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Biomedical subjects

H Niwa

Publications and source records attributed to H Niwa.

At least 73 records · Page 4Linked to original sources

NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.

The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.

Analysis of Variance↗

Cloning of the fatty acid synthetase beta subunit from fission yeast, coexpression with the alpha subunit, and purification of the intact multifunctional enzyme complex.

We have cloned and sequenced the fission yeast (Schizosaccharomyces pombe) fas1+ gene, which encodes the fatty acid synthetase (FAS) beta subunit, by applying a PCR technique to conserved regions in the beta subunit of the alpha6beta6 types of FAS among different organisms. The deduced amino acid sequence of the Fas1 polypeptide, consisting of 2073 amino acids (Mr = 230,616), exhibits the 48.1% identity with the beta subunit from the budding yeast (Saccharomyces cerevisiae). This subunit, with five different catalytic activities, bears four distinct domains, while the alpha subunit, the sequence of which was previously reported by Saitoh et al. (S. Saitoh et al., 1996, J. Cell Biol. 134, 949-961), carries three domains. We have developed a co-expression system of the FAS alpha and beta subunits by cotransformation of two expression vectors, containing the lsd1+/fas2+ gene and the fas1+ gene, into fission yeast cells. The isolated FAS complex showed quite high specific activity, of more than 4000 mU/mg, suggesting complete purification. Its molecular weight was determined by dynamic light scattering and ultracentrifugation analysis to be 2.1-2.4 x 10(6), and one molecule of the FAS complex was found to contain approximately six FMN molecules. These results indicate that the FAS complex from S. pombe forms a heterododecameric alpha6beta6 structure. Electron micrographs of the negatively stained molecule suggest that the complex adopts a unique barrel-shaped cage architecture.

Amino Acid Sequence↗

Prolongation of total permissible circulatory arrest duration by deep hypothermic intermittent circulatory arrest.

OBJECTIVE: We determined whether the duration of permissible circulatory arrest could be prolonged by deep hypothermic intermittent circulatory arrest. METHODS: Twenty-five beagles were cooled on bypass to 18 degrees C to initiate deep hypothermia that was maintained for 3 hours. Five protocols were then studied: group 1, uninterrupted bypass during hypothermia; group 2, arrest for 40 minutes during hypothermia; group 3, arrest for 60 minutes during hypothermia; group 4, arrest for 80 minutes during hypothermia; and group 5, intermittent circulatory arrest, consisting of six cycles of 20 minutes of arrest followed by 10 minutes of systemic recirculation during hypothermia (total, 120 minutes of arrest). The oxyhemoglobin concentration in the brain was measured with near infrared spectrophotometry. RESULTS: In groups 2, 3, and 4, the oxyhemoglobin concentration in the brain decreased continuously after arrest, finally reaching a plateau after 24.9 +/- 1.2 minutes. This finding suggested that the available cerebral oxyhemoglobin was depleted. In contrast, the available cerebral oxyhemoglobin was not depleted during hypothermic intermittent arrest in group 5. The mitochondrial respiratory control index was significantly lower in group 4 than in the other groups (p < 0.05). However, there were no significant differences in the respiratory control index for groups 1, 2, 3, and 5. Moreover, the formation of brain edema was significantly lower in group 5 than in the other groups (p < 0.05). CONCLUSIONS: These results indicate that deep hypothermic intermittent arrest can increase the duration of total permissible circulatory arrest and will be a useful modality when prolonged arrest is anticipated.

Animals↗

Nerve growth factor maintains regulation of intracellular calcium in neonatal sympathetic neurons but not in mature or aged neurons.

