Search PubMed⌕ Search

Biomedical subjects

T Nakajima

Publications and source records attributed to T Nakajima.

At least 127 records · Page 7Linked to original sources
PubMed2001

Serum lipid metabolism abnormalities and change in lipoprotein contents in patients with advanced-stage renal disease.

BACKGROUND: Arteriosclerosis is the major cause of death in patients with chronic renal failure. There is much interest in the lipid metabolism of patients treated with hemodialysis. METHODS: We analyzed low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in chronic renal failure (CRF) patients according to patients on hemodialysis (HD), patients with diabetic nephropathy before initiation of dialysis (DN), and patients with chronic glomerulonephritis in the conservative stage (CGN); and compared the lipid metabolic abnormalities in patients on hemodialysis and those not yet on hemodialysis. We also analyzed the qualitative abnormalities of LDL and HDL and their relationship with the pathological stages. RESULTS: Electrophoretic patterns identified small LDL particles and small HDL particles in the three groups, and the degree of denaturation was more enhanced in CRF patients in the conservative stage than in HD patients. For LDL susceptibility to oxidation LDL (oxLDL) by addition of Cu(2+), the lag time was approximately 57 min in healthy controls and CGN patients, but was prolonged to approximately 75 min in HD and DN patients. For HDL susceptibility to oxidation HDL (oxHDL), HD, DN and CGN patients showed lag times shorter than those found in healthy control subjects. These results showed that LDL and HDL in the serum of CRF patients were in a state of enhanced susceptibility to oxidative modification. In Western blot analysis using anti-human-denatured LDL and anti-human-oxidized HDL monoclonal antibodies, bands of low molecular oxLDL at 150-197 kDa were detected in all CRF patients, with marked tailing in CGN patients. Similarly, bands of small oxHDL particles at 110 and 120 kDa were found in HD, DN and CGN patients. CONCLUSIONS: Oxidative modification of both LDL and HDL occurs in patients with advanced CRF resulting in small lipoproteins. Increased production of oxLDL and oxHDL is the main cause of lipid metabolic abnormality in CRF patients.

Aged↗
PubMed2001

Isolation and sequence determination of peptides in the venom of the spider wasp (Cyphononyx dorsalis) guided by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry.

Micro-scale (sub-pmol) isolation and sequence determination of three peptides from the venom of the solitary spider wasp Cyphononyx dorsalis is described. We isolated two novel peptides Cd-125 and Cd-146 and a known peptide Thr(6)-bradykinin from only two venom sacs of solitary spider wasp Cyphononyx dorsalis without bioassay-guided fractionation, but instead guided by MALDI-TOF MS. The MALDI-TOF MS analysis of each fraction showed the purity and molecular weight of the components, which led to the isolation of the peptides virtually without loss of sample amount. The sequences of the novel peptides Cd-125 (Asp-Thr-Ala-Arg-Leu-Lys-Trp-His) and Cd-146 (Ser-Glu-Thr-Gly-Asn-Thr-Val-Thr-Val-Lys-Gly-Phe-Ser-Pro-Leu-Arg) were determined by Edman degradation together with mass spectrometry, and finally corroborated by solid-phase synthesis. The known peptide Thr(6)-bradykinin (Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg) was identified by comparison with the synthetic authentic specimen. This is the first example for any kinins to be found in Pompilidae wasp venoms. The procedure reported here can be applicable to studies on many other components of solitary wasp venoms with limited sample availability.

Amino Acid Sequence↗
PubMed2001

Biochemical markers in the synovial fluid of glenohumeral joints from patients with rotator cuff tear.

It is known that rotator cuff tears are sometimes accompanied by joint destruction. Our purpose was to elucidate the pathology with this condition. Thirty-two synovial fluid (SF) samples aspirated from the glenohumeral joints of patients with rotator cuff tears, including 7 with partial-thickness and 25 with full-thickness tears of the rotator cuff (10 massive and 15 isolated supraspinatus tendon (SSp) tears), were examined. Collagenase (MMP-1), stromelysin 1 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP-1) and carboxy-terminal type II procollagen peptide (pCOL Il-C) were measured in the SF using the respective sandwich enzyme immunoassays. Glycosaminoglycan (GAG) was also quantified with a cationic dye binding method using 1,9-dimethylmethylene blue. Levels of any molecules except pCOL II-C in the SF appeared to be higher in full-thickness tears than those in partial-thickness tears. Moreover, levels of MMP-1, MMP-3 and GAG in the SF were significantly higher in massive tears of the rotator cuff in comparison with those in isolated SSp tears. Such significance was not observed in the levels of TIMP-1 or pCOL II C in the SF. We examined the relation of those levels with operative findings or clinical parameters from full-thickness tears, and observed significant correlations of the tear size with the levels of MMP-1, MMP-3 and GAG in the SF. Although these marker molecules in SF do not always originate from cartilage, our results may indicate the potential for accelerated cartilage-degrading activity in the glenohumeral joint in massive tears of the rotator cuff.

