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Biomedical subjects

K Komatsu

Publications and source records attributed to K Komatsu.

At least 253 records · Page 14Linked to original sources

A prospective randomized trial of FK506 versus cyclosporine after human pulmonary transplantation.

We have conducted a unique prospective randomized study to compare the effect of FK506 and cyclosporine (CsA) as the principal immunosuppressive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who were randomly assigned to receive either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were similar in age, gender, preoperative New York Heart Association functional class, and underlying disease. Acute rejection (ACR) was assessed by clinical, radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1 g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant. During the first 30 days after transplant, one patient in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P = NS). Although one-year survival was similar between the groups, the number of recipients free from ACR in the FK group was significantly higher as compared with the CsA group (P < 0.05). Bacterial and viral pneumonias were the major causes of late graft failure in both groups. The mean number of episodes of ACR/100 patient days was significantly fewer in the FK group (1.2) as compared with the CsA group (2.0) (P < 0.05). While only one recipient (1/36 = 3%) in the group treated with CsA remained free from ACR within 120 days of transplantation, 13% (5/38) of the group treated with FK remained free from ACR during this interval (P < 0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was similar in both groups. Although the presence of bacterial, fungal, and viral infections was similar in the two groups, ACR occurred less frequently in the FK-treated group as compared with the CsA-treated group in the early postoperative period (< 90 days). Early graft survival at 30 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group.

Adult↗

Inhibitory effects of Rooibos tea, Aspalathus linealis, on X-ray-induced C3H10T1/2 cell transformation.

Oncogenic transformation of mouse C3H10T1/2 cells induced by X-rays was suppressed in the presence of extract of Rooibos tea, Aspalathus linealis. Transformation was reduced with increased concentration of the extract, so that at an extract concentration of 10%, transformation incidence was similar to the spontaneous level. Suppression was also dependent on treatment time with the extract and was maximal when present during the entire incubation period. In contrast, green tea extract at an equitoxic concentration showed no detectable effect on transformation incidence.

Animals↗

Impact of pulmonary hypertension on outcome after single-lung transplantation.

Single lung transplantation for pulmonary hypertension (PH) remains a controversial therapy. We retrospectively studied 48 consecutive recipients of single-lung allografts to determine if preoperative PH was associated with increased mortality or morbidity. Recipients were divided into two groups; those who did have preoperative PH, defined as mean pulmonary arterial pressure less than or equal to 30 mm Hg (n = 29; group 1), and those recipients with PH who had a mean pulmonary arterial pressure greater than 30 mm Hg (n = 19; group II). Mean pulmonary arterial pressure and pulmonary vascular resistance decreased significantly after transplantation in recipients with PH. These values remained significantly higher as compared with those in recipients without pretransplantation PH. Postoperative pulmonary ventilation/perfusion scans demonstrated significant ventilation/perfusion mismatch in lung allografts with pretransplantation PH (p < 0.05). The mean duration of intensive care unit stay was significantly longer in recipients with PH. Although operative mortality was similar between the groups, preoperative PH was associated with significantly lower 1-year survival (53% versus 72%; p < 0.05) and New York Heart Association functional class (p < 0.05). We conclude that preoperative PH in single-lung transplant recipients is associated with significantly increased mortality, prolonged intensive care unit stay, and less symptomatic improvement. Thus, despite a shortage of donor organs, single-lung transplantation may be suboptimal therapy in patients with PH. Further study comparing single versus bilateral lung transplantation for PH is necessary.

Adolescent↗

Intrarenal hemodynamics in low- and high-output cardiac failure in rats.

