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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 1,045 records · Page 58Linked to original sources

Detection of Pneumocystis carinii sequences by polymerase chain reaction: animal models and clinical application to noninvasive specimens.

Pneumocystis carinii is a eukaryotic microbe which causes fatal pneumonia in patients with AIDS. Oligonucleotide primers were used to amplify the 5S rDNA sequence of P. carinii by the polymerase chain reaction (PCR) in various clinical and animal samples. Of 35 independent lung specimens tested, PCR detected the P. carinii sequence in all 23 cases which were known to be P. carinii infected, i.e., 15 from mice, 1 from rat, 3 from human autopsy, and 4 from biopsy of AIDS patients by needle aspiration. The results were consistent with clinical and microscopic diagnosis. The detection was highly sensitive and specific. Direct sequencing of these amplified DNAs revealed homogeneity of 5S rDNA sequences of independent isolates from mice, rats, and humans. Preliminary trials manifested efficacy of the PCR method to detect P. carinii sequences in induced sputum or blood from AIDS patients, the latter case suggesting that P. carinii might enter peripheral blood via phagocytosis or direct intrusion. Development of less-invasive or noninvasive PCR diagnostic techniques to detect P. carinii infection would greatly facilitate therapeutic and prophylactic management of P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗

Role of serum amyloid P component for systemic amyloidosis in transgenic mice carrying human mutant transthyretin gene.

The role of serum amyloid P component (SAP) for systemic amyloidosis in a transgenic mouse model for an autosomal dominant disease, familial amyloidotic polyneuropathy (FAP), was examined. For this purpose, two lines of transgenic mouse were produced by introducing the human mutant transthyretin (TTR) gene and the human SAP gene, respectively. Two lines of transgenic mice were mated to produce double transgenic mice carrying both human mutant TTR gene and human SAP gene. The serum concentration of human SAP in these transgenic mice was about 42 micrograms/ml and was about equal to that in human control serum. In case of single transgenic mice carrying human mutant TTR gene, amyloid deposition starts at around 6 months of age, and the amount of amyloid deposition increases gradually with age. Amyloid deposition is observed in many tissues including heart, kidney and thyroid gland, where amyloid deposition is commonly observed in FAP patients. In double transgenic mice, onset, progression and tissue distribution of amyloid deposition were the same as those in single transgenic mouse. These results clearly suggest that SAP is not important for the initiation and progression of amyloid deposition.

Age Factors↗

Changes in alpha 1- and beta 1-adrenergic receptors and calcium ion binding sites in the fetal myocardium of spontaneously hypertensive rats (SHR).

The present study examined changes in [3H]prazosin, [125I]iodocyanopindolol and [3H]nitrendipine binding to alpha 1- and beta 1-adrenergic receptors and Ca2+ binding sites of cardiac muscle isolated from fetal Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), using the radioligand binding assay method. The catecholamine concentration in the cardiac muscle of both groups was also determined. The Bmax values in beta 1-adrenoceptors and Ca2+ binding sites in SHR cardiac muscle were lower than those of WKY, but values for SHR alpha 1-adrenoceptors were higher than those of WKY. The Kd values of beta 1-adrenoceptors in cardiac muscles of SHRs were also lower than those of WKY. On the other hand, there were no differences between the catecholamine concentrations in fetal SHR and WKY cardiac muscles. Thus, significant differences in both alpha 1- and beta 1-adrenoceptors and Ca2+ binding sites were already present in fetal SHR hearts, thus suggesting that the changes in fetal hearts of SHRs may be caused by genetic defects in the mother rats at early age.

Animals↗

Effects of diazepam administration on melatonin synthesis in the rat pineal gland in vivo.

The effect of diazepam (DZP) on melatonin synthesis in rat pineal gland was investigated in vivo. Subcutaneous injection of DZP (3 mg/kg) 1 h before the start of darkness significantly suppressed nocturnal elevations of pineal N-acetylserotonin (NAS) and melatonin contents in rats, and caused a 2-h delay in reaching the maximum melatonin level in the dark phase. DZP treatment also markedly suppressed the dark-induced increase of pineal N-acetyltransferase activity, which catalyzes the rate-limiting step in melatonin synthesis, but had no effect on hydroxyindole-O-methyltransferase activity, which catalyzes the final step of melatonin formation. Pineal norepinephrine and dopamine contents, in contrast, were not altered by DZP injection. The distribution rate of DZP to the brain reached the highest level 30 min after a single injection, while that to the pineal gland was observed 5 h later (i.e., 4 h after the start of darkness). It is clear that the inhibitory effect of DZP on melatonin synthesis in rat pineal gland appears concomitantly with the increase in the distribution volume of DZP into this gland. These results suggest that the inhibitory effect of DZP on melatonin synthesis results from the drug's direct action on the rat pineal gland.

