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Biomedical subjects

N Nakao

Publications and source records attributed to N Nakao.

At least 91 records · Page 5Linked to original sources
PubMed1996

Prostaglandin E receptor subtypes in mouse osteoblastic cell line.

PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone.

Alprostadil↗
PubMed1996

[Quantitative flow measurement of the vertebro-basilar circulation for positional vertigo by using 2D phase contrast technique].

Quantitative measurements of blood flow in the vertebral and basilar arteries were obtained by the 2D phase contrast (2D PC) technique. In phantom study, flow velocity measured with 2D PC correlated well with actual flow velocity. Sixty-six patients were neurologically normal and 20 had positional vertigo due to vertebrobasilar insufficiency (VBI). Mean velocities (MV) were measured by using a transverse plane in the vertebral arteries at the level of C3 and in the basilar arteries at the level of the sella floor. Volume flow rates (VFR) were calculated as the product of MV and the area of the arteries whose diameters were measured on the basis of pixel counting in the histogram of the signal intensity profile. In the normal group, MV of the left vertebral artery and MV and VFR of the basilar artery showed significant declines as age progressed. In the vertigo group, MV and VFR of the basilar artery were significantly lower than in the normal group. It is concluded that 2D PC technique appears to be fast and easy to handle without cardiac gating to assess blood flow in vessels surrounded by bone tissues.

Adult↗
PubMed1996

Intrahepatic metastases in hepatocellular carcinoma: evidence for spread via the portal vein as an efferent vessel.

BACKGROUND: The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. METHODS: Two hundred thirty-one tumors ( < or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected from the 231 tumors. RESULTS: The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. Radiopaque material injected directly into 23 resected tumors entered the portal vein in only 17 tumors and entered into both the portal and hepatic veins in six tumors. CONCLUSIONS: These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Adult↗
PubMed1995

Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro.

We have examined the effects of either brain-derived neurotrophic factor (BDNF), the BB-isoform of platelet-derived growth factor (PDGF-BB), or a combination of these growth factors on the survival and the morphological development of embryonic striatal neurons grown under serum-free culture conditions. Striatal neurons were identified using immunocytochemistry for "dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton" (DARPP-32). BDNF and PDGF-BB promoted the survival of DARPP-32-positive neurons, with the magnitude of their effects being comparable. A combination of these growth factors exerted no significant additive effects on cell survival. BDNF stimulated morphological differentiation of DARPP-32-containing neurons by increasing the length of neurites, the number of branching points on the neurites, and the soma area. By contrast, PDGF-BB increased the neurite length and the cell body area, but not the number of branching points. BDNF also protected striatal neurons from excitotoxicity induced by N-methyl-D-aspartate, whereas PDGF-BB had no effect under the same treatment conditions as those for BDNF. Thus, BDNF is trophic for striatal DARPP-32-containing neurons in vitro by enhancing the survival, morphological differentiation and resistance to excitotoxicity, and its mechanisms of action are probably different from those of PDGF-BB.

Animals↗
PubMed1995

Clinical and neuropathological features of a neurodegenerative disorder in the central nervous system with progressive head drooping (Kubisagari).

The clinical and neuropathological features of a case of a neurodegenerative disorder with pronounced and progressive head drooping, in Japanese Kubisagari, are reported. This female patient died at the age of 72 years after an approximately 20-year history of peculiar posture with progressive head drooping (Kubisagari) and lordosis (bowed posture), parkinsonism, dysphonia and slight muscle wasting of the face, tongue, neck, and distal portions of the upper extremities. She did not display mental deterioration until the terminal stage of the illness. A simple macroscopic inspection formalin-fixed sections of the central nervous system (CNS) showed prominent atrophic frontal and temporal lobes, brownish discoloration of the putamen and an atrophic pyramidal tract. Light microscopy revealed severe neuron loss with fibrillary gliosis at both the above-mentioned lobes and the putamen. Both the facial and hypoglossal nuclei had almost disappeared. Motor neurons in the spinal cord were moderately to markedly decreased. Neither Bunina nor Lewy bodies, senile plaque, nor Pick's argyrophilic neuronal inclusions were observed, but very occasionally ubiquitin-positive neurons were found in the temporal cortex. In conclusion, the hitherto-unrecognized neuropathological findings in the CNS corresponding to progressive head drooping (Kubisagari) suggest that this is a neurodegenerative disorder of the CNS, possibly an atypical form of amyotrophic lateral sclerosis.