Cardiac failure is multifactorial in causation, and the underlying physiologic mechanisms are variable, yet their renal effects have been considered more homogeneous. To investigate and compare the intrarenal hemodynamic characteristics in two experimental types (low- and high-output) of cardiac failure, renal micropuncture studies were performed in rats after myocardial infarction (MI) and arteriovenous fistula, respectively. Myocardial infarction was produced by ligation of the left main coronary artery and arteriovenous fistula by direct puncture of the aorta and inferior vena cava below the renal arteries. Pressures and interrenal and glomerular dynamics were obtained using classic micropuncture techniques. Both forms of cardiac failure were characterized by elevated left ventricular end-diastolic pressure (LVEDP), reduced mean arterial pressure, and increased cardiac mass. Left ventricular end-diastolic pressure was higher in MI rats, and effective renal plasma flow (ERPF) tended to be reduced in both forms of cardiac failure. There were no apparent differences in effective renal plasma flow between two models. In addition, single-nephron plasma flow and single-nephron glomerular filtration rate were reduced, and single-nephron filtration fraction and glomerular capillary pressure (PG) were increased in both models. These changes were associated with higher afferent and efferent arteriolar resistances and lower ultrafiltration coefficients. Despite these similarities, PG was higher in MI rats, yet LVEDP correlated directly with PG (r = 0.73; P < 0.001) and efferent arteriolar resistances (r = 0.72; P < 0.01). Therefore, although systemic arterial pressure and effective renal plasma flow were similar in both models of cardiac failure, PG was significantly higher in MI rats with higher LVEDP than in arteriovenous fistula rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

vacC, a virulence-associated chromosomal locus of Shigella flexneri, is homologous to tgt, a gene encoding tRNA-guanine transglycosylase (Tgt) of Escherichia coli K-12.

The genetic determinants required for invasion of epithelial cells by Shigella flexneri and for the subsequent bacterial spreading are encoded by the large virulence plasmid. Expression of the virulence genes is under the control of various genes on the large plasmid as well as on the chromosome. We previously identified one of the virulence-associated loci near phoBR in the NotI-C fragment of the chromosome of S. flexneri 2a YSH6000 and designated the locus vacC. The vacC mutant showed decreased levels of IpaC, and IpaD proteins as well as transcription of ipa, an operon essential for bacterial invasion (N. Okada, C. Sasakawa, T. Tobe, M. Yamada, S. Nagai, K. A. Talukder, K. Komatsu, S. Kanegasaki, and M. Yoshikawa, Mol. Microbiol. 5:187-195, 1991). To elucidate the molecular nature of the vacC locus, we cloned the vacC region from YSH6000 on a 1.8-kb SalI-BamHI DNA fragment. The nucleotide sequence of the 1,822-bp vacC clone was highly (> 98%) homologous to the tgt region of Escherichia coli K-12, which is located at 9.3 min on the linkage map. Complementation tests indicated that the vacC function was encoded by an open reading frame expressing a 42.5-kDa protein, which corresponded to the tgt gene of E. coli K-12, coding for tRNA-guanine transglycosylase (Tgt) (K. Reuter, R. Slany, F. Ullrich, and H. Kersten, J. Bacteriol. 173:2256-2264, 1991). The cloned tgt gene from E. coli K-12 restored the virulence phenotype to the vacC mutant of YSH6000. Characterization of the vacC mutant indicated that levels of VirG, a protein essential for bacterial spreading, and VirF, the positive regulator for the expression of the virG and ipaBCD operons, decreased significantly compared with those of the wild type. Similar phenotypic changes occurred in vacC mutants constructed by insertion of a neomycin resistance gene in shigellae and enteroinvasive E. coli strains, consistent with the hypothesis that the vacC (tgt) gene contributes to the pathogenicity of Shigella flexneri.

Amino Acid Sequence↗

Effects of ANG-converting enzyme and alpha 1-adrenoceptor inhibition on intrarenal hemodynamics in SHR.

To investigate the prolonged effects of angiotensin-converting enzyme (ACE) inhibition and alpha 1-adrenoceptor blockade on intrarenal hemodynamics, whole kidney and renal micropuncture studies were performed in male 21-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats treated for 3 wk with quinapril (3 mg/kg), terazosin (1 mg/kg), or in their combination (quinapril 1.5 mg/kg and terazosin 0.5 mg/kg). In WKY, only quinapril significantly reduced mean arterial pressure (MAP) associated with reduced afferent arteriolar resistance; there were no other significant changes. In contrast, all treatments similarly decreased MAP in SHR. Quinapril increased renal plasma flow and decreased filtration fraction. With respect to intrarenal hemodynamics, quinapril increased single-nephron plasma flow and reduced glomerular capillary pressure (from 53.1 to 47.8 mmHg; P < 0.01), associated with reduced afferent (from 4.80 to 3.17 10(10)dyn.s.cm-5; P < 0.01) and efferent (from 1.70 to 1.17 10(10)dyn.s.cm-5; P < 0.01) arteriolar resistances, and increased ultrafiltration coefficient (from 0.037 to 0.052 nl.s-1.mmHg-1; P < 0.05). Terazosin only reduced arteriolar resistance. The combined treatment attenuated either agent's independent effects on glomerular hemodynamics. These data demonstrate that prolonged ACE and adrenergic inhibition therapy alone or in combination produce different effects than when given by vein, suggesting that prolonged renopressor system inhibition may be more effective than adrenergic in SHR.

