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Biomedical subjects

M Hayashi

Publications and source records attributed to M Hayashi.

At least 55 records · Page 3Linked to original sources

Human testicular protein TPX1/CRISP-2: localization in spermatozoa, fate after capacitation and relevance for gamete interaction.

Testicular protein Tpx-1, also known as CRISP-2, is a cysteine-rich secretory protein specifically expressed in the male reproductive tract. Since the information available on the human protein is limited to the identification and expression of its gene, in this work we have studied the presence and localization of human Tpx-1 (TPX1) in sperm, its fate after capacitation and acrosome reaction (AR), and its possible involvement in gamete interaction. Indirect immunofluorescence studies revealed the absence of significant staining in live or fixed non-permeabilized sperm, in contrast to a clear labelling in the acrosomal region of permeabilized sperm. These results, together with complementary evidence from protein extraction procedures strongly support that TPX1 would be mainly an intra-acrosomal protein in fresh sperm. After in vitro capacitation and ionophore-induced AR, TPX1 remained associated with the equatorial segment of the acrosome. The lack of differences in the electrophoretic mobility of TPX1 before and after capacitation and AR indicates that the protein would not undergo proteolytical modifications during these processes. The possible involvement of TPX1 in gamete interaction was evaluated by the hamster oocyte penetration test. The presence of anti-TPX1 during gamete co-incubation produced a significant and dose-dependent inhibition in the percentage of penetrated zona-free hamster oocytes without affecting sperm motility, the AR or sperm binding to the oolema. Together, these results indicate that human TPX1 would be a component of the sperm acrosome that remains associated with sperm after capacitation and AR, and is relevant for sperm-oocyte interaction.

Antibodies↗

Blood flow: a key regulatory component of corpus luteum function in the cow.

Prostaglandin F2alpha (PGF2alpha) is the primary luteolysin in the cow. During the early luteal phase, the corpus luteum (CL) is resistant to the luteolytic effect of PGF2alpha. Once mature, the CL becomes responsive to PGF2alpha and undergoes luteal regression. These actions of PGF2alpha coincide with changes in luteal blood flow (BF): PGF2alpha has no effect on BF in the early CL, but acutely increases BF in the peripheral vasculature of the mature CL within 30 min of PGF2alpha injection. During spontaneous luteolysis, luteal BF increases on Days 17-18 of the estrous cycle, prior to any decrease in plasma progesterone (P). The increase in luteal BF is synchronous with an increase in plasma PGFM levels, suggesting that pulsatile release of PGF2alpha from uterus stimulates the increase in luteal BF. Serial biopsies of these CL showed that mRNA expression for endothelial nitric oxide synthase (eNOS) together with endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) increases on Days 17-18 when the luteal BF is elevated. On Day 19 when plasma P level firstly decreases, eNOS mRNA returns to the basal level whereas ET-1 and ACE mRNA remains elevated. Cyclooxygenase-2 (COX-2) mRNA expression increases on Day 19. In support of these data, an in vivo microdialysis study revealed that luteal ET-1 and angiotensin II (Ang II) secretion increases and precedes PGF2alpha secretion during spontaneous luteolysis. In conclusion, we show for the first time that an acute increase of BF occurs in the peripheral vasculature of the mature CL together with increases in eNOS expression and ET-1 and Ang II secretion in the CL during the early stages of luteolysis in the cow. We propose that the increase in luteal BF may be induced by NO from large arterioles surrounding the CL, and simultaneously uterine or exogenous PGF2alpha directly increases ET-1 and Ang II secretion from endothelial cells of microcapillary vessels within the CL, thereby suppressing P secretion by luteal cells. Taken together, our results indicate that an acute increase in luteal BF occurs as a first step of luteolysis in response to PGF2alpha. Therefore, local BF plays a key role to initiate luteal regression in the cow.

Angiotensin II↗

Long-term effects of statins on arterial pressure and stiffness of hypertensives.

Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The C-reactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

Anticholesteremic Agents↗

Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia.

AIM: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. METHODS: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37-38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at -20 degrees C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at -80 degrees C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at -80 degrees C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. RESULTS: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. CONCLUSIONS: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.

Adult↗

Differentiation of the radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases: importance of multi-voxel proton MRS.

