Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 73 records · Page 4Linked to original sources

PubMed2000

Sequence and functional properties of African green monkey CD4 silencer.

We reported previously that in African green monkey (AGM) CD4 lymphocytes, CD4 mRNA expression undergoes a decrease following in vitro activation, and CD4 cells are therefore subject to loss of CD4 expression on the cell surface. To examine the transcriptional regulation of the CD4 gene in this species. we analyzed the CD4 silencer, which has been identified as a regulatory element responsible for the down regulation of CD4 transcription in CD8 cell lineage cells. Sequence analysis indicated that the CD4 silencer of the AGM was highly homologous to that of humans. However, two nucleotide substitutions were present in one of the nuclear protein binding sites, which was characterized as the FP II site having a strong enhancing effect on transgene expression in CD4 cells. By performing transient transfection assays. we found that the enhancing activities of the CD4 silencer or FP II-containing fragment of the AGM were greatly reduced in a human CD4 cell line as compared to those of human materials. The CD4 mRNA level was significantly decreased in the human CD4 cell line when synthetic oligonucleotide corresponding to the human FP II sequence was added to the culture. These observations imply that FP II-protein interaction might be required for the maintenance of sufficient expression of the CD4 gene, and the enhancing activity mediated by the above interaction might be decreased in the AGM CD4 silencer, due probably to the nucleotide changes occurring at the FP II site.

Animals↗

PubMed2000

Characteristics of intestinal absorption and disposition of glycyrrhizin in mice.

As basic studies to apply an intestinal pressure-controlled colon delivery capsule (PCDC) for glycyrrhizin (GZ), the characteristics of intestinal absorption and disposition of GZ were investigated in mice. In the in vivo study, after intravenous (iv) administration of GZ, 10 mg/kg dose, plasma GZ disappeared from the systemic circulation with t(1/2(alpha)) of 0.0063 h, thereafter, it slowly declined with t(1/2(beta)) of 15.23 h. The area under the plasma drug concentration versus time curve (AUC) values of iv (10 mg/kg), intracolonic (50 mg/kg) and intraduodenum (50 mg/kg) administrations were 115.1, 16.7 and 2.7 microgh/mL, respectively. The AUC values of plasma glycyrrhetic acid (GA), a degradation product after intracolonic and intraduodenum administrations were 2.8 and 8.4 microgh/mL, respectively. In the in situ closed loop study, the concentrations of GZ in plasma and liver after intracolonic administration were significantly increased (p<0.05) in comparison with those after intrajejunum or intraileum administration, while the concentration of GA in plasma and liver after intracolonic administration had trends to increase. These observations clearly suggest that the intracolonic administration is a useful way to improve the oral bioavailability of GZ and to enhance its pharmacological efficacy. These pharmacokinetic results of GZ suggest that GZ is a subject drug to be applied for the PCDC system we previously developed. The PCDCs formulation of GZ will enable us to carry GZ to the colon and enhance the oral bioavailability of GZ.

Animals↗

PubMed2000

Bronchial cuff pressure change caused by left-sided double-lumen endobronchial tube displacement.

PURPOSE: The bronchial cuff pressures (BCPs) of left-sided double-lumen endobronchial tubes (DLTs) manufactured by Rüsch and Mallinckrodt were measured in 80 patients when the tubes were withdrawn to compare the effect of tube design on BCP change. METHODS: During general anesthesia with muscle relaxation, the cephalad surface of the endobronchial cuff was positioned either 2.5 cm distal to the carina (Rüsch Group R-I; n = 20 and Mallinckrodt Group B-I; n = 20) or just below the carina (Rüsch Group R- II; n = 20 and Mallinckrodt Group B- II; n = 20) and the cuff was inflated to 35 cm H2O. The tube was then withdrawn in 0.5-cm steps until the cuff was 2.0 cm proximal to the carina, the position just before the capnogram or pressure-volume loop of tracheal lumen changed. The BCP at each step was measured. The rate of decrease in BCP was defined as the decrease of BCP divided by the length of displacement of DLT. RESULTS: The rates of decrease from the +2.5 cm position to the end point in Group B-I (7.7+/-0.8 cm H2O x cm(-1) and those from the most proximal acceptable position to the end point in Group B-II (19.5+/-4.8 cm H2O x cm(-1) were greater than those in Group R-I (6.9+/-0.9 cm H2O x cm(-1) (P<0.01) and in Group R-II (12.4+/-3.1 cm H2O x cm(-1)) (P<0.01), respectively. CONCLUSION: The BCP decreased in both of the Mallinckrodt and Rüsch DLTs, and the rates of decrease of the former were greater than those of the latter.