Acetylserotonin O-Methyltransferase↗

Effects of adrenergic blockers or bicuculline on diazepam induced changes in rat pineal melatonin synthesis in vivo and in vitro.

The effect of propranolol (PPL), phenoxybenzamine (PBZ) or bicuculline (BCL) on the diazepam (DZP)-induced changes of pineal melatonin synthesis in male rats was examined in vivo and in vitro. Administration of PBZ did not affect the inhibitory action of DZP on pineal melatonin synthesis in vivo. A single injection of PPL inhibited the pineal melatonin synthesis similarly to the administration of DZP alone, but the two drugs together did not exhibit additive or synergistic effects on the melatonin synthesis. Significant decreases in the N-acetyltransferase (NAT) activity and the N-acetylserotonin (NAS) and melatonin contents were observed in the BCL-injected group, being greater than those in the DZP-treated group. Unexpectedly, however, the combination treatment of DZP and BCL causes an increase in the NAT activity and melatonin content compared with the BCL-alone group. Incubation with DZP at higher concentrations resulted in an increase of pineal NAT activity in vitro, but this increase was inhibited by preincubation with PPL, PBZ or BCL. DZP treatment thus appeared to have different effects on pineal NAT activity in vivo and in vitro. These results suggest that both a GABAergic mechanism and peripheral benzodiazepine (BZP) receptors in rat pineal gland may be involved in the modulation of melatonin synthesis by DZP.

Acetylserotonin O-Methyltransferase↗

Anticoagulant heparin-like glycosaminoglycans on endothelial cell surface.

Atherosclerosis is associated with an accumulation of proteoglycans. Proteoglycans and/or glycosaminoglycans, in particular heparan sulfate, produced by endothelial cells are thought to play important roles in diverse vascular functions. Of particular note is that they possess anticoagulant functions, i.e., heparin-like antithrombin cofactor activity. Incubation of antithrombin III with endothelial cell cultures resulted in a specific, saturable binding of this protease inhibitor presumably to the endothelial cell surface. In addition, thrombin inactivation by antithrombin III was accelerated on the endothelial surface, providing strong evidence that heparan sulfate on the surface of endothelial cells exerts a heparin-like activity. beta-D-xyloside or cytokine treatments altered the synthesis of heparan sulfate on the endothelial cell surface, resulting in decreased anti-thrombin III binding and diminished heparin-like anticoagulant activity of endothelial cells. The modulation of endothelial heparin-like compounds by these pharmacologic or physiologic agents may have pathophysiologic implications in thrombosis as well as atherogenesis.

Animals↗

Two-dimensional and Doppler echocardiographic findings in a case of subaortic "fibrous sac".

We described a 37-year-old man with a subaortic "fibrous sac", admitted for congestive heart failure. On 2-dimensional echocardiography a saccular structure was seen to extend from the left coronary cusp of the aortic valve to the outflow tract of the left ventricle. By color Doppler imaging, a grade 3 aortic regurgitation was recognized. Aortic regurgitant flow was recorded from the left coronary cusp to the saccular lesion. When congestive heart failure became exacerbated, the repeat examination showed the regurgitant flow passing through the perforated bottom of this lesion and reaching the left ventricular cavity. On microscopic examination of the excised valve, capillary proliferation and inflammatory changes were recognized near the annular region of the left coronary cusp. The edge of the valve leaflet and the other 2 cusps were intact. It is likely that our patient had a mycotic aneurysm near the aortic ring. We speculate that aortic regurgitation followed inflammation. It dilated the left ventricular cavity and contributed to congestive heart failure. Inflammation also weakened the tissue near the annulus, causing it to protrude into the subaortic region thus forming a small aneurysm. It may have grown to become a large saccular structure under high aortic pressure. That is, it became a "giant" endocardial pocket with inflammatory process. Finally, the rupture of this sac caused a massive aortic regurgitation, exacerbating congestive heart failure.

Adult↗

Nucleotide sequence of celC307 encoding endoglucanase C307 of Clostridium sp. strain F1.