Aged↗
PubMed1995

Transplantation of cultured sympathetic ganglionic neurons into parkinsonian rat brain: survival and function of graft.

The superior cervical ganglia (SCG) of newborn rats, which had been cultured as explants for varying periods of time, were transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway to examine the survival and functional properties of the sympathetic neurons maintained in long-term culture prior to grafting. In the rats given the SCG cultured in vitro for 2 weeks, apomorphine-induced rotational behaviour was satisfactory reduced. The rats receiving the SCG from 4-week-old cultures showed only modest behavioural changes. The grafting of the SCG cultured for 6 weeks in vitro did not affect the rotational behaviour. These behavioural data corresponded with the histological assessment of the graft survival by use of catecholamine histofluorescence. The present results suggest the critical time period in vitro which might allow the cultured sympathetic neurons to be successfully grafted.

Animals↗
PubMed1995

Protective effects of BDNF and NT-3 but not PDGF against hypoglycemic injury to cultured striatal neurons.

Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF) exert trophic effects on striatal neurons in vitro, which raises the possibility that these growth factors might also counteract neuronal death provoked by various insults. We have found that BDNF and NT-3, but neither PDGF-AA nor -BB, added 24 h before the insult ameliorated hypoglycemic neuronal damage induced by 15 or 24 h of glucose deprivation in rat striatal cell cultures. BDNF and NT-3 afforded neuronal protection even when administered 8 or 4 h, respectively, after the onset of hypoglycemia. In normoglycemic striatal cultures exposed to these neurotrophins for several days, there was a slight, nonsignificant increase of the number of surviving microtubule-associated protein-2-positive cells (20-30%) compared to untreated control cultures, but no change of glial cells. Exposure of the cultures to BDNF or NT-3 produced a significant increase in the number of neurons expressing detectable levels of the calcium-binding protein, calbindin, suggesting that a stabilization of calcium homeostasis might be implicated in the neuroprotection. Immunocytochemical analysis revealed that the majority (70-80%) of neurons in the striatal cultures expressed TrkB and TrkC, the functional receptors for BDNF and NT-3, respectively, implying that the effects of the neurotrophins are most likely direct. These data indicate that BDNF and NT-3 can protect striatal neurons against hypoglycemia in vitro and raise the possibility that these neurotrophins could counteract striatal neuronal death induced by hypoglycemic and ischemic insults in vivo.

Animals↗
PubMed1995

Overexpressing Cu/Zn superoxide dismutase enhances survival of transplanted neurons in a rat model of Parkinson's disease.

A high survival rate of grafted dopamine neurons is crucial for reversing neurological deficits following brain tissue transplantation in Parkinson's disease. For unknown reasons the survival rate of transplanted dopamine neurons is only around 10% in experimental animals. The hypothesis that oxidative stress causes the loss of transplanted neurons was tested by grafting neurons from transgenic mice that overexpress Cu/Zn superoxide dismutase. Compared with the survival of those taken from non-transgenic littermates, the survival was 4 times higher for the transgenic dopamine neurons with a concomitant more extensive functional recovery. The results provide direct support for the free radical hypothesis of dopaminergic neuron death in brain tissue grafting.

Amphetamines↗
PubMed1995

[Industrial work and lung cancer].

