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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 73 records · Page 4Linked to original sources
PubMed2001

Machado-Joseph disease associated with an absence of fungiform papillae on the tongue.

The authors report the case of a family with Machado-Joseph disease (MJD) associated with sensory and autonomic disturbances-particularly the absence of fungiform papillae on the tongue and taste buds. Sural nerve biopsy showed a loss of myelinated fibers. Autonomic function tests showed bladder-bowel dysfunction, hypohidrosis, and low coefficients of variation of R-R intervals on electrocardiogram. These findings may be another possible variant or previously unrecognized symptoms in MJD.

Adult↗
PubMed2001

IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis.

IL-4 is a cytokine with anti-inflammatory properties on activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory disease, is characterized by a paucity of IL-4 and an abundance of synovial macrophage-derived mediators. Herein, the effect of a single injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared with the effect of PBS injection into rat ankles. Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduced adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle inflammation, decreasing articular index scores, ankle circumferences, paw volumes, radiographic scores, mean levels of monocyte chemoattractant protein-1, the number of inflammatory cells, and the number of synovial blood vessels. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS groups. After arthritis onset, mean levels of TNF-alpha, IL-1beta, macrophage inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates compared with PBS-treated homogenates. Thus, increased expression of IL-4 via gene therapy administered in a preventative and/or therapeutic manner reduced joint inflammation, synovial cellularity, levels of proinflammatory cytokines, vascularization, and bony destruction in rat AIA, suggesting that a similar treatment in humans may be beneficial.

Adenoviruses, Human↗
PubMed2001

Mode of bleaching phytotoxicity of herbicidal diphenylpyrrolidinones.

A mode of action study of herbicidal diphenylpyrrolidinones was carried out through carotenoid analyses in intact Scenedesmus cells and by a cell-free plant-type phytoene desaturase assay using Escherichia coli transformants. A series of forty-eight diphenylpyrrolidinones decreased the carotenoid content of Scenedesmus cells in the light and inhibited phytoene desaturase. The relationship between substituents at various positions and inhibition of phytoene desaturase is discussed. Using very active bleaching diphenylpyrrolidinones, a 10(-5) M concentration affected neither the zeta-carotene desaturase nor the protoporphyrinogen-IX oxidase. Although some differences in their inhibitory activity were found between the in vivo and cell-free assays, it is concluded that the compounds are essentially bleachers affecting carotenoid biosynthesis in plants. Enzyme kinetics studies with recombinant phytoene desaturase revealed a non-competitive inhibition with respect to the substrate phytoene. A competition against the inhibitor was shown by the cofactor NADP+, suggesting an interaction of pyrrolidinones at the cofactor-binding site of phytoene desaturase.

Biological Assay↗
PubMed2001

G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells.

The aim of this study was to investigate the expression of G-protein coupled receptor kinases (GRKs) mRNA by RT-PCR and GRKs protein by immunohistochemistry in human detrusor cultured smooth muscle. Primary cultures of human detrusor smooth muscle cells were established using the explant method from three normal bladders. The expression of each GRK, beta-adrenergic receptor and muscarinic acethylcholine receptor (mAchR) mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical staining was also performed using primary antibodies for GRKs. The GRK2 and GRK3 transcripts were detected by RT-PCR. The m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes mRNA were also detected. Using immunohistochemistry, both GRK2 and GRK3 were found to be expressed in detrusor smooth muscle cells. These results demonstrated the existence of GRK2 and GRK3 and the co-expression of m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes in detrusor smooth muscle cells. The possibility exists that these kinases play a role in the desensitization mechanism of mAchR and beta adrenergic receptors.

Cell Size↗
PubMed2001

Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreas.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Adenocarcinoma↗
PubMed2001

alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei.

Advanced silver stains and immunohistochemical reactions against alpha-synuclein were used to detect Parkinson's disease-related cytoskeletal abnormalities in select lower brain stem nuclei. Various types of inclusion bodies including inconspicuous and heretofore unnoted granular particles and thread-like Lewy neurites were visualized. Of the nuclei investigated (gigantocellular reticular nucleus, bulbar raphe nuclei, coeruleus-subcoeruleus area), only lipofuscin- or neuromelanin-laden neuronal types showed a propensity to develop the pathological changes. Neuronal types devoid of pigment deposits remained free of the cytoskeletal abnormalities. Fine, dust-like particles and small globular Lewy bodies were encountered solely within the limits of intraneuronal lipofuscin or neuromelanin deposits.

Aged↗
PubMed2001

Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in a CDC45 homolog and interacts genetically with polalpha.

