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Biomedical subjects

Satoshi Takahashi

Publications and source records attributed to Satoshi Takahashi.

At least 19 recordsLinked to original sources
PubMed2026

Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC.

PURPOSE: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non-small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry. RESULTS: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold. CONCLUSIONS: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector-type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy.

Humans↗
PubMed2026

Detection of a Rare Intra-ALK Inversion and ALK Rearrangement in a Lung Adenocarcinoma Patient by FoundationOne Liquid CDx and Successful Treatment with Alectinib: Case Report.

A 50-year-old woman with stage IVB lung adenocarcinoma tested negative for driver mutations using the Oncomine Dx Target Test Multi-CDx system (Thermo Fisher Scientific, Waltham, MA). After undergoing chemotherapy and immunotherapy, FoundationOne Liquid CDx (Foundation Medicine, Inc., Cambridge, MA) identified a rare EML4-ALK gene rearrangement. Treatment with alectinib led to rapid clinical improvement and sustained disease control for more than 7 months. This case highlights the value of next-generation sequencing-based profiling in detecting rare actionable alterations missed by standard tests. We also include a discussion on why the EML4-AKL fusion was not detected in the usual test.

ALK-EML4 rearrangement↗
PubMed2006

Prostate cell lines secrete IL-8 in response to Mycoplasma hominis through Toll-like receptor 2-mediated mechanism.

BACKGROUND: The roles of Toll-like receptor 2 (TLR2) and Mycoplasma in prostate inflammation remain unclear. We investigated whether Mycoplasma induced inflammatory cytokine secretion through TLR2-mediated mechanism in prostate cancer cell line. METHODS: Cell surface expression of TLR2 on PC-3 cells were examined by flowcytometry. PC-3 cells were stimulated with Mycoplasma hominis (M. hominis), and IL-8 secretion and NF-kappaB activation were examined. RESULTS: PC-3 cells expressed TLR2 mRNA and cell surface TLR2 protein. The membrane fraction of M. hominis induced IL-8 secretion from PC-3 cells and NF-kappaB activation in a concentration-dependent manner. Transient transfection of the dominant negative mutant TLR2(P681H) into PC-3 cells attenuated M. hominis-induced IL-8 secretion and NF-kappaB activation. Antibody against the extracellular TLR2 domain significantly suppressed M. homnis-induced IL-8 secretion from the prostate cell lines including PC-3, PrEC, and transformed myofibroblasts. CONCLUSIONS: These results clearly demonstrate that the prostate cell line can secrete inflammatory cytokine in response to M. hominis through a TLR2-mediated mechanism.

Flow Cytometry↗
PubMed2005

Absence of a detectable intermediate in the compound I formation of horseradish peroxidase at ambient temperature.

A microsecond-resolved absorption spectrometer was developed to investigate the elementary steps in hydrogen peroxide (H(2)O(2)) activation reaction of horseradish peroxidase (HRP) at ambient temperature. The kinetic absorption spectra of HRP upon the mixing with various concentrations of H(2)O(2) (0.5-3 mm) were monitored in the time range from 50 to 300 mus. The time-resolved spectra in the Soret region possessed isosbestic points that were close to those between the resting state and compound I. The kinetic changes in the Soret absorbance could be well fitted by a single exponential function. Accordingly, no distinct spectrum of the putative intermediate between the resting state and compound I was identified. These results were consistent with the proposal that the O-O bond activation in heme peroxidases is promoted by the imidazolium form of the distal histidine that exists only transiently. It was estimated that the rate constant for the breakage of the O-O bond in H(2)O(2) by HRP is significantly faster than 1 x 10(4) s(-1).

Chemical Phenomena↗
PubMed2005

Seeding-dependent propagation and maturation of amyloid fibril conformation.

Recent studies of amyloid fibrils have focused on the presence of multiple amyloid forms even with one protein and their propagation by seeding, leading to conformational memory. To establish the structural basis of these critical features of amyloid fibrils, we used the amyloidogenic fragment Ser20-Lys41 (K3) of beta2-microglobulin, a protein responsible for dialysis-related amyloidosis. In 20% (v/v) 2,2,2-trifluoroethanol and 10 mM HCl (pH approximately 2), K3 peptide formed two types of amyloid-like fibrils, f218 and f210, differing in the amount of beta-sheet as measured by circular dichroism spectroscopy and Fourier transform infrared spectroscopy. Atomic force microscopy showed that the fibril with a larger amount of beta-sheet (f210) is thinner and longer. Both fibrils were reproduced by seeding, showing the template-dependent propagation of a fibril's conformation. However, upon repeated self-seeding, f218 fibrils were gradually transformed into f210 fibrils, revealing the conformational maturation. The observed maturation can be explained fully by a competitive propagation of two fibrils. The maturation of amyloid fibrils might play a role during the development of amyloidosis.

