Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 145 records · Page 8Linked to original sources

PubMed1998

Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.

1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.

Animals↗

PubMed1998

Anaplastic transformation of a papillary carcinoma of the thyroid in a patient with Graves' disease with varied activity of thyrotropin receptor antibodies.

We describe a 75-year-old man who had had a lump in his neck for about 15 years. At his first visit to our hospital, poorly differentiated papillary carcinoma of the thyroid was diagnosed by means of aspiration cytology; x-rays revealed the presence of lung metastases. He was thyrotoxic with positive thyroid stimulating antibody (TSAb). He was reluctant to undergo surgery. In an early stage of the treatment for Graves' disease, he became hypothyroid with decreased TSAb activity and strongly positive thyroid stimulation blocking antibody (TSBAb), and rapid growth of the thyroid carcinoma with anaplastic transformation was observed. The increase in the size of the transformed thyroid carcinoma was shown to be exponential by ultrasonography. This is a rare case in which anaplastic transformation of the thyroid papillary carcinoma became apparent during treatment of Graves' disease with varied activity of thyrotropin receptor antibodies.

Aged↗

PubMed1998

The first reported case of intestinal spirochaetosis in Japan.

A 65-year-old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylin-eosin revealed a thick, basophilic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonic mucosa via one of these ends. The patient did not display any clinical symptoms of inflammatory bowel disease, and laboratory tests eliminated an immunodeficiency condition. Thus, in the present case, the intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of intestinal spirochaetosis in Japan.

Aged↗

PubMed1998

[Antifungal susceptibility of clinically isolated Candida albicans by broth microdilution method].

In this study we investigated the antifungal susceptibility of 285 strains of Candida albicans isolates at Kinki University Hospital from March 1995 to December 1996. The antifungal agents tested were fluconazole, miconazole, intraconazole, amphotericin B and flucytosine. The susceptibility testing were performed according to the broth microdilution method standardized by National Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans showed relatively a low MIC value and the MIC90S were calculated at 1 microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml; itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine. There was only one strain that showed high resistance against fluconazole and it showed cross-resistance against miconazole and itraconazole. There were two flucytosine resistant strains. The MICs of amphotericin B were tightly clustered and resistant strain were not observed.

Amphotericin B↗

PubMed1998

A putative multisubunit Na+/H+ antiporter from Staphylococcus aureus.

We cloned several genes encoding an Na+/H+ antiporter of Staphylococcus aureus from chromosomal DNA by using an Escherichia coli mutant, lacking all of the major Na+/H+ antiporters, as the host. E. coli cells harboring plasmids for the cloned genes were able to grow in medium containing 0.2 M NaCl (or 10 mM LiCl). Host cells without the plasmids were unable to grow under the same conditions. Na+/H+ antiport activity was detected in membrane vesicles prepared from transformants. We determined the nucleotide sequence of the cloned 7-kbp region. We found that seven open reading frames (ORFs) were necessary for antiporter function. A promoter-like sequence was found in the upstream region from the first ORF. One inverted repeat followed by a T-cluster, which may function as a terminator, was found in the downstream region from the seventh ORF. Neither terminator-like nor promoter-like sequences were found between the ORFs. Thus, it seems that the seven ORFs comprise an operon and that the Na+/H+ antiporter consists of seven kinds of subunits, suggesting that this is a novel type of multisubunit Na+/H+ antiporter. Hydropathy analysis of the deduced amino acid sequences of the seven ORFs suggested that all of the proteins are hydrophobic. As a result of a homology search, we found that components of the respiratory chain showed sequence similarity with putative subunits of the Na+/H+ antiporter. We observed a large Na+ extrusion activity, driven by respiration in E. coli cells harboring the plasmid carrying the genes. The Na+ extrusion was sensitive to an H+ conductor, supporting the idea that the system is not a respiratory Na+ pump but an Na+/H+ antiporter. Introduction of the plasmid into E. coli mutant cells, which were unable to grow under alkaline conditions, enabled the cells to grow under such conditions.

Amino Acid Sequence↗

PubMed1998

Renal haemodynamic characteristics in patients with lupus nephritis.

