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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 793 records · Page 44Linked to original sources

Overhead work and shoulder-neck pain in orchard farmers harvesting pears and apples.

The effects of overhead work were studied by comparing orchard farmers' musculoskeletal symptoms while bagging pears with those same symptoms while bagging apples. The subjects were 52 Japanese female farmers, who were examined twice an evening in late June for bagging pears, and during another evening of late July for bagging apples, when each task had been almost finished. They were questioned about musculoskeletal complaints of stiffness and pain during each job, and examined for muscle tenderness and pain from joint movement. Arm elevation angles during the work were measured for each type of bagging. The prevalence of stiffness and pain in the neck and shoulder, muscle tenderness in the shoulder regions, and pain in neck motion were found to be significantly higher when bagging pears than apples. Musculoskeletal symptoms of parts other than the neck and shoulder did not differ between the two types of bagging. The working posture of elevating the arm more than 90 degrees was assumed to account for 75% of the time bagging pears, against 40% for bagging apples. Overhead work requiring arm elevation and head extension was considered to be closely related with shoulder-neck disorders among farmers.

Adult↗

Transgenic mice and knockout mutants in the study of oxidative stress in brain injury.

A rapid increase in the need to explore the molecular basis of cellular function and injury in the central nervous system has led neuroscientists to employ transgenic mouse technology. The successful making of transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) activity has made it possible to investigate the role of oxygen free radicals in ischemic and traumatic brain injury in a molecular fashion. It has been demonstrated that the 3-fold increase in SOD-1 transgene activity in SOD-1 Tg mice offers protection against cerebral ischemia and reperfusion in two different models of focal cerebral ischemia, as compared to nontransgenic wild-type littermates. Studies involving traumatic brain injury have also demonstrated that acute injuries, including brain edema and blood-brain barrier permeability, are significantly reduced in SOD-1 Tg mice. Furthermore, chronic neurological deficits, such as beam walking, beam balance, and body weight, are significantly improved in these transgenic animals following traumatic brain injury. In addition to the SOD-1 Tg mice being a useful tool for the study of CNS injury, targeted disruption of the mouse gene for mitochondrial manganese SOD (SOD-2) has been successful. These SOD-2 knockout mutant mice, in addition to the recently developed knockout mutants of neuronal nitric oxide synthase (NOS), are believed to offer a unique opportunity to elucidate the oxidative mechanisms in brain injury following stroke and trauma.

Animals↗

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.

Adult↗

Efficacy of simulated epidural test doses in adult patients anesthetized with isoflurane: a dose-response study.

A recent study demonstrated that an epidural test dose containing 15 micrograms epinephrine was an imperfect marker for intravascular injection during isoflurane anesthesia based on the conventional heart rate (HR) criterion (positive if > or = 20 bpm increase). We have determined the effects of epinephrine doses and isoflurane concentrations on these efficacies in healthy adult patients during isoflurane anesthesia. Eighty patients were randomly assigned to one of four groups according to the simulated test dose injected intravenously (IV) under 1% end-tidal isoflurane and nitrous oxide after endotracheal intubation. The saline group (n = 20) received 3 mL normal saline; the epinephrine 7.5 group (n = 20) received 3 mL 1.5% lidocaine containing 7.5 micrograms epinephrine; the epinephrine 15 and epinephrine 22.5 groups (n = 20 each) received an identical dose and volume of lidocaine but containing 15 and 22.5 micrograms epinephrine, respectively. HR and systolic blood pressure (SBP) were monitored invasively for 4 min after IV injection of the study drug. Although none in the saline group developed a HR increase > or = 20 bpm, 2, 14, and 12 patients elicited positive responses in the epinephrine 7.5, 15, and 22.5 groups (10%, 70%, and 60% sensitivities), respectively. If a positive HR response was defined by an increase of 10 bpm, sensitivities were 55%, 100%, and 100% in the epinephrine 7.5, 15, and 22.5 groups, respectively. On the other hand, none in the saline group, 12 in the epinephrine 7.5 group, and all patients in the epinephrine 15 and 22.5 groups developed maximum SBP increases > or = 15 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Agonists↗

Inhibition of trazodone metabolism by thioridazine in humans.

