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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 577 records · Page 32Linked to original sources

Familial aggregation and covariation of diseases in a Japanese rural community: comparison of stomach cancer with other diseases.

PURPOSE: We investigated familial aggregation as well as familial covariation of diseases by means of a questionnaire survey dealing with family histories of stomach cancer, stroke, hypertension, diabetes and tuberculosis as well as life style among 2,769 inhabitants of a rural community (84% of census population). METHODS: The strength of familial aggregation was shown by an odds ratio (OR) that compared the number of families in which siblings suffered from one of the above diseases among families in which at least one parent suffered from it, and among families in which neither did. Probands were divided into two groups for analysis: an under-55 "young group," and a 55-and-older "old group." RESULTS: The OR for stomach cancer was lowest and insignificant in the young group, and significant (2.2, p < 0.05) only in the old group. The OR for stroke, hypertension, and tuberculosis was 4.5-5.1 (p < 0.05) in the young group but decreased to 2.3-3.2 in the old group. Diabetes increased from 3.9 to 5.7 (p < 0.05) with advancing age. Age-related OR trends were not affected by exposure to cigarette smoke in the past. Stomach cancer showed a borderline familial covariation with diabetes and a borderline inverse covariation with hypertension. Hypertension showed a familial covariation with stroke and diabetes. CONCLUSIONS: Among the investigated diseases, familial aggregation was weakest for stomach cancer. The results suggest that stomach cancer may share a common familial etiologic factor with diabetes and hypotension.

Adult↗

DNA typing from stained sperm-positive vaginal smears: four rape cases.

DNA typing from stained sperm-positive vaginal smears was performed in four cases of sexual assault. In Cases 1 and 2, a 6-month-old and a 6-week-old, Papanicolaou-stained vaginal smear with 99% propanol fixation underwent DNA analysis respectively. In Case 1, the HLA-DQalpha type of the sperm fraction of the smear was able to be determined following PCR, and the possibility of the suspect being the rapist could not be excluded. In Case 2, the possibility that the suspect was the rapist in the crime was excluded based on the results of DNA typing by means of two different single-locus probes. In the remaining two cases, H-E-stained smears after air drying for 4 or 5 months were the material for DNA analysis, and DNA typing was attempted by PCR-based STR system. In Case 3, there was no genetic information from sperm fraction of the smear due to the small number of spermatozoa on the glass slide. Therefore, it was impossible to determine whether the suspect was the rapist or not. In Case 4, sperm DNA from the smear was amplified and typed, and the suspect could be excluded. These four cases demonstrate that stained vaginal smears containing many spermatozoa can be used for DNA analysis in sexual assault cases.

Journal Article↗

Eight cases of suicide by self-cutting or -stabbing: consideration from medico-legal viewpoints of differentiation between suicide and homicide.

The present article describes eight cases of suicide by self-cutting or -stabbing. Seven of the deceased had a history of psychiatric problems. In every case, sharp weapon injuries were observed at typical sites of self-inflicted injury. The self-inflicted injuries varied in severity from a single stab wound to multiple cut wounds. In four cases, hesitation marks were found. Among the remaining four cases without hesitation marks, only one had clothing injuries. Based on the scene investigation by police, it was deduced that each body had been found at or very near the place where the fatal injuries had been sustained. In two cases, toxicological analysis played an important role in discriminating suicide from homicide. In one case, a 52-year-old male stabbed himself fatally after potassium hydroxide ingestion, and in another, a 71-year-old male committed suicide by self-cutting and -stabbing after drinking an alkaline detergent solution. In five of the eight cases, unusual findings such as a single stab wound, multiple cut injuries, no hesitation mark or presence of clothing injuries were found. In these five cases, the psychiatric history of the deceased contributed to furthering our comprehension of these unusual findings. We believe that thorough toxicological analysis and scene investigation as well as autopsy are essential in discriminating between homicide and suicide. Furthermore, forensic pathologists and forensic physicians at the scene should obtain as much information as possible on the victim's previous character including previous psychiatric history in order to elucidate his or her manner of death.

Journal Article↗

Processing down the garden path in Japanese: processing of sentences with lexical homonyms.