Comparative analysis of the diagnostic accuracy of FDG PET, single-voxel, and multi-voxel proton MRS for differentiation between radiation-induced necrosis and tumor recurrence was done in 9 patients with brain metastases treated by gamma knife radiosurgery. In all cases enlargement of the lesion and increase of the perilesional edema were demonstrated by MRI on average 10.6+/-2.6 months after initial treatment. Radiation-induced necrosis was identified in 5 patients (histologically in 2, clinically in 3). In one of these a false positive result of FDG PET was observed, whereas data of proton MRS were always correct. The diagnosis of tumor recurrence was established in 4 patients (histologically in 3, clinically in 1). Among these both FDG PET and single-voxel proton MRS showed false negative results (each method twice), whereas multi-voxel proton MRS always permitted us to establish the correct diagnosis. The present study demonstrates the higher diagnostic accuracy of multi-voxel proton MRS, in comparison with single-voxel proton MRS and FDG PET, for the differentiation of the radiation-induced necrosis and tumor recurrence. Its use is especially important in mixed lesions with co-existence of both post-irradiation changes and viable neoplasm. Monitoring of the treatment response by serial multi-voxel proton MRS seems to be reasonable during follow-up of patients with brain metastases after radiosurgery.

Abnormalities, Radiation-Induced↗

Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?

Malignant transformation of benign neoplasm after radiosurgery is usually diagnosed based on the initial presence of benign tumor, its exposure to ionizing radiation, elapsed time from radiation exposure to malignant progression, and different histological characteristics or growth rate of the regrowing tumor comparing with those originally treated. Three presented cases fulfilled these diagnostic criteria; however, it seems that progression of the tumors (schwannoma, meningioma, chordoma) resulted from the natural course of the disease, rather than represented side effects of gamma knife radiosurgery. Evaluation of the proliferative potential of the benign neoplasm before radiosurgical treatment either directly, if tumor sampling is available, or indirectly, by calculation of the tumor growth rate and/or analysis of the data of the metabolic imaging (PET, MRS) is important for identification of "aggressive" subtypes, precise prediction of prognosis, and confirmation of the radiation-induced malignant transformation in cases of tumor regrowth.

Adult↗

Obesity enhances the induction of plasminogen activator inhibitor-1 by restraint stress: a possible mechanism of stress-induced renal fibrin deposition in obese mice.

BACKGROUND AND OBJECTIVES: Cardiovascular/thrombotic diseases are frequently induced by a variety of stressors. Obese patients are susceptible to thrombotic diseases associated with stress, but the underlying mechanism is still unknown. We have begun to investigate the expression of a primary inhibitor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1), in association with tissue thrombosis, using restraint-stressed obese mice. METHODS AND RESULTS: We analyzed the expression of PAI-1 after restraint (immobilization) stress in genetically obese mice in comparison with their lean counterparts. Dramatic increases in PAI-1 antigen in plasma and in tissue extracts were observed in the obese mice exposed to restraint stress. The induction of PAI-1 mRNA by stress in the tissues was also pronounced in the stressed obese mice as compared with the lean mice, especially in the hearts and adipose tissues. In situ hybridization analysis revealed that strong signals for PAI-1 mRNA were localized in the adipocytes, cardiovascular endothelial cells, and renal glomerular cells of the stressed obese mice. Histological examination revealed that renal glomerular fibrin deposition was detected only in the obese mice after 2 h of restraint stress. CONCLUSIONS: Obesity enhances the stress-mediated PAI-1 induction in the blood and tissues. This phenomenon may be associated with the increased risk of stress-induced renal fibrin deposition in obese subjects.

Adipocytes↗

Convulsive episodes in patients with group A xeroderma pigmentosum.

OBJECTIVES: To clarify the incidence of convulsive episodes in patients with group A xeroderma pigmentosum (XPA). MATERIALS AND METHODS: By investigating the history of convulsive episodes of our 33 XPA patients through either their medical charts or direct interviews with their caretakers. RESULTS: Five patients had several episodes of afebrile convulsion at ages older than 12. With the exception of one patient who began to show convulsive episodes at 13, no other XPA patients exhibited febrile seizures. As far as our 33 XPA patients were concerned, 15% exhibited epilepsy, and 3% experienced febrile seizures. CONCLUSIONS: Japanese XPA patients showed a lower incidence of febrile seizures, while exhibiting a higher incidence of epilepsy. It is assumed that the brain of young patients with XPA is difficult to develop convulsions.

