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Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 145 records · Page 8Linked to original sources

The effect of lithium on methamphetamine-induced regional Fos protein expression in the rat brain.

Lithium has been used widely for the treatment of manic states. Since amphetamines produce effects in humans similar to the symptoms of idiopathic mania, amphetamine administration to animals has been proposed as a model of this condition. To investigate the neurobiologic substrates of the antimanic effects of chronic lithium administration, we investigated its effects on methamphetamine-induced regional Fos protein expression in the rat brain. Chronic lithium administration (14 days; serum lithium concentration, 0.41+/-0.02 mEq/l) significantly reduced the number of neuronal nuclei showing immunoreactivity induced by methamphetamine (2mg/kg) in the prefrontal cortex, caudate/putamen, nucleus accumbens, and central nucleus of the amygdala. These results indicate the structural basis in CNS which is responsible for the antimanic effect of lithium.

Animals↗

Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein.

By the yeast two-hybrid screening of a rat brain cDNA library with the regulatory domain of protein kinase C zeta (PKCzeta) as a bait, we have cloned a gene coding for a novel PKCzeta-interacting protein homologous to the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth and fasciculation. The protein designated FEZ1 (fasciculation and elongation protein zeta-1) consisting of 393 amino acid residues shows a high Asp/Glu content and contains several regions predicted to form amphipathic helices. Northern blot analysis has revealed that FEZ1 mRNA is abundantly expressed in adult rat brain and throughout the developmental stages of mouse embryo. By the yeast two-hybrid assay with various deletion mutants of PKC, FEZ1 was shown to interact with the NH2-terminal variable region (V1) of PKCzeta and weakly with that of PKCepsilon. In the COS-7 cells coexpressing FEZ1 and PKCzeta, FEZ1 was present mainly in the plasma membrane, associating with PKCzeta and being phosphorylated. These results indicate that FEZ1 is a novel substrate of PKCzeta. When the constitutively active mutant of PKCzeta was used, FEZ1 was found in the cytoplasm of COS-7 cells. Upon treatment of the cells with a PKC inhibitor, staurosporin, FEZ1 was translocated from the cytoplasm to the plasma membrane, suggesting that the cytoplasmic translocation of FEZ1 is directly regulated by the PKCzeta activity. Although expression of FEZ1 alone had no effect on PC12 cells, coexpression of FEZ1 and constitutively active PKCzeta stimulated the neuronal differentiation of PC12 cells. Combined with the recent finding that a human FEZ1 protein is able to complement the function of UNC-76 necessary for normal axonal bundling and elongation within axon bundles in the nematode, these results suggest that FEZ1 plays a crucial role in the axon guidance machinery in mammals by interacting with PKCzeta.

Adaptor Proteins, Signal Transducing↗

Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2.

Two closely related genes coding for NELL proteins (NELL1 and NELL2) have been cloned by the yeast two-hybrid screening of a rat brain cDNA library with the regulatory domain of protein kinase C betaI (PKCbetaI) as bait. The rat NELL proteins show about 55% identity with each other and contain several protein motifs assigned to a secretion signal peptide, an NH(2)-terminal thrombospondin-1 (TSP-1)-like module, five von Willebrand factor C domains, and six epidermal growth factor-like domains; the NELL proteins share many protein motifs with TSP-1. The NELL proteins expressed in COS-7 cells are homotrimeric glycoproteins and possess heparin-binding activity. Furthermore, while NELL1 and NELL2 show distinct subcellular localization in cytoplasm, they both are partially secreted into the culture medium of COS-7 cells. Although the NELL1 mRNA is faintly expressed in adult neural cells, the NELL2 mRNA is expressed abundantly, particularly in the pyramidal cells of rat hippocampus, showing neuronal high plasticity. During mouse embryogenesis, expression of the NELL2 mRNA is initiated 7-11 days postcoitum, simultaneously with neural plate formation. These results strongly suggest that the NELL2 protein, similar to but not identical with TSP-1, is involved in the growth and differentiation of neural cells. Additionally, the NELL1 and NELL2 mRNAs were found to be expressed abundantly in Burkitt's lymphoma Raji cells and colorectal adenocarcinoma SW480 cells, respectively. Thus, it is likely that the NELL proteins also participate in the growth, differentiation, and oncogenesis of cancer cell lines.

Amino Acid Sequence↗

Thermal distribution of radio-frequency inductive hyperthermia using an inductive aperture-type applicator: evaluation of the effect of tumour size and depth.

