Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 127 records · Page 7Linked to original sources

PubMed2000

Chemiluminescent detection and imaging of reactive oxygen species in live mouse skin exposed to UVA.

The recent increase of ultraviolet (UV) rays on Earth due to the increasing size of the ozone hole is suggested to be harmful to life and to accelerate premature photoaging of the skin. The detrimental effects of UV radiation on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical (*O(-)(2)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (*OH), and singlet oxygen ((1)O(2)). However, direct proof of such ROS produced in the skin under UV irradiation has been elusive. In this study, we report first in vivo detection and imaging of the generated ROS in the skin of live mice following UVA irradiation, in which both a sensitive and specific chemiluminescence probe (CLA) and an ultralow-light-imaging apparatus with a CCD camera were used. In addition, we found that *O(-)(2) is formed spontaneously and (1)O(2) is generated in the UVA-irradiated skin. This method should be useful not only for noninvasive investigation of the spatial distribution and quantitative determination of ROS in the skin of live animals, but also for in vivo evaluation of the protective ability of free radical scavengers and antioxidants.

Animals↗

PubMed2000

Novel Mn(II)Mn(III)Mn(II) trinuclear complexes with carbohydrate bridges derived from seven-coordinate manganese(II) complexes with N-glycoside.

Reactions of MnX2.nH2O with tris(N-(D-mannosyl)-2-aminoethyl)amine ((D-Man)3-tren), which was formed from D-mannose and tris(2-aminoethyl)amine (tren) in situ, afforded colorless crystals of [Mn((D-Man)3-tren)]X2 (3a, X = Cl; 3b, X = Br; 3c, X = NO3; 3d, X = 1/2SO4). The similar reaction of MnSO4.5H2O with tris(N-(L-rhamnosyl)-2-aminoethyl)amine ((L-Rha)3-tren) gave [Mn((L-Rha)3-tren)]SO4 (4d), where L-rhamnose is 6-deoxy-L-mannose. The structures of 3b and 4d were determined by X-ray crystallography to have a seven-coordinate Mn(II) center ligated by the N-glycoside ligand, (aldose)3-tren, with a C3 helical structure. Three D-mannosyl residues of 3b are arranged in a delta(ob3) configuration around the metal, leading to formation of a cage-type sugar domain in which a water molecule is trapped. In 4d, three L-rhamnosyl moieties are in a delta(lel3) configuration to form a facially opened sugar domain on which a sulfate anion is capping through hydrogen bonding. These structures demonstrated that a configurational switch around the seven-coordinate manganese(II) center occurs depending on its counteranion. Reactions of 3a, 3b, and 4d with 0.5 equiv of Mn(II) salt in the presence of triethylamine yielded reddish orange crystals formulated as [[Mn((aldose)3-tren)]2Mn(H2O)X3.nH2O (5a, aldose = D-Man, X = Cl; 5b, aldose = D-Man, X = Br; 6d, aldose = L-Rha, X = 1/2SO4). The analogous trinuclear complexes 6a (aldose = L-Rha, X = Cl), 6b (aldose = L-Rha, X = Br), and 6c (aldose = L-Rha, X = NO3) were prepared by the one-pot reaction of Mn(II) salts with (L-Rha)3-tren without isolation of the intermediate Mn(II) complexes. X-ray crystallographic studies revealed that 5a, 5b, 6c, and 6d have a linearly ordered trimanganese core, Mn(II)Mn(III)Mn(II), bridged by two carbohydrate residues with Mn-Mn separations of 3.845(2)-3.919(4) A and Mn-Mn-Mn angles of 170.7(1)-173.81(7) degrees. The terminal Mn(II) atoms are seven-coordinate with a distorted mono-face-capped octahedral geometry ligated by the (aldose)3-tren ligand through three oxygen atoms of C-2 hydroxyl groups, three N-glycosidic nitrogen atoms, and a tertiary amino group. The central Mn(III) atoms are five-coordinate ligated by four oxygen atoms of carbohydrate residues in the (aldose)3-tren ligands and one water molecule, resulting in a square-pyramidal geometry. In the bridging part, a beta-aldopyranosyl unit with a chair conformation bridges the two Mn(II)Mn(III) ions with the C-2 mu-alkoxo group and with the C-1 N-glycosidic amino and the C-3 alkoxo groups coordinating to each metal center. These structures could be very useful information in relation to xylose isomerases which promote aldose-ketose isomerization by using divalent dimetal centers such as Mn2+, Mg2+, and Co2+.