Proteins involved in the initiation of DNA replication play critical roles in the assembly and loading of replication complexes at replication origins. To gain further insight into the regulation of initiation, we screened in fission yeast for temperature-sensitive mutants which arrested at the G1/S boundary, and isolated nine mutants which arrested with a 1C DNA content at 36 degrees C. By linkage analysis, two complementation groups were identified which were not allelic to known G1 arrest mutations. One of the mutants isolated, sna41goul, arrested with a G1 DNA content and expressed a pleiomorphic phenotype, i.e., a mixture of cut and cdc phenotypes, at 36 degrees C. The point of arrest was identified as after START but before the hydroxyurea-induced block, by taking advantage of the mutant rad26.a14, which has a defect in an early S phase-specific checkpoint, and by performing reciprocal shift experiments. sna41 goal is allelic to sna41+, which is homologous to the CDC45 gene of budding yeast, and the mutation lies in a motif that is highly conserved in Cdc45-related proteins. The temperature sensitivity of the sna41goal mutant can be suppressed to some extent by ts mutations in polalpha. Our genetic results are consistent with a model in which Cdc45 plays crucial roles in the assembly of the replication apparatus at replication origins.

Carrier Proteins↗
PubMed2001

Trends in treatment for pancreatic cancer.

Although surgical resection is considered to be the only approach that offers a possibility of cure to patients with pancreatic cancer, the prognosis of the disease has not been improved markedly by any surgical procedures in the past 20 years. Large-scale randomized prospective clinical trials are being conducted in the United States and Italy, comparing standard lymph node dissection with extended lymph node dissection. Although preoperative chemoradiation has various advantages in the treatment of pancreatic cancer, it does not contribute to its downstaging and eventual cure. The combination of leucovorin, 5-fluorouracil (5-FU), and extracorporeal irradiation, however, has been proven to improve the patient's quality of life (QOL). Palliative surgery still requires further research in areas such as the examination of morbidity rates and the duration of bypass effects, now that laparoscopic and endoscopic surgery have both been well developed. Recent biological research has revealed the mechanisms of the carcinogenesis and the progression of pancreatic cancer, and, against this background, we assume that more effective trials will be conducted soon. Immunotherapy with dendritic cells, as well as gene therapy with mutant adenovirus, has already been employed clinically. Pancreatic cancer therapy is now facing new prospects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cytokine modulation in acute pancreatitis.

The clinical manifestations of acute pancreatitis (AP) vary significantly from mild to lethal in form, the severity of the disease being largely determined by the actions of various kinds of inflammatory mediators, including cytokines, reactive oxygen species, proteolytic enzymes, and lipids, as well as gaseous mediators. Despite increasing knowledge implicating the involvement of cytokines in the progression of AP, no clinical trials pertaining to cytokine modulation have been performed so far. Progress in intensive care technologies has contributed to the improvement of mortality and morbidity rates in severe AP in the past decade; however, it appears to be reasonable for clinicians to "line up their sights" on the modulation of cytokines as a direct treatment. In contrast to the large body of experimental studies demonstrating the beneficial effects of cytokine modulation on the amelioration of the disease, direct extrapolation from these successful experiments to the clinical situation seems to be extremely difficult.

Acute Disease↗
PubMed2001

Mineral density and histomorphometric assessment of bone changes in the proximal tibia early after induction of type II collagen-induced arthritis in growing and mature rats.

Bone changes in both actively growing (6-week-old) and mature (6-month-old) rats with collagen-induced arthritis (CIA) were investigated in order to clarify the mechanisms of osteoporosis near inflamed joints in patients with early rheumatoid arthritis (RA) and juvenile RA. In female Sprague-Dawley rats, the proximal tibiae from the CIA and control groups early after immunization, when any influence of immobilization due to joint pain and swelling is minimal, were studied using dual X-ray absorptiometry and histomorphometry after double-labeling with tetracycline. Arthritis developed within 10-14 days after immunization in both growing and mature rats. Physical activity, growth, and body weight continued to resemble that of the control group for at least 10 days. The bone mineral density in the proximal tibia did not differ significantly between the CIA and control groups. In growing rats, a highly significant increase in bone resorption, and decreases in bone formation and trabecular bone volume became evident histomorphometrically before visible signs of arthritis had developed. In mature rats, bone formation was markedly decreased without an increase in bone resorption. The differences in the reaction between growing and mature rats reflected a difference in the number of remodeling sites (units) and an uncoupling between osteoblasts and osteoclasts. We conclude that osteoporosis near inflamed joints results from an imbalance between bone resorption and formation caused by immune reactions in the CIA rats. Moreover, a decrease in bone formation may, in part, precede the clinical onset of arthritis.

Animals↗
PubMed2001

Flexible hinge toe implant arthroplasty for rheumatoid arthritis of the first metatarsophalangeal joint: long-term results.