This paper investigates whether or not Japanese sentences with lexical homonyms cause measurable processing difficulties for Japanese speakers. Pairs of sentences involving lexical homonyms were tested with three types of questionnaires (who-did-what questions, difficulty ratings, and misleadingness ratings) and two experimental tests (an eye-movement monitoring experiment and a self-paced reading experiment). In both the difficulty rating and the misleadingness rating questionnaires, "late boundary" sentences, in which a phrase boundary followed a homonymous phrase, were rated as significantly more difficult and more misleading than "early boundary" sentences, where the boundary preceded the homonymous phrase. The results from the eye-movement study and the self-paced reading study showed that the late boundary difficulties were associated with the processing of the regions that followed the homonymous phrases. These results confirmed our prediction that the difficulty of late boundary sentences is likely to be caused by a subject's original misanalysis and subsequent revision. The results are discussed in terms of possible reasons why the early boundary version was preferred in these sentences.

Eye Movements↗

Effects and limitations of prosodic and semantic biases on syntactic disambiguation.

This paper examined the effects of prosody on the syntactic ambiguity resolution of Japanese sentences, especially with reference to the interaction with semantic bias. Syntactically ambiguous sentences with different types of semantic bias were constructed. The degree of bias in each sentence was evaluated through visual presentation experiments. Three types of sentences were selected based on the results of visual presentation experiments, were recorded with prosody maximally favoring each possible interpretation of the sentences, and were used as the stimuli for the auditory presentation experiments. The results showed that prosodic cues can influence the interpretation of a sentence even when the sentence is strongly semantically biased. The results also showed a limitation to prosodic cues. The prosodic biases alone were not sufficient to fully determine the interpretation of the sentences even when the sentences were neutrally biased semantically.

Humans↗

Essential roles of the Fas ligand in the development of hepatitis.

The Fas ligand (FasL) is expressed in activated T cells and induces apoptosis in Fas-bearing cells. A cytotoxic T lymphocyte (CTL) clone specific for hepatitis B surface antigen (HBsAg) causes an acute liver disease in HBsAg transgenic mice. Here we observed that the CTL clone killed hepatocytes expressing HBsAg in a Fas-dependent manner. Administration of the soluble form of Fas into HBsAg transgenic mice prevented the CTL-induced liver disease. In the second model, mice were primed with Propionibacterium acnes. A subsequent challenge with lipopolysaccharide (LPS) killed the mice by inducing liver injury. Neutralization of FasL rescued the mice from LPS-induced mortality, and Fas-null mice were resistant to LPS-induced mortality. These results suggest that FasL has an essential role in the development of hepatitis.

Animals↗

Establishment and characterization of a new erythropoietin-dependent acute myeloid leukemia cell line, AS-E2.

We have established an erythropoietin-dependent human leukemia cell line, AS-E2, from a patient with acute myeloid leukemia. These cells have many characteristics of late erythroid progenitor cells, they are positive for CD36, Glycophorin A, and CD71 but negative for CD41, and positive for benzidine and PAS staining. These cells express GATA-1 and have low affinity erythropoietin (EPO) receptor on their surface. Interestingly, AS-E2 cells are strictly dependent on EPO for their growth and survival; other cytokines including GM-CSF, stem cell factor, or IL-3 cannot support the growth of this cell line. These features are similar to late erythroid lineage cells, like normal BFU-E or CFU-E, and we have demonstrated that EPO stimulation induces the tyrosine phosphorylation of several proteins in AS-E2 cells including the EPO receptor and JAK2 kinase. This new cell line is a useful reagent to study biological and molecular events during the late stages of erythropoiesis, and to understand transforming events in human erythroid cells.

Acute Disease↗

Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity.

Interferon regulatory factor-1 (IRF-1) acts as a transcriptional activator in the interferon system and as a tumor suppressor. The loss of functional IRF-1 has been observed in a significant number of patients with myelodysplastic syndrome (MDS) and leukemia, suggesting a potentially critical role of IRF-1 in human oncostasis. Here we report an alternative mechanism by which IRF-1 may be inactivated. We purified an IRF-1 association molecule which was revealed to be identical to a nuclear factor nucleophosmin (NPM)/B23/numatrin. Functional analysis showed that NPM inhibited the DNA-binding and transcriptional activity of IRF-1. Moreover, NPM was overexpressed in several clinical leukemia samples and human-derived leukemia cell lines. Finally, overexpression of NPM in NIH3T3 cells resulted in malignant transformation. These results suggest the possible involvement of NPM in inactivating IRF-1-dependent anti-oncogenic surveillance in human cancer development.