Carbohydrates↗

PubMed2000

Functional conservation of RNA polymerase II in fission and budding yeasts.

The complementary DNAs of the 12 subunits of fission yeast (Schizosaccharomyces pombe) RNA polymerase II were expressed from strong promoters in Saccharomyces cerevisiae and tested for heterospecific complementation by monitoring their ability to replace in vivo the null mutants of the corresponding host genes. Rpb1 and Rpb2, the two largest subunits and Rpb8, a small subunit shared by all three polymerases, failed to support growth in S. cerevisiae. The remaining nine subunits were all proficient for heterospecific complementation and led in most cases to a wild-type level of growth. The two alpha-like subunits (Rpb3 and Rpb11), however, did not support growth at high (37 degrees C) or low (25 degrees C) temperatures. In the case of Rpb3, growth was restored by increasing the gene dosage of the host Rpb11 or Rpb10 subunits, confirming previous evidence of a close genetic interaction between these three subunits.

Conserved Sequence↗

PubMed2000

Ternary complex formation between VO(IV)-picolinic acid or VO(IV)-6-methylpicolinic acid and small blood serum bioligands.

In order to assess the role of the low molecular mass bioligands of blood serum in vanadium binding, a study was made of the interactions of the complexes formed in the VO(IV)-picolinic acid and VO(IV)-6-methylpicolinic acid systems with various low molecular mass constituents of blood serum, such as oxalate, lactate, citrate and phosphate. The speciation of VO(IV) in these ternary systems and also in the binary VO(IV)-picolinic acid and VO(IV)-6-methylpicolinic acid systems was studied by pH-potentiometry at 25 degrees C and at an ionic strength I = 0.2 M (KCl). The binding modes of the complexes formed were determined by spectral (electronic absorption and EPR) methods. Picolinic acid and 6-methylpicolinic acid were found to form mono and bis complexes through the pyridine nitrogen and carboxylate oxygen, but the presence of the methyl group in 6-methylpicolinic acid surprisingly decreases the stability of its complexes significantly. The results obtained on the ternary systems reveal that mixed ligand complex formation is favoured in these systems, especially with citrate, and must therefore be taken into account in the speciation description of VO(IV) in blood serum.

Citric Acid↗

PubMed2000

Radiation therapy for elderly patient with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The purpose of this study was to profile cervical squamous cell carcinoma in elderly patients undergoing radiation therapy and to study the treatment outcome and side effects of therapy. MATERIALS AND METHODS: A retrospective analysis was carried out from the records of 380 patients with squamous cell carcinoma of the uterine cervix who had been given radiation therapy between 1970 and 1994. The patients were divided into three age groups: under 70 years (youngest group; n = 215), 70 to 79 years (intermediate group; n = 124), and 80 years or older (oldest group; n = 41). Radiation therapy was performed by a combination of external beam therapy and three brachytherapy fractions using low-dose-rate sources. RESULTS: The 5-year overall survival rates in the youngest, intermediate, and oldest groups were 58, 50, and 33%, respectively, while cause-specific survival rates were 68, 70, and 65%, respectively. For the patients with stage III, the 5-year overall survival rates in the youngest, intermediate, and oldest groups were 59, 48, and 36%, respectively, while cause-specific survival rates were 72, 70, and 70%, respectively. There was no statistical significance in the 5-year intrapelvic recurrence rates among the three groups. Grade 3 or 4 complications occurred in 6.5% of the youngest, 11.3% of the intermediate, and 7.3% of the oldest groups. CONCLUSION: Radiation therapy with external beam combined with three fractions of low-dose-rate brachytherapy proved both highly effective and safe for senior patients with cervical squamous cell carcinoma.

Adult↗

PubMed2000

Dermal absorption of N,N-dimethylacetamide in human volunteers.