OBJECTIVE: To clarify the characteristics of renal haemodynamics in patients with lupus nephritis (LN). METHODS: The glomerular filtration rate (GFR) and renal plasma flow (RPF) of 37 patients with active LN were studied longitudinally over an interval of 8 to 144 weeks during treatment with corticosteroids or cytotoxic drugs, or both. All patients had clinical renal disorders and underwent renal biopsies. RESULTS: Analysis of renal biopsy specimens showed that 31 patients had class IV LN. Class II, III, and VLN were present in two patients each. The average GFR increased significantly from 65.4 (SD 33.0) in the pretreatment stage to 86.6 (31.6) ml/min in the post-treatment stage, accompanied by an improvement in urinary or immunological abnormalities, or both. On the other hand, RPF decreased significantly from 625.2 (243.0) to 519.8 (179.0) ml/min. Therefore, the filtration fraction (FF) increased significantly from 10.7 (4.3)% to 16.8 (3.7)%. Low FF was recognised predominantly in patients with class IV LN, but was also observed in patients with other classes. The FF returned towards normal irrespective of the degree of GFR recovery. No significant changes were observed in the levels of blood pressure. CONCLUSION: A reduction in GFR out of proportion to the reduction in RPF as demonstrated by the low FF values was related to the severity of LN or disease activity, or both. Therefore, relative evaluation of GFR and RPF, namely the determination of FF, may be a useful clinical parameter to determine the status of LN.

Acute Disease↗

PubMed1998

Modulation of the inspiratory-related activity of hypoglossal premotor neurons during ingestion and rejection in the decerebrate cat.

Single-unit activities of the bulbar reticular inspiratory neurons directly projecting to hypoglossal motoneurons were studied during fictive ingestion (e.g., swallowing) and rejection elicited by repetitive stimulation of the superior laryngeal nerve and by application of water to the pharynx in immobilized decerebrated cats. The single-unit activity was recorded during 113 episodes of fictive ingestion from 25 inspiratory neurons directly projecting to hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons directly projecting to both hypoglossal and phrenic motoneurons (dual projection neurons) in the regions ventrolateral to the nucleus tractus solitarii and dorsomedial to the nucleus ambiguus. All of single projection neurons ceased inspiratory-related rhythmical discharges coincidentally with the onset of repetitive stimulation of the superior laryngeal nerve. The majority of them (19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority (6/25, 24%, type B) kept silent until the end of repetitive stimulation of the superior laryngeal nerve. During fictive ingestion elicited by application of water to the pharynx, the type-A neurons showed a spike burst activity, whereas the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C) ceased inspiratory-related rhythmical discharges at the onset of repetitive stimulation of the superior laryngeal nerve and showed no activity during fictive ingestion. Likewise, the type-C neurons kept silent during fictive ingestion elicited by application of water to the pharynx. A spike burst was induced during 33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and 6 tested type-C neurons. It is concluded that the premotor neurons involved in the respiratory-related rhythmical activity of hypoglossal motoneurons is responsible for switching from respiration to ingestion and rejection.

Animals↗

PubMed1998

Swallowing-related perihypoglossal neurons projecting to hypoglossal motoneurons in the cat.

Although previous studies have examined the functional role of the neurons in the area ventrolateral to the hypoglossal nucleus (perihypoglossal neurons) in the trigemino-hypoglossal reflex, no convincing evidence for the direct connection from the perihypoglossal neurons to the hypoglossal motoneurons has yet been provided. In addition, the role of the perihypoglossal neurons in swallowing has not been studied. The purpose of this study was to investigate (1) the input-output relationship of the perihypoglossal neurons and (2) whether the afferent feedback was essential for their swallowing-related activity in chloralose-anesthetized cats. Before and after the cats were paralyzed, single-unit activities were recorded extracellularly from 30 perihypoglossal neurons during swallowing elicited by electrical stimulation of the superior laryngeal nerve. These perihypoglossal neurons responded with spike potentials after short latencies to stimulation of the inferior alveolar and hypoglossal nerves. The neurons also responded with spike potentials to single shocks applied to the superior laryngeal nerve, but were activated transiently at the initial phase of repetitive stimulation of the nerve and kept silent until the occurrence of swallowing before and after the animal was paralyzed. They showed burst activities in coincidence with swallowing. Averaging of intracellular potentials of a hypoglossal motoneuron by simultaneously recorded extracellular spikes of a perihypoglossal neuron revealed monosynaptic inhibitory post-synaptic potentials. We conclude that, in the region ventrolateral to the hypoglossal nucleus, there are neurons which relay trigeminal, hypoglossal, and vagal afferents. Furthermore, some of these perihypoglossal neurons are inhibitory hypoglossal premotor neurons that are involved in the central programming of swallowing.