Adult↗

PubMed2000

A staged Fontan approach in patients initially unsuitable for the primary Fontan procedure.

OBJECTIVE: To determine the efficacy of the Glenn procedure in terms of establishing the Fontan procedure. METHODS: Surgical results were investigated in 248 patients undergoing either the total or partial right heart bypass. Of these, the conventional and the bidirectional Glenn procedures were employed in 27 and 58 patients, respectively. RESULTS: Conversion to the Fontan circulation was attempted in 32 of 58 patients initially considered unsuitable for the Fontan circulation and undergoing the bidirectional Glenn procedure, with 2 operative deaths. Of the 27 undergoing the conventional Glenn procedure, 13 have undergone conversion with 2 deaths. Actuarial survival rate after the staged Fontan approach did not statistically differ from that after the primary Fontan procedure. Catheterization in 130 patients with the established Fontan circulation showed no significant differences in ejection fraction, end diastolic volume, and end diastolic pressure of the systemic ventricle, as well as in Cardiac Index, between the group of patients treated with the primary Fontan procedure and the group treated with the staged Fontan procedure. When achieving the bidirectional Glenn procedure, the size of the additional channel from the ventricles to the pulmonary arteries was correlated with the postoperative change in pulmonary arterial size, but such additional forward flow produced insufficient ventricular offloading in 9 of 16 patients with significant atrioventricular valvar regurgitation. CONCLUSION: The staged Fontan strategy has an advantage in patients with complicated circumstances. Whether the primary or the staged Fontan procedure was used, however, did not affect the Fontan circulation itself when once the Fontan circulation was established. The additional forward flow in the bidirectional Glenn physiology, if employed, should be appropriately adjusted, considering both the advantages and the disadvantages of the option.

Child, Preschool↗

PubMed2000

Accurate localization of an insulinoma by preoperative selective intra-arterial calcium injection and intraoperative glucose monitoring.

The role of pre- and intraoperative procedures for the localization of insulinomas has been extensively debated. We report a case of successful treatment using preoperative selective intra-arterial calcium injection and intraoperative glucose monitoring. A 12-year-old boy with hypoglycemic attacks had a large insulinoma in the head of the pancreas on computed tomography. Preoperative selective angiography combined with arterial stimulation-venous sampling (ASVS) by intra-arterial injection of calcium revealed no other insulinomas in the body and tail of the pancreas. Elevation of serum glucose on intraoperative monitoring confirmed complete enucleation of the insulinoma. Preoperative ASVS can accurately localize an insulinoma, and may help to increase the success rate of surgery and avoid blind pancreatectomy.

Blood Glucose↗

PubMed2000

Immunohistochemical detection of apolipoprotein E within prion-associated lesions in squirrel monkey brains.

The interaction of various amyloid precursors and apolipoprotein E (apoE) is important for Congophilic amyloid formation. As for cerebral amyloidoses, although the correlation between amyloid beta protein (Abeta) and apoE in Alzheimer's disease (AD) has been clarified, the interaction of prion protein isoform (PrPsc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrPsc plaques, but to clarify the participation of apoE in the early stage of PDs, apoE deposition in immature lesions without Congophilic amyloid in PDs needs to be examined. In the present study two squirrel monkeys were inoculated with mouse PrPsc derived from sheep scrapie, and showed signs of severe spongiform degeneration. These lesions were immunohistochemically characterized as patchy perivacuolar and diffuse synaptic lesions without Congophilic amyloid. The central portion of the assemblies involving a few patchy perivacuolar lesions was detected by methenamine silver staining and appeared as a plaque-like lesion. ApoE was colocalized in all the plaque-like lesions and in half of the patchy perivacuolar lesions, but not in any diffuse synaptic lesions. These immunohistochemical characteristics indicated that apoE colocalization occurred in moderate mature lesions in PDs, and apoE might play an important role in the aggregation of PrPsc after a conformational change from cellular PrP isoform to PrPsc.

Amyloid beta-Peptides↗

PubMed2000

Result of surgical treatments in patients with coronary-arterial obstructive disease after Kawasaki disease.