3T3 Cells↗

Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia.

Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX patients have experienced spontaneous pubertal changes including breast development and irregular menstruation whereas none of the 46,XY subjects displayed pubertal changes. Eight different mutations were identified. Sixteen patients were either homozygotes or compound heterozygotes for the Q258X mutation. The seven other mutations identified were 189delG, 246insG, 564del13bp, 838delA, Q212X, A218V and M225T. The 189delG, 246insG, 546del13bp and Q212X mutants encode truncated proteins. COS-1 cells transfected with expression vectors encoding cDNAs for the mutant StAR proteins which affect the C-terminus, 838delA, A218V and Q258X, exhibited no steroidogenesis enhancing activity. However, the M225T mutant retained some steroidogenic activity. The patient with the M225T mutation had late onset of this disorder and some capacity to secrete testosterone in response to hCG. These findings suggest: (i) that the Q258X mutation can be used as a genetic marker for the screening of Japanese for lipoid CAH, (ii) that the C-terminus of StAR plays an important role in the protein's activity and (iii) that there are differences in the extent of functional impairment of the testis and ovaries in lipoid CAH.

Adrenal Hyperplasia, Congenital↗

Lactase decline in weaning rats is regulated at the transcriptional level and not caused by termination of milk ingestion.

Lactase activity declines during postnatal development in rats, but little is known about the underlying molecular mechanism of this phenomenon. We attempted to clarify whether the regulation was at the transcriptional or post-transcriptional level and to examine the effects of dietary factors on that regulation. Newborn rats were divided into two groups, prolonged nursing and weaning, at d 21. The prolonged nursing rats were nursed for a further 6 d, whereas weaning rats were separated from their dams and fed nonpurified diet for the same period. The patterns of declining lactase protein and mRNA concentrations during weaning were determined by Western blot and Northern blot analyses, respectively, and compared with lactase activity. There were significant (P < 0.001) correlations between them: r = 0.97 for specific activity vs. protein, r = 0.99 for specific activity vs. mRNA and r = 0.96 for protein vs. mRNA. The lactase activity per milligram DNA showed a pattern similar to that of the specific activity. This result argues against the decline in lactase activity being due to the dilution caused by newly synthesized materials during the weaning period and suggests transcriptional regulation. Furthermore, the prolonged nursing rats showed the same results as weanlings for lactase protein, mRNA, specific activity and activity per milligram DNA. These observations indicate that the regulation of lactase expression is at the transcriptional level and that it is not affected by the termination of milk ingestion.

Actins↗

Traumatic tear of the basilar artery associated with vertebral column injuries.

An unusual case of traumatic basal subarachnoid hemorrhage (SAH) due to a mechanical tear of the basilar artery is reported. A 70-year-old man who had been suffering from cerebrovascular dementia was found dead in a ditch. Externally, subcutaneous hemorrhage with abrasions was observed on the left side of the forehead, face, and lower jaw, together with small contusions in the left superciliary arch. Internally, a 3-mm-long transversal tear of the basilar artery was observed, and dislocations of both C6-C7 and T1-T2 as well as a small fracture of the processus spinosus of C5 were found. No pathological vascular lesions such as aneurysms and vasculitis, other than arteriosclerosis, were observed in the vertebral-basilar system. Ethanol was not detected in the intracardiac blood or in the urine. These findings indicate that when the man fell into the ditch, severe hyperextension occurred as a result of minor blunt forces to the face, and that the traumatic tear of the basilar artery was mechanically caused by overstretching due to hyperextension of the head. It is also suggested that due to his advanced age the muscle tone of the neck might have declined, impairing its defense action, and that head hyperextension might, therefore, occur rather more readily under such conditions.

Aged↗

DNA fragmentation and Prolonged expression of c-fos, c-jun, and hsp70 in kainic acid-induced neuronal cell death in transgenic mice overexpressing human CuZn-superoxide dismutase.

