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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 271 records · Page 15Linked to original sources

Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.

We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNF alpha plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNF alpha in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNF alpha released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.

Animals↗

Whole sequence of spoIIIE-like, sporulation-inhibitory, and transfer gene (spi) in a conjugative plasmid, pSA1.1, of Streptomyces azureus and detection of spi-like gene in the actinomycete chromosome.

The nucleotide sequence of spoIIIE-like and the sporulation-inhibitory and transfer gene (spi) in a conjugative plasmid, pSA1.1, of Streptomyces azureus were examined to detect the promoter region. Using Southern blotting and a spi fragment as probe, spi-like genes were detected in chromosomes of the host and other actinomycetes. These results suggest that there is a spi- and spoIIIE-like gene in chromosomes of some actinomycetes.

Actinomycetales↗

Effects of intravenously administered C-type natriuretic peptide in humans: comparison with atrial natriuretic peptide.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and suggested that CNP might be a local regulator of vascular tone and growth. To evaluate the biological actions of CNP as compared with human atrial natriuretic peptide (hANP), we intravenously administered synthetic CNP (0.43 nmol/kg) and alpha-hANP (0.43 and 0.043 nmol/kg) to healthy humans. The experiments were done on different days in the same five healthy volunteers (31+/-1 yr old). CNP injection caused a transient but significant decrease in both systolic and diastolic blood pressure (-4.3+/-1.3, -4.1+/-1.0 mmHg) with a significant increase in heart rate (+7.6+/-2.6 bpm), and exerted significant diuretic and natriuretic activities (+130+/-80%, +160+/-100% over the basal level). These effects of CNP (0.43 nmol/kg) were comparable to, or less than, those of alpha-hANP (0.043 nmol/kg). CNP injection also significantly suppressed aldosterone secretion (22% reduction as compared with the basal level). Our results demonstrate that intravenously-administered CNP acts as a natriuretic peptide with less potency than ANP.

Adult↗

A rare case of patent ductus arteriosus in a dog with glomerular mesangiolysis.

Rare case of patent ductus arteriosus (PDA) was observed in a 2-year and 9 month-old Miniature Dachshund which had been diagnosed as severe cardiac failure. Pulmonary artery from the right ventricle connected to dilated ductus arteriosus, and pulmonary artery-ductus arteriosus-descending aorta formed a continuous duct, which seemed to be the main route of bloodstream. Ascending aorta from the left ventricle was hypoplastic, and connected to the dilated ductus arteriosus. Glomerular mesangiolysis due to heart failure was also observed in the kidney.

Animals↗

Eight-year observation and comparative study of specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B: terminal acquired immunodeficiency syndrome in a cat infected with FIV petaluma strain.

Three specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) strains Petaluma, TM1 and TM2, respectively were observed for over 8 years. Without showing any significant clinical signs of immunodeficiency syndrome (AIDS) for 8 years and 4 months of asymptomatic phase, the Petaluma-infected cat exhibited severe stomatitis/gingivitis, anorexia, emaciation, hematological and immunological disorders such as severe anemia, lymphopenia, thrombocytopenia, and decrease of CD4/CD8 ratio to 0.075, and finally died with hemoperitoneum at 8 years and 8 months post-infection. Histopathological studies revealed that the cat had systemic lymphoid atrophy and bone marrow disorders indicating acute myelocytic leukemia (aleukemic type). Plasma viral titer of the cat at AIDS phase was considerably high and anti-FIV antibody titer was slightly low as compared with the other FIV-infected cats. In addition, immunoblotting analysis using serially collected serum/plasma samples of these cats revealed that antibodies against FIV proteins were induced in all the infected cats, however in the Petaluma-infected cat anti-Gag antibodies disappeared during the asymptomatic period. These results suggested that plasma viral load and anti-FIV Gag antibody response correlated with disease progression, and supported FIV-infected cats as a suitable animal model of human AIDS.

Acquired Immunodeficiency Syndrome↗

Free muscle transfer can restore hand function after injuries of the lower brachial plexus.

