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Biomedical subjects

K Ishizaka

Publications and source records attributed to K Ishizaka.

At least 19 recordsLinked to original sources

Heavy-fermion-like state in a transition metal oxide LiV2O4 single crystal: indication of Kondo resonance in the photoemission spectrum.

We have performed a vacuum ultraviolet laser excited photoemission spectroscopy on a d-electron heavy-fermion-like material LiV2O4 single crystal. We observed a sharp peak structure in the density of states at approximately 4 meV above the Fermi level (E(F)). The evolution of the peak height corresponds well with the crossover behavior to the heavy-fermion-like state as observed in the thermal and transport properties. The position, shape, and temperature (T) dependence of the peak structure is quite similar to the Kondo resonance observed in conventional f-electron heavy Fermion compounds.

Journal Article↗

Commensurate-incommensurate crossover of charge stripe in La2-xSrxNiO4 (x approximately 1/3).

The temperature (T) dependence of the charge-stripe order in La2-xSrxNiO4 has been investigated in the vicinity of x approximately 1/3 by synchrotron radiation x-ray diffraction measurements. With decreasing T, a prominent commensurate-incommensurate (C-IC) crossover is observed in the x<1/3 region, while for the x>1/3 region the IC order is dominant over the whole T range. Such a C-IC crossover is interpreted as the entropy-driven self-doping of the charge stripes, and its x dependence indicates the clear electron-hole asymmetry with the x=1/3 compound as the Mott insulator.

Journal Article↗

Magnetic control of ferroelectric polarization.

The magnetoelectric effect--the induction of magnetization by means of an electric field and induction of polarization by means of a magnetic field--was first presumed to exist by Pierre Curie, and subsequently attracted a great deal of interest in the 1960s and 1970s (refs 2-4). More recently, related studies on magnetic ferroelectrics have signalled a revival of interest in this phenomenon. From a technological point of view, the mutual control of electric and magnetic properties is an attractive possibility, but the number of candidate materials is limited and the effects are typically too small to be useful in applications. Here we report the discovery of ferroelectricity in a perovskite manganite, TbMnO3, where the effect of spin frustration causes sinusoidal antiferromagnetic ordering. The modulated magnetic structure is accompanied by a magnetoelastically induced lattice modulation, and with the emergence of a spontaneous polarization. In the magnetic ferroelectric TbMnO3, we found gigantic magnetoelectric and magnetocapacitance effects, which can be attributed to switching of the electric polarization induced by magnetic fields. Frustrated spin systems therefore provide a new area to search for magnetoelectric media.

Journal Article↗

Involvement of apoptosis in the control of Sertoli and pre-meiotic germ cell numbers in the developing rabbit testis.

The numbers of Sertoli and pre-meiotic germ cells in the developing rabbit testis were investigated as an initial step in determining the physiological meaning of the control of cell number in the testis by apoptosis. Sections were stained immunohistochemically for the detection of apoptotic cells and counterstained with haematoxylin. The number resulting from subtraction of the number of apoptotic cells from the total cell number was defined as the viable cell number. The number of viable premeiotic germ cells in the adluminal compartment of seminiferous tubules decreased during the pre-natal period, although neither apoptotic nor necrotic figures were detected. After birth, the numbers of total and apoptotic Sertoli and pre-meiotic germ cells increased, maintaining a stable ratio of their viable cell populations until the induction of meiosis. During induction of meiosis, the increase in the number of viable Sertoli cells was significantly accelerated because of the rapid decrease in the number of apoptotic Sertoli cells. Just after spermatids were formed the number of viable spermatogonia increased, reflecting an active supply of differentiated sper matogonia entering meiosis. In conclusion, apoptosis of Sertoli and pre-meiotic germ cells plays an important role in the acquisition of a suitable ratio of both cell types, and in providing intratubular environments for further progression of spermatogenesis, by controlling numbers of both cell types during the post-natal period.

Animals↗

Doping dependence of pseudogap and related charge dynamics in Nd2-xCexCuO4.