To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

Adult↗

[A case of tsutsugamushi disease which occurred in south western Shikoku].

We report a case of tsutsugamushi disease found in south western Shikoku. A 64-year-old male who lived in Towa Village in Kochi, developed a fever and headache on April 6, 1994, and was admitted to Uwajima City Hospital on April 15, with a ten-day history of illness. He had an eschar on the right anterior side of the breast and an enlargement of the right axillary lymph node, without a rash. Laboratory data showed mild liver injury and atypical lymphocytes with 6% in peripheral blood. After his blood was drawn for rickettsial isolation, the minocycline was administered. His symptoms improved rapidly and was discharged in good condition. We successfully isolated the causative agent, Rickettsia tsutugamushi, and designated it as the Shiba strain. High antibody titer against the Kato, Karp and Gilliam strains was detected in serum on admission and increased during the course of the disease. In Shikoku, tsutsugamushi disease is rare and only 13 cases were reported during last ten years. Especially in south western district of Shikoku, there have been no case reported since 1960. This case is important epidemiologically and suggests that we should pay attention to this disease.

Anti-Bacterial Agents↗

Circadian expression of the dnaK gene in the cyanobacterium Synechocystis sp. strain PCC 6803.

The expression of the dnaK gene in the cyanobacterium Synechocystis sp. strain PCC 6803 was continuously monitored as bioluminescence by an automated monitoring system, using the bacterial luciferase genes (luxAB) of Vibrio harveyi as a reporter of promoter activity. A dnaK-reporting bioluminescent Synechocystis strain was constructed by fusing a promoterless segment of the luxAB gene set downstream of the promoter region of the Synechocystis dnaK gene and introduction of this gene fusion into a BglII site downstream of the ndhB gene in the Synechocystis chromosome. Bioluminescence from this strain was continuously monitored and oscillated with a period of about 22 h for at least 5 days in continuous light. The phase of the rhythm was reset by the timing of the 12-h dark period administered prior to the continuous light. The period of the rhythm was temperature compensated between 25 and 35 degrees C. Thus, the bioluminescence rhythm satisfied the three criteria of circadian rhythms. Furthermore, the abundance of dnaK mRNA also oscillated with a period of about 1 day for at least 2 days in continuous light conditions, indicating circadian control of dnaK gene expression in Synechocystis sp. strain PCC 6803.

Base Sequence↗

Bacterial luciferase as a reporter of circadian gene expression in cyanobacteria.

To allow continuous monitoring of the circadian clock in cyanobacteria, we previously created a reporter strain (AMC149) of Synechococcus sp. strain PCC 7942 in which the promoter of the psbAI gene was fused to Vibrio harveyi luciferase structural genes (luxAB) and integrated into the chromosome. Northern (RNA) hybridization and immunoblot analyses were performed to examine changes in abundance of the luxAB mRNA, the native psbAI mRNA, and the luciferase protein to determine whether bioluminescence is an accurate reporter of psbAI promoter activity in AMC149. Under constant light conditions, the mRNA abundances of both luxAB and psbAI oscillated with a period of approximately 24 h for at least 2 days. The expression of these two genes following the same pattern: both mRNAs peaked in the subjective morning, and their troughs occurred near the end of the subjective night. The amount of luciferase protein also oscillated with a period of approximately 24 h, and the protein rhythm is in phase with the bioluminescence rhythm. The rhythm of the luciferase mRNA phase-leads the rhythms of luciferase protein and in vivo bioluminescence by several hours. Comparable results were obtained with a short-period mutant of AMC149. Together, these results indicate that the bioluminescence rhythm in AMC149 is due primarily to circadian oscillation of psbAI promoter activity in this cyanobacterium.

Circadian Rhythm↗

A single retroviral gag precursor signal peptide recognized by FBL-3 tumor-specific cytotoxic T lymphocytes.