Amino Acid Sequence↗
PubMed2005

Activation of CD1d-independent NK1.1+ T cells in the large intestine by Lactobacilli.

Among digestive organs, the liver and the large intestine are abundant in T cells expressing NK1.1. NK1.1+ T cells in the liver are mostly CD1d-dependent whereas those in the large intestine are CD1d-independent. In this study, we investigated the effects of Lactobacilli on NK1.1+ T cells in the digestive organs of mice. C57BL/6 mice were orally given a dietary supplement prepared from mixed cultures of eight strains of Lactobacilli. Oral administration of Lactobacilli to mice resulted in the selective expansion of NK1.1+ T cells in the large intestine. These colon NK1.1+ T cells activated by Lactobacilli were found to express IFN-gamma mRNA. The level of IFN-gamma in the serum was also elevated by the administration of Lactobacilli. Our results suggest that Lactobacilli selectively activate CD1d-independent NK1.1+ T cells in the large intestine to produce IFN-gamma and therefore modulate Th1 immune responses.

Animals↗
PubMed2005

Specifically collapsed intermediate in the early stage of the folding of ribonuclease A.

Nature of the burst-phase signals of protein folding has been the subject of much debate as to whether the signals represent the formation of early intermediates or the non-specific collapse of unfolded polypeptides. To distinguish the two possibilities, the submillisecond folding dynamics of ribonuclease A (RNase A) was examined, and compared with those of the disulfide bond-ruptured analog of RNase A (r-RNase A). The circular dichroism measurements on RNase A showed the burst-phase signal within 320 micros after the initiation of the folding reaction, which was identical to that observed for r-RNase A. In contrast, the burst phase increase in the extrinsic fluorescence from 1-anilino-8-naphthalene sulfonate (ANS) was observed for RNase A but not for r-RNase A. The kinetic titration experiment of the ANS fluorescence intensity showed the presence of a specific binding site for ANS in the fast-refolding component of RNase A. The small-angle X-ray scattering measurements at approximately 22 ms after initiating the folding reaction demonstrated that the burst phase conformations of the medium and slow-refolding components of RNase A were distinctly smaller than that of r-RNase A. These results indicated the difference in the burst phase conformations of RNase A and r-RNase A. Since r-RNase A is denatured in the physiological solution condition, the burst-phase signal of RNase A was interpreted as the formation of the folding intermediate with specific conformations.

Anilino Naphthalenesulfonates↗
PubMed2005

Nuclear magnetic resonance characterization of the refolding intermediate of beta2-microglobulin trapped by non-native prolyl peptide bond.

beta(2)-Microglobulin (beta2-m), a light chain of the major histocompatibility complex type I, is also found as a major component of amyloid fibrils formed in dialysis-related amyloidosis. Denaturation of beta2-m is considered to initiate the formation of fibrils. To clarify the mechanism of fibril formation, it is important to characterize the intermediate conformational states at the atomic level. Here, we investigated the refolding of beta2-m from the acid-unfolded state by heteronuclear magnetic resonance and circular dichroism spectroscopies. At low temperature, beta2-m refolded slowly, accumulating a rate-limiting intermediate with non-native chemical shift dispersions for several residues, but with compactness and secondary structures similar to those of the native protein. beta2-m has a cis proline residue at Pro32, located on the turn connecting the betaB and betaC strands. The slow refolding phase disappeared upon mutation of Pro32 to Val, indicating that Pro32 is responsible for the accumulation of the intermediate. The distribution of the perturbed residues in the intermediate suggests that the non-native prolyl peptide bond of Pro32 affects large areas of the molecule. A cis proline residue is common to various immunoglobulin domains involved in amyloidosis, implying that a non-native prolyl peptide bond that might occur under physiological conditions is related to the amyloidogenicity of these immunoglobulin domains.

Acids↗
PubMed2005

Coexistence of competing species by the oscillation of polymorphisms.

Scale-eating cichlids in Lake Tanganyika exhibit genetically determined lateral asymmetry, especially in their mouth-opening. Frequencies of the morphs oscillate due to strong frequency-dependent selection caused by the switching of prey's attention, and its delayed effect by their growth period. Two scale-eaters coexist in similar densities at south shore of the lake, with their morph frequencies oscillating in phase. We investigated the effect of the oscillation in morph frequencies to the coexistence of competing species. If the difference of two species' growth period is large, the oscillation facilitates the coexistence of the two species, while small difference of growth periods hinders their coexistence. In the latter case, the species with shorter growth period drives the other species to the extinction.

Animals↗
PubMed2005

Craniocervical junction venous anatomy around the suboccipital cavernous sinus: evaluation by MR imaging.