We report the long-term clinical results and survival rate of the implant in flexible hinge toe implant arthroplasty of the first metatarsophalangeal joint, combined with a shortening oblique osteotomy of the metatarsal neck in the lateral toes, in patients with rheumatoid arthritis. Between 1983 and 1990, arthroplasty was performed on 97 feet in 66 patients. Twenty-seven patients died; follow-up information was available for 60 feet in the remaining 39 patients, who were followed for an average of 12 years. Twenty-nine patients (74%) were satisfied with the outcome after surgery, 7 were satisfied but had some pain or recurrent deformities, and 3 were unsatisfied. Radiologically, visible fracture was identified in nine implants. Four implants were removed because of infection (n = 2) or recurrent deformity (n = 2); no implant was removed because silicone synovitis developed. With revision as the endpoint, the implant survival rate was 93% at 10 years, and with radiographic implant fracture as the endpoint, the implant survival rate was 87% at 10 years. Shortening oblique osteotomy of the lateral toes appeared to decrease the rate of implant fracture and should be performed concomitantly with implantation when rheumatoid forefoot deformities are being reconstructed.

Adult↗
PubMed2001

Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer.

BACKGROUND: No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). METHODS: From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. RESULTS: The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The frequencies of lymph node metastasis in early gastric, m-, and sm-cancers were 8.9%, 2.5%, and 17.6%, respectively. Node involvement was associated with a higher frequency of undifferentiated than differentiated histology, as well as with greater tumor size. The incidences of lymph node metastasis in m-cancers with a diameter of less than 4 cm, and in sm-cancers with a diameter below 1 cm were 1.3% (37/2837) and 4.9% (4/82), respectively. These metastases rarely extended beyond the first tier. CONCLUSION: N0 and M-cancers, m-cancers less than 4 cm in diameter, and sm-cancers no larger than 1 cm in diameter may be appropriate indications for limited surgery.

Chi-Square Distribution↗
PubMed2001

Changes in NADPH diaphorase expression in the fish visual system during optic nerve regeneration and retinal development.

The various functions of nitric oxide (NO) in the nervous system are not fully understood, including its role in neuronal regeneration. The goldfish can regenerate its optic nerve after transection, making it a useful model for studying central nervous regeneration in response to injury. Therefore, we have studied the pattern of NO expression in the retina and optic tectum after optic nerve transection, using NADPH diaphorase histochemistry. NO synthesis was transiently up-regulated in the ganglion cell bodies, peaking during the period when retinal axons reach the tectum, between 20-45 days after optic nerve transection. Enzyme activity in the tectum was transiently down-regulated and then returned to control levels at 60 days after optic nerve transection, during synaptic refinement. To compare NO expression in the developing and regenerating retina, we have looked at NO expression in the developing zebrafish retina. In the developing zebrafish retina the pattern of staining roughly followed the pattern of development with the inner plexiform layer and horizontal cells having the strongest pattern of staining. These results suggest that NO may be involved in the survival of ganglion cells in the regenerating retina, and that it plays a different role in the developing retina. In the tectum, NO may be involved in synaptic refinement.

Animals↗
PubMed2001

Microsatellite-centromere mapping in the loach, Misgurnus anguillicaudatus.

Primer sets for 15 polymorphic microsatellite loci were developed in the loach, Misgurnus anguillicaudatus (Cobitidae) by molecular cloning and sequencing techniques. Mendelian inheritance was confirmed for the 15 loci by examining the genotypic segregation produced with the primer sets in two full-sib families. The loci were mapped in relation to their centromere in four gynogenetic diploid lines, which were induced by inhibition of the second meiotic division after fertilization with genetically inert sperm. Microsatellite-centromere recombination rates ranged between 0.06 and 0.95 under the assumption of complete interference. Thus, these loci are distributed from the centromeres to the telomeres of their respective chromosomes. The success of mitotic gynogenesis, produced by suppression of the first cleavage, was verified by homozygosity at three diagnostic microsatellite loci that exhibited high gene-centromere meiotic recombination rates in the same family. The differences in heterozygosity levels observed with these markers were attributed to differences in the temporal application of heat shock following inert sperm activation.

Animals↗
PubMed2001

Germ-line chimera by lower-part blastoderm transplantation between diploid goldfish and triploid crucian carp.