A notable pseudogap ( Delta(PG) as large as 0.2-0.4 eV) has been found below a characteristic temperature T(*) in the optical conductivity spectrum for metallic but nonsuperconducting crystals of Nd2-xCexCuO4 (x<0.15). The Delta(PG) and T(*) decrease with doping x, holding the relation of Delta(PG) approximately 10k(B)T(*). The Drude-like component is observed to evolve concomitantly with the pseudogap. The T(*) almost coincides with another characteristic temperature T0 that scales the Hall coefficient. These results indicate that the charge transport in the underdoped region is under the strong influence of the pseudogap state.

Journal Article↗

Suppression of spermatogenesis in ipsilateral and contralateral testicular tissues in patients with seminoma by human chorionic gonadotropin beta subunit.

OBJECTIVES: The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. METHODS: Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen's score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. RESULTS: A significant linear relationship (r = -0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. CONCLUSIONS: A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.

Adult↗

Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) was intensely expressed in mitochondria in the midpiece of human spermatozoa by immunostaining with anti-PHGPx monoclonal antibodies. The PHGPx not only reduced phospholipid hydroperoxide but also scavenged hydrogen peroxide in human spermatozoa. We found a dramatic decrease in the level of expression of PHGPx in the spermatozoa of some infertile males by immunoblotting with anti-PHGPx monoclonal antibodies. These individuals accounted for about 10% of the group of 73 infertile males that we examined. All seven patients with PHGPx-defective spermatozoa were classified as suffering from oligoasthenozoospermia, a defect in which both the number and the motility of spermatozoa are significantly below normal. Males with PHGPx-defective spermatozoa accounted for 26% of the 27 infertile males with oligoasthenozoospermia. No defects in expression of PHGPx in spermatozoa were observed in 31 fertile volunteers. After a 3-h incubation, the relative number of motile spermatozoa with low-level expression of PHGPx was significantly lower than that of spermatozoa with normal expression of PHGPx. The PHGPx-defective spermatozoa failed to incorporate rhodamine 123, revealing a loss of mitochondrial membrane potential. Ultrastructual analysis of mitochondria by electron microscopy demonstrated that the morphology of mitochondria in PHGPx-defective spermatozoa was abnormal. The results suggest that failure of the expression of mitochondrial PHGPx in spermatozoa might be one of the causes of oligoasthenozoospermia in infertile men.

Antibodies, Monoclonal↗

[Clinical experience of in situ extracorporeal shock wave lithotripsy using ESL-500A for bilateral ureteral stones and ureteral stones in a solitary, or a functionally solitary kidney].

Extracorporeal shock wave lithotripsy (ESWL) using ESL-500A was performed for the treatment of 18 cases of bilateral ureteral stones and 3 cases of a solitary or a functionally solitary kidney with ureteral stones from September 1991 to February 2000. Sixteen cases of the former and all 3 cases of the latter were treated by in situ ESWL, and the other 2 cases of bilateral ureteral stones were treated with auxiliary procedures. No residual stones were observed in any cases except for one of bilateral ureteral stones treated by in situ ESWL. The results show that in situ ESWL using ESL-500A seems to be useful for the treatment of bilateral ureteral stones and ureteral stones in a solitary kidney, including a functionally solitary kidney. However, auxiliary treatment will be needed in cases of urinary tract infection, undetectable stones by ultrasonography, or bilateral large stones.

Adolescent↗

[A case of papillary adenocarcinoma of the prostate which was difficult to diagnose].

We report a case of papillary adenocarcinoma of the prostate found by urethroscopy. An 84-year-old male visited our hospital complaining of initial hematuria in July 1997. No abnormal findings were detected despite repeated urological examinations until endoscopic examination revealed fine papillary tumors in the prostatic urethra along with benign prostatic hyperplasia-like prominent left lobe of the prostate in June 2000. Serum prostate specific antigen (PSA) level was 4.1 ng/ml. He underwent transurethral resection of the urethral tumors and the prominent lobe, which was found to contain packed papillary tumors. Both of these tumors were well differentiated papillary adenocarcinoma most likely originating from the prostate because PSA immunostaining was positive. The prostate was irradiated postoperatively. Papillary adenocarcinoma localized in the prostate is difficult to diagnose preoperatively.

Adenocarcinoma, Papillary↗

[Transitional cell carcinoma of the ureter with inverted proliferation accompanied with papillary bladder tumor: a case report].