Adult↗
PubMed2001

Potential anti-androgenic activity of roxithromycin in skin.

Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts. The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity. While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.

Androgen Antagonists↗
PubMed2001

A convenient method for discriminating between natural and depleted uranium by gamma-ray spectrometry.

A convenient method for discriminating between natural and depleted uranium reagent was developed by measuring and analyzing the gamma-ray spectra of some reagents with no standard source. The counting rates (R) of photoelectric peaks of gamma-rays from nuclides with the same radioactivity divided by their emission probability (B) are expressed as a function of gamma-ray energy. The radioactivities of 234Th and 234mPa and 21.72 times that of 235U are equal to the radioactivity of 235U in natural uranium. Therefore, the plot of 21.72-fold R/B for 235U should be on a curve fitted to the points for 234Th and 234mPa in natural uranium. Depleted uranium with a 235U isotopic composition of less than 0.68% could be discriminated from natural uranium in the case of a reagent containing 4.0 g of uranium.

Algorithms↗
PubMed2001

Vascular invasion in squamous cell carcinomas of human oral mucosa.

The process of vascular invasion of human oral squamous cell carcinomas was histologically and immunohistochemically studied in surgical and autopsy specimens. Hematoxylin-eosin, Masson's trichrome, and immunohistochemical stainings for Ulex europaeus I lectin binding, CD31, and type IV collagen were done to differentiate lymphatic and blood vessels and to demonstrate basement membranes in vascular walls and around carcinoma cell nests was observed. With growth of tumor, there was mechanical disruption of vascular walls and endothelial cells by carcinoma cell nests. After disrupting vascular walls, they invaded into the lumen as clusters, not as single cells. At the blood vessel invasion sites, inflammatory reactions were seen around carcinoma cell nests inside as well as outside lumina with microthrombotic reactions due to endothelial injury. At the lymphatic invasion sites, carcinoma cell nests maintained their volume inside the lumen and the cells adhered tightly to each other, and inflammatory reaction was scarcely seen. These findings showed that mechanical pressure has an important role in the vascular invasion of human oral squamous cell carcinoma.

Animals↗
PubMed2001

Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice.

We examined the effects of a third generation bisphosphonate [YM-175; disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate] on osteoclasts in osteosclerotic (oc/oc) mice to elucidate the cellular mechanism for incorporation of the bisphosphonate. Osteoclasts of oc/oc mice were in direct contact with bone matrix but devoid of ruffled borders. Tartrate-resistant acid phosphatase (TRAPase) showed spotty localization intercellularly, whereas vacuolar H(+)-ATPase (V-ATPase) immunoreactivity was observed homogeneously in the cytoplasm. Upon injection of bisphosphonate, most osteoclasts lost cell polarity and were detached from bone surfaces. The detached osteoclasts underwent apoptosis as characterized by condensation of chromatin, absence of Golgi apparatus, and formation of many vesicles in the cytoplasm. Both TRAPase and V-ATPase were evenly distributed in the cytoplasm. The pyknotic nuclei of osteoclasts revealed DNA fragments as evidenced by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The results indicate that osteoclasts lacking ruffled borders in oc/oc mice incorporated the bisphosphonate from a site different from ruffled borders and that bisphosphonate may directly affect osteoclasts without mediating its deposition to the bone matrix.

Animals↗
PubMed2001

Functional human IgE specific for Dermatophagoides farinae antigen is produced in SCID mice reconstituted with peripheral mononuclear cells derived from healthy persons and patients with asthma.