One pattern of injury to the brachial plexus shows recovery of the fifth and sixth cervical nerves but little else. These patients have useful shoulders and functional elbow flexion, but elbow and wrist extension is weak or absent. Their hand function is negligible. We restored hand function in three such patients using free functioning muscle transfer for finger flexion and transfer of the sensory rami of the intercostal nerve to the ulnar nerve for sensation. Supplementary operations to restore elbow and wrist extension were necessary in one patient.

Adult↗

Purification and characterization of chaperonins 60 and 10 from Methylobacillus glycogenes.

Two proteins belonging to the group I chaperonin family were isolated from an obligate methanotroph, Methylobacillus glycogenes. The two proteins, one a GroEL homologue (cpn60: M. glycogenes 60 kDa chaperonin) and the other a GroES homologue (cpn10: M. glycogenes 10 kDa chaperonin), composed a heteropolymeric complex in the presence of ATP. Both proteins were purified from crude extracts of M. glycogenes by anion-exchange (DEAE-Toyopearl) and gel-filtration (Sephacryl S-400) chromatography. The native molecular weights of each chaperonin protein as determined by high-performance liquid chromatography (HPLC) gel-filtration were 820 000 for cpn60 and 65 000 for cpn10. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the subunit molecular weights of cpn60 and cpn10 were 58 000 and 10 000, respectively. Both cpn60 and cpn10 possessed amino acid sequences which were highly homologous to other group I chaperonins. M. glycogenes cpn60 displayed an ATPase activity which was inhibited in the presence of cpn10. The chaperonins also displayed an ability to interact with and facilitate the refolding of Thermus malate dehydrogenase and yeast enolase in a manner similar to that of GroEL/ES. The similarities between the Escherichia coli GroE proteins are discussed.

Adenosine Triphosphatases↗

Effects of indomethacin on sunburn and suntan reactions in hairless descendants of Mexican hairless dogs.

The inhibitory effects of topical indomethacin (IM)-treatment on sunburn and suntan reactions after ultraviolet (UV)-irradiation were investigated in the dorsal skin of hairless descendants of Mexican hairless dogs. Skin color, plasma prostaglandin E2 (PGE2) and histological features were examined. At 1 day after UV-irradiation, the IM-untreated sites showed prominent erythema, while the IM-treated sites exhibited few visible erythematous reactions. From 4 days after UV-irradiation, both the IM-treated and -untreated sites began to develop skin pigmentation. Assessment of skin color changes, using a colorimeter, reflected precisely the color changes in visual sunburn and suntan reactions. Plasma PGE2 concentration began to increase from 2 hours after UV-irradiation, reached the maximal values at 24 hours and recovered at 96 hours after UV-irradiation. Histologically, at 1 day after UV-irradiation, the IM-untreated sites showed remarkable epidermal degeneration (thickening and sunburn cells) and moderate alteration in the dermis. On the other hand, the IM-treated sites showed only minor histological changes. At 4 days after UV-irradiation, deposition of melanin granules was found in both the IM-treated and -untreated sites. At 7 days after UV-irradiation, pigmentation became more prominent in the stratum basale. These results revealed that UV-induced erythematous reactions of hairless dogs were closely related to the action of PGE2. Visually and histologically, topical IM-treatment had apparent inhibitory effects on erythematous reactions, while this agent showed no protective effects on epidermal pigmentation after UV-irradiation.

Administration, Topical↗

Morphological and morphometrical study on the dorsal skin of Wistar and WBN/ILA-Ht rats in their developing stage. Evaluation of the proliferation and apoptotic processes.

The detailed histology of the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats (HtRs) was examined in their developing stage (at 3 and 7 weeks of age) using Wistar rats (WRs) as controls. As a result, except for the existence of time-lag in the hair follicular cycle and some quantitative differences, there were no essential qualitative differences between the two strains. The follicular epithelial cell number and the amounts of tonofilaments and trichohyalin granules were less in HtRs than in WRs in the same phase of hair follicular cycle. In addition, the diameter of hair shaft was significantly larger in WRs than in HtRs at 7 weeks of age. The number of proliferating cell nuclear antigen (PCNA)-positive epidermal basal cells decreased in HtRs and increased in WRs from 3 to 7 weeks of age, respectively. Apoptosis was sparsely observed in the sebaceous gland epithelial cells, keratinizing portion of hair cuticules and inner root sheath in both strains, but the frequency of apoptosis in the hair follicle was somewhat higher in 7-week-old HtRs. HtRs are considered to be useful experimental animals for dermatotoxicological studies.