An 85-year-old female was referred to our hospital with chief complaints of right flank pain and gross hematuria. Ultrasonography demonstrated right hydroureteronephrosis and a thumb head-sized solid mass in the lower third of the right ureter. Cystoscopy revealed papillary tumors near the right ureteral orifice. Under the preoperative diagnosis of right ureteral tumor and bladder tumor, transurethral resection of bladder tumor, right nephroureterectomy and partial cystectomy were performed. The gross specimen of the ureter contained a 5 x 3 x 1 cm, polypoid and smooth-surfaced tumor. The pathological diagnosis of the ureteral tumor was transitional cell carcinoma with inverted proliferation, grade 1 >> grade 2. On the other hand, the bladder tumor was papillary transitional cell carcinoma, grade 1. This is a case in which tumor development showed two different types.

Aged↗

Posttranslational modification of the glycosylation inhibiting factor (GIF) gene product generates bioactive GIF.

Glycosylation inhibiting factor (GIF) and macrophage migration inhibitory factor (MIF) share an identical structure gene. Here we unravel two steps of posttranslational modifications in GIF/MIF molecules in human suppressor T (Ts) cell hybridomas. Peptide mapping and MS analysis of the affinity-purified GIF from the Ts cells revealed that one modification is cysteinylation at Cys-60, and the other is phosphorylation at Ser-91. Cysteinylated GIF, but not the wild-type GIF/MIF, possessed immunosuppressive effects on the in vitro IgE antibody response and had high affinity for GIF receptors on the T helper hybridoma cells. In vitro treatment of wild-type recombinant human GIF/MIF with cystine resulted in preferential cysteinylation of Cys-60 in the molecules. The cysteinylated recombinant human GIF and the Ts hybridoma-derived cysteinylated GIF were comparable both in the affinity for the receptors and in the immunosuppressive activity. Polyclonal antibodies specific for a stretch of the amino acid sequence in alpha2-helix of GIF bound bioactive cysteinylated GIF but failed to bind wild-type GIF/MIF. These results strongly suggest that cysteinylation of Cys-60 and consequent conformational changes in the GIF/MIF molecules are responsible for the generation of GIF bioactivity.

Amino Acid Sequence↗

An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model.

Immunization of BALB/c mice with alum-adsorbed OVA, followed by three bronchoprovocations with aerosolized OVA, resulted in the development of airway hyperresponsiveness (AHR) and allergic inflammation in the lung accompanied by severe infiltration of eosinophils into airways. In this murine asthma model, administration of monoclonal anti-IL-5 Ab before each Ag challenge markedly inhibited airway eosinophilia, but the treatment did not affect the development of AHR. Immunization and aerosol challenges with OVA following the same protocol failed to induce AHR in the mast cell-deficient W/Wv mice, but induced AHR in their congenic littermates, i.e., WBB6F1 (+/+) mice. No significant difference was found between the W/Wv mice and +/+ mice with respect to the IgE and IgG1 anti-OVA Ab responses and to the airway eosinophilia after Ag provocations. It was also found that reconstitution of W/Wv mice with bone marrow-derived mast cells cultured from normal littermates restored the capacity of developing Ag-induced AHR, indicating that lack of mast cells was responsible for the failure of W/Wv mice to develop Ag-induced AHR under the experimental conditions. However, the OVA-immunized W/Wv mice developed AHR by increasing the frequency and Ag dose of bronchoprovocations. The results suggested that AHR could be developed by two distinct cellular mechanisms. One would go through mast cell activation and the other is IgE/mast cell independent but an eosinophil/IL-5-dependent mechanism.

Aerosols↗

Presence of the 55 kDa glycosylation inhibiting factor in human serum.

An ELISA system for the human glycosylation inhibiting factor (GIF) was established using polyclonal antibodies against highly purified 13 kDa recombinant human GIF, and the concentration of GIF in the sera of healthy donors and patients with various diseases was determined. GIF was detected in the sera of most healthy individuals and its concentration tended to increase with age. It was also found that the serum GIF levels markedly increased in some patients with rheumatoid arthritis or malignant tumors. Analysis of serum samples by SDS-PAGE and immunoblotting revealed a 55 kDa protein that has both the GIF antigenic determinant and the TCR alpha chain determinant. A 13 kDa GIF was not detected in the sera. In view of our previous findings on antigen-specific GIF from murine suppressor T cell hybridomas indicating that the 55 kDa GIF is a post-translationally formed conjugate of a TCR alpha chain with 13 kDa GIF, we suspect that the 55 kDa GIF detected in human sera is a human homologue of the murine 55 kDa GIF.

