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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 487 records · Page 27Linked to original sources

Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects.

The authors investigated the single oral dose kinetics of zotepine and its relationship with prolactin response and side effects in 14 healthy male volunteers. Each subject took a single oral 25-mg dose of zotepine, and plasma concentrations of zotepine, prolactin, and their side effects were monitored up to 36 hours after dosing. The means +/- SD of the time of maximal plasma concentration (tmax), the apparent oral clearance, the apparent volume of distribution, and the elimination half-life (t1/2) were 3.8 +/- 1.2 hours, 4.6 +/- 4.2 1/h.kg, 109.0 +/- 59.0 1/kg, and 21.0 +/- 8.9 hours, respectively. The change in prolactin concentrations and side effect scores were parallel with that of drug concentrations, although no significant correlation was found between these three parameters at any time-point. The current results clearly indicate that the tmax and t1/2 of zotepine are much longer than those previously reported, which are reflected in the changes in prolactin concentrations and side effect scores.

Administration, Oral↗

Primary ductal adenocarcinoma of the lacrimal gland.

The morphological similarity of salivary and lacrimal gland tumors is known. Many clinicopathological studies and characteristics of salivary duct carcinoma, which bears histological similarities to mammary duct carcinoma, have been recently reported; however, only one case of lacrimal duct carcinoma is reported. A second case of lacrimal duct carcinoma is presented. A 67-year-old male with a painless mass in the right upper eyelid underwent total removal of the tumor mass. Microscopic examination of the tumor mass revealed ductal adenocarcinoma of the lacrimal gland, which was the equivalent of salivary duct carcinoma. The immunohistological studies of the lacrimal duct carcinoma showed similar results to those reported for salivary duct carcinoma. The recurrent tumor in the subdural spaces was removed 2 years after the initial surgery and the patient is followed as an outpatient.

Adenocarcinoma↗

Prolactin response to bromperidol treatment in schizophrenic patients.

The prolactin response to an antipsychotic drug, bromperidol was studied in 24 schizophrenic in-patients (13 males. 11 females). Eight patients were given 6 mg/day, 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma concentrations of bromperidol and reduced bromperidol were measured by high-performance liquid chromatography, and that of prolactin was measured by radioimmunoassay. Bromperidol treatment significantly (P < 0.01) increased plasma concentration of prolactin each week. The mean +/- S.D. of the delta-prolactin (the mean concentration during treatment minus the pretreatment concentration) was 13.3 +/- 12.4 ng/ml. Multiple regression analysis showed that the delta-prolactin concentration was significantly greater in females than in males (P < 0.05) and correlated to plasma concentrations of bromperidol (P < 0.001) and reduced bromperidol (P < 0.0001). These results suggest that the prolactin response to bromperidol treatment depend on plasma concentrations of both bromperidol and reduced bromperidol and gender, and that reduced bromperidol is involved in the pharmacological effects during bromperidol treatment.

Adult↗

A period-extender gene, pex, that extends the period of the circadian clock in the cyanobacterium Synechococcus sp. strain PCC 7942.

We cloned the pS1K1 plasmid in the process of apparently "complementing" a circadian clock mutant of cyanobacterium Synechococcus sp. strain PCC 7942, SP22, which has a 22-h period (T. Kondo, N. F. Tsinoremas, S. S. Golden, C. H. Johnson, S. Kutsuna, and M. Ishiura, Science 266:1233-1236, 1994). Sequence analysis revealed that SP22 did not have a mutation in the genomic DNA segment carried on pS1K1, and the sp22 mutation was later found in a recently cloned new clock gene, kaiC. Therefore, the period-extender gene pex that was carried on pS1K1 was a suppressor gene for the sp22 mutation. The pex gene encoded a protein of 148 amino acid residues. No meaningful homologs were found in DNA or protein databases including the Synechocystis genome database. The pex gene was transcribed from 129 and 164 bp upstream of the translation initiation codon as 0.6-kb transcripts. The Pex protein was detected as a fusion protein with a molecular mass of 15 kDa by the epitope tag fusion method using a c-Myc epitope tag. Disruption of the pex gene in wild-type cells shortened the period of the rhythms by 1 h, although it did not affect other properties of the rhythms, whereas its overexpression extended the period by 3 h with a concomitant reduction in the amplitude of the rhythms. In various clock mutants examined, overexpression caused arrhythmicity. Thus, Pex is likely to function as a modifier of the circadian clock in Synechococcus.