Kainic acid (KA) neurotoxicity was examined in transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD-1). The doses of KA required to produce seizures, the severity of the seizures, and the regions damaged were similar in SOD-1 Tg and non-transgenic wild-type mice. Intraperitoneal KA injection induced seizure-related neuronal damage in the CA3 and CA1 regions of the hippocampus and in other regions of the brain in both SOD-1 Tg and wild-type mice. These damaged neurons were labeled with the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) technique up to 72 h, although no significant difference in the number of TUNEL-positive neurons was observed between SOD-1 Tg and wild-type mice. In situ hybridization showed that c-fos, c-jun, and hsp70 genes were expressed in the hippocampus, cortex, and other regions of the brain after KA treatment. The expression of these genes was maximal 1 to 4 h following KA treatment but persisted longer in the hippocampus and other regions in SOD-1 Tg compared with wild-type mice; however, cell death in the hippocampus, assessed using cresyl violet staining, was similar in SOD-1 Tg and wild-type mice. The data show that superoxide radicals modulate both immediate early gene and heat shock gene expression after KA-induced seizures. The prolonged expression of c-fos, c-jun, and hsp70 in SOD-1 Tg compared with wild-type mice may indicate that hippocampal neurons survive longer in SOD-1 Tg than in wild-type animals; however, cell death as well as the seizure threshold, seizure severity and the pattern of regional vulnerability were not affected substantially by increased levels of SOD in the brain.

Animals↗

Calcineurin inhibitor, FK506, prevents reduction in the binding capacity of cyclic AMP-dependent protein kinase in ischemic gerbil brain.

We examined the effects of FK506, a specific inhibitor of calcineurin, on the binding capacity of cyclic AMP-dependent protein kinase (cAMP-DPK) in gerbils subjected to 2-h cerebral hemispheric ischemia. FK506 (0.1 mg/kg) was infused intravenously at 15 min prior to the induction of ischemia by common carotid artery occlusion. The binding capacity of cAMP-DPK was evaluated by autoradiographic analysis of the cAMP binding, and cerebral blood flow (CBF) was measured by the [14C] iodoantipyrine method. In the sham-operated gerbils. FK506 significantly increased mean arterial blood pressure and tended to decrease CBF, suggesting that FK506 may constrict systemic blood vessels as well as cerebral blood vessels. On the other hand, cAMP binding was not altered by FK506 in the sham-operated gerbils. In the ischemia group of gerbils, FK506 prevented any significant reduction of cAMP binding in the hippocampus CA1 and cerebral cortices on the ischemic side, whereas it exerted no significant influence on the cAMP binding of the nonischemic side. The values of CBF were comparable between the vehicle-treated gerbils and FK506-treated gerbils in the ischemic regions. Preservation of cAMP binding indicates that intracellular signal transduction via cAMP-DPK can be maintained by FK506 despite ischemia, suggesting that this agent may be beneficial for reducing ischemic tissue damage.

Animals↗

Evaluating exocrine function tests for diagnosing chronic pancreatitis.

To evaluate the effectiveness of exocrine function tests in diagnosing chronic pancreatitis (CP), we compared the sensitivity and specificity of duodenal intubation with tubeless tests. While the secretin test (ST) was necessary to diagnose CP, especially in noncalcified CP, and tubeless tests demonstrated insufficient sensitivity to diagnose CP, the combination assay of tubeless tests was specific enough to diagnose severe exocrine dysfunction. Our studies found the sensitivity of secretin testing to diagnose definite CP to be 87%. In patients with probable CP, 60% had mild exocrine insufficiency and 40% had normal function. The false-positive rate of the ST results in nonpancreatic diseases, except diabetes mellitus, was 5%. The correlation between morphological changes in endoscopic retrograde pancreatography (ERP) and exocrine function evaluated by ST was 74%. In patients with calcified CP, 81% had parallel results between ERP and the ST, but in noncalcified CP, 47% had parallel results. In patients with severe or moderate exocrine insufficiency demonstrated by ST, abnormally low levels were observed in 63% by N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test, 61% by fecal chymotrypsin test (FCT), and 44% by pancreatic amylase (PA). In patients with normal exocrine function demonstrated by ST, abnormally low levels were observed in 28% by BT-PABA test, 28% by FCT, and 10% by PA. A combination assay of BT-PABA test, FCT, and PA improved the specificity for diagnosing CP but not the sensitivity.

