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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 91 records · Page 5Linked to original sources

Grouping prurigo: report of cases.

Grouping prurigo was reported as a new clinical entity by Ofuji et al. in 1977 and 1988. No further cases have been reported since. Herein we report four cases of grouping prurigo and discuss the possible relationship between this condition and other diseases in the prurigo group, including chronic pruritic papular dermatitis in adult men, which was reported by Chang et al. in 1999. Since grouping prurigo and chronic pruritic papular dermatitis in adult men share approximately the same characteristics in both clinical and histopathological findings, we concluded that these two disorders may be the same entity, characterized by grouped pruritic solid papules on the trunk.

Abdomen↗

Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect.

The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be distributed on the surface of the colonic mucosa. AM and PAMP showed dose-dependent antimicrobial activity against E. coli. The results suggest that the novel vasoactive peptides AM and PAMP play an important role in mucosal defence.

Adrenomedullin↗

Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development.

Six4 is a member of the Six family genes, homologues of Drosophila melanogaster sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscles. To elucidate the biological roles of Six4, we generated Six4-deficient mice by replacing the Six homologous region and homeobox by the beta-galactosidase gene. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of the heterozygous mutant embryos revealed expression of Six4 in cranial and dorsal root ganglia, somites, otic and nasal placodes, branchial arches, Rathke's pouch, apical ectodermal ridges of limb buds, and mesonephros. The expression pattern was similar to that of Six1 except at the early stage of embryonic day 8.5. Six4-deficient mice were born according to the Mendelian rule with normal gross appearance and were fertile. No hearing defects were detected. Six4-deficient embryos showed no morphological abnormalities, and the expression patterns of several molecular markers, e.g., myogenin and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4.

Animals↗

Side chain-dependent binding of antitumor indoloquinoxaline derivatives to DNA: comparative spectroscopic and viscometric measurements.

NCA0424 (1) and its side chain positional isomer, NCA0465 (2), are indoloquinoxaline derivatives with potent antitumor activity. To investigate the effect of side chain position for binding with DNA, the interactions of 2 with various B-form DNAs were studied by spectroscopic (circular dichroism (CD), fluorescence and UV) and viscosity measurements and were compared with those of 1. The binding preference for the base sequence was different in each case. The CD spectra showed that 2 formed an asymmetric binding of indoloquinoxaline ring with adenine in DNA, whereas such a base selectivity was not found with 1. The binding features are discussed based on association constants and thermodynamic parameters, indicating the importance of the side chain position for binding specificity for DNA.

DNA↗

State-dependent inhibition of L-type Ca2+ channels in A7r5 cells by cilnidipine and its derivatives.

Using a whole-cell patch-clamp technique, state-dependent inhibition of dihydropyridines (DHP)s was investigated on L-type channels in A7r5 cells. Cilnidipine, its derivatives (D-342 and D-69) and nimodipine inhibited the Ba2+ current. However, cilnidipine and D-342, but not D-69 or nimodipine, accelerated current decay. The apparent rank order for the effects on the DHP-sensitive decaying component was different from that obtained for inhibition of the peak current. The dissociation constants for cilnidipine in the resting and inactivated states were estimated to be 190 and 12 nM, respectively. Cilnidipine, but not other DHP derivatives, created a faster and voltage-independent component (r= 37 ms). The linear relationship between the tau(-1) of the current decay and the cilnidipine concentration provided a value of 471 nM for the dissociation constant in the open state, suggesting that the current decay is mediated by one-to-one lower affinity binding of cilnidipine molecules to their binding site. The present study demonstrates that structurally related DHPs act in distinct ways to inhibit the L-type channel in the resting, open and inactivated states. Cilnidipine and some related DHPs probably exert their blocking action on the open channel by binding to a receptor distinct from the known DHP-binding site.

Animals↗

Chloride channels and their functional roles in smooth muscle tone in the vasculature.