The celC gene, encoding endoglucanase C, of Clostridium thermocellum was recently sequenced while a promoter region was not identified. In this study, the nucleotide sequence of celC307 of Clostridium sp. strain F1 was identified and compared with that of the C. thermocellum gene. The open reading frame was composed of 1029 nucleotides and the deduced amino acid sequence corresponded to a protein of a molecular weight of 40,905. We identified promoter sequences (TGGACA and TATAAT) at a position about 150 nucleotides upstream of the initiation codon. Six substitutions were found in the coding region, 3 leading to amino acid replacements. Five substitutions and 1 deletion of a nucleotide were found in the region upstream of the initiation codon, 1 present at the promoter sequence. Overproduction of endoglucanase C307 (EGC307) in Escherichia coli strongly inhibited the cell growth of the host strain. Around 50% of EGC307 produced in E. coli was detected in the periplasmic fraction. The N-terminal amino acid sequence suggested that this protein was exported into the periplasm without processing of a signal peptide.

Amino Acid Sequence↗

Expression of prolactin gene in incubating hens.

Steady-state levels of the 1.38-kb mRNA encoding the prolactin prohormone, measured by northern and dot blotting using a radioactive cDNA probe, rose 10-fold with concomitant increases in concentrations of prolactin in anterior pituitary and plasma from non-incubating to incubating stages in Gifujidori bantam hens. Daily injections of a low dose of thyrotrophin-releasing hormone (TRH, 0.25 micrograms/kg) for 4 days caused no changes in the concentrations of prolactin of the mRNA, but a high dose (2.5 micrograms/kg) of TRH did induce a significant increase in prolactin mRNA levels compared to saline controls. The results suggest that gene expression for prolactin increases substantially during the incubation period and TRH may contribute, at least in part, to the increase in transcription of prolactin mRNA for prolactin biosynthesis in Gifujidori bantam hens.

Animals↗

Otoplasty in microtia.

Microtia patients encountered over 9 years from 1978 to 1986 were listed. The total number of patients for the period was 155, 113 males and 42 females. The microtia occurred on the right side in 93 cases, on the left in 50 cases and bilaterally in 12 cases. Surgery was performed in 115 cases during the period. We applied a modification of the Brent method and have to date obtained good results. This method has several advantages: 1) Use of 7th and 8th rib cartilage means a relatively small amount of material, minimal surgical invasion and short operation time; 2) A more naturalistic auricle with clear grooves and ridges; 3) Preschool start completion of auricle reconstruction is possible, which contributes to the peace of mind of patient and parents.

Cartilage↗

Ten-year statistics and observation of facial bone fracture.

Six hundred and seventy-four cases of facial bone fracture in the past 10 years were studied with respect to age and sex, region, cause, classification, and treatment at our clinic. About half of the cases of the single fractures of nasal bones were caused by sports and fights. Of the other cases of facial bone fracture, about 40% were caused by traffic accidents. Reduction of facial bone fracture should be performed as soon as possible from a functional as well as cosmetic point of view. Hence precise diagnosis and refined techniques of repairing are mandatory to avoid postoperative complications.

Adolescent↗

Augmented Na,K-ATPase gene expression in spontaneously hypertensive rat hearts.

Abnormalities in cardiovascular Na,K-ATPase ion-transport function and regulation may play an important role in the pathogenesis of hypertension. However, it is not known whether these abnormalities are secondary to the effects of hypertension, such as increased pressure, or reflect an intrinsic abnormality in Na,K-ATPase gene expression and regulation. A genetic model of hypertension was used to address this issue. Na,K-ATPase alpha subunit gene expression in hearts was compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Pre-hypertensive, 4-week old SHR hearts exhibited an approximately 4 fold elevation in alpha 1 and 8 fold elevation in alpha 2 mRNA levels compared with age-matched WKY hearts. These SHR mRNA levels remained almost equivalent throughout the development of hypertension at 8 and 16 weeks of age. WKY alpha 1 and alpha 2 mRNA levels exhibited a progressive increase during the same time period. The neonatal alpha 3 mRNA isoform was detected only in pre-hypertensive (4-week) SHR hearts. We conclude that cardiac Na,K-ATPase alpha subunit gene expression is significantly altered in SHR even before the onset of hypertension. These findings suggest that an abnormality in cardiac Na,K-ATPase gene expression constitutes an early, if not primary, event in spontaneous hypertension.

Animals↗

[Relationship between exercise endurance capacity and cardiovascular risk factors in seventh decade subjects].