BACKGROUND: Whether normal peripheral blood mononuclear cells (PBMCs) transferred to severe combined immunodeficient (SCID) mice produce specific IgE remains unclear. METHODS: Mice received injections of Dermatophagoides farinae antigen (Df)-stimulated PBMCs from healthy persons (IgE RAST score of 0). RESULTS: High titers of Df-specific IgE were detected. The Df-specific IgE activity produced was comparable to or higher than that produced by cells from patients with asthma although the time to maximal production was longer. IgE derived from PMBCs of healthy persons or patients with asthma induced histamine release from cultured human basophils that had been stimulated with Df antigen or an anti-IgE antibody. Treatment of Df-stimulated PBMCs with a high dose, but not a low dose, of interleukin-4 stimulated production of Df-specific IgE by PMBCs from healthy persons or patients with asthma. In contrast, intravenous injection of IFN-gamma into reconstituted SCID mice decreased Df-specific IgE production by PBMCs from patients with asthma. In PMBCs from healthy persons, IgE class-switching may occur later and block the effects of treatment with IFN-gamma. CONCLUSIONS: PBMCs from healthy persons and persons with asthma have clones reactive to allergen and produce functional IgE specific for relevant antigens in mite-sensitive bronchial asthma.

Allergens↗
PubMed2001

Involvement of urban living environments in atopy and enhanced eosinophil activity: potential risk factors of airway allergic symptoms.

BACKGROUND: Airway allergic diseases, such as bronchial asthma and allergic rhinitis, have increased, especially in urban areas. These diseases are characterized by airway inflammation with enhanced eosinophil activity, and the risk of disease development has been shown to increase with the prevalence of atopy. METHODS: Questionnaires were administered to 426 healthy adult women aged 30-74 years, living in an urban area of Osaka, Japan, to survey individual living environments and airway allergic symptoms such as cough, sputum, and wheezing. Moreover, serum house-dust-mite (Dermatophagoides pteronyssinus, [Der p])-specific immunoglobulin E (IgE) and serum eosinophil cationic protein (ECP) were examined by radioimmunoassay, and the atopic status (atopic sensitization) and enhanced eosinophil activity were assessed as Der p-specific IgE RAST scores of 2-6 and ECP levels of more than 10 ng/ml, respectively. RESULTS: Intensive use of electric air conditioners in hot weather (odds ratio: 2.07 [95% CI: 1.11-3.87]) and mold proliferation in the kitchen (2.77 [1.34-5.73]) significantly increased the risk of atopic sensitization. Poor home ventilation and family smoking appeared to be positively but not significantly associated with atopic sensitization. Personal smoking and intensive use of the air conditioner appeared to be positively related to enhanced eosinophil activity. Atopic status showed significant involvement in the development of wheezing, and the development of cough was significantly associated with enhanced eosinophil activity. CONCLUSIONS: The results suggest that some urban styles of living are involved in atopic sensitization and enhanced eosinophil activity in the Japanese urban population, probably due to living conditions, such as indoor dampness and poor home ventilation, caused by tight insulation, which increase exposure to indoor air pollutants, such as respirable mite allergens and tobacco smoke.

Adult↗
PubMed2001

Interleukin-10 gene promoter polymorphism in Japanese patients with adult and early-onset periodontitis.

BACKGROUND: IL-10 is an anti-inflammatory cytokine, which may modulate disease expression in chronic inflammatory periodontal disease. 3 dimorphic polymorphisms within the IL-10 gene promoter have recently been identified and appear to influence regulation of its expression. AIM: The aim of the present study was to investigate whether the promoter polymorphisms are associated with adult periodontitis (AP) and generalized early-onset periodontitis (G-EOP). METHODS: Genomic DNA was obtained from 34 AP patients, 18 G-EOP patients and 52 controls. The promoter region between -506 and -1140 was amplified by polymerase chain reaction, and polymorphisms were detected by nucleotide sequencing. RESULTS: The haplotype frequencies in Japanese were quite different from those of Caucasian and were even slightly different from those of southern Chinese with systemic lupus erythematosus. We found no significant difference in allele or haplotype frequencies between patients and controls. CONCLUSIONS: IL-10 production may be regulated within the complex cytokine network in chronic inflammatory periodontal disease, rather than the gene polymorphisms.

Adult↗
PubMed2001

Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins.

1. The mechanism of Na(+) channel block by three macrocyclic polyamine derivatives and two spider toxins was studied with voltage clamp and internal perfusion method in squid axons. 2. All these chemicals specifically block Na(+) channels in the open state only from the internal surface, and do not affect K(+) channels. 3. The blocking effect is enhanced as the depolarizing pulse becomes larger. Blocked channels are unable to shift to the inactivated state. 4. In the case of cyclam and guanidyl-side armed cyclam (G-cyclam), quick release of these chemicals from the binding sites is proven by the increase in the tail current and prolongation of the time course of the off gating current. On the other hand, in the presence of N-4 and the spider toxins, their detachment was delayed significantly. 5. Molecular requirements for the block of Na(+) channels by these molecules are the presence of positive charge and hydrophobicity.