Although evidence of important contributions by Cl- channels to agonist-induced currents have been reported in vascular smooth muscle cells, the functional roles played by Cl- channels in the smooth muscle contraction and in setting the membrane potential remain essentially obscure. All of the admittedly few papers published have focused on the physiological roles of Cl- channels in the contraction and membrane depolarization elicited by agonists. At present, it seems likely that in vascular cells: a) Cl- conductance contributes to membrane depolarization, with the subsequent contraction being due to Ca2+ release from the intracellular store sites, and b) Cl- movements through the membrane of the Ca2+ store sites also regulate Ca2+ release and Ca2+ uptake from/into the store sites. As a Ca2+-dependent Cl- current is most easily demonstrated under quasi-physiological conditions (by the perforated patch-clamp method), the contribution made by Cl- channels to smooth muscle function may be more important than previously thought. The development of the new, selective Cl--channel blockers as well as the identification and gene engineering of the channel molecules are essential if we are to advance our knowledge of the physiology and pharmacology of the Cl- channels residing in vascular smooth muscle cells.

Animals↗

Solitary infantile myofibromatosis in the lateral orbit floor showing spontaneous regression.

Infantile myofibromatosis is a rare benign tumour usually occurring early in infancy. We describe the case of a 10-year-old boy with solitary infantile myofibromatosis in the left lateral orbit floor which regressed spontaneously. Although our patient was older than previously reported cases and showed bony destruction confirmed by computed tomography (CT), this tumour was diagnosed as infantile myofibromatosis based on immunohistochemical findings. The tumour disappeared spontaneously six months after incisional biopsy, that also indicated this tumour was an infantile myofibromatosis.

Child↗

Sequential computed tomography images demonstrating characteristic changes in fibrous dysplasia.

Images of fibrous dysplasia (FD) on computed tomography (CT) or magnetic resonance imaging (MRI) vary depending on the relative proportions of the fibrous and osseous components. Based on analysis of the literature, Camilleri suggested that structural changes revealed by conventional radiography may be indicative of the progression of FD. Here we describe the case of a boy who presented at 12 years of age with monostotic FD located in the right maxilla. The lesion first appeared as a lamellar, "onion peel"-like structure on CT; then over the course of the next five years, the structure became what has been termed an "egg-shell lesion", before eventually assuming the form of a "ground-glass lesion".

Adult↗

Audiological findings in patients with myoclonic epilepsy associated with ragged-red fibres.

Sensorineural hearing loss is a common symptom in patients with myoclonic epilepsy associated with ragged-red fibres (MERRF), one of the mitochondrial encephalomyopathies, although the lesion causing hearing loss in such cases remains unknown. Here we describe the audiological features in three MERRF patients, all of whom exhibited a point mutation in their mitochondrial DNA at nucleotide 8344. Pure-tone threshold audiometry revealed bilateral, sloping-type, sensorineural hearing loss in all three patients. Distortion product otoacoustic emissions, electrocochleography, and auditory brainstem responses were variable, even differing between the right and left ears of the same patient. Taken together, our findings suggest that the primary lesion underlying hearing loss in MERRF patients is in the cochlea, although a retrocochlear lesion may be involved in some patients.

Adolescent↗

Biosynthesis and secretion of adrenomedullin and proadrenomedullin N-terminal 20 peptide in a rat model of endotoxin shock.

To study the biosyntheses and pathophysiological roles of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) in septic shock, we compared the time course of plasma concentrations of these peptides and blood pressure in rats injected with either 0.9% saline (control group) or lipopolysaccharide (LPS group). The plasma AM concentration in the LPS group did not increase 30 and 60 min after LPS injection, at which time points the blood pressure remained low. Thereafter, AM rapidly increased, and it amounted to 35 times the basal value 4 h after injection, when the blood pressure returned to the basal level. The increment of plasma PAMP in the LPS group was lower than that of AM. We also examined the tissue concentration of AM and PAMP--as well as the tissue expression of proadrenomedullin (proAM) mRNA--in the LPS and control groups. LPS significantly increased the tissue concentrations of AM and PAMP in the lung, but decreased them in the adrenal gland and cardiac atrium. The LPS injection augmented proAM gene transcription in the lung, adrenal gland and aorta. In an immunohistochemical examination, AM staining was intense in alveolar endothelial cells of the lung in the LPS group. Thus, this septic shock model had high plasma levels of PAMP as well as AM, while the biosynthesis and secretion of the two peptides may have been differentially regulated in various tissues of rats injected with LPS. The present results suggest that these two bioactive peptides may play different roles in the pathophysiology of septic shock.