In a hospital-based case-control study, 316 lung cancer cases and 536 controls were interviewed for their occupational, smoking, passive smoking, cancer in the family and residential histories as well as social economic status, by trained interviewers, using a standardized questionnaire. Cases and controls were matched by hospital, sex and age. The study was carried out between 1st July 1990 and 31st January 1991 in 14 hospitals in the Metropolitan Region of S. Paulo, the most highly industrialized and urbanized region in Brazil. Score criteria were developed for the ordering of the individuals of the study by occupational exposure to know carcinogens to the lung, in order to evaluate this exposure during the occupational life of each person. The criteria accumulated information on exposure to carcinogens as regards type, sector of work and time in each employment. The unconditional logistic regression analysis showed an odds ratio of 1.97 (95% IC: 1.52 to 2.55) for the highest exposure group. This result showed that workers linked to the production sectors of several industries have about twice the risk of developing lung cancer as workers involved in non-industrial activities.

Adult↗
PubMed1995

[Corticosteroid responsive inflammatory myopathy with autoantibody against Golgi apparatus].

A 51-year-old woman of progressive myopathy predominantly involving proximal groups of limb-muscle was reported. Serum enzymes originating from the skeletal muscle always remained within normal range, and a positive autoantibody against Golgi apparatus and the SS-A (Ro) antibody in serum were noted. In muscle biopsy performed twice, extensive degenerating/regenerating fibers and sparce inflammatory cells between connective tissue elements in light microscopy, and disrupted lamellar structure of Golgi apparatus in electron microscopy were observed. Corticosteroid therapy was markedly effective. In the present case of a "so-called" limb-girdle syndrome, humoral autoantibodies, especially against Golgi apparatus, could induce a metabolic disturbance in the muscle fiber.

Autoantibodies↗
PubMed1994

Lazaroids improve the survival of grafted rat embryonic dopamine neurons.

In rodent models of Parkinson disease in which transplants of dissociated rodent and human embryonic mesencephalic tissue, rich in dopamine neurons, have been studied, only 5-20% of the dopamine neurons survive the implantation procedure. We have investigated the effects of inhibiting free radical generation with two lazaroids, U-74389G and U-83836E, on the survival of embryonic rat dopamine neurons. U-74389G is a 21-aminosteroid, and U-83836E combines the piperazinyl pyrimidine portion of 21-aminosteroids with the antioxidant ring of alpha-tocopherol. In an initial study, we found that the lazaroids markedly prolonged the period after tissue dissociation that an embryonic mesencephalic cell suspension exhibits high cell viability in vitro, as assessed by using a dye exclusion method. In a second series of experiments, addition of lazaroids to dissociated mesencephalic graft tissue increased the yield of surviving rat dopamine neurons 2.6-fold after implantation in the dopamine-denervated rat striatum. The improved survival correlated with an earlier onset of graft-induced functional effects in the amphetamine-induced rotation test. Thus, inhibition of free radical generation can significantly increase the yield of grafted embryonic dopamine neurons. Addition of lazaroids to the graft preparation is a relatively simple modification of the transplantation protocol and could readily be applied in a clinical setting. Moreover, since iron-dependent lipid peroxidation has been suggested to play a role in the death of nigral dopamine neurons in Parkinson disease and lazaroids are particularly potent inhibitors of such processes, the findings may have implications for the pathogenesis of this disease.

Animals↗
PubMed1994

Lazaroids improve the survival of cultured rat embryonic mesencephalic neurones.

We have studied the effects of two lazaroids, U-74389G and U-83836E, on the survival of cultured rat dopamine neurones. Lazaroids are inhibitors of free radical formation and lipid peroxidation. Dissociated embryonic mesencephalic neurones were cultivated for 2 or 7 days under serum-free conditions with or without the addition of 0.3 microM of one of the lazaroids. Both lazaroids enhanced the survival of tyrosine hydroxylase immunoreactive, dopaminergic neurones both after 2 and 7 days in vitro to around 111-120% and 175-180% of controls, respectively. Since the total number of neurones was also increased following lazaroid treatment, it is unlikely that lazaroids exert their effects on only dopamine neurones. These findings suggest that oxidative stress plays an important role in the death of cultured embryonic dopamine neurones and that lazaroids may be potent neuroprotective agents in situations where dopaminergic neurones degenerate.