Adolescent↗

Cystic adenomyosis with florid glandular differentiation mimicking ovarian malignancy.

We report a case of cystic adenomyosis, presenting as a huge exophytic cystic mass with florid glandular differentiation. MR findings of the mass mimicked ovarian carcinoma associated with endometriosis. The presence of signal voids bridging the uterus and tumour should suggest a mass of uterine origin. Hyperintense protuberance in a hypointense loculus on T(2) weighted images may suggest benign disease. However, surgical exploration and resection is still required to exclude an ovarian malignancy.

Adult↗

[Surgical treatment of lung cancer in octagenarian patient].

Because average life span of Japanese is getting longer, we sometimes meet elder lung cancer patients of over 80. They often have many complications, so we are worried about how to treat them. Recently we met 8 elder patients with lung cancer, and we performed surgical operation for them. Six patients performed partial lung resection or lobectomy had no complications after operation. But 2 patients with respiratory disorder who performed lobectomy and chest wall resection had some complications after operation. In such patients, careful postoperative management is needed, and continuous positive airway pressure (CPAP) ventilation with pressure support (PS) may be useful to prevent respiratory complications.

Age Factors↗

ACE inhibitor and AT1 antagonist stimulate duodenal HCO3- secretion mediated by a common pathway - involvement of PG, NO and bradykinin.

Recent study demonstrated that duodenal HCO3- secretion is affected by modulation of the renin-angiotensin system. We examined the effects of enalapril (angiotensin-converting enzyme (ACE) inhibitor) or losartan (angiotensin AT1 receptor antagonist) on duodenal HCO3- secretion in rats and investigated the mechanisms involved in the renin-angiotensin system-related HCO3- response. A proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Enalapril increased the HCO3- secretion in a dose-dependent manner, with a decrease in arterial blood pressure (MBP), and these effects were significantly attenuated by pretreatment with indomethacin, L-NAME and FR172357 (a selective bradykinin B2 receptor antagonist). Although losartan alone did not affect the HCO3- secretion, despite reducing MBP, the agent dose-dependently increased the HCO3- secretion in the presence of angiotensin II, and this response was totally antagonized by prior administration of FR172357, indomethacin and L-NAME. Bradykinin also dose-dependently increased the HCO3- secretion with no change in MBP, though transient, and again the effects were blocked by indomethacin, L-NAME and FR172357. Both prostaglandin (PG) E2 and the nitric oxide (NO) donor NOR-3 also increased the HCO3- secretion, the latter effect being inhibited by indomethacin. These results suggest that both an ACE inhibitor and AT1 antagonist (in the presence of angiotensin II) increase duodenal HCO3- secretion via a common pathway, involving bradykinin, NO and PGs. It is also assumed that bradykinin releases NO locally, which in turns stimulates HCO3- secretion mediated by PGs.

Angiotensin II Type 1 Receptor Blockers↗

Laparoscopic esophagectomy.

Minimally invasive esophagectomy is emerging as an alternative option to open esophagectomy for benign and malignant esophageal diseases. This article provides a detailed review of the history of minimally invasive esophagectomy and an update on the currently accepted techniques for minimally invasive esophagectomy and its outcomes.

Esophagectomy↗

Experimental model of knee contracture in extension: its prevention using a sheet made from hyaluronic acid and carboxymethylcellulose.