Adult↗

Preoperative concurrent chemoradiotherapy against muscle-invasive bladder cancer: results of partial cystectomy in elderly or high-risk patients.

BACKGROUND: Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients. METHODS: Thirty-seven patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (50-100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder. RESULTS: Median follow-up was 12 months (range 2-37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years. CONCLUSIONS: Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy.

Aged↗

Sexual dimorphism in the regulation of meiotic process in the rabbit.

Meiosis, mitosis, and apoptosis during fetal and postnatal periods were investigated in order to explore mechanisms of sexual dimorphism in initiation of germ cell meiosis. Gonads were obtained from Japanese white rabbits from 23 to 51 days postcoitum (dpc). Gonadal thin sections were stained with hematoxylin and eosin. Germ cell alkaline phosphatase and apoptosis were detected with histochemical and immunohistochemical methods, respectively. In the ovary, meiotic germ cells were initially recognized at 29 dpc and arrested after enclosure within follicles. Similarly, meiotic germ cells were recognized outside seminiferous tubules at 29 dpc, but no meiotic figures were identified in intratubular spaces. Apoptotic germ cells were not recognized in the intratubular spaces before 35 dpc, and no apoptotic figures were recognized in the ovary during the period studied. In conclusion, the initiation of meiosis in testicular interstitial tissue at the time comparable to that in the ovary indicates that germ cells of both sexes have the ability to enter meiosis during the same stage of fetal development; and it appears most likely that delayed initiation of meiosis in the intratubular space is attributable to meiosis-inhibiting substance(s) present in seminiferous tubules.

Animals↗

Immunosuppressive activities of recombinant glycosylation-inhibiting factor mutants.

We have shown previously that glycosylation-inhibiting factor (GIF) in culture supernatants of suppressor T cell (Ts) hybridomas had bioactivity, while the same cells contained a substantial quantity of inactive GIF in cytosol. Mass-spectrometric analysis of GIF in the culture supernatant and cytosol of a Ts hybridoma provided direct evidence that GIF protein was posttranslationally modified in the Ts cells, and that the GIF bioactivity is associated with the posttranslationally modified species. Assuming that conformational changes induced by the posttranslational modifications are responsible for generation of bioactivity, we constructed cysteine mutants of human rGIF (rhGIF) in which cysteine at position 57, 60, or 81 was replaced with Ala, and the mutants were expressed in Escherichia coli. Replacement of Cys57 or Cys60 with Ala resulted in generation of bioactivity, while replacement of Cys81 with Ala failed to do so. It was also found that replacement of Cys57 with Ala and carboxymethylation of a sulfhydryl group in Cys60 synergistically increased the GIF bioactivity of the GIF derivatives. A mutated GIF protein, in which Cys57 and Asn106 in the rhGIF were replaced with Ala and Ser, respectively, had immunosuppressive effects on the IgE and IgG1 Ab responses of BDF1 mice to DNP-OVA, while wild-type rhGIF did not. Evidence was obtained that the mutated GIF suppressed Ag priming of Th cells for the Ab responses and proliferative response.

Animals↗

Snowboarding injuries of the abdomen: comparison with skiing injuries.

A retrospective study was conducted to identify the characteristics of snowboarding injury of the abdomen in comparison with those of alpine skiing injuries. Between December 1988 and April 1997, 1579 patients were treated for snowboarding injuries and 9108 patients were treated after skiing accidents. 19 patients (1.2%) in snowboarding and 64 (0.7%) in skiing had abdominal injuries. The abdominal injury rate in snowboarders was significantly higher than that in skiers. Snowboarders with abdominal injuries were similar to skiers with respect to epidemiology but the patterns of injury in the two groups showed several distinct differences. Riding mistakes after jumping for the snowboarders (31.6%) was significantly higher than that for the skiers (0%). The main organs involved in snowboarding and skiing injuries were kidney, liver and spleen. The incidence of solitary renal injury in snowboarding (68.4%) was significantly higher than that in skiing (29.7%).

Abdominal Injuries↗