Adrenergic alpha-1 Receptor Antagonists↗

Structural and functional characterization of estrogen sulfotransferase isoforms: distinct catalytic and high affinity binding activities.

Estrogen sulfotransferase (EST) purified from the guinea pig (gp) adrenal gland consists of multiple charge isoforms with isoelectric points (pls) ranging from 6.5 to 5.2. Four individual isoforms were isolated for use in antibody production, as well as for tryptic fragmentation analysis. The multiple charge isoforms manifested a high degree of relatedness as evidence by complete immunocross-reactivity. This relatedness was further demonstrated by peptide mapping analysis, which revealed essentially identical elution profiles for three of the isoforms, whereas the fourth most acidic isoform, although similar to the other three isoforms, demonstrated some differences. To further explore the nature of the charge isoforms, native gpEST and EST expressed by CHO-K1 cells transfected with the gpEST cDNA were subjected to additional biochemical characterization. An interesting finding was that, in addition to EST activity, gpEST bound estradiol with a high affinity [dissociation constant (Kd) 10 nM]; furthermore, the binding activity was absolutely dependent on the cofactor, adenosine-3',5'-diphosphate (3',5'-ADP). An unexpected and novel finding was that only the most basic pl 6.5 isoform was catalytically active, while estradiol-binding activity was associated with a more acidic isoform (pl 5.5-5.2); however, it has not as yet been possible to definitively assign the binding activity to a specific isoform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

[The effect of doxorubicin on the unimpeded eruption rates of rat mandibular incisors].

We examined the effects of daily injections of doxorubicin, an anti-tumor drug, on unimpeded eruption rates, pulp cells, odontoblasts, periodontal ligament and dentine formation in the rat mandibular incisor. The experimental animals were intraperitoneally injected with 5 mg of doxorubicin/kg body weight/day for a period of 7 days. The eruption rates decreased gradually; and on the seventh day, the mean eruption rate had decreased to 14% of the control value. In addition, we noticed marked destruction of pulp cells and periodontal cells at the basal region of the incisor. The amount of dentine formation was measured using the tetracycline labeling method, but significant decreases in dentine formation were not observed. These results suggest that destruction of the basal tissues is related to inhibition of incisor eruption rates, but that tooth eruption is not related to dentine formation.

Animals↗

[Identical twins with different types of jejunal atresia].

This is a report of identical twins who were associated with different types of jejunal atresia, whose mother had no problems during her gestation. One was associated with a membranous atresia, and the another multiple jejunal atresia. Identical twins, both of whom are associated with intestinal atresia are very rare. The anomalies of these infants might be resulted from congenital factor and secondary circulatory disturbance.

Adult↗

[Effect of calcium antagonist (benidipine) and alpha 1 blocker (urapidil) on renal hemodynamic responses to two acute environmental stresses in spontaneously hypertensive rats (SHR)].

Renal hemodynamic responses were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto Rats (WKY) to two acute stresses: environmental stress (foot shock (FS) and air jet (AS)). The effects of calcium channel blocker (benidipine) and alpha 1 blocker (urapidil) on these responses were studied using an ultrasonic pulsed Doppler flowmeter. The increments in mean arterial pressure (MAP) and renal vascular resistance (RVR) were greater in SHR during both stresses. On the other hand, the decrease in the renal blood flow (RBF) with these stresses almost disappeared with renal denervation. These renal hemodynamic responses in SHR disappeared with alpha 1 blocker (urapidil), but not with calcium channel blocker (benidipine). The sympathetic nervous system became hyperactive in SHR under environmental stress, Which induced specific renal hemodynamic change. These results suggest that investigations on essential hypertension should focus on clarifying not only systemic hypertensive reaction, but also changes in renal hemodynamics. Furthermore, it is necessary for antihypertensive therapy to take these hemodynamic changes into consideration.