Several dominant T-cell receptors of cytotoxic T-lymphocyte (CTL) clones specific for FBL-3 tumor antigen were clonally amplified in mixed lymphocyte tumor cell cultures derived from an individual immune mouse. Every CTL clone analyzed had a common specificity for a single epitope in the precursor to cell membrane-associated nonstructural gag-encoded protein, Pr75gag, which can be minimally identified by nine amino acid residues, SIVLCCLCL. This epitope is located within the hydrophobic signal sequence motif that mediates translocation of the protein into the endoplasmic reticulum. These novel observations suggest that expression of Pr75gag in FBL-3 tumor cells led to the amplification of CTLs which recognize the signal sequence of the nonstructural gag-encoded glycoprotein precursor.

Amino Acid Sequence↗

Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.

The familial occurrence of allergic diseases was studied in 478 individuals and their family members. The results showed that there was pronounced familial clustering. Total serum IgE concentrations of atopic patients and their parents were well correlated. Moreover, the concentration of specific IgE of the patients and their parents was also well correlated, suggesting that IgE production was genetically determined. To determine if major structural abnormalities of IGHE, IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2 genes in all 55 leukocyte DNAs. We could not find any large deletions or duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high serum IgE concentrations.

Adolescent↗

A method of image analysis for primary angle closure glaucoma.

The anterior segment of the eye is displayed on the video monitor using a slitlamp apparatus (slitlamp 75SL, Zeiss, Germany) combined with a video camera and the video image is then analyzed with a computer to convert the optimal image into the true image. The profile of the true image of the anterior eye segment allows us to estimate the pupil-blocking force, which is the posteriorly directed vector exerted in the iris tissue, according to Mapstone's theory. In mensuration by digitizer on 3 occasions from a single video image of a given normal eye, the Pbf was -0.0255 +/- 0.0011 lambda (= Young's module). And the pupil-blocking force of 10 procedures in a given glaucomatous eye was +1.092 +/- 0.018 lambda.

Anterior Eye Segment↗

Retinal detachment in patients with atopic dermatitis. 5-year retrospective survey.

We surveyed data collected in our department over the past 5 years on all patients under the age of 30 years who had presented for repair of retinal detachment. Of 52 such patients, 10 (19.2%) had a documented history of atopic dermatitis. Three (27.3%) of the 11 eyes (10 patients) with atopic dermatitis exhibited a break in the ciliary epithelium in the pars plicata and pars plana, the most characteristic finding in this group. Surgical reattachment of the retina was accomplished in all 11 eyes. To repair a tear in the ciliary epithelium in atopic cases, we prefer using an encircling procedure to reconstruct an artificial ora serrata.

Adult↗

Neutrophil elastase associated with alveolar macrophages from older volunteers.

We focused on the role of neutrophil elastase (NE) in alveolar macrophages (AMs), and evaluated the esterolytic activity using an NE-sensitive substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA) in AMs from 36 older healthy volunteers (61 +/- 2 yr mean age +/- standard error) and examined the relationship to chronic effects of cigarette smoking and also to the presence of low attenuation areas (LAAs) on the computed tomographic (CT) scans. The AMs from the subjects with LAAs showed significantly higher activity than those from the current smokers without LAA (1.16 +/- 0.40 versus 0.34 +/- 0.07 nM, respectively, p < 0.05). Although the study of inhibitory profile revealed that the esterolytic activity could not be attributed to NE alone, the NE activity seemed to dominate in AMs at least from some who had higher esterolytic activity. We then examined the releasability of NE from cultured AMs in 10 subjects. The immunologic NE complex with alpha 1-protease inhibitor (alpha 1-PI) was released significantly higher in the LAA(+) group than in the LAA(-) group (17.4 +/- 6.5 versus 1.8 +/- 0.6 micrograms/L, respectively, p < 0.05). These data suggest that NE in AMs may play a role in the development of emphysematous changes in susceptible smokers.

Adult↗

Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema.

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.

Aged↗

A topographical and ultrastructural study of sensory trigeminal nerve endings in the rat temporomandibular joint as demonstrated by anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP).