Adrenomedullin↗

The repeatability of left ventricular volume assessment by a new ambulatory radionuclide monitoring system during head-up tilt.

The precise measurement of changes in left ventricular volume is important to elucidate the mechanisms of neurally mediated syncope. This study was conducted to determine whether or not a brand-new ambulatory radionuclide monitoring system (C-VEST system) can be clinically used to easily and precisely measure left ventricular volume and function in tilt testing. To assess the repeatability of the C-VEST system, 12 healthy volunteers (mean age 24+/-4 years old) underwent 20 minute head-up tilt testing and we measured the temporal changes in left ventricular volume and ejection fraction twice a day (first and second studies). To investigate the changes in the C-VEST measurements and the detector position in the first and second studies, tilt testing was performed with an 80-degree passive tilt, which is the same as the standard procedure used in diagnosing neurally mediated syncope. The coefficient of repeatability for both the C-VEST and detector position was well within the clinical range (coefficient of repeatability in left ventricular volume ranged from 1.7 to 2.8; coefficient of repeatability in the detector position ranged from 2.3 to 3.1). Precise evaluation of the left ventricular volume can be achieved by an ambulatory radionuclide monitoring system in tilt testing.

Adult↗

Justification of measurement of eight congeners levels instead of twenty congeners of dioxins for mass screening of human exposure.

Measurement of blood dioxin levels to monitor human exposure is tedious and expensive work, although high-resolution mass spectrometers equipped with high-resolution gas chromatography are becoming relatively common in Japan. The Ministry of Health and Welfare and the Environmental Agency require measurement of 17 dioxins, seven PCDDs and 10 PCDFs, according to a statement in "Dioxin Measurement Guidelines" published in 1997. Additionally, three coplanar polychlorinated biphenyls, for which TEFs were determined, have been included for measurement ad libitum. Recently, we have examined 316 blood samples from four groups of subjects, living in areas 5 km away from any incinerator (A), within 2 km from incinerators that emitted slightly higher levels of dioxins than the allowed level (higher than 80 ng/Nm3) (B), within 2 km of an incinerator which emitted a high level of dioxin (C), and workers at this incinerator (D), for dioxin levels by measuring 20 congeners, including three coplanar PCBs. The average pg TEQ/g lipid values were 23.8 +/- 12.3, 25.6 +/- 11.6, 39.1 +/- 18.8 and 100.7 +/- 127.4 for A, B, C and D, respectively. It was found that more than 90% of the total TEQs of the subjects in all groups were accounted for by eight congeners, 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD, 2,3,4,7,8-PeCDF, 3,3',4,4',5-PeCB, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF and 2,3,4,6,7,8-HxCDF. This is also the case for a further 30 blood samples that had no connection with incinerators. Further, regression analysis of the 346 samples leads to an equation of y = 1.109x - 1.077, with a correlation coefficient, r = 0.9996. Here, y = total pg TEQ of 20 congeners/g lipid of blood, and x = total pg TEQs of eight congeners/g lipid. Accordingly, we propose that measurement of eight instead of 20 congeners is appropriate to obtain dioxin TEQ values of blood, at low cost, with high accuracy and with high efficiency, in a short time.

Adult↗

Dioxins in bile in relation to those in the human liver and blood.