We examined the effects of nerve growth factor on the regulation of intracellular calcium levels of superior cervical ganglion neurons in terms of postnatal maturation and ageing. Rat superior cervical ganglion neurons from three age groups (neonatal: 0 to one-day-old, young adult: three to six-month-old, and aged: more than 24-month-old) were dissociated and cultured in the presence or absence of 100 ng/ml of nerve growth factor. Intracellular free calcium levels ([Ca2+]i) were measured using the fura-2 microfluorometry. Nerve growth factor treatment increased the resting [Ca2+]i of neonatal neurons, although it had no effect on those of mature and aged neurons. We further examined the effects of nerve growth factor on the transient increase of [Ca2+]i induced by methacholine (0.1 mM), caffeine (20 mM) or high-potassium medium (40 mM K+). Nerve growth factor pre-treatment significantly increased the population of neonatal superior cervical ganglion neurons which responded to methacholine, whereas almost all young adult and aged neurons responded to methacholine regardless of pre-treatment of nerve growth factor. Caffeine induced a cyclic alteration of [Ca2+]i (oscillation) in 45% of the neonatal superior cervical ganglion neurons when they were maintained without nerve growth factor, but nerve growth factor treatment suppressed the oscillation to 10% of neurons. In contrast to neonatal neurons, all of the young adult and aged neurons showed only a transient increase of [Ca2+]i in response to caffeine independent of nerve growth factor treatment. There was no significant effect of nerve growth factor on K+ depolarization-induced [Ca2+]i elevations at any of the ages studied. Nerve growth factor did not substantially alter the pattern of the transients induced by these three agents. Our results indicate that exogenous nerve growth factor is necessary to maintain normal acetylcholine receptor-mediated [Ca2+]i responses as well as Ca(2+)-induced Ca2+ release from intracellular calcium storage in neonatal superior cervical ganglion neurons. In mature superior cervical ganglion neurons, Ca2+ homeostasis becomes independent of exogenous nerve growth factor, and Ca2+ homeostasis and its independency are well preserved in aged neurons.

Aging↗

Deep hypothermic intermittent circulatory arrest--an adjunct technique for operations on aneurysms involving the aortic arch.

Aneurysms involving the aortic arch were repaired in 12 patients using a technique known as deep hypothermic intermittent circulatory arrest (DHICA). This technique consists of repeated cycles of 20 min of circulatory arrest and 10 min of cerebral and systemic reperfusion. Aneurysms were of the following types: 2 true atherosclerotic aneurysm, 8 aortic dissections, and 2 traumatic aneurysm. There were 2 operative deaths caused by coagulopathy as a result of hepatic failure and difficulty with left ventricular venting. The frequency of circulatory arrest ranged from 2 to 5 cycles, and total circulatory arrest ranged from 20 to 71 min (mean 43.6 min). The lowest tympanic temperature ranged from 17.7 to 19.2 degrees C. No permanent cerebral complications occurred in 10 patients. We believe that this adjunct technique offers excellent results in the surgical treatment of aneurysms involving the aortic arch.

Adult↗

The protective effect of a persistent trigeminal artery on brain stem infarctions: a follow-up case report.

A persistent trigeminal artery (PTA) represents an embryonic vascular anastomosis connecting the carotid and basilar arterial systems. Little is known about its protective role in cases of basilar artery occlusion. We followed up a 63-year-old man who had suffered a brain stem infarction due to basilar artery stenosis and was found to have a PTA. Although a second brain stem infarction due to basilar artery occlusion developed, the circulation to the brain stem was well maintained via collateral flow from the PTA, and the patient demonstrated good recovery. A PTA may function as an anastomosis between the carotid and basilar systems, thus preventing a more serious infarction.

Arteriosclerosis↗

[Surgical treatment for lung cancer invading thoracic aorta].

We experienced three surgical cases of lung cancer invading thoracic aorta, and discussed some problems in order to improve the surgical outcome. In the first case, the patient had a ruptured descending aortic aneurysm into a tumor of left lung. Following urgent graft replacement of descending aorta, left pneumonectomy was carried out, but the patient died of bone marrow dissemination which was probably caused by aspiration of the tumor cells on cardiopulmonary bypass. In the second case, the patient underwent resection of the left upper lobectomy combined with resections of the left subclavian artery and distal aortic arch, but died of perforation of aortic arch due to vascular injury by cross clamp. In the third case, an operation was successfully performed for lung cancer invading the aortic arch. Left upper lobectomy with associated resection of aortic arch, left subclavian and common carotid arteries was performed. Both arteries were replaced with a Gelseal Graft.

Adenocarcinoma↗

[Gastrointestinal bleeding (introduction)].

Gastrointestinal (GI) bleeding is a common and important problem for all clinicians. Patients may present with signs of bleeding, such as hematemesis, melena, or hematochezia. The patient must first be hemodynamically stabilized. Initial assessment of patients with GI bleeding includes thorough history taking and physical examination. Patients with acute bleeding or an unstable condition must be resuscitated immediately and the source of bleeding must be localized to the upper or lower GI tract. Panendoscopy is often the initial diagnostic test and is useful to stop GI bleeding, at the same time.

Emergency Medical Services↗

Chondrosarcoma originating from the trachea.