The present study evaluated the venous anatomy of the craniocervical junction, focusing on the suboccipital cavernous sinus (SCS), a vertebral venous plexus surrounding the horizontal portion of the vertebral artery at the skull base. MR imaging was reviewed to clarify the venous anatomy of the SCS in 33 patients. Multiplanar reconstruction MR images were obtained using contrast-enhanced three-dimensional fast spoiled gradient-recalled acquisition in the steady state (3-D fast SPGR) with fat suppression. Connections with the SCS were evaluated for the following venous structures: anterior condylar vein (ACV); posterior condylar vein (PCV); lateral condylar vein (LCV); vertebral artery venous plexus (VAVP); and anterior internal vertebral venous plexus (AVVP). The SCS connected with the ACV superomedially, with the VAVP inferolaterally, and with the AVVP medially. The LCV connected with the external orifice of the ACV and superoanterior aspect of the SCS. The PCV connected with the posteromedial aspect of the jugular bulb and superoposterior aspect of the SCS. The findings of craniocervical junction venography performed in eight patients corresponded with those on MR imaging, other than with regard to the PCV. Contrast-enhanced 3-D fast SPGR allows visualization of the detailed anatomy of these venous structures, and this technique facilitates interventions and description of pathologies occurring in this area.

Adult↗
PubMed2005

Specific collapse followed by slow hydrogen-bond formation of beta-sheet in the folding of single-chain monellin.

Characterization of the conformational landscapes for proteins with different secondary structures is important in elucidating the mechanism of protein folding. The folding trajectory of single-chain monellin composed of a five-stranded beta-sheet and a helix was investigated by using a pH-jump from the alkaline unfolded to native state. The kinetic changes in the secondary structures and in the overall size and shape were measured by circular dichroism spectroscopy and small-angle x-ray scattering, respectively. The formation of the tertiary structure was monitored by intrinsic and extrinsic fluorescence. A significant collapse was observed within 300 micros after the pH-jump, leading to the intermediate with a small amount of secondary and tertiary structures but with an overall oblate shape. Subsequently, the stepwise formation of secondary and tertiary structures was detected. The current observation was consistent with the theoretical prediction that a more significant collapse precedes the formation of secondary structures in the folding of beta-sheet proteins than that of helical proteins [Shea, J. E., Onuchic, J. N. & Brooks, C. L., III (2002) Proc. Natl. Acad. Sci. USA 99, 16064-16068]. Furthermore, it was implied that the initial collapse was promoted by the formation of some specific structural elements, such as tight turns, to form the oblate shape.

Circular Dichroism↗
PubMed2005

Stereospecific amyloid-like fibril formation by a peptide fragment of beta2-microglobulin.

Understanding the role of the L/D-stereospecificity of amino acids is important in obtaining further insight into the mechanism of the formation of amyloid fibrils. Beta(2)-microglobulin is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. A 22-residue peptide of beta(2)-microglobulin, Ser20-Lys41 (L-K3 peptide), obtained by digestion with Acromobacter protease I, formed amyloid-like fibrils in 50% (v/v) 2,2,2-trifluoroethanol and 10 mM HCl at 25 degrees C, as confirmed by thioflavin T fluorescence, circular dichroism spectra, and atomic force microscopy images. A synthetic K3 peptide composed of D-amino acids (D-K3 peptide) formed similar fibrils but with opposite chirality as indicated by circular dichroism spectra. A mixture of L-K3 and D-K3 peptides also formed fibrils, although the L- and D-amino acid composition of each fibril is unknown. To examine the possible cross-reactivity between L- and D-enantiomers, we carried out seeding experiments in which preformed seeds were extended by monomers. The results revealed that only the homologous extensions proceed smoothly, i.e., the growth of L-seeds by L-monomers or D-seeds by D-monomers. The results suggest that, while the fibrils derived from L- and D-peptides form in a similar manner but with opposite stereochemistry, a cross-reaction between them is prevented because the geometry of the mixed sheet cannot satisfy dominant factors for beta-sheet stabilization.

Amino Acid Sequence↗
PubMed2005

Incidence of and risk factors for surgical site infection in patients with radical cystectomy with urinary diversion.