Treatment once extension contracture of the knee has completed is difficult and costly. The most effective treatment might be the prevention of contracture, especially after joint injury. In order to establish an effective method for contracture prevention we first made an extension contracture in rabbit knees, then studied the effect of a sheet made from hyaluronic acid and carboxymethyl cellulose (HA/CMC) for the prevention of knee contracture. One hundred and twenty two mature male Japanese white rabbits were divided into three groups: (1) group B (n=42), where bony holes were made at the medial and lateral epicondyles, (2) group H (n=40), where HA/CMC sheets were placed on the bony holes, and (3) group S (n=40),where only arthrotomy was performed. All surgical procedures were performed on the right knees. All right knees were fixed at 45 degrees using external fixators; this is the maximum extension angle the rabbit is able to tolerate and still walk. At 1, 3, and 6 weeks after surgery, we measured the moment necessary to flex the knee using a special device. We defined the moment as flexion moment (FM). Forty four left knees were also tested as group N, not operated on and serving as the healthy side. In all groups, FM was increased parallel to the increment of flexion angle from 45 degrees to 115 degrees . At many flexion angles, the FM in group B was higher than those of group S at 3 and 6 weeks. The FM in group H was significantly lower than those of group B at 85 degrees and 95 degrees of flexion at 6 weeks after the operation. By macroscopic observation, the area and degree of adhesion were greater in group B than those of group S. In group H, adhesions around the bony hole were less evident than in group B at 6 weeks after the operation. By histological examination, dense granulation tissue was found adjacent to the bony hole in group B at 3 and 6 weeks after the operation. In contrast, in group H the amount of granulation tissue was smaller at 3 and 6 weeks after the operation than those of group B. The usage of HA/CMC sheet should be effective for prevention of contracture occurring after trauma such as treatment for intra-articular fracture.

Analysis of Variance↗

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

OBJECTIVE: Drug resistant epilepsy associated with hypothalamic hamartoma (HH) can be cured by microsurgical resection of the lesion. Morbidity and mortality risks of microsurgery in this area are significant. Gamma Knife Surgery's (GKS) reduced invasivity seems to be well adapted. In view of the severity of the disease and risks of surgical resection it is crucial to evaluate GKS for this indication. A first retrospective study has shown a very good safety and efficacy level but for a more reliable evaluation a prospective study would be required. METHODS: Between Oct 1999 and July 2002, 30 patients with HH and associated severe epilepsy were included. Seizure semiology (video EEG) and frequency, behavioural disturbances, neuropsychological performance, endocrinological status, sleep electroclinical abnormalities, MR imaging, and visual function were systematically evaluated before and after GKS (6, 12, 18, 24, 36 months). Twenty patients had experienced precocious puberty at a median age of 3,7 (0-9). Range of maximum diameter was from 7,5 to 23 mm with only 3 larger than 18 mm. The median marginal dose was 17 gy (14-20). RESULTS: Sufficient follow up for final evaluation is not yet available. Only 6 patients have a follow-up of more than 12 months and 19 more than 6 months. However a lot of very dramatic changes did occur during that period in this group. Among the 19 patients with more than 6 months of follow-up, a lot had already experienced an increase of gelastic seizures around 3 months (3), an improvement in their seizure rate (18), behaviour (9), sleep (3), and EEG background activity (3), a cessation of partial complex seizures (7). No complications have occurred till now except one patient experiencing at 5 months a hyperthermia without infection and concomitant increase of gelastic seizures both ceasing suddenly and spontaneously after 15 days. CONCLUSION: Our first results indicate that GKS is as effective as microsurgical resection and very much safer. GKS also allows to avoid the vascular risk related to radiofrequency lesioning or stimulation. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a serious evaluation of the role of GKS. Results are faster and more complete in patients with smaller lesions inside the 3rd ventricle (grade II). The early effect on subclinical discharges turns out to play a major role in the dramatic improvement of sleep quality, behaviour, developmental acceleration at school.

Adolescent↗

Acute effect of milnacipran on the relationship between the locus coeruleus noradrenergic and dorsal raphe serotonergic neuronal transmitters.