4-Aminobenzoic Acid↗

No effect of the anticholinergic drugs trihexyphenidyl and biperiden on the plasma concentrations of bromperidol and its reduced metabolite.

Effects of the anticholinergic drugs trihexyphenidyl and biperiden on plasma concentrations of bromperidol and its reduced metabolite were studied. Subjects comprised 20 schizophrenic inpatients taking bromperidol, 6-18 mg/ day for 1-9 weeks. Patients were randomly allocated to one of two treatment sequences: trihexyphenidyl-biperiden (n = 12) or biperiden-trihexyphenidyl (n = 8). Each sequence consisted of two 2-week phases, with no washout period between the two phases. The daily dose of trihexyphenidyl was 8 mg and that of biperiden 6 mg. Plasma concentrations of bromperidol and reduced bromperidol were measured using high-performance liquid chromatography (HPLC). There was no significant difference in plasma bromperidol or reduced bromperidol concentrations among baseline, trihexyphenidyl and biperiden phases: 7.3 +/- 3.7 versus 7.2 +/- 4.1 versus 7.0 +/- 4.3 ng/ml and 2.0 +/- 2.1 versus 2.2 +/- 2.1 versus 1.9 +/- 2.0 ng/ml, respectively. The present study thus suggests that neither trihexyphenidyl nor biperiden affects plasma concentrations of bromperidol and its reduced metabolite.

Adult↗

Increased plasma concentrations of bromperidol and its reduced metabolite with levomepromazine, but not with thioridazine.

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks. In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with > or = 2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n = 17) significantly (p < 0.001) increased plasma concentrations of bromperidol (7.3 +/- 4.1 versus 10.2 +/- 4.8 ng/ml) and reduced bromperidol (1.8 +/- 1.4 versus 4.5 +/- 3.3 ng/ml). Thioridazine (n = 16) did not significantly change plasma concentrations of bromperidol (9.1 +/- 5.7 versus 8.6 +/- 5.5 ng/ml), while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.

Adult↗

Long-term efficacy of a self-retaining intraurethral catheter for the treatment of prostatic obstruction.

BACKGROUND: Transurethral prostatectomy is a standard treatment modality for infravesical obstruction with benign prostatic hyperplasia. However, some patients cannot undergo this procedure, so alternative devices or surgical procedures have recently been developed. METHODS: We treated 26 patients with prostatic outflow obstruction by placement of a self-retaining intraurethral catheter (IUC). All patients had coexisting medical complications which contraindicated transurethral prostatectomy. RESULTS: In the short-term, the treatment was successful in 96.2% of the patients, however, longer follow-up demonstrated a significant failure rate, and the 3-year success rate declined to 12.5%. The majority of late failures were associated with urinary tract infections. CONCLUSION: These results showed that although placement of an IUC to treat prostatic obstruction was effective in the short-term, its long-term efficacy was highly limited.

Aged↗

Circadian rhythm of the cyanobacterium Synechocystis sp. strain PCC 6803 in the dark.

The cyanobacterium Synechocystis sp. strain PCC 6803 exhibited circadian rhythms in complete darkness. To monitor a circadian rhythm of the Synechocystis cells in darkness, we introduced a PdnaK1::luxAB gene fusion (S. Aoki, T. Kondo, and M. Ishiura, J. Bacteriol. 177:5606-5611, 1995), which was composed of a promoter region of the Synechocystis dnaK1 gene and a promoterless bacterial luciferase luxAB gene set, as a reporter into the chromosome of a dark-adapted Synechocystis strain. The resulting dnaK1-reporting strain showed bioluminescence rhythms with a period of 25 h (on agar medium supplemented with 5 mM glucose) for at least 7 days in darkness. The rhythms were reset by 12-h-light-12-h-dark cycles, and the period of the rhythms was temperature compensated for between 24 and 31 degrees C. These results indicate that light is not necessary for the oscillation of the circadian clock in Synechocystis.

Circadian Rhythm↗