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Let H(D)be the linear space of all analytic functions on the open unit disc Dand Hp(D)the Hardy space on D. The characterization of complex linear isometries on Sp={f∈H(D):f′∈Hp(D)}was given for 1≤p<∞by Novinger and Oberlin in 1985. Here, we characterize surjective, not necessarily linear, isometries on S∞.

Let 0 ∈ I [??] R be an open interval and let [C.sup.1](I,[C.sup.x) be the set of all continuously differentiable functions from I to [C.sup.x], where [C.sup.x] is the set of all non-zero complex numbers. If h: I → [C.sup.x] is a continuous function with M = [sup.sub.t∈I |[∫.sub.0.sup.t]|h(s)|ds| < ∞, then for each ζ ≥ 0 and f ∈ [C.sup.1](I, [C.sup.x]) satisfying |[[f'(t)]/[h(t)f(t)]] - 1|≤ζ (∀t∈I) there exists [f.sub.0] ∈ [C.sup.1](I, [C.sup.x]) such that [f'.sub.0](t) = h(t)[f.sub.0](t) and that max{|[[f(t)]/[[f.sub.0](t)]] - 1|,|[[[f.sub.0](t)]/[f(t)]] - 1|}≤[e.sup.Mζ] - 1 for all t ∈ I. We give an example that the constant [e.sup.Mζ] - 1 can not be improved in general. We also prove that the assumption [sup.sub.t∈I] |[t.∫.0]|h(s)|ds| < ∞ is essential for Ger type stability. Keywords and Phrases: Exponential functions, Hyers-Ulam stability, Hyers-Ulam-Rassias stability, Ger type stability, 1. Introduction It seems that the stability problem of functional equations had been first raised by S. M. Ulam (cf. [(24), Chapter VI]). 'For what metric groups G is it [...]

OBJECTIVE--Increased urinary, excretions of several plasma proteins with different molecular radii RESEARCH DESIGN AND METHODS--Urinary excretion rates of proteins mentioned above in timed overnight urine samples were evaluated in 61 [...]

For a locally compact Hausdorff space L, we denote by C0(L,R)the Banach space of all continuous real-valued functions on Lvanishing at infinity equipped with the supremum norm. We prove that every surjective phase-isometry T:C0+(X,R)→C0+(Y,R)between the positive cones of C0(X,R)and C0(Y,R)is a composition operator induced by a homeomorphism between Xand Y. Furthermore, we show that any surjective phase-isometry T:C0+(X,R)→C0+(Y,R)extends to a surjective linear isometry from C0(X,R)onto C0(Y,R).

Background: Somatic alteration of the von Hippel-Lindau disease tumor suppressor gene (VHL) is one of the most common genetic changes observed in the sporadic, clear-cell subtype of renal cell carcinoma (RCC). However, the prognostic utility of VHL mutations has not been examined. The purpose of this study was to explore the association between VHL mutations and the risk of death from sporadic clear-cell RCC. Methods: A total of 187 Japanese patients with clear-cell RCC who underwent nephrectomy from October 1986 through December 1995 were examined for somatic VHL gene alteration. Clinicopathologic and survival data were also collected. Kaplan-Meier analyses and Cox proportional hazards models were used to explore associations. All statistical tests were two-sided. Results: A VHL alteration (mutation or hypermethylation) was detected in 108 RCC tumor samples: intragenic mutations in 98 (52%) and hypermethylation in 10 (5.3%). VHL alterations were strongly associated with better cancer-free survival and cancer-specific survival for the 134 patients with stage I-III clearcell RCC treated by radical nephrectomy (log-rank P = .024 and .023, respectively). These associations were more statistically significant among patients with relatively advanced disease (stage III [P = .014 and .010, respectively] or stage II + III [P = .002 and .009]) or higher grade tumors (G3 or higher [P = .013 and .032] or G2 or higher [P = .013 and .018]) and among patients who presented with symptoms (P = .005 and .012). VHL alterations remained an independent prognostic factor for patients with stage I-III tumors after adjustment for sex, age, stage, grading, and symptomatic presentation. VHL alterations were not associated with cancer-specific survival for the 53 patients with stage IV tumors treated with palliative or adjunctive nephrectomy (log-rank P = .760). Conclusion: The VHL alteration status may provide useful prognostic information, as a biomolecular marker, for patients with stage I-III clear-cell RCC who have undergone nephrectomy.