Afferent Pathways↗

PubMed1998

[Influence of nitric oxide synthetase inhibitor on the blood pressure action of clonidine in rats].

We are investigating the influence of NO synthetase inhibitor on the clonidine-induced cardiovascular actions in urethane-anesthetized rats. The systemic blood pressure was measured from right femoral artery, heart rate from the pressure pulse under inhalation of O2. Nw-nitro-L-arginine-methylester (L-NAME, 5 mg/kg), NO synthetase inhibitor, administered intravenously increased blood pressure slightly, although decreased heart rate. The responses to L-NAME were stable about 10 min after the injection. Clonidine (5 mg/kg) administered intravenously indicated the transient increase blood pressure and following continuous decrease of blood pressure. The early transient hypertension of clonidine was potentiated by pretreatment with L-NAME and later continuous hypotension was markedly inhibited. While, the early transient hypertension of clonidine was inhibited by pretreatment with L-arginine and later continuous hypotension was potentiated. The hypertension and tachycardia of intravenous tyramine was enhanced by L-NAME. Clonidine administered into the cerebroventricle did not indicate the early transient hypertension, though produced the later continuous hypotension. These results suggest that L-NAME modifies the cardiovascular responses to clonidine and NO may participate in the modulation.

Animals↗

PubMed1998

Comparison of craniofacial and dentoalveolar morphologies of three Japanese monozygotic twin pairs with cleft lip and/or palate discordancy.

OBJECTIVE: In this study, we analyzed the craniofacial and dentoalveolar morphologies of three pairs of monozygotic twins discordant for cleft lip and/or palate (CL/P) in order to evaluate the effects of environmental factors on growth and development. DESIGN: Craniofacial and dentoalveolar morphologies revealed by analyses of cephalograms and dental casts were compared for each pair of twins discordant for CL/P. SUBJECTS: In case 1, the subjects were 10-year-old male twins, one of whom had a repaired unilateral cleft lip and alveolus and one of whom had an unrepaired unilateral cleft lip. In case 2, the subjects were 13-year-old female twins, one of whom had a repaired bilateral cleft lip and palate and one of whom had an unrepaired unilateral cleft lip. In case 3, the subjects were 9-year-old female twins, one of whom had a repaired unilateral cleft lip and palate and one of whom had no cleft. RESULTS: Cephalometric analysis disclosed distinguished intrapair differences in the maxillary and mandibular morphologies in cases 2 and 3. However, the tooth axes of the incisors in operated subjects were consistently influenced in all three cases. Dental cast analysis indicated that the shapes and sizes of the alveolar and dental arches in the operated subjects were affected in case 2 and, more severely, in case 3, while they looked fairly similar in case 1. CONCLUSIONS: Cephalometric and dental cast analyses demonstrated characteristic intrapair differences between the twins discordant for CL/P according to each cleft type. These morphological differences indicate that surgical closure of clefts may have considerable effects on craniofacial and dentoalveolar growth and development in CL/P patients.

Adolescent↗

PubMed1998

Morphologic analysis of dentofacial structure in patients with acromegaly.

The purpose of this study was to investigate the morphologic changes of the oral and maxillofacial skeletal structure in patients with acromegaly and the correlation between growth hormone, age at onset, and duration. Fifty-four acromegalic patients (28 men and 26 women) were compared with 45 normal adults (23 men and 22 women) using casts and cephalometric analysis. The incisor relationship was classified into four types: edge-to-edge bite, crossbite, maxillary incisor protrusion, and normal bite. Many cases of edge-to-edge bite and crossbite were observed in acromegalic patients. The most characteristic craniofacial skeletal differences in patients with acromegaly were protruded glabella and increased anterior face height. Enlargement of the ascending ramus and prominence of the mandible, chin, and mouth were the most noticeable profile characteristics of acromegalic patients. Male patients tended to demonstrate downward mandibular advancement and crossbite, while females showed extension of the ascending ramus, downward displacement of mandible, bimaxillary alveolar protrusion, and edge-to-edge bite.

Acromegaly↗

PubMed1998

Morphologic changes in the upper airway structure following surgical correction of mandibular prognathism.