Acute Disease↗

Indications for and results of single, bilateral, and heart-lung transplantation for pulmonary hypertension.

The indications for single, bilateral, and heart-lung transplantation for patients with pulmonary hypertension remain controversial. We retrospectively analyzed the results from 11 single, 22 bilateral, and 24 heart-lung transplant procedures performed between January 1989 and January 1993 on 57 consecutive patients with pulmonary hypertension caused by primary pulmonary hypertension (n = 27) or Eisenmenger's syndrome (n = 30). Candidates with a left ventricular ejection fraction less than 35%, coronary artery disease, or Eisenmenger's syndrome caused by surgically irreparable complex congenital heart disease received heart-lung transplantation. All other candidates received single or bilateral lung transplantation according to donor availability. Although postoperative pulmonary artery pressures decreased in all three allograft groups, those in single lung recipients remained significantly higher than those in bilateral and heart-lung recipients. The cardiac index improved significantly in only the bilateral and heart-lung transplant recipients. A significant ventilation/perfusion mismatch occurred in the single lung recipients as compared with bilateral and heart-lung recipients because of preferential blood flow to the allograft. Graft-related mortality was significantly higher and overall functional recovery as assessed by New York Heart Association functional class was significantly lower at 1 year in the single as compared with bilateral and heart-lung recipients. Thus bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function. Other candidates will still require heart-lung transplantation.

Adolescent↗

Cloning and sequence analysis of the 5'-flanking region of the estrogen sulfotransferase gene: steroid response elements and cell-specific nuclear DNA-binding proteins.

A 2954 bp region of the guinea pig estrogen sulfotransferase gene was cloned and sequenced including 2888 nt upstream of the cap site. This represents the first cloning of the promoter region of a steroid sulfotransferase gene. The 5'-flanking region was found to contain a conventional TATA box variant and sequences homologous to estrogen and glucocorticoid response elements. Gel mobility shift assays detected the presence of nuclear proteins in adrenocortical SW-13 and Y-1 cells that bind specifically to 30 mer DNA sequences containing either estrogen or glucocorticoid response elements. In contrast, gel shift experiments using 3T3 fibroblast cells failed to demonstrate similarly upshifted bands. Block deletion studies indicated that regulation of basal estrogen sulfotransferase promoter activity was located within the first 1000 bp upstream of the transcription initiation site.

Adrenal Cortex↗

Hemopoietic stem-cell compartment of the SCID mouse: double-exponential survival curve after gamma irradiation.

It has been reported that SCID (severe combined immunodeficiency, scid/scid) mice are more radiosensitive than normal mice. In the present studies, graded doses of radiation were given to bone marrow cells from SCID mice, and double-exponential survival curves were observed for day-9 and day-12 colony-forming units in the spleen (CFU-S). Single-exponential curves were found for SCID CFU in in vitro assays for granulocyte/macrophage-CFUs and erythroid burst-forming units, as reported elsewhere. Since the size of this more resistant fraction seems to decrease with stem-cell maturation, the finding implies that this fraction is a primitive subpopulation of the stem-cell compartment. The mean lethal dose (D0), however, of this less sensitive SCID CFU-S is much less than the D0 of regular CFU-S in normal littermates. Spleen colonies produced by SCID bone marrow were relatively small and abortive. The size of these colonies decreased nearly exponentially with increasing doses of radiation. These colonies were believed to be produced by this less sensitive fraction of the stem cells, which carried residual injuries. The colonies produced by the sensitive fraction have disappeared, being killed by a relatively low dose of radiation. This observation might account for the high lymphomagenesis arising from primitive hemopoietic stem cells in SCID mice, because the smallness of the colonies suggests that there is unrepaired or misrepaired damage. Furthermore, this less sensitive fraction might be a source of the "leaky" change of T and B cells, possibly due to the induction of an equivocal repair system which appears in the later stages of life in the SCID mice.

Animals↗

Transforming growth factor(TGF)-beta 1 induces leukemic cell-growth-promoting activity in fibroblast cells.