Amino Acid Sequence↗

Moesin is not a receptor for measles virus entry into mouse embryonic stem cells.

The involvement of moesin in measles virus (MV) entry was investigated with moesin-positive and -negative mouse embryonic stem (ES) cells. MV infection of these cells was very ineffective and was independent of moesin expression. Furthermore, when these cells were transfected to express human CD46, a 100-fold increase in syncytium formation was observed with these cells and was independent of the expression of moesin. The only obvious difference between moesin-positive and -negative ES cells was the shape of the syncytia formed. Moesin-negative ES cells expressing or not expressing human CD46 formed separate pieces of fragmented syncytia which were torn apart during spreading, whereas ES cells expressing moesin exhibited typical syncytia. In addition, moesin was not detected on the surface of any murine cells or cell lines that we have tested by a flow cytometric assay with moesin-specific antibodies. These findings indicate that murine moesin is neither a receptor nor a CD46 coreceptor for MV entry into mouse ES cells. Moesin is involved in actin filament-plasma membrane interactions as a cross-linker, and it affects only the spreading and shape of MV-mediated syncytia.

Animals↗

Application of a novel method for subsequent evaluation of sinusoids and postsinusoidal venules after ischemia-reperfusion injury of rat liver.

Although several intravital fluorescence microscopic studies demonstrated that microcirculatory derangement is induced during liver ischemia-reperfusion, these data were obtained from randomly selected microvascular areas and microvessels. Repeated observation of the identical microvessels has not been performed yet. Using a specially designed cover glass, it is now possible to relocate desired sites of observation repeatedly over the whole reperfusion time. The aim of this study was to determine the impact of reperfusion time on hepatic microvascular perfusion state. Twenty minutes of ischemia induced a significant decrease in sinusoidal perfusion rate (29.1 +/- 10.2%) as compared with baseline values (98.0 +/- 0.3%). At 30, 60, and 120 min of reperfusion, the percentage of perfused sinusoids recovered to 62.8 +/- 6.6, 67.5 +/- 5.7, and 77.2 +/- 5.4%. The number of stagnant leukocytes in the same sinusoids was 6.2 +/- 1.9/lobule at baseline and increased to 22.3 3.6/lobule at 120 min of reperfusion. The number of leukocytes adhering within postsinusoidal venules was 53.5 12.5/mm2 before ischemia and increased to 414.2 62.5/mm2 at 120 min of reperfusion. We have demonstrated that during 120 min of reperfusion, there was a steady increase in both sinusoidal and venular leukocyte adhesion along with an attenuation of the initially severely depressed sinusoidal perfusion. A no-reflow phenomenon at an early phase of reperfusion and subsequent reflow were proven.

Animals↗

Ultrasound biomicroscopic findings in a case of cyclodialysis.

Ultrasound biomicroscopy (UBM) with a high frequency can be used to evaluate the structure of the anterior eye segment in vivo. A 24-year-old male was referred to us after 1 month of follow-up by a local ophthalmologist, because of decreased visual acuity and hypotony after a blunt eye injury. A cyclodialysis cleft in the 2- to 4-o'clock position and a cavernous pattern all over the choroid were found using UBM. The patient underwent surgical treatment to close the cleft. Even after the recovery of intraocular pressure (IOP), the peripheral ciliary body around 360 degrees was still separated from the sclera when examined by UBM. Despite the detached ciliary body, keeping IOP within normal levels is an interesting finding. UBM is helpful in the diagnosis and treatment of traumatic cyclodialysis.

Adult↗

Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q.

We report the results of pathologic and biochemical studies in a patient with 6q-linked autosomal recessive juvenile parkinsonism (AR-JP). Neuronal loss and gliosis were restricted to the substantia nigra and the locus ceruleus. No Lewy bodies were found, but neurofibrillary tangles and argyrophilic astrocytes were seen in the cerebral cortex and brainstem nuclei. The later findings, which have not been reported previously in AR-JP, suggest the pathologic heterogeneity of 6q-linked AR-JP.

Brain↗

Genetic analysis of a Hoxd-12 regulatory element reveals global versus local modes of controls in the HoxD complex.