Ischemia/reperfusion injury is the most common cause of acute kidney injury. We previously revealed that pre-treatment with yohimbine or JP-1302 attenuated renal ischemia/reperfusion injury by inhibition of α2C-adrenoceptor antagonist. The aim of the present study is to investigate the effects of post-treatment with JP-1302 on renal ischemia/reperfusion injury in rats. Male Sprague Dawley rats were randomly divided into four groups: sham operation, ischemia/reperfusion, pre-treatment with JP-1302 (3.0 mg/kg) and post-treatment with JP-1302 groups. In ischemia/reperfusion injury, renal functional parameters, such as blood urea nitrogen, plasma creatinine and creatinine clearance, deteriorated after reperfusion. Renal venous norepinephrine concentrations, as well as inflammatory molecules in the kidney increased after reperfusion. Both pre- and post-treatment with JP-1302 improved renal dysfunction, tissue damage, renal venous norepinephrine concentrations and inflammatory molecules expression in the kidney. In conclusion, these results suggest that post-treatment with JP-1302 protects on ischemia/reperfusion-induced acute kidney injury by suppressing cytokine upregulation via α2C-adrenoceptors.

We developed a time-resolved force microscopy technique by integrating atomic force microscopy using a tuning-fork-type cantilever with the delay time modulation method for optical pump-probe light. We successfully measured the dynamics of surface recombination and diffusion of photoexcited carriers in bulk WSe2, which is challenging owing to the effect of the tunneling current in time-resolved scanning tunneling microscopy. The obtained results were comprehensively explained with the model based on the dipole-dipole interaction induced by photo illumination.

In 2022, Hatori gave a sufficient condition for complex Banach spaces to have the complex Mazur–Ulam property. In this paper, we introduce a class of complex Banach spaces Bthat do not satisfy the condition but enjoy the property that every surjective isometry on the unit sphere of such Badmits an extension to a surjective real linear isometry on the whole space B. Typical examples of Banach spaces studied in this note are the spaces Lip([0,1])of all Lipschitz complex-valued functions on [0, 1] with norm ‖a‖B=|a(c)|+L(a), where cis a fixed element in [0, 1], and the space C1([0,1])of all continuously differentiable complex-valued functions on [0, 1] equipped with the norm |f(0)|+‖f′‖∞.

Background and Objective: Doxorubicin, an anthracycline anti-cancer drug, is effective for breast cancer and childhood lymphoma. Chronic cardiotoxicity has been known as a critical adverse effect of doxorubicin and is attributed to its metabolite doxorubicinol produced by carbonyl reductase 1 (CBR1, SDR21C1). Some flavonoids have been reported to act as inhibitors for CBR1, therefore, commercially available juices containing flavonoids are likely to be applicable as a prophylactic treatment against doxorubicin-induced cardiotoxicity by suppression of doxorubicinol production. In the study, fruit juices containing flavonoids were investigated for inhibitory effects on CBR1. Method: Recombinant CBR1 protein was subjected to in vitro enzymatic assays with/without juices. An apple juice and a grapefruit juice were selected in the present study as candidates capable of inhib-iting CBR1. Results: The enzymatic assays revealed that both juices potently inhibit the CBR1-mediated metabolic conversion of doxorubicin to doxorubicinol in concertation-dependent manner. The concentrations required for obtaining 50% inhibition (IC50) were 0.0012% (v/v) and 0.0014% (v/v) for apple and grapefruit juices, respectively. Additionally, it is worth noting that these juices showed inhibitory effects on doxorubicin metabolism by CBR1 even at very low concentrations (0.0001% (v/v)). Conclusion: An apple juice and a grape fruit juice showed strong inhibitory effects on doxorubicin metabolism by CBR1 in vitro. These results suggest that the intake of flavonoid-containing juices can be a promising measure for protection against doxorubicin-induced cardiac toxicity, enabling patients to keep higher adherence with routine use in light of safety, economic performance and stable supply to market.

We prove that every commutative JB∗-triple, represented as a space of continuous functions C0T(L),satisfies the complex Mazur–Ulam property, that is, every surjective isometry from the unit sphere of C0T(L)onto the unit sphere of any complex Banach space admits an extension to a surjective real linear isometry between the spaces.

Tip-enhanced Raman scattering (TERS) spectral measurements of nanocomposite styrene–butadiene rubber (SBR) and multiwalled carbon nanotubes (MWCNTs) films were used to explore the local molecular interaction between nanocomposites. TERS spectra from geographically separated points were attributable to SBR or MWCNTs, showing great potential for investigating local film inhomogeneity within several tens of nanometers. Such inhomogeneity has never been observed by confocal Raman measurements. TERS bands due to SBR phenyl groups were strong when MWCNT bands were strong, whereas vinyl-group TERS bands were strong when the MWCNT bands were weak. Analysis of the findings suggests that the local distribution of polymer chains is modified with changes in the orientation of the phenyl rings by π–π interactions between the polymer chains and the MWCNTs.