The purpose of this study was to investigate morphologic changes in oropharyngeal structures in mandibular prognathic patients after orthognathic surgery. The study consisted of 25 patients (12 males and 13 females) with mandibular prognathism who underwent surgical and orthodontic treatment. A set of 4 standardized lateral cephalograms were obtained from each subject preoperatively and at 3 months, 6 months, and 1 year postoperatively. Morphologic changes in upper airway structures were evaluated longitudinally by gender. Parameters of the anteroposterior width of the pharynx significantly decreased at 3 and 6 months in both genders, and these parameters tended to rebound to the preoperative values 1 year postoperatively in females, but not in males. The hyoid bone significantly descended inferiorly 1 year postoperatively in males, while there were no significant changes in females. The distance between the hyoid bone and the third vertebra gradually decreased in males postoperatively; however, there were no significant changes in females. The cross-sectional area of the hypopharynx significantly decreased 1 year postoperatively in males, but not in females. These results indicate that the upper airway morphology changed differently in males and females following surgery. To compensate for skeletal changes following surgery, it appears that males and females responded in different ways to preserve a functional upper airway.

Adult↗

PubMed1998

Evidence for apoptosis signal-regulating kinase 1 in the regenerating palatal epithelium upon acute injury.

Apoptosis signal-regulating kinase 1 (ASK1), a recently identified mitogen-activated protein (MAP) kinase kinase kinase, is a key element in the mechanism of stress- and cytokine-induced apoptosis. However, pathophysiologic roles of ASK1 in vivo are poorly understood. In the present study, we analyzed the ASK1 expression in injured rat palate using an immunohistochemical approach to investigate the roles of ASK1 during the process of wound healing. In the normal rat palatal epithelium, a weak cytoplasmic staining of ASK1 was observed in keratinocytes of the prickle cell layer. After mucoperiosteal injury of the palate, ASK1 was clearly observed in the suprabasal keratinocytes surrounding the wound. ASK1 expression was most evident at Day 2 after injury in the edge of the migrating epithelium. Thereafter, the intensity of ASK1 staining decreased gradually until the re-epithelialization was completed at Day 10 to 14. A staining with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labeling method identified a number of apoptotic keratinocytes in the suprabasal layers at the healing edge. Active induction of epithelial apoptosis was readily detectable from Day 5 after injury. In double-staining analysis, the temporal and spatial pattern of ASK1 expression correlated well with the appearance of apoptotic keratinocytes. p38 MAP kinase, a downstream component of ASK1, was found to be activated at the sites of ASK1 expression, suggesting that increased expression of ASK1 leads to activation of downstream MAP kinase signaling pathway in vivo. These results suggest a significant contribution of ASK1 to the epithelial apoptosis in the process of mucoepithelial wound repair.

Animals↗

PubMed1998

[Continuous intraportal chemotherapy for prevention of metachronous hepatic metastasis in colorectal cancer].

Fifty-five colorectal cancer patients who had continuous intraportal chemotherapy between 1990 and 1993 (treated group) and 130 colorectal cancer patients who did not have portal chemotherapy between 1982 and 1993 (untreated group) were studied to clarify the effects of continuous intraportal chemotherapy on the prognosis. After a catheter was placed in the portal vein through the right gastroepiploic vein at the time of radical operation, 10 mg of MMC was continuously infused for 4 hours at operation and 500 mg/day of 5-FU was continuously infused for 7 days postoperatively. The toxicities of this therapy were not serious. The five-year survival rate was 65.3% in the treated group and 65.6% in the untreated group. The five-year disease-free survival rate was 69.8% in the treated group and 58.6% in the untreated group, with no significant difference. In stage II patients, however, the five-year disease-free survival rate in the treated group was slightly higher than in the untreated group (90.0% vs 70.3%, p = 0.073), and the rate of hepatic recurrence in the treated group was significantly lower than in the untreated group. These results suggest that continuous intraportal chemotherapy may prevent metachronous hepatic metastases in stage II colorectal cancer patients.

Aged↗

PubMed1998

Potential contribution of endothelin to renal abnormalities in glycerol-induced acute renal failure in rats.