OBJECTIVE: To determine the efficacy of coronary artery bypass grafting (CABG) in young patients with coronary-arterial obstructive disease subsequent to Kawasaki disease. METHODS: CABG was employed in 100 patients. Age at operation ranged from 1 to 23 years at a mean of 10+/-5 years. The number of bypass grafts placed was 1-5/patient (a mean of 1.7+/-0.8). The left internal-thoracic artery (ITA) was used as a graft in 99 patients; the right internal thoracic artery in 39, the gastroepiploic artery in nine and the saphenous vein in 21. RESULTS: All patients survived the procedures. In the follow-up of 6.7+/-4.5 years, two patients died, one because of a traffic accident and the other due to sudden death. Considerable myocardial ischemia recurred postoperatively in 15, because of either obstruction of the bypass grafts or progression of other coronary-arterial obstructions. Of these, symptoms spontaneously regressed without interventional procedures in four, reoperation was indicated in four and catheter intervention was efficiently carried out in the remaining seven. Another two patients had episodes of critical ventricular arrhythmia; one of them with severe left ventricular dysfunction subsequently underwent cardiac transplantation. The patency rates of the arterial grafts were 94, 82 and 78% at 1, 5 and 10 years, respectively, and this was higher than that of the venous grafts (82, 63 and 36%, respectively). Strenuous exercise is currently prohibited in 15 patients, while the remaining 83 patients are doing well with no obvious restriction in their daily lives. CONCLUSION: Collaborating with catheter interventions, CABG using the arterial grafts can provide attractive results in patients with obstructive coronary arteries associated with Kawasaki disease.

Adolescent↗

PubMed2000

Total cavopulmonary connection in children with body weight less than 10 kg.

OBJECTIVE: To evaluate the results after total cavopulmonary connection (TCPC) in small children, our clinical experience was retrospectively reviewed. METHODS: Of 164 patients undergoing TCPC, the body weight at operation was less than 10 kg (8.8+/-1.1 kg) in 54, including 21 with visceral heterotaxy. The superior caval vein (SVC) was anastomosed to the pulmonary arteries in a bidirectional fashion. To construct a channel draining the inferior caval vein (IVC), an extended polytetrafluoroethylene (ePTFE) tube was placed intraatrially (in 15 patients) or outside the heart (in 13), its diameter being 14 mm in two patients, 16 mm in 12, and 18 mm or greater in 14. A heterologous pericardial baffle was used for intraatrial rerouting in 12 patients. A pedicled autologous pericardial roll was tailored as an extracardiac conduit in 11 patients, and the pulmonary trunk was directly anastomosed to IVC orifice in three. RESULTS: Seven patients, including five with right isomerism, died in the intermediate term because of infection of the ePTFE tube in two, respiratory problems in three, atrioventricular valvar regurgitation in one, and pulmonary venous obstruction in one. Postoperative catheterization showed; SVC pressure, 11+/-2 mmHg without a pressure gradient between SVC and IVC; systemic ventricular end diastolic pressure, 5+/-2 mmHg; end diastolic volume, 122+/-54% of the anticipated normal value; ejection fraction, 0. 56+/-0.11; and cardiac index, 2.9+/-0.7 l/min per m(2). With the follow-up of 1-116 (35+/-31) months, the IVC channel has not become obstructive in all, except for one, in whom a pedicled pericardial roll was severely obstructed because of its tortuous extracardiac course crossing in front of the vertebrae. Postoperative growth was generally stable, although body weights and heights were smaller in the majority of patients when compared with the anticipated standards for Japanese children. CONCLUSION: TCPC can be justifiably established in small children. The use of autologous tissues seemed preferable for constructing the IVC channel unless anatomic orientation was unsuitable.

Blood Vessel Prosthesis Implantation↗

PubMed2000

Stromal cell-independent differentiation of human cord blood CD34+CD38- lymphohematopoietic progenitors toward B cell lineage.