A luteinizing hormone receptor (lhr) cDNA with high identity to other fish lhrs was fully cloned from the ovary of the Japanese eel (Anguilla japonica). The genes for two gonadotropin receptors (Gthr), follicle-stimulating hormone receptor (fshr) and lhr, were differentially expressed during oogenesis, which was artificially induced by salmon pituitary extract, a gonadotropin-rich source. Transcript abundance of fshr was significantly elevated at the early vitellogenic stage and peaked at the late vitellogenic stage, while lhr gene expression rapidly induced at the late vitellogenic stage and thereafter remained at a high level. The abundance of fshr and lhr transcripts was highest in the ovary in female eels. In addition to the ovary, forebrain was a major site for the fshr transcript, although the level did not change with reproductive status. Furthermore, it was examined how eel Gthrs were activated by two mammalian chrionic gonadtropin (CG), equine CG (eCG) and human CG (hCG), that have been used for study of fish reproduction as substitutes for homologous Gths. Both CGs specifically activated eel Lhr, but not Fshr, although the degree of effectiveness was different; thus the concentration of hCG (0.1 ng/ml) required for significant activation of Lhr was much lower than that of eCG (100 ng/ml). These data on gene expression and ligand-activation of Gthrs suggest that Fsh and Lh act differentially in the regulation of reproductive function in Japanese eel. [ABSTRACT FROM AUTHOR]

2-tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect, whereas it is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (BQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-tert-butyl-2,3-epoxy-4-benzoquinone (TBE), which induces chromosomal aberration. The reductases for BQ and TBE may be protective against the toxicity of the two p-quinones, but the responsible human enzymes remain unidentified. In this study, we compared the ability of 12 human recombinant enzymes in the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase superfamilies to reduce BQ and TBE. Among them, AKR1B10 was the most efficient catalyst of the stoichiometric two-electron reduction of BQ and TBE into BHQ and TBEH, respectively. BQ and TBE are more cytotoxic towards endothelial cells than BHQ and TBEH, and their cytotoxicity was decreased by the overexpression of AKR1B10 in the cells. Additionally, AKR1B10 gene expression in human HCT116 cells was up-regulated by treatments with BHQ, BQ and TBE. These results suggest a role for the enzyme in protection at least against the toxicity of the two p-quinone metabolites of BHQ.

Aims/Introduction: To clarify clinical characteristics related to optimal glycemic control achieved after adding once‐daily pre‐dinner biphasic insulin aspart 70/30 (BIAsp 30) in Japanese type 2 diabetic (T2D) patients with oral antidiabetic drug (OAD) failure.

The incidence and clinical significance of the TMPRSS2:ERGgene fusion in prostate cancer has been investigated with contradictory results. It is now common knowledge that significant variability in gene alterations exists according to ethnic background in various kinds of cancer. In this study, we evaluated gene fusions involving the ETSgene family in Japanese prostate cancer. Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reverse-transcriptase polymerase chain reaction to detect the common TMPRSS2:ERGT1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERGfusion transcripts. We identified 54 TMPRSS2:ERG-positive cases (54/194, 28%) and two HNRPA2B1:ETV1-positive cases (2/194, 1%). The SLC45A3-ELK4 transcript, a fusion transcript without structural gene rearrangement, was detectable in five cases (5/194, 3%). The frequencies of both TMPRSS2:ERG-and non-TMPRSS2:ERG-positive cases were lower than those reported for European, North American or Brazilian patients. Internodular heterogeneity of TMPRSS2:ERGwas observed in 5 out of 11 multifocal cases (45%); a frequency similar to that found in European and North American cases. We found a positive correlation between the TMPRSS2:ERGfusion and a Gleason score of ≤7 and patient age, but found no relationship with pT stage or plasma prostate-specific antigen concentration. To exclude the possibility that Japanese prostate cancer displays novel TMPRSS2:ERGtranscript variants or has unique 5′ fusion partners for the ETSgenes, we performed 5′ RACE using fresh-frozen prostate cancer samples. We identified only the normal 5′ cDNA ends for ERG, ETV1and ETV5in fusion-negative cases. Because we identified a relatively low frequency of TMPRSS2:ERGand other fusions, further evaluation is required before this promising molecular marker should be introduced into the management of Japanese prostate cancer patients.

The incidence and clinical significance of the TMPRSS2:ERG gene fusion in prostate cancer has been investigated with contradictory results. It is now common knowledge that significant variability in gene alterations exists according to ethnic background in various kinds of cancer. In this study, we evaluated gene fusions involving the ETS gene family in Japanese prostate cancer. Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reverse-transcriptase polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERG fusion transcripts. We identified 54 TMPRSS2:ERG-positive cases (54/194, 28%) and two HNRPA2B1:ETV1-positive cases (2/194, 1%). The SLC45A3-ELK4 transcript, a fusion transcript without structural gene rearrangement, was detectable in five cases (5/194, 3%). The frequencies of both TMPRSS2:ERG- and non-TMPRSS2:ERG-positive cases were lower than those reported for European, North American or Brazilian patients. Internodular heterogeneity of TMPRSS2:ERG was observed in 5 out of 11 multifocal cases (45%); a frequency similar to that found in European and North American cases. We found a positive correlation between the TMPRSS2:ERG fusion and a Gleason score of ≤7 and patient age, but found no relationship with pT stage or plasma prostate-specific antigen concentration. To exclude the possibility that Japanese prostate cancer displays novel TMPRSS2:ERG transcript variants or has unique 5′ fusion partners for the ETS genes, we performed 5′ RACE using fresh-frozen prostate cancer samples. We identified only the normal 5′ cDNA ends for ERG, ETV1 and ETV5 in fusion-negative cases. Because we identified a relatively low frequency of TMPRSS2:ERG and other fusions, further evaluation is required before this promising molecular marker should be introduced into the management of Japanese prostate cancer patients.