A new radio-frequency (RF) inductive hyperthermia device using an inductive aperture-type applicator (IATA) is proposed. This paper reports the evaluation of the heating characteristics of the IATA using a computer simulation and clinical thermal parameters obtained during treatment of superficial and subsurface-seated tumours. The configuration of the IATA is a one-turn square column-like coil whose bottom plate is set to face the heating target. The IATA has advantages over RF capacitive-type heating, such as: generating less heat in the subcutaneous fat layer; less convergency of electric line of force at the edge of the applicator; and no physical contact with the target lesion. The induced magnetic fields and electrical currents within the heating substance are simulated using computer-assisted design software for electro-magnetic analysis. A total of 40 superficial and subsurface tumours are treated with the IATA. Invasive thermometry is performed continuously for 110 sessions using multi-sensor probes of an optical thermometer. Thermal parameters (Tmax, Tmin, Tave) are assessed based on the tumour size and depth. The treated tumours are categorised into three groups according to tumour depth: group 1 (< 3 cm, n = 28), group 2 (3-5 cm, n = 35) and group 3 (> 5 cm, n = 47). The computer simulation shows that induced electrical currents run without convergency, parallel to the surface of the heating material. All thermal parameters of group 3 are significantly higher than those of group 1 and 2 (p < 0.05), indicating that the larger lesions tend to abtain a higher temperature distribution. In conclusion, RF inductive hyperthermia using the IATA results in effective temperature distributions in superficial and subsurface tumours, with large tumours being most effectively heated.

Aged↗

Occurrence of ganglioside GD3 in neoplastic astrocytes. An immunocytochemical study in humans.

GD3 immunocytochemical analysis was performed in 25 human specimens obtained by autopsy and biopsy from patients with astrocytomas, anaplastic astrocytomas, cerebellar astrocytomas and glioblastoma multiforme (GM), using the ABC method. Extraction of the ganglioside fraction from GM was used for thin-layer chromatography (TLC) analysis to confirm the specificity of anti-GD3 monoclonal antibody (DSG-1). Normal astrocytes were not immunoreactive for GD3. Neoplastic astrocytes of low- to high-grade tumours were GD3 immunoreactive. In GM, the multinucleated giant cells were also immunoreactive. All immunoreactivity present was within the cytoplasm. In TLC analysis, enzyme immunostaining of gangliosides from GM with DSG-1 showed only one positive band, which had the same TLC migration rate as GD3, indicating that GD3 of the ganglioside fraction from GM is the antigen detected by DSG-1. The presence of GD3 within the cytoplasm of neoplastic astrocytes showing invasive and proliferative properties, is of considerable interest. The implications and possible significance of the presence of GD3 in the cytoplasm in glioma cells are discussed.

Adolescent↗

Intra-operative premature rupture of the cerebral aneurysms. Analysis of the causes and management.

The causes and management of intra-operative premature rupture are analysed and discussed. During the past 6 years, the authors, performed 398 consecutive direct surgical interventions for ruptured cerebral aneurysms. Intra-operative premature rupture is defined as a rupture which occurs before the securing of the parent arteries or the neck of the aneurysm and is out of control, at least temporarily. The causes and management were retrospectively analyzed by reviewing video tape recordings. Intra-operative premature ruptures which met the above definition occurred in 24 cases (6.0%). The causes were as follows: 1.) dural opening and arachnoid opening (8.3%), 2.) haematoma removal (12.5%), 3.) brain retraction (16.7%), 4.) aneurysm dissection (62.5%). A double suction technique was used to control bleeding and haemostasis with a small piece of cotton or a temporary clip, performed in 20 cases (83.3%). However, in cases with premature rupture immediately after the dural or arachnoid opening, the extension of the haematoma into the subarachnoid space resulted in severe brain swelling and partial resection of the brain had to be done to secure temporary clipping. The double suction technique and primary haemostasis using a small piece of cotton or temporary clip resulted in good outcome even in cases with premature rupture. However, very early premature rupture also occurred although its incidence was extremely rare. The removal of part of the brain can secure the working space but the outcome was poor.

Adult↗

Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension.