To extend our previous light microscopic observations concerning the distribution of trigeminal sensory nerves in the synovium of the rat temporomandibular joint, we investigated the detailed distribution and fine structure of sensory nerve endings at the light and electron microscopic level by the anterograde transport method using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the trigeminal ganglion. At the light microscopic level, HRP-labeled nerve fibers were observed in the joint capsule and peripheral portion of the disc. The anterior portion of the disc was more densely innervated than the posterior portion, while no nerves were found in the central portion. At the electron microscopic level, HRP reaction products were observed intra-axonally in the thinly myelinated (A delta) and unmyelinated (C) axons in the anterior portion of the joint capsule, and were also localized in the extracellular space surrounding the unmyelinated fibers and terminals. In the subsynovial layer of the synovial membrane, the majority of labeled axons located near blood vessels or among the collagenous fibrils were covered by Schwann cell sheaths, although some naked axon terminals without sheaths were also found. These unsheathed terminals contained mitochondria, small clear vesicles, and large granular vesicles, and were close to the synovial A and/or B cells near the joint cavity. The minimum distance between the terminals and synovial cells was 75 nm. This is the first demonstration of trigeminal sensory nerve terminals close to synovial lining cells or joint cavity and suggests that neuropeptides such as substance P may be released close to the synovial lining cells or joint cavity.

Animals↗

S-methylation in Parkinson's disease.

We report thiolmethyltransferase (TMT) activity in RBC membrane preparations from patients with Parkinson's disease (PD), normal controls, and patients with symptomatic parkinsonism. Unlike previous reports, our report found no significant decrease in TMT activity in PD patients compared with normal controls. Low S-methylation capacity does not appear to be a risk factor for PD in Japanese patients.

Aged↗

Pergolide in the treatment of Parkinson's disease.

Three trials evaluated the efficacy and safety of pergolide. Eighty-six de novo patients and 314 patients already receiving levodopa were enrolled in an open-label study. Of the de novo patients, 47.5% showed a marked or moderate improvement and 32% showed a mild improvement. In the levodopa add-on group, 53.8% showed marked or moderate improvement and 36.3% showed mild improvement. In a short-term, double-blind study, the efficacy of pergolide was compared with that of bromocriptine. One hundred seventy-two patients were randomized to receive pergolide, and 173 were randomized to receive bromocriptine. In de novo patients, bromocriptine (n = 49) and pergolide (n = 49) demonstrated similar efficacy. However, significantly more levodopa-treated patients in the pergolide group, compared with the bromocriptine group, demonstrated marked or moderate improvements in several items of the rating scale score. In a long-term study, 151 of 314 patients receiving pergolide in combination with levodopa remained in the study for 3 years, and 127 for 4 years, and in these patients the initial improvement was maintained. In 18 of 62 de novo patients, the initial improvement was maintained for up to 3 years. These trials indicate that pergolide has efficacy in patients with Parkinson's disease, either as monotherapy or in combination with levodopa.

Double-Blind Method↗

Disposition of DN-2327, a new anxiolytic, in rats, dogs, and monkeys.

The disposition of DN-2327 after oral dosing of 14C-labeled DN-2327 ([14C]DN-2327) to rats, dogs and monkeys was studied. DN-2327 was absorbed from the small intestine after oral administration. In the plasma of these animals, a small amount of unchanged compound and M-I were detected, with M-II (a pharmacologically active metabolite) as a major component. The concentration of the unchanged compound in rat plasma attained a peak (Cmax 0.002 microgram/ml), then declined, with a half-life (t1/2) of 3 h. Tmax, Cmax and t1/2 of DN-2327 in dogs and monkeys were 0.6 h, 0.332 microgram/ml and 1.5 h, and 2.3 h, 0.036 microgram/ml and 6.2 h, respectively. About 60, 75 and 48% of the radioactivity dosed was absorbed in rats, dogs and monkeys, respectively, whereas the bioavailability in rats, dogs and monkeys was less than 1, 34 and 10%, respectively, indicating that DN-2327 had been subjected to the first pass effect. In rats given [14C]DN-2327 orally, the radioactivity was distributed widely in various tissues, including the brain. In the brain regions, DN-2327 and M-II were distributed and M-II was major component, indicating that the pharmacological effects of DN-2327 may depend largely on M-II. In these animals, [14C]DN-2327 was excreted in feces via bile mostly as metabolites. During repeated oral administration, DN-2327 and its metabolites did not accumulate in rat tissues, except in the kidney.

Administration, Oral↗