Two gonadotropins (Gths), follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), control gonadal steroidogenesis and gametogenesis in vertebrates, including teleost fish. Here, we report on the production of biologically active recombinant Fsh (rec-Fsh) and Lh (rec-Lh) in Japanese eel using DrosophilaS2 cells. The three subunits composing Gths, i.e., glycoprotein hormone, alpha polypeptide (Cga), follicle-stimulating hormone, beta polypeptide (Fshb), and luteinizing hormone, beta polypeptide (Lhb), were at first independently produced and were proven to be glycosylated and secreted as the mature peptides. Each beta subunit, along with its Cga, was simultaneously coexpressed to produce heterodimeric rec-Fsh and rec-Lh that were subsequently highly purified. The biological activity of rec-Gths was demonstrated in various in vitro assays. The rec-Gths differentially activated their receptors, which resulted in an increase in 11-ketotestosterone (11KT) secretion, a differential alteration of gene expression of steroidogenic enzymes in immature testis, and the induction of the complete process of spermatogenesis in vitro. The data strongly suggest that Fsh and Lh differentially play important roles in the reproductive physiology of the Japanese eel. By contrast, these rec-Gths exhibited little activity in the gonad when administered in vivo. This difference between in vitro and in vivo bioactivity is probably due to the qualitative nature of glycosylation in S2 cells, which resulted in degradation of the recombinant protein in vivo. These differences in the carbohydrate moieties need to be elucidated and ameliorated..

Follicle-stimulating hormone (FSH) plays important roles in spermatogenesis. However, the biologic activity of FSH can vary in different vertebrate classes, and the definitive function of FSH has not been established. In this study, we investigated the functions of FSH on spermatogenesis using an in vitro culture system for Japanese eel testis. The eel Fsh receptor was expressed in testis tissue during the whole process of spermatogenesis, mainly by Leydig cells that produce steroid hormones and by Sertoli cells surrounding type A spermatogonia and early type B spermatogonia. In an in vitro organ culture, recombinant eel Fsh (r-eFsh) induced complete spermatogenesis from the proliferation of spermatogonia to spermiogenesis during 36 days of culture; also, spermatozoa were observed in the testicular fragments. Spermatogenesis induced by r-eFsh was inhibited by trilostane, a specific inhibitor of 3beta-hydroxysteroid dehydrogenase. However, trilostane did not inhibit spermatogenesis induced by 11-ketotestosterone. These results clearly show that the main function of FSH in eel is to induce spermatogenesis via stimulating androgen production.

Using two species of teleost fish, Japanese huchen (Hucho perryi) and common carp (Cyprinus carpio), we investigated whether sex steroids are involved in early oogenesis in vitro. Ovarian fragments were cultured to examine the effects of a progestin, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (DHP), and an estrogen, estradiol-17 beta (E2). DHP and E2 significantly promoted DNA synthesis in ovarian germ cells, as judged by 5-bromo-2-deoxyuridine (BrdU) incorporation into these cells. Furthermore, to detect the initiation of the first meiotic division of early oogenesis, we assessed ultrastructurally the occurrence of synaptonemal complexes (SCs) and analyzed by immunohistochemistry the expression of a meiosis-specific marker, Spo11. In huchen, a higher percentage of oocytes with SC was seen in DHP-treated ovarian fragments than in control or E2-treated ovarian fragments. Spo11 was expressed in germ cells after DHP treatment of carp ovarian explants. These data suggest that the progression of germ cells through early oogenesis involves two sex steroids: E2, which acts directly on oogonial proliferation, and DHP, which acts directly on the initiation of the first meiotic division of oogenesis.

We consider continuously differentiable means, say-means. As for quasi-arithmetic means, we need an assumption thathas no stationary points so thatmight be continuously differentiable. Introducing quasi-weights for-means would give a satisfactory explanation for the necessity of this assumption. As a typical example of a class of-means, we observe that a skew power meanis a composition of power means ifis an integer.

We give a new interpretation of Hua's inequality and its generalization. From this interpretation, we know the best possibility of those inequalities.