Vertebrate Hoxd genes are essential determinants of limb morphogenesis. In order to understand the genetic control of their complex expression patterns, we have used a combined approach involving interspecies sequence alignments in parallel with transgenic analyses, followed by in vivo mutagenesis. Here, we report on the identification of a regulatory element that is located in the vicinity of the Hoxd-12 gene. While this element is well conserved in tetrapods, little sequence similarity was scored when compared to the cognate fish DNA. The regulatory potential of this region XI (RXI) was first assayed in the context of a Hoxd-12/lacZ reporter transgene and shown to direct reporter gene expression in posterior limb buds. A deletion of this region was generated by targeted mutagenesis in ES cells and introduced into mice. Analyses of animals homozygous for the HoxDRXI mutant allele revealed the function of this region in controlling Hoxd-12 expression in the presumptive posterior zeugopod where it genetically interacts with Hoxa-11. Downregulation of Hoxd-12 expression was also detected in the trunk suggesting that RXI may mediate a rather general function in the activation of Hoxd-12. These results support a model whereby global as well as local regulatory influences are necessary to build up the complex expression patterns of Hoxd genes during limb development.

Animals↗

Differential localization of two types of transferrin: produced by human fibroblasts or incorporated from culture medium.

In a previous paper, we demonstrated that cultured human fibroblasts synthesize transferrin (Tf). Two types of Tf are present; one is produced by the cells and the other is internalized from the culture medium. To study the metabolism of intracellular Tf, we investigated the subcellular localization of the two types of Tf in human fibroblasts by immunocytochemical and fluorescence-labeling techniques. The internalized Tf was found to be localized in the perinuclear area, and the synthesized Tf was associated with microtubules, forming a fibrous structure in the cytoplasm. When the cells were treated with colchicine which depolymerizes microtubules irreversibly, the synthesized Tf lost its fibrous structure and spread out in cytoplasm, but the internalized Tf remained around the nucleus. These results suggest that the two types of Tf are regulated differently in the cells.

Cell Nucleus↗

Alteration in levels of unsaturated fatty acids in mutants of Escherichia coli defective in DNA replication.

We previously reported that mutations in the dnaA gene which encodes the initiator of chromosomal DNA replication in Escherichia coli caused an alteration in the levels of unsaturated fatty acids of phospholipids in membranes. In this study, we examined fatty acid compositions in other mutants which are defective in DNA replication. As in the case of temperature-sensitive dnaA mutants, temperature-sensitive dnaC and dnaE mutants, which have defects in initiation and elongation, respectively, of DNA replication showed a lower level of unsaturation of fatty acids (ratio of unsaturated to saturated fatty acids) compared with the wild-type strain, especially at high temperatures. On the other hand, temperature-sensitive mutants defective in cellular processes other than DNA replication, such as RNA synthesis and cell division, did not show a lower level of unsaturation of fatty acids compared with the wild-type strain. These results suggest that the inhibition of DNA replication causes a lower level of unsaturation of fatty acids in Escherichia coli cells.

Bacterial Proteins↗

Vectorcardiographic evaluation of myocardial infarct size: departure parameters are superior to conventional spatial parameters.

To determine whether the departure parameters derived from a "departure loop" of a vectorcardiogram are more accurate than conventional spatial parameters in evaluating myocardial infarct size, 74 patients with first-onset myocardial infarction (MI) were studied. The correlation between the departure parameters (amplitudes in scalar leads of the departure loop) and the percent defect volume of thallium myocardial scintigrams (%DV) was compared with that of the spatial parameters (magnitude, azimuth, and elevation of the original QRS loop). In anteroseptal MI, the amplitude of a 20-msec vector in the z-axis and the azimuth of a 30-msec vector (H30) were significantly correlated with %DV (r=0.783, p<0.001 and r=0.572, p<0.05). In anteroseptal MI with involvement of the lateral wall, the amplitude of a 30-msec vector in the x-axis and H30 showed significant correlation with %DV (r=0.802, p<0.001 and r=0.772, p<0.01). In inferior and inferoposterior MI, the amplitude of a 30-msec vector in the y-axis and the elevation of a 30-msec vector were significantly correlated with %DV (r=0.920, 0.891, p<0.001 and r=0.871, 0.678, p<0.01, respectively). In conclusion, the departure parameters are more accurate than the spatial parameters for evaluation of myocardial infarct size.

Aged↗

Increased conversion ratio of tryptophan to niacin in severe food restriction.

The effect of food restriction on the conversion ratio of tryptophan to niacin was investigated, because it is known that the conversion ratio is influenced by nutritional factors. A 20% casein diet was fed to rats ad libitum (control), 1/2 the food of the control. 1/4 the food of the control, or starved for 9 days, and urine samples were collected to measure the urinary excretion of such tryptophan metabolites as kynurenic acid, xanthurenic acid, and nicotinamide. The conversion ratio in the 1/2, 1/4, or starving group increased at day 1 of the experiment, but returned to the original value from day 2. Only in the starving group did the conversion ratio extremely increase from day 6 to day 9, being about 5-times higher than that of the original value on day 9. The possible mechanism by which the conversion ratio increased during food restriction is discussed.