Animals↗

Lectin histochemistry of dorsal skin of Wistar-derived hypotrichotic WBN/Ila-Ht rats.

A lectin histochemical study was carried out on the dorsal skin of Wistar-derived hypotrichotic WBN/Ila-Ht rats (HtRs) and Wistar rats (WRs) at 3, 7 and 24 weeks of age to clarify the lectinhistochemical characteristics of the skin during their development. The lectins examined were Concanavalia ensiformis (Con A), Dolichos biflorus agglutinin (DBA), Griffonia simpliciolia (GS-I), Helix pomatia agglutinin (HPA), Arachis hypogaea (PNA), Glycine maximus agglutinin (SBA), Ulex europeus agglutinin (UEA-I) and Triticum vulgaris agglutinin (WGA). None of the nucleated cell layers of the epidermis had DBA-binding sites, but they were all stained intensely with HPA and weakly with Con A irrespective of the strain and age of the rats. As to the other 5 lectins, the intensity of binding activity was generally weaker in HtRs than in WRs and at 3 weeks of age than at 7 or 24 weeks of age, respectively. Among them, UEA-I mainly bound to the spinous cell layer but not to the basal cell layer, suggesting that alpha-L-fucose would be expressed on the cell surface according to the differentiation of keratinocytes. In addition, GS-I, HPA and UEA-I bound to the hair follicle epithelium and many lectins stained sebaceous gland epithelial cells. In conclusion, except for the binding intensity of some lectins, there were no specific differences between HtRs and Wrs in the lectinhistochemical characteristics of the dorsal skin epidermis. The present data on the rat skin would be useful from the viewpoint of comparative lectinhistochemistry.

Animals↗

Changes in location and number of tartrate-resistant acid phosphatase (TRAP)-positive cells during the development of type II collagen-induced arthritis in DBA/1J mice.

The authors investigated changes in the location and number of osteoclasts and their precursors during the development of articular lesions in type II collagen-induced arthritis in mice using tartrate-resistant acid phosphatase (TRAP) staining. The limb joints were examined at 6 to 15 weeks after the second immunization. The number of TRAP-positive cells increased as the articular lesions progressed. TRAP-positive macrophage-like cells were found in the hyperplastic synovial tissue and bone marrow stroma in the early stage. In the advanced stage, in addition to many TRAP-positive osteoclasts on the bone surface, TRAP-positive macrophage-like cells were observed in the pannus apart from the bone surface in the pannus-joint junctions. The above mentioned TRAP-positive macrophage-like cells are considered to be osteoclast precursors.

Acid Phosphatase↗

Antibody to hepatitis B e positive hepatitis induced by withdrawal of steroid therapy for polymyositis: response to interferon-alpha and cyclosporin A.

A 57-year-old woman was admitted with symmetrical proximal muscle weakness, liver dysfunction, abnormal muscle enzymes, and she was an antibody to hepatitis B e (anti-HBe) positive hepatitis B virus (HBV) carrier. Biopsy of her left quadriceps femoris showed myositis, so prednisolone was started at 40 mg/day. However, her hepatic function deteriorated and liver biopsy after 4 months showed acute hepatitis with partial submassive necrosis. Treatment with interferon-alpha and cyclosporin A progressively reduced the transaminase and HBV-DNA levels. Early treatment with interferon-alpha plus cyclosporin A can control exacerbation of hepatitis B.

Alanine Transaminase↗

Impact of diffusional oxygen transport on oxidative metabolism in the heart.

The resistance for the oxygen molecule to diffuse from the capillary blood to the cell surface produces remarkably large gradients of oxygen partial pressure (PO2) in the extracellular space. In addition, the intracellular radial gradients of PO2 may not be ignored particularly when the cellular oxygen consumption is increased. These PO2 gradients together result in a quite low intracellular PO2 in the cardiomyocyte in vivo. Thus, the cellular oxidative metabolism may be limited by diffusional transport of oxygen from the capillary blood to mitochondria. In this review, quantitative aspects and physiological relevances of the PO2 gradient in the myocardium are discussed.