Algorithms↗
PubMed2001

Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities.

Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.

Animals↗
PubMed2001

Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum.

Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.

Adult↗
PubMed2001

Postoperative speech development based on cleft types in children with cleft palate.

BACKGROUND: The purpose of this historical cohort study was to compare the speech development of children with three types of cleft palate while controlling for some confounding factors. METHODS: Subjects included 28 children with bilateral cleft lip and palate (BCLP), 74 with unilateral cleft lip and palate (UCLP), 33 with isolated cleft palate (ICP), and 168 normal control children. Children with cleft palate attended a speech clinic in Fukuoka, had attained adequate velopharyngeal function after palatoplasty carried out within 18 months after birth, and had no syndromic diseases, persistent hearing loss, mental retardation, or central nervous system problems. RESULTS: Children with BCLP began using two-word sentences later than other children (3 months, P<0.01). However, the difference based on sex was also statistically significant. Female patients started using two-word sentences earlier than male patients (2 months, P<0.01). Children with BCLP had lower verbal scores on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) than other children (12.4-14.9 points, P<0.01). There was no significant difference based on sex. CONCLUSIONS: The results of this research indicate the following: speech development of children with ICP and UCLP was similar to that of normal children; however, speech development of children with BCLP was delayed compared with other children with or without cleft palate.

Age Factors↗
PubMed2001

Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture.

Mammalian circadian clock genes Per1 and Per2 are rhythmically expressed not only in the suprachiasmatic nucleus where the mammalian circadian clock exists, but also in other brain regions and peripheral tissues. The induced circadian oscillation of Per genes after treatment with high concentrations of serum or various drugs in cultured cells suggests the ubiquitous existence of the oscillatory mechanism. These treatments also result in a rapid surge of expression of Per1. It has been shown that multiple signaling pathways are involved in Per1 gene induction in culture cells. We used a dispersed primary cell culture made up of mouse cerebellar granule cells to examine the stimuli inducing the mPer genes and their signaling pathways in neuronal tissues expressing mPer genes. We demonstrated that mPer1, but not mPer2, mRNA expression was dependent on the depolarization state controlled by extracellular KCl concentration in the granule cell culture. Nifedipine treatment reduced mPer1 induction, suggesting that mPer1 mRNA expression depends on intracellular calcium concentration regulated through a voltage-dependent Ca2+ channel. Transient mPer1 mRNA induction was observed after elevating KCl concentration in the medium from 5 mM to 25 mM. This increased expression was suppressed by a calmodulin antagonist, or CaMKII/IV inhibitor, but not by MEK inhibitors. Addition of pituitary adenylate cyclase-activating polypeptide-38 to the medium also induced transient Per1 gene expression. This induction was mimicked by dibutyryl-cAMP and suppressed by a protein kinase A (PKA) inhibitor, but not by MEK inhibitors. These results suggest that Ca2+/calmodulin-dependent protein kinase II/IV- and PKA-dependent pathways are involved in high-KCl and PACAP-induced mPer1 induction, respectively, and neural tissues use multiple signaling pathways for mPer1 induction similar to culture cells.

Animals↗
PubMed2001

Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5).

D,L-threo-beta-Benzyloxyaspartate (D,L-TBOA), an analog of threo-beta-hydroxyaspartate (THA) possessing a bulky substituent, is a potent non-transportable blocker for the excitatory amino acid transporters, EAAT1, 2 and 3, while L-threo-beta-methoxyaspartate (L-TMOA) is a blocker for EAAT2, but a substrate for EAAT1 and EAAT3. To characterize the actions of these THA analogs and the function of EAAT4 and EAAT5, we performed electrophysiological analyses in EAAT4 or EAAT5 expressed on Xenopus oocytes. In EAAT4-expressing oocytes, D,L-TBOA acted as a non-transportable blocker, while L-TMOA like D,L-THA was a competitive substrate. In contrast, D,L-THA, D,L-TBOA and L-TMOA all strongly attenuated the glutamate-induced currents generated by EAAT5. Among them, L-TMOA showed the most potent inhibitory action. Moreover, D,L-THA, D,L-TBOA and L-TMOA themselves elicited outward currents at negative potentials and remained inward at positive potentials suggesting that D,L-TBOA and L-TMOA, as well as D,L-THA, not only act as non-transportable blockers, but also block the EAAT5 leak currents. These results indicate that EAATs 4 and 5 show different sensitivities to THA analogs although they share properties of a glutamate-gated chloride channel.

Amino Acid Transport System X-AG↗