Animals↗
PubMed1994

Selective sub-dissection of the striatal primordium for cultures affects the yield of DARPP-32-containing neurones.

We have studied the effect of selectively dissecting the lateral (LGE) and medial (MGE) ganglionic eminences of the striatal primordium on the yield of DARPP-32-immunoreactive striatal neurones in serum-free cultures maintained for 2 or 5 days. The LGE cultures yielded an approximately four-fold higher number of DARPP-32-positive neurones compared with the MGE cultures, without an accompanying difference in total cell numbers. In both types of culture, there was a 70% reduction in DARPP-32 positive neurones from 2 to 5 days in vitro. In conclusion, the LGE is a rich source of striatal precursors and the present culture system provides a good model for the study of factors that may prevent striatal neuronal death.

Animals↗
PubMed1994

Platelet-derived growth factor exerts trophic effects on rat striatal DARPP-32-containing neurons in culture.

The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat strial neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF-BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.

Animals↗
PubMed1994

Personal computer-based small PACS for radiotherapy--analog image filing system for radiotherapy.

The purpose of this study is to evaluate the usefulness of a personal computer-based small PACS using analog video images. The analog video recorder, personal computer, and display monitor constitute our system. An analog video recorder is composed of a laser disk recorder for still images and a video cassette recorder for moving images. The acquired video images are managed by a personal computer and database software. The serial communication ports of the personal computer and a video recorder are connected with the reverse cable, and the video recorder is controlled by the personal computer using our program. This system enables filing of multi-modality images including moving images and is used for following up and treatment planning of the patients who received radiotherapy.

Aftercare↗
PubMed1994

Immunostaining of dystrophin and utrophin in skeletal muscle of dystrophinopathies.

Immunostaining of biopsied skeletal muscle of 4 Duchenne (DMD), 12 Becker muscular dystrophy (BMD) and 3 DMD carriers' was performed using monoclonal antibodies against dystrophin and utrophin. In DMD, dystrophin-negative staining was observed except for revertant fibers which showed different stain patterns for each antibody. In 7 BMDs, there was faint/patchy stain in cases of deletion between exons 45-52, while in one case there was deletion between exons 12-17 and no stain was noted relevant to the deletion site. Moreover, in 2 cases of undetectable deletion, antibodies which recognize a terminal portion of the C-terminal domain revealed the absent stain. In DMD, the utrophin-positive fibers corresponded to dystrophin-negative fibers. In BMD, this relationship did not necessarily occur in each fiber. In DMD carriers, a cluster of dystrophin-negative fibers which was positive for utrophin were prominent. In dystrophinopathy, the immunostaining of dystrophin and utrophin is useful, in combination with dystrophin gene analysis to make a definite diagnosis.

Adolescent↗
PubMed1994

Pretreatment with interleukin-1 enhances survival of sympathetic ganglionic neuron grafts.

The effects of pretreatment with interleukin-1 (IL-1) on neurite growth and cell survival of rat superior cervical ganglion (SCG) explants were examined. Neonate rat SCG explants were cultured with serum-containing growth media. Pretreatment with IL-1 beta (30 U/ml) for 3 hours stimulated neurite outgrowth of the SCG explant, which was inhibited by the addition of anti-nerve growth factor (NGF) antibody to the growth medium. Adult rat autologous SCG with the same pretreatment and non-treated ganglia were transplanted into the lateral ventricle. Histological evaluation of the grafts 2 weeks after transplantation revealed that the pretreated SCG cells survived better. Pretreatment with IL-1 may achieve the NGF-mediated neurotrophic effect in sympathetic ganglionic neurons resulting in enhanced graft survival.

Animals↗