Animals↗

Computer-aided diagnosis for detection of interstitial opacities on chest radiographs.

OBJECTIVE: Our objective was to evaluate the impact of a computer-aided diagnostic scheme on radiologists' interpretations of chest radiographs with interstitial opacities by performing an observer test using receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: Twenty chest radiographs with normal findings and 20 chest radiographs with abnormal findings were used. Each radiograph was divided into four quadrants. One hundred twenty-nine quadrants (80 normal and 49 abnormal quadrants) were used for testing because we excluded 31 equivocal quadrants. Sixteen independent observers (10 residents and six attending radiologists) participated in this study. The radiologists' performance without and with computer assistance, which indicated cases with normal and abnormal findings by various markers, was evaluated by ROC analysis. RESULTS: The diagnostic accuracy of the observers improved by a statistically significant magnitude when computer-aided diagnosis was used. Thus, the values for the area under the ROC curve obtained with and without the computer-aided diagnostic output were .970 and .948 (p = .0002), respectively, for all observers; .969 and .943 (p = .0006), respectively, for the residents' subgroup; and .972 and .960 (p = .162), respectively, for the attending radiologists' subgroup. The value for the area under the ROC curve for the computerized scheme by itself was .943. CONCLUSION: Our computer-aided diagnostic scheme can assist radiologists in the diagnosis or exclusion of interstitial disease on chest radiographs.

Adolescent↗

Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes.

Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg x kg(-1) x day(-1) pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 +/- 8, 45 +/- 13, and 76 +/- 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10(-5) to 10(-4) mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.

Adipocytes↗

[Renal tubular acidosis type II secondary to gamma-light chain excretion in an elderly patient with multiple myeloma].

A 73-year-old woman was admitted to the geriatric ward of the University of Tokyo Hospital with anemia, osteepeina, and renal dysfunction. Although symptoms typical of multiple myeloma such as punched-out lesions and hyperproteinemia were not found, protein electrophoresis revealed that lambda type Bence-Jones protein was excreted in urine. Multiple myeloma was diagnosed. Furthermore, renal dysfunction was accompanied renal tubular acidosis type II (proximal type). Renal dysfunction in patient with multiple myeloma in usually caused by so-called myeloma casts in the distal tubules, but renal tubular acidosis type II is rarely observed. It is possible that injury of the proximal renal tubular eithelium by Bence-Jones protein resulted in renal tubular acidosis type II in this patient.

Acidosis, Renal Tubular↗

[Clinical significance of electrically evoked auditory brainstem response].

Electrically evoked auditory brainstem responses (EABR) were recorded in 31 postlingually deafened adults, who had recently received cochlear implants (mini-system, Cochlear Ltd). The wave consisted of three distinct positive peaks labeled P1, P2, and P3 with latency of 1.35 (+/- 0.14), 2.17 (+/- 0.18) and 4.08 (+/- 0.31) ms, respectively. The P3 threshold (EABR-T) and slope (EABR-S) were 0.9 (+/- 0.47) mA and 0.6 (+/- 0.28) muv/mA, respectively. The relationships between the EABR parameters (EABR T and -S of the P3 wave) and age, duration of deafness, promontory test and subjective response (T and C-level) were investigated. The scattergram showed a strong negative linear relationship between EABR-S and subjective T-level. This finding suggests that EABR-S is good measure of postoperative perception.

Adult↗

[Clinical features in patients with delayed endolymphatic hydrops].

We report clinical features in patients with delayed endolymphatic hydrops (DEH) with juvenile unilateral deafness. Among 23 patients with DEH, 15 cases were diagnosed as ipsilateral DEH and 8 cases as contralateral DEH. The distribution of onset age showed two peaks at ages of < 30 years and > 40 years. In 80% of the ipsilateral DEH cases, the onset of episodic vertigo was at younger ages. On the other hand, in 75% of the contralateral DEH cases, the onset of fluctuation hearing loss of the contralateral ear was at older ages. Ispilateral DEH and Meniere's disease may show different pathophysiologies. The incidence of dominant negative summating potential in the better-hearing ear was 20% in the ispilateral DEH cases and 60% in the contralateral DEH cases. It is suggested that endolymphatic hydrops is in the better-hearing ear of contralateral DEH.

Adult↗