We examined the circadian rhythm of urinary sodium excretion and the effects of sodium restriction on rhythm in both dipper and nondipper types of essential hypertension. Patients (n = 26) with essential hypertension were maintained on relatively high- (10 to 12 g/d of sodium chloride) and low-sodium (1 to 3 g/d) diets for 1 week each. On the last day of each diet, 24-hour blood pressures (BPs) were measured every 30 minutes noninvasively with an automatic device, and on the last 3 days, urinary samples were collected for both daytime (7:00 AM to 9:30 PM) and nighttime (9:30 PM to 7:00 AM). Eight patients were classified as dippers based on a more than 10% reduction in mean arterial pressure (MAP) from daytime to nighttime on a high-sodium diet, and 18 patients were classified as nondippers. A nocturnal decrease in urinary sodium excretion rate (U(Na)V) on the high-sodium diet was observed in dippers (from 7.5 +/- 2.1 during the day to 5.3 +/- 2.5 mmol/h at night; P < 0.0001), but not in nondippers (6.7 +/- 2.1 v 7.6 +/- 2.3 mmol/h; not significant). In nondippers, the night-day ratio of sodium excretion was significantly reduced from 1.2 +/- 0.4 to 0.8 +/- 0.3 (P < 0.003) by sodium restriction; at the same time, the night-day ratio of MAP was reduced from 0.98 +/- 0.04 to 0.93 +/- 0.05 (P < 0.05). In dippers, the night-day ratios of MAP and U(Na)V were not affected by sodium restriction, and both ratios remained constant at less than 1. Before sodium restriction, the night-day ratio of sodium excretion correlated with that of MAP (r = 0.78; P < 0.0001), whereas there was no significant correlation (r = -0.05) after sodium restriction. These findings showed that the circadian rhythm of renal sodium excretion differed between the two types of essential hypertension. The enhanced nocturnal natriuresis and diminished nocturnal BP fall on a high-sodium diet, recognized in nondippers, were both normalized by sodium restriction, resulting in circadian rhythms with nocturnal dips in U(Na)V and BP.

Adult↗

Cardiovascular complications in patients with primary aldosteronism.

Primary aldosteronism (PA) is widely believed to be a relatively benign form of hypertension associated with a low incidence of vascular complications. However, several recent studies showed that cardiovascular complications were not rare in PA. PA is known as one of the most typical forms of sodium-sensitive hypertension. Recently, we found that the sodium sensitivity of blood pressure was a marker for greater risk for cardiovascular complications, especially stroke, in patients with essential hypertension. Therefore, we investigated cardiovascular complications in 58 patients with PA confirmed to be Conn's adenoma. Cardiovascular complications were found in 34% of 58 patients. Coronary artery disease was found in only one patient (1.7%), as angina pectoris. Stroke was found in nine patients (15.5%), four patients (6.9%) with cerebral infarctions and five patients (8.6%) with cerebral hemorrhages. Proteinuria and renal insufficiency were found in 14 (24.1%) and 4 (6.9%) patients, respectively. The incidence of cerebral infarction and renal insufficiency was greater in men than women. The prevalence of proteinuria was greater in patients with than without stroke (P = 0.03) among those aged older than 40 years. These results indicated that cardiovascular complications, especially stroke and proteinuria, were common in patients with PA, and proteinuria might be an indicator for stroke as target-organ damage.

Cardiovascular Diseases↗

Extracapsular cataract extraction with a sutureless incision for dense cataracts.

PURPOSE: To evaluate the use of extracapsular cataract extraction (ECCE) via a sutureless incision for dense cataracts. SETTING: Nagata Eye Clinic, Nara, Japan. METHODS: This retrospective study comprised 51 eyes of 45 consecutive patients with dense cataracts who had ECCE with a sutureless incision between January 1996 and April 1998. A scleral incision from 6.0 to 8.5 mm was made at 12 o'clock or between 9 and 12 o'clock (oblique incision). Measures of outcome included postoperative visual acuity, surgically induced astigmatism (polar value method and vector analysis), complications, and changes in corneal endothelial cell density and morphology. RESULTS: Self-sealing was achieved in 45 eyes (88.2%), but additional sutures were required in 6 (11.8%). Intraoperative complications included posterior capsule rupture in 3 eyes (5.9%) and iris prolapse in 2 (3.9%). Corneal flattening against the preoperative steep meridian was observed in the 12 o'clock incision group (0.24 diopter [D] +/- 1.23 [SD]) and in the oblique incision group (0.17 +/- 0.89 D). By vector analysis, the surgically induced vector was 1.41 +/- 0.72 D in the 12 o'clock incision group and 1.02 +/- 0.66 D in the oblique incision group. After surgery, the mean cell loss was 8.2% +/- 12.5%. There were no significant differences, however, between other preoperative and postoperative morphometric indexes. CONCLUSION: This fast, safe, and inexpensive technique may be a viable treatment for dense cataracts with large, hard nuclei.