A deep-sea yeast, Cryptococcus liquefaciensstrain N6, produces two polygalacturonases, p36 and p40 (N6-PGases). These N6-PGases were highly active at 0–10 °C in comparison to a PGase from Aspergillus japonicus. The hydrolytic activity of these N6-PGases remained almost unchanged up to a hydrostatic pressure of 100 MPa at 24 °C with a very small activation volume of −1.1 ml/mol. At 10 °C, however, the activation volume increased to 3.3 or 5.4 ml/mol (p36 and p40, respectively), suggesting that the enzyme–substrate complexes can expand at their transition states. We speculate that such a volume expansion upon forming the enzyme–substrate complexes contributes to decreasing the activation energy for hydrolysis. This can account for the high activity of N6-PGases at low-temperature.

We prove that a Jordan homomorphism from a Banach algebra into a semisimple commutative Banach algebra is a ring homomorphism. Using a signum effectively, we can give a simple proof of the Hyers-Ulam-Rassias stability of a Jordan homomorphism between Banach algebras. As a direct corollary, we show that to each approximate Jordan homomorphismfrom a Banach algebra into a semisimple commutative Banach algebra there corresponds a unique ring homomorphism near to.

The inequality discovered by L. K. Hua in 1965 has been generalized in several directions. In this paper, we adopt a certain conjugate method to give a simple and fundamental inequality on two functions on a semigroup, which is the key to the proof of many generalizations of Hua's inequality.

Suppose A is a Banach algebra without order. We show that an approximate multiplier T:A→A is an exact multiplier. We also consider an approximate multiplier T on a Banach algebra which need not be without order. If, in addition, T is approximately additive, then we prove the Hyers-Ulam-Rassias stability of T .

Let h be an entire function and Th a differential operator defined by Thf=f′+hf . We show that Th has the Hyers-Ulam stability if and only if h is a nonzero constant. We also consider Ger-type stability problem for |1−f′/hf|≤ε .

Let B be a strictly real commutative real Banach algebra with the carrier space ΦB . If A is a commutative real Banach algebra, then we give a representation of a ring homomorphism ρ:A→B , which needs not be linear nor continuous. If A is a commutative complex Banach algebra, then ρ(A) is contained in the radical of B .

Organ confined renal cell carcinoma can be cured in the majority of patients, whereas more extensive lesions have a poor prognosis. Therefore, the development of a useful biomarker for early diagnosis as well as postoperative metastatic status would contribute to the appropriate therapy for renal cell carcinoma. To diagnose renal cell carcinoma preoperatively we developed a novel urinary test and detected occult lymph node micrometastasis using a molecular approach.

Let F be a Banach algebra. We give a necessary and sufficient condition for F to be finite dimensional, in terms of finite type n -homogeneous F -valued polynomials.

Under fresh-water cultivation conditions, spermatogenesis in the Japanese eel is arrested at an immature stage before initiation of spermatogonial proliferation. A single injection of human chorionic gonadotropin can, however, induce complete spermatogenesis, which suggests that spermatogenesis-preventing substances may be present in eel testis. To determine whether such substances exist, we have applied a subtractive hybridisation method to identify genes whose expression is suppressed after human chorionic gonadotropin treatment in vivo. We found one previously unidentified cDNA clone that was downregulated by human chorionic gonadotropin, and named it ‘eel spermatogenesis related substances 21’ (eSRS21). A homology search showed that eSRS21 shares amino acid sequence similarity with mammalian and chicken Müllerian-inhibiting substance. eSRS21 was expressed in Sertoli cells of immature testes, but disappeared after human chorionic gonadotropin injection. Expression of eSRS21 mRNA was also suppressed in vitro by 11-ketotestosterone, a spermatogenesis-inducing steroid in eel. To examine the function of eSRS21 in spermatogenesis, recombinant eSRS21 produced by a CHO cell expression system was added to a testicular organ culture system. Spermtogonial proliferation induced by 11-ketotestosterone in vitro was suppressed by recombinant eSRS21. Furthermore, addition of a specific anti-eSRS21 antibody induced spermatogonial proliferation in a germ cell/somatic cell co-culture system. We conclude that eSRS21 prevents the initiation of spermatogenesis and, therefore, suppression of eSRS21 expression is necessary to initiate spermatogenesis. In other words, eSRS21 is a spermatogenesis-preventing substance.

Most of the organic conductors based on CH-TTP derivatives, where CH-TTP is 2-(4,5-cyclohexeno-1,3-dithiol-2-ylidene)-5-(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentanlene, behave metallic down to low temperatures. An X-ray crystal structure analysis of CHEO-TTP(ReO 4 ) 0.38 revealed that the arrangement of the donors is close to that of the κ-BEDT-TTF salts. The band structure calculated with the tight-binding approximation suggests that the ReO 4 − salt has a closed Fermi surface similar to those of the κ-type superconductors.