To study the cytokine regulation of early stages of human B-lymphopoiesis, we developed a stroma-free two-step culture system. Single human cord blood CD34+CD38- cells were individually cultured by micromanipulation with interleukin (IL)-3, stem cell factor (SCF), fIt3 ligand (FL), IL-6 and granulocyte colony-stimulating factor (G-CSF). About 10% of the cells formed primary colonies, which were individually tested for myeloid and B-lymphoid potentials by reculturing aliquots of the primary colony cells into secondary myeloid and B-lymphoid cultures. One third of the primary colonies proved capable of differentiation into CD19+IgM+ cells, as well as into myeloid lineage cells. RT-PCR analyses revealed that some cells in the primary culture had already matured to express B cell-specific transcripts. Thus, the combination of IL-3, SCF, FL, IL-6 and G-CSF supported the differentiation of CD34+CD38- lymphohematopoietic progenitors toward B cell lineage in addition to myeloid lineages. Screening of cytokines to identify the minimum requirement of cytokines in the primary culture revealed that IL-3 and SCF were essential and that the addition of FL, and to a lesser extent IL-6 or G-CSF, to the combination of IL3 and SCF remarkably enhanced the primary colony formation and the generation of CD19+ cells in the secondary B-lymphoid culture.

Antigens, CD34↗

PubMed2000

Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene.

To obtain functional evidence for DCC as a tumour suppressor associated with endometrial cancer, the human DCC cDNA encoding a complete open reading frame (ORF) was transfected into highly tumorigenic human endometrial carcinoma cells, HHUA and Ishikawa in which DCC expression was completely deleted. Reconstituted expression of DCC in HHUA had little effect on in vitro growth, but suppressed tumour formation in mice completely. The clones from Ishikawa had abundant DCC expression similar to that in normal endometrium. Their growth in vitro was suppressed and showed apoptotic phenotype. Lower levels of DCC expression in the prolonged passaged clones did not induce apoptosis, but still had the potential to suppress tumorigenicity. These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer.

Animals↗

PubMed2000

Peripheral blood extrathymic CD4(+)CD8(+) T cells with high cytotoxic activity are from the same lineage as CD4(+)CD8(-) T cells in cynomolgus monkeys.

We have previously reported that CD4/CD8 double-positive (DP) T cells with the resting memory phenotype are present in the periphery of healthy cynomolgus monkeys. In the present study, we performed functional studies on the T cells. The expression of CD4 and CD8 on DP, CD4 single-positive (SP) or CD8 SP T cells was stable in cultures with either mitogen or anti-CD3 antibody stimulation. In spite of lacking CD28 expression, DP T cells showed similar proliferative ability and apoptosis sensitivity to CD4 SP and CD8 SP T cells. DP T cells showed both helper and cytotoxic activities. Although the helper activity of DP T cells was lower than that of CD4 SP T cells, cytotoxic activity was comparable to that of CD8 SP T cells. Fresh DP T cells killed target cells mainly by the perforin-granzyme pathway. In addition, fresh DP T cells expressed a high level of mRNA for IFN-gamma and produced a high level of IFN-gamma when they were activated by anti-CD3 antibody ligation. On the other hand, several expanded DP T cell clones shared TCR V(beta) with expanded CD4 SP T cell clones, strongly suggesting that those two corresponding clones with DP and CD4 SP phenotypes might be derived from the same ancestor T cell. These results showed that the DP T cells are a novel T cell subset with functions overlapping with those of CD4 SP and CD8 SP T cells, and that they might play protective and regulatory roles in secondary immune response in cynomolgus monkeys.

Animals↗

PubMed2000

Salt-dependent folding of long duplex DNA by histone H1.

It is found that T4 phage DNA complexed with histone H1 assembled into a string-of-bead structure, when the complex is prepared by a gentle diluting procedure from a high salt solution (2 M NaCl) to a low salt solution (50 mM NaCl). We used fluorescence microscopy to perform the real-time observation on formation and motion of a string-of-bead structure. Spatial histone H1 distribution on the DNA-H1 complex is observed by immuno-fluorescence microscopy.

Bacteriophage T4↗

PubMed2000

Isolation of two novel genes, down-regulated in gastric cancer.

Using a differential display technique, we identified two genes that are down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. The down-regulated expression of these genes in gastric cancer tissue was confirmed by northern blotting analysis and RT-PCR. One, CA11, was a novel gene expressed predominantly in the stomach and was depleted in all of the gastric cancer cell lines examined. The other gene, GC36, was homologous to the digestive tract-specific calpain gene, nCL-4. The expression of both GC36 and nCL-4 was suppressed or depleted in gastric cancer cell lines of differentiated and poorly differentiated types. This is the first report of genes, the expression of which is down-regulated with considerable frequency in gastric cancer.