OBJECTIVES: We investigated the potential for the dermal absorption of N,N-dimethylacetamide (DMAC: CAS No. 127-19-5) vapor, the biological half-life of N-methylacetamide (NMAC) in urine as the biological exposure item of DMAC, and the adjustment method for urinary concentrations. METHODS: Twelve healthy male volunteers (mean age 25.2 years, range 21-43 years) were exposed to DMAC for 4 h on two occasions at intervals of 96 h or above. Each volunteer sat inside a whole-body-type exposure chamber for the dermal exposure experiment or outside the chamber for the inhalation exposure experiment. The temperature and relative humidity in the chamber were controlled at approximately 26 degrees C and 40% in order to keep the skin (90% naked) of the volunteers dry. DMAC concentrations were 6.1 +/- 1.3 ppm for dermal exposure and 6.1 +/- 1.3 ppm for inhalation exposure. Urine samples were collected from 0 h through 36 h and at 48 h and 72 h after the exposure. Extrapolations from exposure concentrations for 4 h to 10 ppm for 8 h were performed. RESULTS: Mean dermal absorption was estimated to be 40.4% of the total DMAC uptake. The biological half-lives of urinary NMAC were 9.0 +/- 1.4 h and 5.6 +/- 1.3 h via skin and lung, respectively. Mean NMAC in urine just after 5 consecutive workdays (8 h/day) at 10 ppm DMAC exposure was assumed to be 33.7 mg/g x Cr (18.6-70.0 mg/g x Cr). Creatinine-adjusted NMAC concentration in urine for each volunteer within 12 h after the exposure was more closely correlated with the total excretion amount of NMAC up to 36 h than with urinary-volume-adjusted or specific-gravity-adjusted NMAC concentration in both the dermal and inhalation exposure experiments. CONCLUSIONS: DMAC vapor was significantly absorbed through the skin. Estimated NMAC values indicate that 20 mg/g x Cr NMAC seems to be appropriate as the biological exposure index.

Acetamides↗

PubMed2000

Metallokinetic analysis of disposition of vanadyl complexes as insulin-mimetics in rats using BCM-ESR method.

Among vanadium's wide variety of biological functions, its insulin-mimetic effect is the most interesting and important. Recently, the vanadyl ion (+4 oxidation state of vanadium) and its complexes have been shown to normalize the blood glucose levels of streptozotocin-induced diabetic rats (STZ-rats). During our investigations to find more effective and less toxic vanadyl complexes, the vanadyl-methylpicolinate complex (VO-MPA) was found to exhibit higher insulin-mimetic activity and less toxicity than other complexes, as evaluated by both in vitro and in vivo experiments. Electron spin resonance (ESR) is capable of measuring the paramagnetic species in biological samples. We have developed the in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) method to analyze the ESR signals due to stable organic radicals in real time. In the present investigation, we have applied this method to elucidate the relationship between the blood glucose normalizing effect of VO-MPA and the global disposition of paramagnetic vanadyl species. This paper describes the results of vanadyl species in the circulating blood of rats following intravenous administration of vanadyl compounds. ESR spectra due to the presence of vanadyl species were obtained in the circulating blood, and their pharmacokinetic parameters were estimated using compartment models. The results indicate that vanadyl species are distributed considerably to the peripheral tissues, as estimated by BCM-ESR, and eliminated from the body through the urine, as estimated by ESR at 77 K. The exposure of vanadyl species in the blood was found to be enhanced by VO-MPA treatment. Given these results, we concluded that the pharmacokinetic character of vanadyl species is closely related with the structure and antidiabetic activity of the vanadyl compounds.

Animals↗

PubMed2000

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma.

BACKGROUND/AIM: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn,Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma. METHODS: In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated. RESULTS: The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (>4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC. CONCLUSIONS: Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.

Adult↗

PubMed2000

Neurogenesis in the superior olivary complex in the rat.

In a previous paper we provided evidence that crossed projection neurons are generated earlier than uncrossed projection neurons in the lateral superior olive. The aim of the present study was to determine if other major nuclei of the superior olivary complex (SOC), the medial superior olivary (MSO), the superior paraolivary (SPN) and the medial trapezoid (MTB) nuclei, are distinguished by their neuronal constitutions of birthdates. Pregnant rats were injected intraperitoneally with 5-bromodeoxyuridine (BrdU), the thymidine analogue, to label the neurons on one of the embryonic (E) days E11-E16. When the progeny rats reached adulthood, the brains were processed for BrdU immunohistochemistry. The MSO was mostly composed of neurons generated on E12 (95%). The remaining neurons in the MSO completed their neurogenesis by E13. The SPN neurons were generated from E12 to E14 with a peak on E13 (80%). Regardless of the morphological heterogeneity, the SPN consisted of a single population of neurons in terms of neurogenesis. The MTB neurons were generated from E13 to E16 with a peak on E14 (73%). In contrast to the previous assumption, no topographical relationship existed between neurogenesis and tonotopicity within each nucleus of the SOC.