Three major phases compose spermatogenesis: mitotic proliferation of spermatogonia, meiosis of spermatocytes, and spermiogenesis, the restructuring of spermatids into flagellated spermatozoa. The process is fuelled by stem cells that, when dividing, either self-renew or produce spermatogonia that are committed to proliferation, meiosis, and spermiogenesis. During all phases, germ cells are in close contact with and require the structural and functional support of Sertoli cells. In contrast to germ cells, these somatic cells express receptors for sex steroids and follicle-stimulating hormone (FSH), the most important hormones that regulate spermatogenesis. A typical Sertoli cell response to an endocrine stimulus would be to change the release of a growth factor that would then mediate the hormone's effect to the germ cells. Recent studies in the Japanese eel have shown, for example, that in the absence of gonadotropin Sertoli cells produce a growth factor (an orthologue of anti-Müllerian hormone) that restricts stem cell divisions to the self-renewal pathway; also estrogens stimulate stem cell renewal divisions but not spermatogonial proliferation. Gonadotropin or 11-ketotestosterone (11-KT) stimulation, however, induces spermatogonial proliferation, which is in part mimicked by another Sertoli cell-derived growth factor (activin B). Since FSH (besides luteinizing hormone, LH) stimulates steroidogenesis in fish, and since FSH is the only gonadotropin detected in the plasma of sexually immature salmonids, increased FSH signalling may be sufficient to initiate spermatogenesis by activating both Sertoli cell functions and 11-KT production. Another important androgen is testosterone (T), which seems to act via feedback mechanisms that can compromise FSH-dependent signalling or steroidogenesis. The testicular production of T and 11-KT therefore needs to be balanced adequately. Further research is required to elucidate in what way(s) 11-KT stimulates later stages of development, such as entry into meiosis and spermiogenesis. At this period, LH becomes increasingly important for the regulation of androgen production. Results from mammalian models suggest that during the later phases, the control of germ cell apoptosis via Sertoli cell factors is an important regulatory mechanism. In many species, sperm cells cannot fertilize eggs until having passed a maturation process known as capacitation, which includes the acquisition of motility. Progestins that are produced under the influence of LH appear to play an important role in this context, which involves the control of the composition of the seminal plasma (e.g., pH values).

In higher vertebrates, considerable progress has been made in understanding the endocrine regulation of puberty; however, in teleosts, the regulatory mechanisms of spermatogenesis during the first annual cycle remain unclear. The present study was conducted to understand the regulatory mechanisms of spermatogenesis throughout the different stages of the first spermatogenic cycle and to check the ability of various steroids and hormones to induce in vitro spermatogonial proliferation in Japanese huchen (Hucho perryi ). The results indicate that the serum level of 11-ketotestosterone (11-KT) was positively associated with germ cell type; the level first began to rise with the appearance of late-type B spermatogonia and continued to increase gradually throughout the active spermatogenic stages and spermiogenesis, reaching a peak value 2 wk before spawning, and then declined. During the spermatogenic stages, the serum concentration of 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-DP) was undetectable. Only a small peak was detected with the appearance of spermatocytes and spermatids, and at the time of spawning, the level increased dramatically, reaching its maximum value with the onset of milt production. Despite the high variation in serum levels of 17β-estradiol (E2) both between months and among the individuals, E2was found during the whole reproductive cycle. From these results, we concluded that 1) 11-KT is necessary for the initiation of spermatogenesis and sperm production, and it probably plays a role in spermiation, 2) 17α,20β-DP is essential for the final maturation stage, could play a significant role in the mitosis phase and meiosis process, and probably participates in the regulation of spawning behavior, and 3) estrogen is an indispensable male hormone that plays a physiological role in some aspects of testicular functions, especially during the mitotic phase. The three steroids were also able to induce DNA synthesis, spermatogonial renewal, and/or spermatogonial proliferation in vitro.

OBJECTIVES

In this study, we examined the in vitro effects of insulin-like growth factor I (IGF-I) in the presence or absence of 11-ketotestosterone (11-KT: the spermatogenesis-inducing hormone) on the proliferation of Japanese eel (Anguilla japonica) testicular germ cells. Initially, a short-term culture (15 days) of testicular tissue with only type A and early type B spermatogonia (preproliferated spermatogonia) was carried out in Leibovitz-15 growth medium supplemented with different concentrations of recombinant human IGF (rhIGF)-I or -II in the presence or absence of 10 ng/ml of 11-KT. Late type B spermatogonia (proliferated spermatogonia) were observed in treatments of 100 ng/ml of both rhIGF-I and -II in combination with 11-KT, indicating the onset and progression of spermatogenesis. In all tested rhIGF-I concentrations (except 0.1 ng/ml) supplemented with 11-KT, late type B spermatogonia were detected in at least one individual. Then, we proceeded with an in vitro 45-day culture of testicular tissue with 100 ng/ml of rhIGF-I in the presence or absence of 10 ng/ml of 11-KT to test the long-term effects of rhIGF-I on the spermatogenetic cycle. The presence of all types of germ cells, including spermatozoa, in the testis cultured with the admixture of the two hormones indicated that the germ cells underwent complete spermatogenesis whereas no germ cell proliferation was observed when the rhIGF-I was applied alone. These results suggest that IGF-I in the presence of 11-KT plays an essential role in the onset, progress, and regulation of spermatogenesis in the testis of the Japanese eel.