Aged↗

Determinants of circadian blood pressure rhythm in essential hypertension.

It has been postulated that the lack of nocturnal blood pressure fall in patients called nondippers is associated with more serious end organ damages by hypertension than in dippers whose blood pressure falls during the night. Recently, we found that sodium restriction shifted circadian rhythm of blood pressure from that of a nondipper to a dipper in patients with essential hypertension. In the present study, we aimed to clarify these important findings from the different approaches, and examined which factors affected the diurnal rhythm of blood pressure. A total of 70 patients with essential hypertension were maintained on high and low sodium diets for 1 week each. Nocturnal fall in mean arterial pressure was calculated in each patient, and, based on multiple regression analysis, independent factors affecting this nocturnal fall were examined. Thirty-eight patients were classified as non-sodium-sensitive, whereas 32 were considered sodium sensitive, based on a >10% change in 24-h mean arterial pressure by sodium restriction. In all 70 patients, sodium sensitivity of blood pressure, as well as an interaction between sodium sensitivity and sodium restriction, were identified as independent factors affecting the nocturnal fall. In sodium-sensitive types, in addition to sodium restriction, glomerular filtration rate was identified, whereas, in non-sodium sensitive types, there was no significant factor. Based on multiple regression analysis, the present study reached the same important conclusion as our previous findings: namely, that the enhanced sodium sensitivity was an independent determinant for the diminished nocturnal fall in essential hypertension and that sodium restriction could restore the nocturnal decline, especially in patients with enhanced sodium sensitivity whose nocturnal decline was diminished. Reduced renal sodium excretory capability may be one of the mechanisms involved in nondipping.

Adult↗

Regulation of cadherin-mediated cell-cell adhesion by the Rho family GTPases.

Reports in the past two years have shown that Cdc42, Rac1, and Rho - belonging to the Rho small GTPase family - participate in the regulation of cadherin-mediated cell-cell adhesion. IQGAP1, an effector of Cdc42 and Rac1, interacts with cadherin and beta-catenin and induces the dissociation of alpha-catenin from the cadherin-catenins complex leading to disruption of cell-cell adhesion: activated Cdc42 and Rac1 counteract the effect of IQGAP1. Thus, Cdc42 and Rac1 appear to regulate cadherin-mediated cell-cell adhesion acting through IQGAP1.

Animals↗

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III: Novel 2-alkyl substituents containing cationic heteroaromatics linked via a C-N bond.

The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.

Animals↗

The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.

The small G protein Rho has emerged as a key regulator of cellular events involving cytoskeletal reorganization. Here we report the 2.2 A crystal structure of RhoA bound to an effector domain of protein kinase PKN/PRK1. The structure reveals the antiparallel coiled-coil finger (ACC finger) fold of the effector domain that binds to the Rho specificity-determining regions containing switch I, beta strands B2 and B3, and the C-terminal alpha helix A5, predominantly by specific hydrogen bonds. The ACC finger fold is distinct from those for other small G proteins and provides evidence for the diverse ways of effector recognition. Sequence analysis based on the structure suggests that the ACC finger fold is widespread in Rho effector proteins.

Amino Acid Motifs↗

Anabolic effect of aminoterminally truncated fibroblast growth factor 4 (FGF4) on bone.