Animals↗

PubMed2000

Effects of static magnetic field on dissolved oxygen levels in aqueous solutions containing copper(II), iron(II), and heme iron(III) complexes.

Trace metal ions like copper and iron play important roles such as binding, transport, and storage of molecular dioxygen in a wide variety of living systems. The effects of static magnetic fields on the dissolved oxygen (DO) levels in aqueous solutions containing copper(II), iron(II), and their bioligand complexes were investigated. The DO levels in aqueous solutions containing the stable copper(II) complexes such as Cu(II)-Arg, His, GGH and BSA systems increased when the applied magnetic field increased. However, the magnetic field-dependent changes of DO levels were not observed by the unstable Cu(II) complexes such as Cu(II)-Lys, Gly, Gly-His and Hb systems. Especially, DO levels in aqueous solutions containing Cu(II)-His or BSA complexes increased 1.1-fold to those of the control levels at 200 mT of the applied magnetic field. In contrast, DO levels in aqueous solutions containing iron(II) decreased significantly when the magnetic field increased, which in turn promoted the Fe(II)-induced lipidperoxidation in liposomes. DO levels in aqueous solutions containing Fe(II)-His complex decreased 0.9-fold to those of the control levels at 200 mT of the magnetic field for 30 min. While, the magnetic field-dependent changes of DO levels increased significantly in aqueous solutions containing heme iron(III)-complexes, suggesting that heme iron(III) is reduced to heme iron(II) under exposure of the magnetic field and thus the incorporation of molecular dioxygen in aqueous solutions is enhanced. These results indicate that the effect of the magnetic fields on DO levels in aqueous solutions must be discussed in terms of a concept: formation of intermediate complexes consisting of molecular dioxygen-copper or iron and bioligands under physiological conditions and the following enhancement of incorporation of molecular dioxygen by the complexes, that in turn activate the molecular dioxygen.

Journal Article↗

PubMed2000

Reaction of beta-alkannin (shikonin) with reactive oxygen species: detection of beta-alkannin free radicals.

beta-Alkannin (shikonin), a compound isolated from the root of Lithospermum erythrorhizon Siebold Zucc., has been used as a purple dye in ancient Japan and is known to exert an anti-inflammatory activity. This study aimed to understand the biological activity in terms of physico-chemical characteristics of beta-alkannin. Several physico-chemical properties including proton dissociation constants, half-wave potentials and molecular orbital energy of beta-alkannin were elucidated. This compound shows highly efficient antioxidative activities against several types of reactive oxygen species (ROS), such as singlet oxygen ((1)O2). superoxide anion radical (.O2), hydroxyl radical (.OH) and tert-butyl peroxyl radical (BuOO.) as well as iron-dependent microsomal lipid peroxidation. During the reactions of beta-alkannin with 1O2, .O2- and BuOO., intermediate organic radicals due to beta-alkannin were detectable by ESR spectrometry. Compared with the radicals due to naphthazarin, the structural skeleton of beta-alkannin, the beta-alkannin radical observed as an intermediate in the reactions with (1)O2, and .O2- was concluded to be a semiquinone radical. On the other hand, during the reactions of beta-alkannin and naphthazarin with BuOO., ESR spectra different from the semiquinone radical were observed, and proposed to result from the abstraction of hydrogen atoms from phenolic hydroxyl groups of beta-alkannin by BuOO.. Based on the ROS-scavenging abilities of beta-alkannin, the compound was concluded to react directly with ROS and exhibits antioxidative activity, which in turn exerts anti-inflammatory activity.

Acetonitriles↗

PubMed2000

The use of free jejunal autograft for the treatment of vaginal agenesis: surgical methods and long-term results.

Two young women with congenital vaginal agenesis were treated with free jejunal autograft. At follow-up of 5 and 2 years there was no significant constriction without long term use of stents and obturators. Mucosal secretion of the grafted tissue was reduced within a few months postoperatively but still remained high necessitating a cotton napkin. Nonetheless, it provided a suitable condition with appropriate lubrication for sexual intercourse. Our experience indicates that the free jejunal autograft may be the ideal operation for selected patients.

Adult↗

PubMed2000

Treatment of finger avulsion injuries with innervated arterialized venous flaps.