We report a tracheal chondrosarcoma in a 54-year-old man, treated with neodymium:yttrium-aluminum garnet laser vaporization via fiberoptic bronchoscopy followed by surgical resection. Chondrosarcomas of the trachea are extremely rare tumors. To our knowledge, there are 9 cases of chondrosarcoma of the trachea reported in the English-language literature, to which we add the tenth.

Biopsy↗

Experimental reconstruction of the mediastinal trachea with a wing-shaped reversed esophageal flap.

BACKGROUND: In cases of extensive tracheal resection in which direct end-to-end anastomosis is impossible there is a need for reconstruction. Nevertheless, with the present lack of reliable artificial trachea, no reconstruction method is available to assure safe replacement of the mediastinal trachea. METHODS: After tubular resection of the mediastinal trachea in mongrel dogs, the trachea was reconstructed using a wing-shaped reversed esophageal flap. A silicone tube was used as an internal stent. RESULTS: In group I (16 animals), three tracheal rings were resected; in group II (4 animals), six tracheal rings; in group III (6 animals), eight tracheal rings; and in group IV (5 animals), eight tracheal rings and the lining of the greater omentum. Safe reconstruction was accomplished in all cases in groups I and II, 2 of 6 cases in group III, and 2 of 5 cases in group IV. The omentopexy failed to prevent incomplete closure, yet served to minimize inflammation in the mediastinum. CONCLUSIONS: A reversed esophageal autograft can be considered as a tracheal replacement.

Animals↗

Diffuse cystic change of a term placenta with a normal newborn.

We recently encountered a case of term placenta with a diffuse cystic lesion of the villi. A 19-year-old primipara at 36 weeks of gestation underwent cesarean section due to breech presentation with premature rupture of the membranes; she delivered a mature male baby of 2,502 g with an Apgar score of 9/9. The placenta was 940 g in weight and 29 x 20 x 3 cm in size, and macroscopically had multiple cystic lesions (3-8 mm in diameter) that resembled hydatidiform moles. However, histopathological examination revealed that the severe hydropic change was localized in the stem villi but not remarkable in the terminal chorionic villi. Moreover, abnormal proliferation of the trophoblast was not observed. However, the hypertrophic change was observed in the vascular wall of stem villi, in which hyperplasia of smooth muscle-like cells was present. The urinary hCG levels at 1 month and 2 months after delivery were less than 50 IU/l. These findings indicate that the multiple cystic lesions of the placenta in this case are essentially different from those of a trophoblastic disease, and that the diffuse cystic lesion of the villi might have been secondary to changes in the local circulation.

Actins↗

Identification of pancreatic beta cell-related genes by representational difference analysis.

A knowledge of beta cell-specific gene expression provides a basis for identifying proteins potentially involved in beta cell function and pathology. To identify candidate beta cell-specific genes, we applied the PCR-based subtractive hybridization technique of representational difference analysis (RDA) to the mouse SV40-transformed endocrine cell lines, betaTC3 and alphaTC1. Following three successive subtractions of alphaTC1 complementary DNA from betaTC3 complementary DNA, difference products were cloned into pUC19 and nucleotide sequences determined. Comparison of 91 sequences against the databases identified 11 known and 8 novel genes. Known genes included previously reported beta cell-specific genes, insulin I/II and islet amyloid polypeptide, as well as other non-beta cell-specific genes such as those for insulin-like growth factor II, selenoprotein P, neuronatin, prohormone convertase, and type 1 protein kinase A regulatory subunit. By Northern blot hybridization, expression of the majority of known and novel genes was restricted to betaTC3 cells. Novel genes BA-12, -13, -14, and -18 were expressed not only in betaTC3 cells, but also in normal pancreatic islets and a limited number of other tissues. The deduced amino acid sequence of BA-14 showed significant homology with members of the cadherin superfamily indicating that BA-14 may encode a cadherin-like molecule potentially involved in beta cell adhesion events during islet ontogeny. In betaTC3 cells, none of the novel genes were regulated at the RNA level by high glucose. However, in parallel studies, transcription of BA-12 was significantly increased by both sodium butyrate and nicotinamide, suggesting that this gene may play a role in pancreatic beta cell growth and/or differentiation. In this study, we have demonstrated that cRDA is an effective strategy for systematically mapping differences in gene expression between two related but functionally-distinct endocrine cells. Its application to experimental animal models of islet-cell regeneration may facilitate the discovery of potential factors that mediate beta cell growth and differentiation.