Animals↗

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.

Adolescent↗

Enzyme-linked immunosorbent assay for serological survey of equine arteritis virus in racehorses.

To examine antibodies against equine arteritis virus (EAV), an enzyme-linked immunosorbent assay (ELISA) using purified virus antigen was developed. The results of ELISA were compared with those of serum neutralization (SN) tests. The ELISA absorbance values and the SN titers in sera collected weekly from EAV-infected horses showed a similar pattern. The ELISA could detect antibody to EAV in horses experimentally infected with not only a homologous virus strain, which was used as the ELISA antigen, but also a heterologous strain. Using the ELISA, serum samples collected in 1996 from racehorses in three prefectures (Hokkaido, Ibaraki, and Shiga) were examined and there was no evidence of recent EAV infection among these racehorse populations in Japan. The ELISA should be a simple and highly specific method for rapid screening of EAV infection in racehorses.

Animals↗

Urinary excretion of pancreatic stone protein in diabetic nephropathy.

Urinary pancreatic stone protein (PSP) levels were measured in 68 diabetic patients and 170 healthy controls to investigate the relationship between the progression of diabetic nephropathy and PSP excretion. Urinary albumin, N-acetyl-beta-glucosaminidase (NAG), alpha1-microglobulin, creatinine clearance, and the blood PSP level were also determined in the diabetic patients. The urinary glucose level and glycemic control did not influence the urinary PSP level. In patients with normoalbuminuria (urinary albumin <20 mg/gCr, n=31), microalbuminuria (20-200 mg/Cr, n=19), and macroalbuminuria (>200 mg/gCr, n=18), the mean urinary PSP level was 347, 507, and 860 microg/gCr, respectively. These levels were significantly higher than the level in normal volunteers (168 microg/gCr, p<0.01). A significant positive correlation was observed between the urinary PSP level and the NAG or alpha1-microglobulin levels (p<0.01). There was a stronger correlation with alpha1-microglobulin. Blood PSP levels were also elevated in patients who had renal impairment with a decreased creatinine clearance. In conclusion, urinary PSP excretion was increased from the initial stage of diabetic nephropathy and this increase became more marked as nephropathy progressed. Increased PSP excretion may reflect renal tubular dysfunction.

Acetylglucosaminidase↗

An increase in the threshold of citric acid-induced cough during chest wall vibration in healthy humans.

This study tested the hypothesis that the afferent input from the respiratory muscles may be involved in the neural mechanisms inducing cough responses. Coughing was evoked in conscious healthy humans by the inhalation of citric acid aerosol of several concentrations either during or not during chest wall vibration (100 Hz) at the right second intercostal space or during vibration of the right thigh. The mean threshold citric acid concentration to induce coughing was significantly higher during chest wall vibration (geometric mean, 131.8 mg/ml) than without vibration (75.9 mg/ml). Vibration after topical anesthesia of the chest wall skin did not significantly change the threshold concentration of citric acid. The threshold citric acid concentration during vibration of the right thigh did not significantly differ from that without vibration. We concluded that inputs from the chest wall afferent, presumably from the intercostal muscle or costovertebral joint, may have an inhibitory effect on the initiation of coughing at the higher neural structure in conscious humans.

Administration, Inhalation↗

A selective transthyretin-adsorption column for the treatment of patients with familial amyloid polyneuropathy.

A transthyretin (TTR)-adsorption column has been developed for the removal of variant TTR from the plasma of patients with familial amyloid polyneuropathy (FAP). The adsorbent is an ion-exchange resin made of porous beads of polyvinyl alcohol gel covalently bound with dimethylaminoethanol. This column was used for three patients with type I FAP. It reduced the concentrations of both normal and variant TTR in the plasma to about half of their pre-adsorption levels. Except for thyroxine, retinol-binding protein and IgM, other proteins in serum were not significantly decreased and there were no adverse effects in long term clinical usage of this TTR-adsorption column. In this trial, we did not obtain concrete evidence that TTR-adsorption therapy can stop or delay the progression of the disease in a FAP patient. However, if we are able to apply this technique more frequently and effectively, TTR-adsorption therapy using our column might be useful for the treatment of FAP patients.

Adsorption↗