Complete degloving injury of the digits not amenable to revascularization may leave poor cosmetic and functional results. We used innervated venous flaps from the dorsum of the foot in two patients with traumatic finger degloving injuries. All the flaps successfully provided coverage over the denuded fingers. Good sensation and nearly full rage of motion of the fingers were obtained. There were no donor-site problems. The advantages of this flap are preservation of a major artery of the donor site, easy elevation without deep dissection, and providing a thin, nonbulky tissue and good sensation. The innervated arterialized venous flap is a useful method that provides functional and cosmetic coverage to the severe avulsion injury of the finger.

Adult↗

PubMed2000

Inhibitory effects of Alpinia speciosa K. SCHUM on the porphyrin photooxidative reaction.

It is thought that the beta-carotene defense mechanism against photosensitivity involves the inhibition of singlet oxygen formation, a kind of active oxygen. When we screened chemical substances obtained from plants indigenous to Okinawa, known to have residents with the longest life span in Japan, we found that Alpinia speciosa K. SCHUM (Japanese name: gettou), which is used as a food preservative, has an activity similar to that of beta-carotene. We measured the amount of lipid peroxide (LPO) formed from a hematoporphyrin-containing rat liver microsomal suspension irradiated with visible light. The inhibitory effect of Alpinia speciosa on LPO formation was confirmed when the addition of increasing concentrations of Alpinia speciosa extract led to a decrease in the amount of LPO formed. Moreover, the reaction mechanism that affects the amount of singlet oxygen formed was measured, and the effect of the extract was determined by the ESR trapping technique. It was found that the extract effectively inhibited the formation of singlet oxygen. The extract of Alpinia speciosa contains dihydro-5,6-dehydrokawain. It was confirmed that dihydro-5,6-dehydrokawain, which is a water-soluble compound, has singlet oxygen quenching activity. We synthesized five derivatives of kawain and found that dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl] phosphorothionate has the strongest singlet oxygen quenching activity. The use of the compound from Alpinia speciosa that exhibits singlet oxygen quenching activity as an inhibitory agent of the phototoxic reaction in porphyria is expected.

Animals↗

PubMed2000

Branching morphogenesis during kidney development.

Epithelial tissues such as kidney, lung, and breast arise through branching morphogenesis of a pre-existing epithelial structure. They share common morphological stages and a need for regulation of a similar set of developmental decisions--where to start; when, where, and in which direction to branch; and how many times to branch--decisions requiring regulation of cell proliferation, apoptosis, invasiveness, and cell motility. It is likely that similar molecular mechanisms exist for the epithelial branching program. Here we focus on the development of the collecting system of the kidney, where, from recent data using embryonic organ culture, cell culture models of branching morphogenesis, and targeted gene deletion experiments, the outlines of a working model for branching morphogenesis begin to emerge. Key branching morphogenetic molecules in this model include growth factors, transcription factors, distal effector molecules (such as extracellular matrix proteins, integrins, proteinases and their inhibitors), and genes regulating apoptosis and cell proliferation.

Animals↗

PubMed2000

Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct.

Several xenobiotic (organic cation and anion) transporters have recently been identified, although their endogenous substrates, if such exist, remain unknown. When we initially identified NKT, also known as OAT1, the first member of the organic anion transporter (OAT) family (Lopez-Nieto CE, You G, Bush KT, Barros EJ, Beier DR, and Nigam SK. J Biol Chem 272: 6471-6478, 1997), we noted its expression in the embryonic kidney. We have now demonstrated its transporter function and more fully examined the spatiotemporal expression patterns of representative organic ion transporters, [NKT (OAT1), Roct, OCT1, and NLT, also known as OAT2] during murine development. In the kidney, NKT (OAT1), OCT1, and Roct transcripts appeared at midgestation, coinciding with proximal tubule differentiation, and gradually increased during nephron maturation. A similar pattern was observed for NLT (OAT2) in the liver and kidney, although, in the kidney, NLT (OAT2) transcription did not increase as dramatically. The roughly cotemporal expression of these related transporters in the developing proximal tubule may indicate common transcriptional regulation. Expression during embryogenesis in extrarenal sites could suggest a role in the formation and maintenance of nonrenal tissues. Importantly, all four genes were expressed in unexpected places during nonrenal organogenesis: Roct in the fetal liver (temporally coinciding with the onset of hematopoiesis) and neural tissue; NKT (OAT1) in the fetal brain; OCT1 in the ascending aorta and atrium; and NLT (OAT2) in the fetal lung, intestine, skin, and developing bone. Because these gene products mediate the transport of a broad range of metabolites and toxins, it seems likely that, apart from their known functions, these transporters play a role in transport of organic molecules, perhaps including those with morphogenetic activity. These genes could also play important developmental roles independent of transport function.