Amino Acid Sequence↗

[Intrapulmonary laceration revealed by computed tomography in a patient with pneumomediastinum].

An 18-year-old man had bronchial asthma and a pneumomediastinum. A computed tomographic scan of the chest revealed the pneumomediastinum, intrapulmonary laceration of the S1b, and a small amount of air in the perivascular space from V1a to V1. Increased pressure in intrapulmonary airways may have resulted in ruptured S1b alveoli and air leakage into the interstitium between the surrounding secondary lobules. The air may have moved along the perivascular space (pulmonary vein) toward the hilum, and eventually into the mediastinum. We know of no previous report of pneumomediastinum in which images of intrapulmonary lesions are presented. In this case computed tomography revealed the mechanism by which the pneumomediastinum probably developed.

Adolescent↗

Chemical nature of the light emitter of the Aequorea green fluorescent protein.

The jellyfish Aequorea victoria possesses in the margin of its umbrella a green fluorescent protein (GFP, 27 kDa) that serves as the ultimate light emitter in the bioluminescence reaction of the animal. The protein is made up of 238 amino acid residues in a single polypeptide chain and produces a greenish fluorescence (lambda max = 508 nm) when irradiated with long ultraviolet light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide -Ser65-Tyr66-Gly67-. GFP has been used extensively as a reporter protein for monitoring gene expression in eukaryotic and prokaryotic cells, but relatively little is known about the chemical mechanism by which fluorescence is produced. To obtain a better understanding of this problem, we studied a peptide fragment of GFP bearing the chromophore and a synthetic model compound of the chromophore. The results indicate that the GFP chromophore consists of an imidazolone ring structure and that the light emitter is the singlet excited state of the phenolate anion of the chromophore. Further, the light emission is highly dependent on the microenvironment around the chromophore and that inhibition of isomerization of the exo-methylene double bond of the chromophore accounts for its efficient light emission.

Amino Acid Sequence↗

Endoderm-specific gene expression in embryonic stem cells differentiated to embryoid bodies.

Mouse embryonic stem cells can differentiate into various cell types within cell aggregates called embryoid bodies (EBs). This structure consists of ectodermal, mesodermal, and endodermal tissues, which resemble the embryo of egg-cylinder stage. After 8-10 days in culture, about half of the EBs expand into large cystic structures homologous to visceral yolk sac of postimplantation embryos. To study endoderm differentiation at molecular level, we examined expression of endoderm marker genes during the processes of EB development. alpha-Fetoprotein (AFP) and transthyretin (TTR) transcripts increased at the stage when embryoid bodies began to form yolk-sac-like structures and were expressed strongly thereafter. Expression of hepatocyte nuclear factor (HNF) 4, a variant form of HNF1 (also called HNF1beta), and HNF3beta started before the onset of AFP and TTR expression. HNF1 (also called HNF1alpha) expression began a few days after the onset of the expression of the transcription factors described above. Serum albumin (ALB) transcript was only found in late large cystic EBs. Also, AFP gene expression preceded ALB gene expression. These results suggest that the patterns of endoderm gene expression during EB development reflect the order found during mouse development in vivo, and EB formation may serve as an in vitro system to study the differentiation process.

Animals↗

Preattentive and focal attentional processes in schizophrenia: a visual search study.

Using a visual search task, the present study investigated preattentive and focal attentional processes in schizophrenic patients. The performance of 15 schizophrenic patients and 20 normal subjects was compared in three search tasks: feature search, 2-D feature search, and conjunction search. The target item was a red 'X' in all search tasks, and the distractor items were red 'O' in the feature search, green 'O' in the 2-D feature search, and red 'O' and green 'X' in the conjunction search. Set size total number of items presented in the display was 4, 16, or 25. Reaction times (RTs) for the subject's correct detection of target presence and absence were measured, and slopes of linear function relating RT to set size were computed. In the feature and the 2-D feature search, the schizophrenic subjects showed nearly zero slopes as did the normal subjects, indicating that in the preattentive process the schizophrenic patients functioned at a normal level. In the conjunction search, the schizophrenic subjects showed steeper slopes than the normal subjects for target absence (but not for target presence), suggesting that there was a deficit in the focal attentional process. Those results are consistent with the view of Callaway and Naghdi (1982) that a deficit in schizophrenic patients is mainly confined to the attentional process (cf., Lieb et al., 1994).

Adult↗