The production of the leukemic cell-growth-promoting factor (LGF) in TGF-beta 1-treated fibroblast cells was studied. BALB/c3T3 mouse fibroblast (3T3) cells cultured in Eagle's medium containing a low concentration of TGF-beta 1 (0.04-1 ng/ml) secreted 3-5 times more LGF than the cells cultured in the absence of TGF-beta 1. The amount of LGF secretion was dose-dependent on the concentration of post-cultured medium and time-dependent after the addition of TGF-beta 1. Similar findings were obtained in human diploid fibroblasts, WI-38 cells. LGF is a 18KD glycoprotein that is acid-stable but heat-unstable.

3T3 Cells↗

Possible advantages of aluminum-chloro-tetrasulfonated phthalocyanine over hematoporphyrin derivative as a photosensitizer in photodynamic therapy.

The potency of aluminum-chloro-tetrasulfonated phthalocyanine (AlS4Pc) as a photosensitizer in photodynamic therapy was evaluated in in vitro and in vivo studies. Compared with hematoporphyrin derivative (HpD), the following advantages of AlS4Pc were revealed: (1) AlS4Pc was less toxic than HpD in vitro without light irradiation. (2) AlS4Pc showed more photodynamic-dependent cytotoxicity and anti-tumor effect in the red area of the spectrum (> 660 nm) at which tissue penetration is high. (3) AlS4Pc appeared to be removed more rapidly from normal tissues such as muscle and skin. (4) AlS4Pc showed less photodynamic-dependent cytotoxicity in vitro and milder cutaneous phototoxicity in vivo with UVA irradiation. On the basis of these observations, AlS4Pc shows considerable promise as a photosensitizer for PDT.

Animals↗

The effect of velocity of loading on the biomechanical responses of the periodontal ligament in transverse sections of the rat molar in vitro.

Stress-strain relations of this ligament in transverse sections of the mandibular first molar were examined over a wide range of velocities of loading from 1 to 10(4) mm/24 h. With increasing velocities, the maximum shear stress, tangent modulus and failure strain-energy density increased but the maximum shear strain decreased. The mechanical responses at the highest velocity for the molar ligament were compared with those previously found for the incisor ligament. Mechanical strength, stiffness and toughness were greater for the molar than for the incisor ligament; the molar ligament therefore has more extensible fibres or a different fibre arrangement. Comparison of the mechanical responses at the slowest velocity suggests that, though the stress level was greatly reduced (presumably because of stress relaxation), the fibre components of the molar ligament still reacted at this velocity. It is also suggested that the differences in the ratios of the mechanical measures in 10(4)-1 mm/24 h between the two types of teeth are due partly to their different periodontal fibre architectures.

Alveolar Process↗

Molecular cloning and heterogeneity of the human hepatitis C virus (HCV) genome.

The Japanese variant of the hepatitis C virus (HCV-N) genome, consisting of 9440 nucleotides in length, was cloned from a small amount (2 ml) of plasma from a single Japanese carrier by using RT-PCR and modified RT-PCR. The HCV-N genome has a long open reading frame that encodes a 3014 amino acid polyprotein with 340 and 57 bases of 5' and 3' non-coding sequences, respectively. HCV-N has a 4-amino-acid insertion in the NS5 region as compared to other HCV isolates, but this insertion is found to be very rare upon direct sequencing of that region. Comparative sequence analysis of all the complete and partial HCV sequences that were reported indicates that HCV can be subdivided into at least 4 groups. The HCV-N isolate has a high homology with HCV-J and HCV-BK (> 90%) and so belongs to group II, but shows less similarity to HCV-1 (> 78%, group I) and least to HC-J6 (> 67%, group III). Among these HCV isolates, the 5' non-coding region was the most conserved (> 93%) since it plays an important role in replication. The RT-PCR assay to detect HCV-RNA, using the primers deduced from this region, was very sensitive and specific. The putative core protein could become an important target for immunoassay because of a high degree of amino acid sequence similarity in that region. A high degree of diversity and a low similarity between each HCV isolate in the putative envelope protein play an important role in the chronicity of HCV infection and development of immunopreventive agents, such as immunoglobulin and vaccine for that infection.

Base Sequence↗