Fibroblast growth factor 4 (FGF4), a member of the FGF family, plays several important roles in bone development during embryogenesis. Systemic administration of FGF4 increases bone mass in rats, which suggests the potential therapeutic usefulness of this growth factor in treatment for osteopenia and in bone regeneration. We investigated the length of FGF4 required to exert its anabolic effects, because this information may be useful in developing new molecules to mimic the effects of FGF4. Because the active site of FGF family molecules is in the carboxylterminal region, we produced aminoterminally truncated recombinant human FGF4s (rhFGF4s) of different sizes. Human FGF4 cDNA containing almost the full length of the coding region (573 bp, 191 amino acid residues) was inserted into pUC18 vector and then deleted from the 5' end using the ExoIII system. Each of the deleted FGF4 cDNAs was subcloned into a pET29(+) expression vector. Differently sized recombinant proteins were expressed in the BL21(DE3)pLysS Escherichia coli strain and then purified. The growth-stimulative effects on NIH3T3 cells of each recombinant protein were examined by means of MTT colorimetric assay. Full-length and the shortened recombinant proteins, which stimulated NIH3T3 cell growth, were then subcutaneously administered into male ddY mice (6 weeks old) every day for 2 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). The rhFGF4 of 134 amino acid residues, the region homologous to other members of the FGF family, exerted a growth-stimulative effect on NIH3T3 cells comparable to the full-length version of FGF4; however, the shortest version, with 111 amino acid residues, showed a limited growth-stimulative effect. Systemic administration of the rhFGF4 of 134 amino acid residues increased the bone mineral density (BMD) of femurs at a dose of 0.1 mg/kg, which was comparable to that of the full-length rhFGF4. DEXA analysis, pQCT analysis, soft X-ray photos, and contact microradiographs revealed an increase in femoral trabecular bone in FGF4-treated animals; an increase in bone formation was also evident upon histomorphometric analysis. These results indicate that the region of FGF4 that is homologous to other FGF family members provides a sufficient anabolic effect in bone and that this recombinant protein is potentially useful as a therapeutic agent in bone.

3T3 Cells↗

Role of insulin resistance in the genesis of sodium sensitivity in essential hypertension.

We recently showed that cardiovascular morbidity was higher in sodium sensitive type of essential hypertension than in the non-sodium sensitive type. It was examined whether sodium sensitivity was associated with insulin resistance, an important atherosclerotic cardiovascular risk factor in essential hypertension. Fifty-three patients with essential hypertension, who had normal (n = 12) and impaired (n = 41) glucose tolerance, were placed on high (12-15 g NaCl/day) and low (1-3 g) sodium diets for 1 week each to determine sodium sensitivity. Fasting plasma glucose and insulin concentrations were measured on a regular sodium diet. The homeostasis model assessment insulin resistance index (fasting glucose [mmol/L] x fasting insulin [mU/L]/22.5) was 1.40+/-0.10 and 1.47+/-0.14 in non-sodium sensitive and sodium sensitive groups. The insulin resistance index was positively correlated with the sodium sensitivity index, while was negatively correlated with fractional excretion of sodium (FE(Na)) obtained during a high sodium diet. In addition, the insulin resistance index had a positive relationship with overall creatinine clearance. Sodium sensitivity index was also negatively correlated with FE(Na) obtained during a high sodium diet. These results showed that insulin resistance might participate in the genesis of sodium sensitivity in essential hypertension by enhancing tubular sodium reabsorption, as reflected in decreased FE(Na) and augmented creatinine clearance. Insulin resistance seemed elevated in sodium sensitive state of essential hypertension, leading to future cardiovascular events.

Absorption↗

Demonstration of ganglioside GD3 in human reactive astrocytes.

Astrocytes are the cells that actively participate in the process of lesion repair in the central nervous system (CNS), and reactive astrocytosis of varying degrees becomes apparent with time in any pathological condition occurring in the normally developed postnatal CNS. Ganglioside GD3 (II3a(NeuAca2-8NeuAc)-LacCer, GD3) in reactive astrocytes from autopsied patients with Creutzfeldt-Jakob disease (CJD) and old cerebral infarction was investigated immunocytochemically, using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Reactive astrocytes in CJD and cerebral infarction demonstrated GD3-immunoreactivity within the cytoplasm. Normal astrocytes were negative. The present data raise the possibility that GD3 in reactive astrocytes has biological implications for the properties of the cells, such as cellular motility.

Aged↗

Add-on polytherapy with antidepressants and its significance in inpatients with major depression.

Add-on polytherapy with antidepressant agents was reviewed in 42 inpatients with major depression diagnosed according to the ICD-10 criteria. Twenty-eight (67.7%) patients were treated with two or more antidepressants. The most frequent combination consisted of a tricyclic antidepressant and a non-tricyclic antidepressant. Nineteen (67.8%) patients of the polytherapy group were treated with a dosage equivalent to 150 mg/day of tricyclic antidepressant. Clinically, not every patient with major depression can tolerate the adverse side effects induced by an effective dose of a single tricyclic antidepressant. From this viewpoint, add-on polytherapy with antidepressants could be one of the treatment options, especially for such intolerant patients.

Adult↗