Germ-line chimerism was successfully induced by blastoderm transplantation from donor triploid crucian carp, which reproduces gynogenetically, to recipient diploid goldfish, which reproduces bisexually. Lower part of donor blastoderm including primordial germ cells (PGCs) was sandwiched between recipient blastoderm at the mid- to late-blastula stage. When donor grafts were prepared from intact embryos or ventralized ones by removing vegetal yolk hemisphere at the 1- to 2-cell stage, malformations including double axes were observed in the resultant chimeras transplanted with grafts from intact embryos at the hatching stage, while a few malformations in those from ventralized embryos. PGCs originated from donor grafts were observed around the gonadal anlage at 10 days post-fertilization in chimeras. When ploidy of erythrocytes and epidermal cells in chimeric fish was examined by flow-cytometry, no triploid cells were detected at 1- and 5-year-old chimeras. Three-year-old chimeric fish (n = 5) laid eggs originated from the donor together with those from the recipient. The frequency of eggs from the donor crucian carp blastoderm varied from 3.1 to 89.3% between chimeras.

Animals↗
PubMed2001

Phospholipase A2 mediates ischemic injury in the hippocampus: a regional difference of neuronal vulnerability.

Although it is well known that the hippocampal CA1 subfield is highly vulnerable to ischemic injury, cellular mechanisms leading to this neuronal degeneration are not fully understood. Using organotypic cultures of rat hippocampal slices, we determined whether phospholipase A2 (PLA2) is activated in response to ischemic conditions (OGD; oxygen and glucose deprivation). The PLA2 activity in the pyramidal cell layer increased immediately following a 35-min exposure to OGD, which was likely to be mediated by selective activation of cytosolic Ca2+-dependent PLA2 subtype (cPLA2). This enhancement lasted for at least 24 h. Interestingly, no apparent increase was detected in the dentate gyrus. Twenty-four hours after the OGD exposure, neuronal death was detected mainly in the CA1 region of hippocampal slices. To examine whether the PLA2 activation is causally or protectively involved in the ischemic injury, we investigated the effect of pharmacological blockade of PLA2 on the OGD-induced neuronal death. The PLA2 inhibitor bromophenacyl bromide efficiently prevented the cell death in a concentration-dependent manner. Similar results were obtained for the selective cPLA2 inhibitor AACOCF3. However, the Ca2+-independent PLA2 inhibitor bromoenol lactone and the secretory PLA2 inhibitor LY311727 were virtually ineffective. These results suggest that cPLA2 plays a causative role in the neuronal death following OGD exposure. Thus, the present study may provide novel therapeutic targets for the development of neuroprotective agents.

Animals↗
PubMed2001

The expression of thyrotrophin-releasing hormone receptor 1 messenger ribonucleic acid in human pituitary adenomas.

OBJECTIVE: Thyrotrophin-releasing hormone (TRH) paradoxically induces the release of growth hormone (GH) when injected intravenously into acromegalic patients, although the mechanism of this action is unknown at present. Several research groups have reported that the level of TRH receptor-1 (TRHR-1) mRNA expression is variable in pituitary adenomas, and does not correlate with the degree of paradoxical GH response to TRH administration in a limited number of acromegalic patients. We aimed to compare the expression levels of TRHR-1 mRNA among various types of pituitary adenoma and to clarify whether these levels correlate with the degree of pituitary hormone response to TRH. PATIENTS: Pituitary adenoma tissue was obtained by surgery from 14 patients with acromegaly, four with prolactinomas, nine with nonfunctioning adenomas and one with a TSH-producing adenoma. METHODS: The level of human TRHR-1 mRNA expression in each adenoma was quantified using the competitive reverse transcription polymerase chain reaction (RT-PCR) METHOD: For amplification of a TRHR-1 cDNA fragment, a sense primer was designed according to the sequence in exon 2 and an antisense primer designed according to the sequence located at the region in exon 3 that does not encode for the alternative splicing-generated short form of TRHR-1 mRNA. RESULTS: TRHR-1 mRNA was detected in all pituitary adenomas examined and did not correlate with their size. The mean level of TRHR-1 mRNA expression was significantly lower in GH-producing adenomas than in prolactinomas and nonfunctioning adenomas (1.4 +/- 0.4 x 10(-2) attomol/microg total RNA, 10.7 3.4 x 10(-2) attomol/microg total RNA, and 7.2 +/- 3.3 x 10(-2) attomol/g total RNA, respectively). The ratio of plasma peak GH induced by TRH administration to the basal level of plasma GH in the patients with acromegaly correlated positively with the level of TRHR-1 mRNA expression in their GH-producing adenomas (r = 0.620, P = 0.0179). The responsiveness of plasma PRL and gonadotrophin to TRH in the patients with prolactinoma and nonfunctioning pituitary adenoma did not significantly correlate with the levels of TRHR-1 mRNA expression in their pituitary adenomas, respectively. CONCLUSIONS: The findings of the present study suggest that the level of TRHR-1 mRNA expression varies among different types of pituitary adenoma. Furthermore, in acromegaly, the responsiveness of plasma GH to TRH administration appears to at least partially depend on the level of TRHR-1 mRNA expression in the GH-producing pituitary adenoma.

Acromegaly↗