Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

The aim of this study was to clarify vascular endothelial growth factor (VEGF) expression and angiogenesis in the patellar tendon (PT) autograft in the early phase after anterior cruciate ligament (ACL) reconstruction using a rabbit model. The right knees of 30 Japanese white rabbits underwent ACL reconstruction using the medial third of the PT complex. We evaluated the grafted tendon at 1, 2, 3, 4, and 8 weeks after ACL reconstruction by immunohistology for proliferating cell nuclear antigen, VEGF, and CD31, which is a marker for vascular endothelial cells. At week 1 , few cells were observed at the midsubstance of the grafted tendon. A number of proliferating cells were observed at the surface area of the PT graft 2 weeks after graft transplantation, while no vessel formation was observed in the graft at the same time. VEGF was highly expressed 2-3 weeks postoperatively. Vessel formation in the PT graft increased with time from 3 to 8 weeks after ACL reconstruction. The rates of proliferating cells and VEGF-expressing cells decreased with time from 3 to 8 weeks. This study has suggested that VEGF is involved in the graft remodeling process particularly at the early phase after ACL reconstruction.     

Effects of a new dihydropyridine calcium antagonist on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2- yl)-1,4- dihydropyridine 3-carboxylate (DHP-218), a new dihydropyridine calcium antagonist, on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding to the cardiac muscle and brain membranes were investigated in vitro. Vascular smooth muscles: Calcium-induced contraction of the rat aorta in high K+ solution was inhibited by DHP-218 with the pA2 value of 9.11. The IC50 value for the inhibitory effects of this compound in high K+-induced and phenylephrine-induced contraction was 6.3 nmol/l and 66 nmol/l, respectively. Vasodilatory effects of this drug on various blood vessels of rabbits contracted by high K+ appeared to a similar extent. The onset of the vasodilatory effect was very slow and the recovery rate of vasodilatory response after washout with the bathing solution containing high K+ or phenylephrine was also very slow. Cardiac muscles: Negative chronotropic and inotropic actions were observed at concentrations more than 30 and 100 nmol/l, respectively. Duration of the plateau phase of normal action potential was shortened and the amplitude and duration of slow action potential were reduced at concentrations more than 1 mumol/l. Very high vasculoselectivity was observed. Displacement of [3H]-nitrendipine binding: The pattern of displacement of [3H]-nitrendipine binding by DHP-218 was very similar to that of other 1,4-dihydropyridines but this compound was about 70 times less potent than nifedipine in [3H]-nitrendipine displacement capacity. These results indicate that DHP-218 has specific vasodilatory action due to calcium antagonism, but association and dissociation rates with tissue and receptors were different from those of nifedipine.     

胃癌大肠转移的X线钡灌肠表现

目的:分析胃癌大肠转移的X线钡灌肠表现。方法:104例胃癌入院术前检查发现结肠转移或胃癌术后转移入院治疗的病例。分析钡灌肠初次发现大肠转移征象的年龄、发现胃癌原发病变距初次发现大肠转移的间隔时间、转移病变的发生部位和病变造成的X线钡灌肠图像上的肠管变形和粘膜面的改变。结果:104例胃癌结肠转移,男67例,女37例。胃癌术前检查中发现结肠转移者32例,术后发现的大肠转移中,多数转移发生在手术后3年内(占91.3%)。胃癌原发灶的肉眼形态BorrmannⅢ型(28例)和BorrmannⅣ型(65例)者占89.4%,组织学中以低分化腺癌和印戒细胞癌为主要成分者占91.3%。X线钡灌肠检查显示大肠转移的好发部位为横结肠(80),其次为直肠(50)。转移灶可累及多节段肠管,其中横结肠中1/3段(47),横结肠左1/3(44),横结肠右1/3(39)和直肠腹膜返折之上(39)。X线显示肠管单侧变形者227处,双侧变形者96处。黏膜面表现为梳齿状黏膜纹聚集改变253处,颗粒结节状改变23处,外压性改变20处,弥漫性改变62处。结论:胃癌大肠转移的好发部位为横结肠和直肠,结肠黏膜面的梳齿状黏膜纹聚集为胃癌大肠转移的主要X线钡剂灌肠表现。     

Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.     

Histochemical studies on hyaluronic acid in the developing human retina

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and theStreptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks’ gestation to the neonatal stage.     

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Endoscopic observation of pathophysiology of ventricular diverticulum

Background Although there have been reports dealing with ventricular diverticulum (VD) analyzed by cisternography and computed tomography (CT), those focusing on magnetic resonance imaging (MRI) or neuroendoscopic findings are rare. Case report We present a case of noncommunicating hydrocephalus caused by aqueductal stenosis with cystic lesion located in supracerebellar region. Third ventriculostomy was performed on this case. The conventional CT and MRI were compatible with usual VD, but neuroendoscopic examination suggested otherwise. The endoscopic view inside of the cystic lesion demonstrated passing veins and no membrane. We diagnosed this cystic lesion as a unique subtype of advanced VD mimicking spontaneous ventriculostomy. Endoscopic observation of the cyst was very useful for accurate diagnosis and safe treatment.