Alternative Splicing↗

PubMed2000

Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness.

BACKGROUND: Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with broad substrate specificity which can be activated by membrane type 1 (MT1) matrix metalloproteinase in vitro. These may play a critical role in cancer aggressiveness. AIMS: To examine the clinical significance of collagenase-3 expression and the cooperative role of MT1-MMP in human oesophageal carcinomas. PATIENTS: Forty five individuals with oesophageal carcinoma who underwent surgery without preoperative treatment. METHODS: The tumour/normal (T/N) ratios of collagenase-3 and MT1-MMP mRNA expression in 45 human oesophageal carcinomas were determined by northern blot analysis. The production and localisation of collagenase-3 and MT1-MMP proteins were investigated by immunohistochemistry, western blot analysis, and zymography. RESULTS: The mean T/N ratio of collagenase-3 mRNA was 3.5 and that of MT1-MMP 2.1. There was a significant correlation between collagenase-3 and MT1-MMP mRNA expression (p<0.001). Twenty two cases with a collagenase-3 T/N ratio >3.5 showed a significantly higher frequency of vascular involvement and lymph node metastasis, and tended to be at a more advanced stage than 23 cases with a T/N ratio < or =3.5 (p<0.05). Western blot analysis and zymography demonstrated production of collagenase-3 protein in tumour tissues but not in normal tissues. Immunohistochemical studies revealed that collagenase-3 was localised predominantly in tumour cells and MT1-MMP was detected in the same collagenase-3 positive cells; there was a significant association between collagenase-3 and MT1-MMP protein expression (p<0.05). With regard to prognosis, the survival time for subjects in the high collagenase-3 group (T/N ratio >3.5) was significantly worse (p<0.05). CONCLUSIONS: These data suggest that production of collagenase-3 together with MT1-MMP is implicated in tumour aggressiveness and prognosis in human oesophageal carcinomas.

Adult↗

PubMed2000

Sequence analysis and variation of EBNA-1 in Epstein-Barr virus-related herpesvirus of cynomolgus monkey.

OBJECTIVES: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is an important protein for immortalization and tumorigenesis of infected cells. EBNA-1 gene variants may play a role in tumorigenesis. We determined the nucleotide and amino acid (aa) sequences of EBNA-1 in EBV-related herpesviruses from cynomolgus monkeys (cynomolgus-EBV) which induced malignant lymphomas in its natural host and in rabbits, and compared them with sequences of EBV and other lymphocryptoviruses (LCVs). METHODS: Polymerase chain reaction and direct sequencing methods were performed using extracted DNA from cynomolgus-EBV-infected cell lines. RESULTS: The amino acid sequences of cynomolgus-EBV EBNA-1 from two cell lines (Si-IIA: 588 aa; Ts-B6: 619 aa) which are antigenically cross-reactive to human EBV EBNA-1 showed homology with human EBV (Si-IIA: 53%; Ts-B6: 58%) and other LCVs from baboons (54 and 52%) and rhesus monkeys (60 and 58%), especially in the C-terminal unique domain. Homology of the EBNA-1 sequence between Si-IIA and Ts-B6 was 92%. The sequence difference between EBV and the related LCVs was manifested mainly in the length of the internal repeat 3-corresponding region, which contains serine in the glycine/alanine repeat region of nonhuman LCVs. CONCLUSION: Sequence variation of cynomolgus-EBV EBNA-1 from different cell lines was observed. However, their sequences show a relatively high homology with human EBV and share the common features of EBNA-1 of EBV and other LCVs.

Amino Acid Sequence↗

PubMed2000

Colon delivery efficiencies of intestinal pressure-controlled colon delivery capsules prepared by a coating machine in human subjects.