A new sandwich-type immunoassay method utilizing an anti-peptide antibody column and a fluorescence-labeled antibody (FLA) was proposed and applied to the measurement of the concentrations of insulin and insulin B-chain. In this method an immunoadsorbent coupled with an anti-peptide antibody was packed in a small column. A target protein was adsorbed on the anti-peptide antibody in the column, coupled with the FLA as a secondary antibody in sandwich manner and then eluted by an eluent containing an antigen peptide to the anti-peptide antibody. The concentration of the target protein was determined form the fluorescent intensity of the eluted FLA. It was possible to determine the concentrations within 30 min, and the higher sensitivity was obtained in comparison with the direct method using an immunoaffinity column.

In this work, we examined the functions of the female hormone “estrogen” on spermatogenesis of the Japanese eel (Anguilla japonica).Estradiol-17β (E2), a natural estrogen in vertebrates, was present in the serum and its receptor was expressed in the testis during the whole process of spermatogenesis. Spermatogonial stem cell renewal was promoted by E2implantation but was suppressed by tamoxifen (an antagonist of estrogen). In vitro,10 pg/ml of E2was sufficient to induce spermatogonial stem cell division in cultured testicular tissue, therefore confirming the in vivoobservations. These results clearly show that estrogen is an indispensable “male hormone” in the early spermatogenetic cycle.

In the cultivated male Japanese eel, spermatogonia are the only germ cells present in the testis. Weekly injections of human chorionic gonadotropin (HCG) can induce complete spermatogenesis from proliferation of spermatogonia to spermiogenesis. In some cases, however, HCG injection fails to induce complete spermatogenesis. Testicular morphological observations revealed that HCG-injected eels could be classified into three types based on their testicular conditions. Type 1 eels had a well-developed testis and the milt could be acquired by hand-stripping. In type 2 eels, spermatogenesis was also induced by HCG injection, but testicular size was remarkably smaller than that of type 1 eels, and the milt could not be hand-stripped. At the end of the experiment, type 2 fish had only spermatogonia and a small amount of spermatozoa, but no spermatocytes or spermatids, in their testis. Type 3 eels had thready testis, which did not develop any germ cells during the experimental period. These results suggest that, despite elevations of plasma 11-ketotestosterone levels, HCG injections were not successful in inducing the completion of spermatogenesis in type 2 and type 3 eels. In most spermatogonia of type 2 eels, meiosis was not induced by HCG injections. Furthermore, only few mitotic divisions had occurred as evidenced by the presence of 2³ to 2⁶ late type B spermatogonia in most cysts. This suggests that spermatogonial stem cells undergo four or five, and occasionally six, mitotic divisions before the interruption of spermatogenesis in type 2 eels. It is proposed that those numbers of mitotic divisions are related to a mediator that regulates entry of spermatogonia of the Japanese eel into meiosis.

Several derivatives of higher homologues of bis-fused TTF, BDT-TTPY (1) and DT-TTP (2), have been synthesized. Cyclic voltammograms of 1 and 2consist of three-pairs of double-electron and five-pairs of single electron redox waves, respectively. Most of cation radical salts obtained by the chemical doping with appropriate oxidants showed relatively high conductivity (s`rt =10-2-101 S cm1 on compressed pellets).

Several cation radical salts of MeEtDTET, EtDTET and CPDTET were prepared. Many of them showed metallic conducting behavior down to 1.4-4.2 K. X-ray crystal structure analysis of (CPDTET)2(SbF6)0.87 revealed that this salt has a two-dimensional "K-type" arrangement of donor molecules.

Since intravesical recurrence of superficial bladder cancer (Ta, T1) after transurethral resection (TUR) is frequent, adjuvant therapy to reduce the recurrence rate has been extensively investigated. Although intravesical chemotherapy has been employed for 30 years or more, neither the exact effect on the bladder epithelium nor the optimal dose and administration schedule has yet been clarified. In recent years, several derivatives of Adriamycin (ADR) have been developed, and 4'-epirubicin (FARM) is one of them. This drug has been shown to have antitumor effects almost equal to those of ADR and to produce less toxicity when given systemically as chemotherapy. In an attempt to clarify the effect of intravesical FARM in the prevention of recurrence of superficial bladder cancer, we conducted a prospective randomized trial to compare the effects of equal doses of FARM and ADR given by intravesical instillation after TUR in cases of highly recurrent superficial bladder cancer. A total of 73 patients with recurrent superficial bladder cancer were randomized to receive TUR and either 30 mg FARM or 30 mg ADR by intravesical instillation every 2–4 weeks for 1 year. The prophylactic effect on recurrence and the toxic effects of these drugs were investigated. The current results show that FARM provides efficacy almost equal to that of ADR in the prevention of recurrence in these patients. However, FARM also caused almost the same local toxic effects (bladder irritation, among others) as ADR. On the basis of these preliminary results, FARM is surmised to be one of the agents as beneficial as ADR in the prevention of recurrence of superficial bladder cancer.