The present studies sought to investigate the effect of milnacipran called the serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor (SNRI) on the interaction of central locus coeruleus noradrenergic and dorsal raphe nucleus serotonergic functional activity by utilizing in vivo microdialysis. A single administration of milnacipran (60 mg/kg, s.c.) markedly decreased the levels of NA and its metabolite, 4-hydroxy-3-methoxymandelic acid (HMMA), in the locus coeruleus and the levels of, a metabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) in the dorsal raphe nucleus. Combined administration of yohimbine (2 mg/kg, s.c.),?alpha(2)-adrenoceptor?antagonist, at 2 h after milnacipran (60 mg/kg, s.c.) led to a significant increase in NA levels in the locus coeruleus, although yohimbine alone had no effect on these levels. Under similar experimental condition, 5-HIAA levels in the dorsal raphe nucleus remained unchanged. NAN-190 (1 mg/kg, s.c.), 5-HT(1A) receptor partial agonist, alone markedly decreased the levels of 5-HIAA in the dorsal raphe nucleus, although this level was not affected by WAY100635, the selective 5-HT(1A) receptor antagonist. WAY100635 recovered the milnacipran-induced decrease of 5-HIAA levels in the dorsal raphe nucleus to control levels. On the other hand, NAN-190 did not affect the milnacipran-induced decrease of 5-HIAA levels. Behavioral signs (locomotion and rearing) were markedly observed following milnacipran alone or combined administration of milnacipran and yohimbine. However, the behavioral signs after coadministration of milnacipran and WAY100635 or NAN-190 were relatively poor. These results may suggest that an increase of NA in the locus coeruleus with the treatment of yohimbine after milnacipran results from negative feedback following the blockade of alpha(2)-adrenoceptors achieved with yohimbine, and that WAY100635 but not NAN-190 recovered milnacipran-induced decrease of 5-HIAA in the dorsal raphe nucleus to control levels by preventing the activation for the presynaptic 5-HT(1A) autoreceptor.

Adrenergic Uptake Inhibitors↗

Northern blot and in situ hybridization analyses for the development of myristoylated alanine-rich c-kinase substrate mRNA in the monkey cerebral cortex.

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major neuron-specific substrate for protein kinase C, and is involved in both neurite outgrowth and synaptic plasticity. Using both Northern blot and in situ hybridization techniques, we investigated whether the expression of MARCKS mRNA in the monkey cerebral neocortex and hippocampus changed during the developmental period. In each of four neocortical areas examined, i.e. the prefrontal area (area FD of [Illinois Monographs in the Medical Sciences (1947) 1]), the temporal association area (TE), the primary somatosensory area (PB), and the primary visual area (OC), the Northern blot analysis showed that the amount of MARCKS mRNA was high during the fetal and early postnatal periods, and decreased sharply between postnatal day 70 and postnatal month 6. The in situ hybridization experiments showed that the expression of MARCKS mRNA was decreased in every layer of neocortical areas at postnatal month 6 or later. In the primary sensory areas (areas PB and OC), the degree of decrease was higher in the supragranular layers (layers II and III) than in the infragranular layers (layers V and VI). In the hippocampus, the developmental change in the amount of MARCKS mRNA was small, but the in situ hybridization revealed a prominent decrease in Ammon's horn in monkeys on postnatal month 8 and later. These findings indicate that region-specific expression of MARCKS mRNA is established around postnatal month 6. We suggest that the extensive expression of MARCKS mRNA is one of the molecular bases of high plasticity in the infant cerebral cortex.

Animals↗

Kidney transplantation from non-heart-beating donors: analysis of organ procurement and outcome.

INTRODUCTION: Most donors in Japan have been non-heart-beating donors (NHBD), so-called "marginal donors." In Western countries kidney transplants from NHBD have also been increasing. We analyzed 120 kidneys harvested from NHBD with regard to organ procurement, renal function, graft survival, and the donor factors that affected graft survival. METHODS: Donors were moved into the operating room after cardiac arrest. A double-balloon catheter was inserted into the abdominal aorta via laparotomy. In situ cooling by Euro-Collins solution was started at 500 mL/min. We did not performed cannulation into the femoral artery or vein prior to cardiac arrest. RESULTS: Warm ischemia time (WIT) was 18.6 minutes. Among 108 kidneys (90%) used for transplantation, 102 kidneys functioned. There were no cases of bilateral nonfunctioning kidneys. The delayed graft function (DGF) rate was 86%; however, the death-censored graft survival was 80.0% at 5 years and 62.9% at 10 years. Kidneys implanted after more than 24 hours of total ischemia time required a significantly longer period of hemodialysis. Donor risk factors that affected graft survival included WIT >/= 20 minutes, donor age >/= 50 years, and serum creatinine level at admission > 1.0 mg/dL. CONCLUSIONS: Organ procurement without cannulation prior to cardiac arrest entailed a long WIT and a high DGF rate. However, the graft survival was good. It has been necessary to use grafts from NHBD despite the inherent risk factors. It is important to reduce kidney damage both at the organ procurement and during the posttransplant management.

Heart Arrest↗