Large quantities of pressure-controlled colon delivery capsules (PCDCs) were prepared by a Hicoater-mini pharmaceutical coating machine and colon delivery efficiencies were evaluated in man. Caffeine powder as a model drug was suspended with a polyethylene glycol (PEG) 1000 suppository base at 50 degrees C, and was hardened in no. 0- and no. 2-sized capsular shapes. The capsule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 +/- 1.1 mg to 45.3 +/- 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 56 +/- 1 microm to 64 +/- 1 microm. With no. 2 PCDCs, the mean coating thickness increased from 50 micro +/- 1 microm to 57 +/- 1 microm by increasing the coating weight of ethylcellulose from 8.1 +/- 0.5 mg to 11.2 +/- 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56 +/- 1 microm (type 1) and 64 +/- 1 microm (type 2), as well as no. 2 PCDCs, having thicknesses of 50 +/- 1 microm (type 3) and 57 +/- 1 microm (type 4), were used for in-vivo evaluation in man. After oral administration of test preparations containing 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of caffeine in the saliva was used as a parameter for the estimation of the release time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 +/- 0.3 h for type- 1 and 5.3 +/- 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4.3 +/- 0.5 h for type 3 and 5.3 +/- 0.3 h for type 4. There were good correlations between ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64 +/- 1 microm for no. 0 capsules and of 57 +/- 1 microm for no. 2 capsules were thought to deliver caffeine to the human colon efficiently.

Adult↗

PubMed2000

Pharmacokinetic interactions between HIV-1 protease inhibitors in rats: study on combinations of two kinds of HIV-1 protease inhibitors.

The drug interactions between four human immune deficiency virus (HIV-1) protease inhibitors have been characterized by in-vitro metabolic studies using rat liver microsomal fractions and in-vivo oral administration. In this study, a new HPLC analytical method developed by us was used for the simultaneous determination of saquinavir and nelfinavir in rat plasma and microsomes. The metabolic clearance rates (Vmax/Km) of saquinavir, nelfinavir, and indinavir were 170.9 +/- 10.9, 126.1 +/- 4-4, and 73.0 +/- 2.0 microL min(-1) (mg protein)(-1), respectively. Ritonavir was the strongest inhibitor with inhibition constants (Ki) of 1.64 microM for saquinavir, 0.95 microM for indinavir, and 1.01 microM for nelfinavir. Nelfinavir was the second strongest inhibitor with Ki's of 2.35 microM for saquinavir and 2.14 microM for indinavir. Indinavir was the third strongest inhibitor with Ki's of 2.76 microM for nelfinavir and 3.55 microM for saquinavir. Saquinavir was the weakest inhibitor for the other three HIV- 1 protease inhibitors. After oral co-administration in combination with another HIV-1 protease inhibitor, the AUCs of saquinavir, indinavir, and nelfinavir were significantly increased compared with mono-treatment. The AUCs of saquinavir were increased about 10.1-, 3.1- and 45.9-fold in the presence of indinavir, nelfinavir and ritonavir, respectively. The AUCs of indinavir were increased about 6.8-, 5.9- and 9.4-fold in the presence of nelfinavir, saquinavir and ritonavir, respectively. The AUCs of nelfinavir were increased about 2.2-, 6.6- and 8.5-fold in the presence of indinavir, saquinavir and ritonavir, respectively. The in-vivo effects observed after co-administration of two kinds of HIV-1 protease inhibitor were not always expected from in-vitro data, suggesting the presence of other interaction processes besides metabolism in the liver. These results provide useful information for the treatment of AIDS patients receiving combination therapy with two HIV-1 protease inhibitors.

Animals↗

PubMed2000

Atomic force microscopic evidence for Z-band as a rigid disc fixing the sarcomere structure of skeletal muscle.

Atomic force microscopic images of single skeletal myofibrils showed periodical broad filamentous bands interspaced with narrow rigid bands corresponding to the sarcomere structures of skeletal muscle (Yoshikawa, Y., Yasuike, T., Yagi, A., and Yamada, T. 1999. Biochem. Biophys. Res. Comm., 256: 13-19). In order to identify the narrow rigid bands, comparative studies were made for intact single myofibrils and those treated with calcium-activated neutral protease by use of atomic force microscopy. It was found that (a) the periodical narrow rigid bands present in intact myofibrils were completely absent in myofibrils treated with calcium-activated neutral protease, and that (b) myofibrils treated with calcium-activated neutral protease were very fragile compared with intact myofibrils. As calcium-activated neutral protease selectively removes Z-bands of myofibrils (Reddy, M. K., Etlinger, J. D., Rabinowitz, M., Fischman, D. A., and Zak, R. 1975. J. Biol. Chem., 250: 4278-4284), these results clearly indicate that (a) the narrow rigid bands are the Z-bands, and that (b) the Z-bands are the essential disc supporting the sarcomere structure of skeletal muscle.

Animals↗