Aging↗

PubMed2000

Matrix metalloproteinases and their inhibitors regulate in vitro ureteric bud branching morphogenesis.

Mammalian kidney development is initiated by the mutual interaction between embryonic metanephric mesenchyme (MM) and the ureteric bud (UB), leading to tightly controlled UB branching morphogenesis. In a three-dimensional cell culture model, which employs MM cell-derived conditioned medium (BSN-CM) to induce UB cell branching morphogenesis in extracellular matrix (ECM) gels (Sakurai H, Barros EJ, Tsukamoto T, Barasch J, and Nigam SK. Proc Natl Acad Sci USA 94: 6279-6284, 1997), branching morphogenesis was inhibited by both chemical agents (ilomastat and 1,10-orthophenanthroline) and a physiological protein factor [tissue inhibitor of metalloproteinases (TIMP)-2], known to act as matrix metalloproteinase (MMP) inhibitors. In addition, UB branching was inhibited in isolated UB culture (Qiao J, Sakurai H, and Nigam SK. Proc Natl Acad Sci USA 96: 7330-7335, 1999) by TIMP-2 and ilomastat, suggesting a direct role for MMPs in UB branching. Gelatin zymography and enzymatic measurement of MMP activity revealed that MMPs could originate from at least three different sources: the conditioned medium, the ECM, and the UB cells themselves. In the UB cells, transcription of several MMPs [gelatinase A (MMP2) and B (MMP9), stromelysin (MMP3), MT1-MMP] and TIMPs was altered by BSN-CM and changed as more complex branching structures formed. The ECM appeared to serve as both a reservoir for MMPs and modulated their expression because different ECM compositions altered the total MMP activity as well as specific subsets of MMPs expressed by the UB cells (as determined by zymography and Northern analysis). In the context of UB branching morphogenesis during kidney development, our data suggest a complex model in which soluble factors produced by the MM, in the context of specific ECM components, modulate the expression of specific subsets of MMPs and TIMPs in the UB, which alter as structures develop and the matrix environment changes. This suggests distinct roles for different subsets of MMPs and their inhibitors during different phases of branching morphogenesis.

Animals↗

PubMed2000

Arrhythmogenic right ventricular cardiomyopathy with an initial manifestation of severe left ventricular impairment and normal contraction of the right ventricle.

A case of arrhythmogenic right ventricular cardiomyopathy (ARVC) with an initial manifestation of severe impairment of the left ventricle (LV) and normal contraction of the right ventricle (RV) is presented. A 43-year-old man was admitted to hospital because of congestive heart failure following a common cold. The LV function was diffusely and severely hypokinetic. Coronary arteriogram revealed normal vessels. An endomyocardial biopsy specimen obtained from the RV septum revealed mild infiltration of lymphocytes with focal myocytes necrosis and so healing myocarditis was suspected. The specimen did not include any fatty replacement of myocytes. Since then, the patient suffered from recurrent congestive heart failure as well as nonsustained ventricular tachycardia and required frequent hospitalization. Progressive impairment, dilation, and thinning of both ventricles were observed on serial echocardiographic examinations. Although the RV gradually enlarged and became impaired, severe dilatation and impairment of the LV has always been predominant in the patient's clinical course. After medical follow-up for 10 years, he died suddenly of ventricular fibrillation and pump failure. The autopsy revealed extensive fibrofatty replacement of myocytes in both the ventricles, extending from the outer layer to the inner layer of myocardium in the RV and to the middle layer in the LV. These features were compatible with arrhythmogenic right ventricular cardiomyopathy or perimyocarditis, although only the rightsided bundle of the interventricular septum was completely replaced by fatty tissue, which can not be explained as a sequel of perimyocarditis. Moreover, apoptosis was present in the myocyte nuclei of the myocardial layers bordering the area of fatty replacement. Therefore, myocarditis may have triggered or accelerated the process of apoptosis leading to ARVC.

Adult↗