In radical cystectomy (RC), surgical-site infection (SSI) remains one of the most frustrating postoperative complications. Only a few reports have assessed SSI after RC according to the guideline authorized by the Centers for Disease Control and Prevention (CDC guideline). In this study, using the guideline, we assessed the incidence, causative organisms, classification, and risk factors for SSI in patients receiving RC with urinary diversion (UD). The subjects of this study were 104 patients who underwent RC with UD at the Department of Urology, Sapporo Medical University Hospital, between January 1996 and December 2003. As prophylactic antimicrobial agents, intravenous cephalosporins or penicillins were started before surgery and maintained until postoperative day 3. Patients who had preoperative bacteriuria were treated with antimicrobial agents before operation to eradicate the bacteria or reduce their number. The CDC guideline was used for the diagnosis of SSI. The overall incidence of SSI was 33%. The most frequent type of SSI was superficial incisional infection (71%). Methicillin-resistant Staphylococcus aureus (MRSA) was the most frequently isolated organism, accounting for 38% of the causative organisms. Operation time was shown to be a significant risk factor for SSI. Preoperative antibacterial chemotherapy for bacteriuria was not sufficiently efficacious to decrease the incidence of SSI. In our study, the incidence of SSI after RC was 33%, although 71% of the infections were superficial. It is necessary to establish more appropriate countermeasures to prevent SSI after RC with UD; in particular, that caused by MRSA.

Adult↗
PubMed2005

Surgical antimicrobial prophylaxis in transurethral ureterolithotripsy.

The aim of this study was to establish a standard protocol for surgical antimicrobial agents for patients who received transurethral ureterolithotripsy (TUL). We retrospectively reviewed the medical charts of patients who received TUL. From October 2002 to December 2003, 2 days (total, four times) of antimicrobial prophylaxis (AMP) was done, and from January 2004 to December 2004, single prophylaxis was done. We analyzed the incidence of postoperative fever and other factors associated with TUL and compared these factors between the 2-day-AMP and single-AMP groups. Of 135 patients with TUL, 66 patients were in the single-AMP group and 69 in the 2-day-AMP group. The incidences of postoperative fever were 4.5% in the single-AMP group and 11.6% in the 2-day-AMP group. No statistically significant difference was found in the incidence of postoperative fever between the two groups. Our study showed that single AMP was effective for patients receiving a TUL operation. In the future, a prospective randomized study will be needed for a large series, with various types of lithotripters being included.

Adult↗
PubMed2005

A patient with seminal vesiculitis prior to acute chlamydial epididymitis.

This is the first report of a case of seminal vesiculitis prior to acute chlamydial epididymitis. At the first visit to the clinic, the patient wished to check whether he had Chlamydia trachomatis in his genital tract, because his wife had been diagnosed as having chlamydial cervicitis. He had no specific symptoms at that time; however, transrectal ultrasonograpy (TRUS) revealed swelling of seminal vesicles, which suggested the presence of seminal vesiculitis. Two days after the first visit, he had high-grade fever and was diagnosed as having acute epididymitis caused by C. trachomatis. We had previously reported that seminal vesiculitis was always complicated with acute epididymitis, so this case could provide important evidence that seminal vesiculitis might precede acute epididymitis. It suggested that acute epididymitis could be affected by seminal vesiculitis via the retrograde transmission route.

Acute Disease↗
PubMed2005

Incidence of sexually transmitted infections in asymptomatic healthy young Japanese men.

The aim of this study was to estimate the incidence rates of asymptomatic sexually transmitted infections (STI) in young men in Sapporo, Japan. A survey of 204 healthy male volunteers was conducted. First-voided urine specimens were used for detection of Chlamydia trachomatis and Neisseria gonorrhoeae with polymerase chain reaction assay, and cotton swab wiping of the external genitalia was used for detection of human papillomavirus (HPV) with the Hybrid Capture method. The incidence rates were 3.4% for C. trachomatis and 5.9% for HPV. No N. gonorrhoeae was detected. In sexually active men who had regular sexual intercourse, the detection rate of C. trachomatis was 4.7% and that of HPV was 8.0%. Our study showed that the incidence rates of asymptomatic STIs were not negligible, and that we should provide screening programs for young men with a high risk for such unrecognized infections and study their natural histories.

Chlamydia Infections↗
PubMed2005

Clinical relevance of nucleic acid amplification test for patients with urinary tuberculosis during antituberculosis treatment.

The nucleic acid amplification test (NAAT) has been valuable in the diagnosis of urinary tuberculosis; however, no studies have attempted to determine the significance of NAAT post treatment. We encountered three patients with urinary tuberculosis who underwent sequential NAAT during antituberculosis chemotherapy and post treatment. All patients were diagnosed as having urinary tuberculosis by positive NAAT and specific renal deformity revealed by imaging. In two of the three patients, positive culture results were obtained and one was negative in standard culture. During antituberculosis chemotherapy, a negative NAAT was obtained from 3 to 5 months after the start of treatment and no positive culture results were obtained during the same period. At the end of chemotherapy, 6 months or more after the start of medication, all patients had negative NAAT results. These results suggest that NAAT for Mycobacterium tuberculosis provides an effective and rapid detection method for urinary tuberculosis both pre- and post-treatment.

Aged↗