The levels of 20 dioxin congeners, 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and three coplanar polychlorinated biphenyls (Co-PCBs), in bile were examined in comparison with those in the blood and liver, in 27 autopsy cases. Total-TEQ values were the same in the bile (43.2 +/- 30.9 pg TEQ/g lipid) and blood (43.1 +/- 24.2 pg TEQ/g lipid), and three times higher in the liver (127.8 +/- 57.4 pg TEQ/g lipid). Highly chlorinated PCDDs and PCDFs have a tendency to accumulate in the liver, and their levels in bile and blood were relatively low compared with those in the liver, with 1,2,3,4,6,7,8-heptachlorodibenzofuran having the highest tendency among the 20 congeners. Daily excretion in bile was calculated to be 54 pg TEQ at age 65, by assuming that daily bile secretion is 750 ml and is concentrated 7.5-fold in the gallbladder. The correlation between bile and blood total-TEQ was high, with a correlation coefficient of 0.89 among the 27 autopsy cases. Thus, the regression equation of y = 1.14x - 6.02 will provide us levels in bile (total TEQ per g lipid), knowing the blood total-TEQ level, where x is total-TEQ per g lipid of the blood. Furthermore, accumulation of dioxins was estimated to be 0.99, 0.70 and 1.91 pg TEQ/g lipid/year in bile, blood and liver, respectively.

Age Factors↗

Pneumonitis induced by ou-gon (scullcap).

A 53-year-old Japanese man with recurrent interstitial pneumonia was referred to us. The patient had taken a traditional herb medicine, otsu-ji-to, before the onset of pneumonia. A provocation test for each herbal ingredient contained in otsu-ji-to revealed that the pneumonitis had been induced by ou-gon (scullcap). Lymphocytosis with the CD8+ T-cell subset predominance was found in the bronchoalveolar lavage fluid and lymphocytic alveolitis was noted in the transbronchial lung biopsy specimen after the provocation test. Ou-gon, or scullcap, should be included in the list of drugs with definite causal association with pneumonitis.

Biopsy↗

Pharmacological characterization of KUR-1246, a selective uterine relaxant.

The aim of the present study was to evaluate the efficacy and beta 2-adrenoceptor (AR) selectivity of KUR-1246, a new uterine relaxant. Inhibition of spontaneous or drug-induced uterine contractions by KUR-1246 was evaluated in pregnant rats and rabbits by an organ bath method or by a balloon method. The selectivity of KUR-1246 was assessed simultaneously in organs isolated from late-pregnant rats. The affinity of KUR-1246 for human beta 1-, beta 2-, and beta 3-ARs was determined using two radioligands. KUR-1246 suppressed both spontaneous and drug-induced contractions in isolated uteri, the rank order of potency being isoproterenol > KUR-1246 > terbutaline > ritodrine. ICI-118551 (selective beta 2-AR antagonist) competitively antagonized the KUR-1246-induced inhibition of spontaneous uterine contractions, but CGP-20712A (selective beta 1-AR antagonist) and SR-58894A (selective beta 3-AR antagonist) did not. All beta-AR agonists tested produced significant inhibition of spontaneous uterine contractions in vivo: ED(30) value for KUR-1246 was 0.13 microg/kg/min, a potency about 6 times and 400 times greater than that of terbutaline and ritodrine, respectively. In contrast, the positive chronotropic effect was minimal in KUR-1246-treated rats. KUR-1246 displaced radioligand binding to beta 1-, beta 2-, and beta 3-ARs, the pK(i) values being 5.75 +/- 0.03, 7.59 +/- 0.08, and 4.75 +/- 0.03 for beta 1-, beta 2-, and beta 3-ARs, respectively. For the selectivity of KUR-1246 for human beta 2-AR, we obtained values of 39.2 ([IC(50) for beta 1-AR]/[IC(50) for beta 2-AR]) and 198.2 ([IC(50) for beta 3-AR]/[IC(50) for beta 2-AR]), indicating an apparently higher affinity for human beta 2-AR than for other beta-AR subtypes. The present study clearly demonstrated that KUR-1246 is a more selective beta 2-AR agonist than the drugs presently used for relaxing uterine muscle.

Acetamides↗

[Cytokine].

It remains to be elucidate whether measurements of cytokines in serum have any clinical significance. In this article, the clinical uses of cytokines are reviewed. The purposes of clinical use of cytokines are: 1) for the immunological treatment of malignancy; and 2) as hematopoietic growth factors. During the clinical use of cytokine, measurements of cytokine in serum might be important to estimate clinical efficacy and the clinical course.

Cytokines↗