We studied the possible participation of endothelin-1 (ET-1) in the pathogenesis of renal damage in glycerol-induced acute renal failure (ARF). Cortical mRNA expression of ET-1 increased, peaking at 10 hr postinjury, but this did not occur in the medulla, plasma concentration and urinary excretion of ET-1 also increased in this model. There was no change in ETA receptor mRNA, whereas the ETB receptor tended to be down-regulated in the kidney after glycerol administration. In situ hybridization study demonstrated that elevated expression of prepro ET-1 was predominantly localized in cells in the proximal tubules of the nephritic kidney. The administration (30-3 mg/kg) of S-0139, (+)-disodium 27-[(E)-3-[2-[(E)-3-carboxylatoacryloylamino]-5-hydroxyphenl ]acrylayl oxy]-3-oxoolean-12-en-28-oate, an ETA selective antagonist, after initiation of insult offered dose-dependent prevention against ARF, demonstrating preventing of renal function impairment and mortality. These findings indicate that ET-1 participates in the pathogenesis of acute tubular injury in glycerol-induced ARF and that ETA antagonist may be useful in the treatment of some types of human ARF.

Acute Kidney Injury↗

PubMed1998

Analysis of renal pathology and drug history in 158 Japanese patients with rheumatoid arthritis.

To clarify the characteristics of renal pathology and its correlation with disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), renal biopsy findings from 158 Japanese RA patients with urinary abnormalities and/or renal dysfunction were analyzed retrospectively in the period between 1979 and 1996. Urologic abnormality and urinary tract infection were ruled out in all patients. Light and immunofluorescence (IF) microscopy were performed in all patients. Mesangial proliferative glomerulonephritis (MesPGN) was diagnosed in 54 patients, membranous nephropathy (MN) in 49, and secondary amyloidosis (AM) in 30. Renal dysfunction was more frequent in patients with AM (22/30) than in patients without (40/128). Forty of 49 MN patients developed renal disorders during DMARDs therapy. The prevalence of DMARD-related MN increased during the period of observation. The fact that DMARDs are of very frequent use in recent Japanese RA patients may reflect the prevalence of MN in this study. Two thirds of patients with MesPGN developed renal disorders when no DMARDs were used. One half of 54 MesPGN patients demonstrated IgA glomerulonephritis (GN) by IF. The prevalence of primary renal diseases in Japan may reflect the frequency of IgA GN in Japanese RA patients. Furthermore, diffuse thinning of the glomerular basement membrane (GBM) was observed in 30 of 81 patients with electron microscopy. RA itself may underlie the pathogenesis of GBM thinning, and drugs used for RA treatment may also accelerate the development of this lesion. In conclusion, although MesPGN, MN, and AM may be relatively more common, IgA GN and GBM thinning also were other frequent entities in Japanese RA patients. No correlation was observed between DMARDs and renal disorders excepting MN.

Adolescent↗

PubMed1998

Three-dimensional computer-graphic demonstration of facial soft tissue changes in mandibular prognathic patients after mandibular sagittal ramus osteotomy.

The purpose of this study is to demonstrate the three-dimensional changes in facial soft tissues in prognathic patients after orthognathic surgery. The soft tissue and skeletal tissue changes were analyzed with a noncontact three-dimensional digitizing system and roentgenographic cephalometry, respectively. Forty prognathic patients with or without asymmetry, who received only mandibular sagittal ramus osteotomy, were included in the study. The preoperative and 3-month postoperative digitized soft tissue images were superimposed from the nose to the forehead. Changes in the facial soft tissue were illustrated using a computer graphic image with tomographic cross sections at 1-cm intervals. Sagittal soft tissue dislocations of 75 facial measurement points were also calculated. Examination of patients with minimum transverse movement of the mandible revealed significant correlation between soft tissue and related hard tissue dislocation in the sagittal dimension in most landmarks at and below the upper lip. This noncontact three-dimensional digitizing system is very useful in analyzing facial soft tissue changes caused by orthognathic surgery.

Adult↗

PubMed1998

[Death at home: home care for terminal cancer patients].

For the past seven years, we provided home hospice care for 26 terminal cancer patients. Seven patients died at home and nineteen patients were readmitted and died in our hospital. There was no difference in the mean age, sex, primary disease, nutrition management, pain control, informing of disease between the patients who died at home and the patients who died in the hospital was longer than that of patients who died at home. According to our questionnaire on home care, the satisfaction of patients and their families with home care was more than 80% in both groups. But patients who died at home needed more care than patients who died in the hospital because the former had more care helpers than the latter. In fact, only patient's families as care helpers and often took care of their patient. Both the physical and mental burden of patient's families increased, at last it was too difficult for them to continue home care. Therefore the home care system must be arranged support both the mental and physical status of the patients and their families.

Aged↗