Evidence suggests that physical activity is related to lower coronary risk factors in middle-aged subjects, but to date data are lacking for older persons. A total of 32 healthy male subjects in their seventh decade (64 +/- 3 years) were divided into 2 groups based on maximal exercise tests (Bruce protocol). Group I consisted of 14 individuals who showed "excellent" work capacity (exercise duration of greater than or equal to 10 min, 11 +/- 1 min), and Group II 18 individuals with "fair" work capacity (7.5 +/- 1 min). None of them showed ECG evidence of ischemia in these tests. As compared with Group II, Group I showed lower casual and 24 hour ambulatory blood pressure (136 +/- 21 vs 114 +/- 11 mmHg for the average daily systolic pressure respectively), higher apo A-I levels (116 +/- 36 vs 139 +/- 20 mg/dl) and lower apo B/A-I ratios. There was no significant difference in triglycerides, total and HDL cholesterol or apo-B levels between these two groups. Body mass index and smoking habits were similar in Groups I and II. These results suggest that even in older persons, excellent physical fitness is related to lower cardiovascular risk factors.

Aged↗

[Computer-aided visuospatial cognitive-performance test].

The validity of a newly developed computer-aided "Visuospatial Cognitive-Performance Test" (VCP-Test) was examined in two populations, 68 normal elderly volunteers (mean age, 69.5% years) and 25 patients with dementia (mean age, 68.2 years). None of the cases in the two groups had either motor impairment or ataxia. The VCP-Test was a kind of vigilance task in which a subject is required to tap the key corresponding to the local change-over of the image on the computer display as quickly as possible. After 40 trials, consecutive data of performance efficiency were automatically displayed on the LCD display and printed out. A significant negative correlation between the VCP-Test and age in normal elderly population was recognized. Moreover, the relationship between the VCP-Test and the Hasegawa Dementia Scale (HDS), and the Mini-Mental State (MMS) was also significant in patients with dementia. In conclusion, the VCP-Test was considered to be useful for geriatric neurobehavioral functional assessment and for the detection of dementia.

Aged↗

[Long-term single dose chemoprophylaxis of recurrent urinary tract infection in elderly female subjects].

To evaluate the efficacy of the single dose chemoprophylaxis of recurrent urinary tract infection (UTI) in the elderly, 20 female inpatients (mean age 81.4) who had one or more culture documented UTIs in the past 12 months were studied. They were randomly assigned to be treated for 6 months either with chemoprophylaxis (200 mg of norfloxacin) or conventional therapy (without any antimicrobials except when overt UTI occurred). After a 4 months of washout period, the protocols were exchanged with each other and next 6 months of trial was carried out. All cases were followed at least 4 months after the discontinuance of the chemoprophylaxis. The difference of efficacy between the two modalities was evaluated by periodical examinations of urine cultures, urinalysis and inflammatory markers. During chemo-prophylaxis, the frequency of the symptomatic UTI (bacteriuria greater than 10(4)/ml, pyuria greater than 5/HPF, CRP greater than +) was 0.267/patient.year which was significantly lower than during conventional therapy (2.97/patient.year, p less than 0.01). This prophylactic effect remained 4 months after the discontinuance of the drug. On the other hand, bacteriuria was persistent in more than half of patients with chemoprophylaxis. Minimal inhibitory concentration of norfloxacin for separated bacteria revealed that the resistant species steeply increased from 4 to 6 months after the beginning of chemoprophylaxia. These species disappeared 4 months after the drug was discontinued. Optimal durations of chemoprophylaxis and drug-holidays were discussed.

Aged↗

[Congenital lower urinary tract obstruction and enuresis in children].

We reviewed enuretic children among patients with congenital lower urinary tract obstructions experienced in the Department of Urology, Hyogo College of Medicine during 16 years from 1974 to 1989. Among 612 patients with congenital lower urinary tract obstructions, 139 (22.7%) had enuresis nocturna and/or diurna. The incidence of enuresis was 24.7% with posterior urethral valve (77 cases), 50.0% with anterior urethral valve (6 cases), 23.8% with congenital bulbar urethral stenosis in boys (303 cases) and 19.9% with congenital distal urethral stenosis in girls (226 cases). Diurnal enuresis was more common in enuresis associated with congenital lower urinary tract obstructions than in usual enuresis. In urodynamic examinations, more than half of enuretic children with congenital lower urinary obstructions showed hyperactive detrusor activity. Treatment of congenital lower urinary tract obstructions through operation resulted in cure or amelioration of enuresis in about 80% of the patients. Enuresis associated with lower urinary tract obstruction or neurogenic bladder is sometimes called complicated enuresis and it is an important role of a urologist to differentiate complicated enuresis from simple enuresis.

Adolescent↗