects on the impaired cardiovascular system caused by ageing.

Aging↗

Esophageal carcinoma with tracheal stenosis due to tumor invasion and long survival after chemoradiotherapy.

For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.

Combined Modality Therapy↗

Structural analysis and genetic variation of the 16S-23S rDNA internal spacer region from Micrococcus luteus strains.

AIMS: To clone and sequence the 16S-23S ribosomal DNA (rDNA) internal spacer region (ISR) from Micrococcus luteus. METHODS AND RESULTS: The primer pair for 16S-23S rDNA ISR amplified a fragment of about 850 bp in length for two strains, JCM3347 and JCM3348 and a fragment of about 790 bp for a strain, ATCC9341. After sequencing the ISRs were identified by the comparison of the ISRs and the flanking regions of ISR. CONCLUSIONS: Although the sequence difference of the ISR occurred at only one position between the two JCM strains, the highly variable length (440 and 370 bp) and sequence similarity (about 40%) were demonstrated between the ISRs of the two JCM strains and a ATCC strain. SIGNIFICANCE AND IMPACT OF THE STUDY: A CCTCCT sequence was first detected at the 3'-end of the 16S rDNA of the three strains. Moreover, highly similar sequence to the 21-bp region containing a putative rRNA processing site was observed in the ISR of the three strains. Interestingly, no intercistronic tRNAs were demonstrated in the ISRs from the three strains.

Base Sequence↗

Hypofibrinogenemia caused by a nonsense mutation in the fibrinogen Bbeta chain gene.

Congenital hypofibrinogenemia, fibrinogen Tottori II, caused by a nonsense mutation in the fibrinogen Bbeta chain gene, was found in a 68-year-old Japanese female. The plasma fibrinogen level was 99.2 mg dL(-1) as determined by the thrombin time method. No overt molecular abnormalities were observed in purified patient fibrinogen by SDS-PAGE analysis. After sequencing all exons and exon-intron boundaries of three fibrinogen genes, we found a heterozygous single point mutation of T-->G at position 3356 of the patient fibrinogen Bbeta chain gene. This nucleotide mutation results in a nonsense mutation (TAT sequence for Bbeta 41Tyr to TAG sequence for a translation termination signal). The mutation was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis, since this nucleotide mutation results in a new NheI recognition sequence at this position. These data indicated that the nonsense mutation of the fibrinogen Bbeta chain gene caused a truncated fibrinogen Bbeta chain, which may not be assembled in the fibrinogen molecule.

Aged↗

Theoretical investigation of an artificial joint with micro-pocket-covered component and biphasic cartilage on the opposite articulating surface.

This paper presents a theoretical investigation of a geometrically idealized artificial joint with micro-pocket-covered component and biphasic cartilage on the opposite articulating surface. The fluid that exudes from the biphasic cartilage fills and pressurizes the micro-pockets. In this way, a poro-elasto-hydrodynamic regime of lubrication is developed. Assuming that lower friction would result in lower adhesive wear, and neglecting the fatigue as well as the abrasive wear, the proposed bearing system hypothetically could reduce the amount of wear debris. Equations of the linear biphasic theory are applied for the confined and unconfined compression of the cartilage. The fluid pressure and the elastic deformation of the biphasic cartilage are explicitly presented. The effective and equilibrium friction coefficients are obtained for the particular configuration of this bearing system. The micro-pockets geometrical parameters (depth, radius, surface distribution and edge radius) must be established to reduce the local contact stresses, to assure low friction forces and to minimize the biphasic cartilage damage. The influence of the applied pressure, porosity of the micro-pocket-covered component, filling time, cartilage elasticity, permeability and porosity upon the micro-pockets depth is illustrated. Our results are based upon the previously published data for a biphasic cartilage.

Biomimetic Materials↗

Angiogenesis after sintered bone implantation in rat parietal bone.

We studied the effect of bone substitutes on revascularization and the restart of blood supply after sintered bone implantation in comparison with synthetic hydroxyapatite implantation and fresh autogenous bone transplantation (control) in rat parietal bones. Methods for the study included the microvascular corrosion cast method and immunohistochemical techniques were also used. The revascularization of the control group was the same as that for usual wound healing in the observations of the microvascular corrosion casts. The sintered bone implantation group was quite similar to that of the control group. In the synthetic hydroxyapatite group, immature newly-formed blood vessels existed even on the 21st day after implantation and the physiological process of angiogenesis was interrupted. Immunohistochemically, vascular endothelial growth factor (VEGF), which activates angiogenesis, appeared at the early stages of both the control group and the sintered bone implantation group. VEGF reduced parallel with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1), which obstructs angiogenesis, and the angiogenesis passed gradually into the mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at the early stage of the implants. The appearance of VEGF lagged and it existed around the pores of hydroxyapatite even on the 21st day of the implantation. Proliferation and wandering of endothelial cells continued without any maturing of the vessels. These findings suggest that the structure and the components of the implant material affect angiogenesis after implantation as well as new bone formation.

Animals↗