A novel dimer model for poly(m-aniline), two amino groups of which are effectively shielded by surrounding nitro groups, has been prepared in good yield and characterised by X-ray crystallographic, electrochemical and EPR studies. A 2:1 weak charge transfer complex with tetracyano-p-quinodimethane has been prepared and showed a moderate electrical conductivity (sigma;rt=1.3103 Scm1) in the single crystalline form. The X-ray crystal structure of the complex has also been examined in connection with the electrical conductivity.

The cobalt-60, γ-radiation induced copolymerization of ethylene with tetrafluoroethylene was carried out in the gas phase and in the liquid phase by using five solvents (liquefied carbon dioxide, carbon tetrachloride, ethylchloride, chloropentafluoroethane, and 1,2-dichloro-tetrafluoroethane) at a dose rate of 25000 rad/hr under a pressure of 300 kg/cm2at 30°C. A lower rate of the copolymerization and a copolymer of a lower molecular weight were obtained in liquid carbon dioxide and carbon tetrachloride than in the gas phase without a solvent. In ethyl chloride, the rate increased slightly, but the molecular weight decreased. On the other hand, both the rate and the molecular weight increased markedly in the fluorocarbon solvents. As a result of a detailed investigation of the copolymerization in 1,2-dichloro-tetrafluoroethane, a linear increase in the copolymerization rate and the copolymer molecular weight with the amount of solvent was noted, and there was no noticiable influence of the solvent on the copolymer composition. A kinetical discussion indicated that the addition reaction of tetrafluoroethylene to radicals produced by the influence of primary radiation on the reaction mixture is an important step in initiating the copolymerization. Also, the propagation reaction seemes to be strongly promoted by the fluorocarbon solvents.

Crossed ectopic testis is an uncommon anomaly. A 10-month-old boy with a crossed ectopic testis and a common vas deferens is presented. At operation 2 testes were in the left inguinal canal. The seminal vesiculogram showed that both vasa deferentia fused to form a common lumen, and then formed a common stem on the left side and opened into the posterior urethra. The spermatic arteriogram revealed that each testis was supplied from the right and left sides, respectively. No testis or vas deferens was located in the right retroperitoneal space. These features suggested that the testes developed from both sides and subsequently descended to the left side.

Summary In an attempt to improve the poor prognosis of invasive and/or high-grade bladder cancer after total cystectomy, we tried a combination of regional irradiation with hyperthermia (RH) therapy and systemic M-VAC (methotrexate, vinblastine, Adriamycin, and cisplatin) chemotherapy followed by surgery. The short-term results of these treatments were evaluated. A total of 17 patients received the combination of RH and M-VAC therapy between January 1989 and July 1990, and 12 then underwent total cystectomy. Of the 17 patients, 14 were evaluable for tumor response. The objective response rate was 64% (9/14), with 4 patients achieving a complete remission that was confirmed by histological examination. Nausea and vomiting were inevitable, and 71% (12/17) of the patients developed leukopenia. However, these side effects were not serious. Considering the previous results obtained using RH therapy in the absence of chemotherapy for this disease, no significant difference in the tumor response was detected between the RH only group and the RH plus M-VAC group. The long-term results cannot yet be evaluated, but we will continue to follow these patients in the future so as to clarify the usefulness of M-VAC therapy as preoperative therapy.

Meiosis is a unique and critical process in reproduction. Although the key molecular components of meiosis have been identified, the molecular mechanisms regulating the entry into this pathway remain unclear. We previously demonstrated that a progestin in teleost fish, 17alpha, 20beta-dihydroxy-4-pregnen-3-one, is essential for meiotic initiation, and up-regulates taurine synthesis and the production of trypsin in Sertoli cells. In the present study, we found that trypsin promotes the uptake of taurine into germ cells through the up-regulation of solute carrier family 6 (neurotransmitter transporter, taurine), member 6 (Slc6a6) expression. We further found that this up-regulation of the taurine signal is required for Spo11a expression and meiotic initiation.

Oxidative stress has been implicated in pathogenesis of many diseases, but few studies describe its influence on spermatogenesis. In this study, we analyzed the direct influence of hypoxanthine (Hx)-induced reactive oxygen species (ROS) on spermatogenesis in fish using the Japanese eel (Anguilla japonica) testicular organ culture system. Testicular fragments of eels were cultured in 0.1–100 μM Hx with or without 10 ng/ml 11-ketotestosterone (11-KT). Immunohistochemistry for 5-bromo-2-deoxyuridine showed that Hx treatment at a low dose (1 μM) already inhibits 11-KT-induced germ cell proliferation after culture. An in situ TUNEL assay and 8-hydroxy-2′-deoxyguanosine immunohistochemistry revealed an intense germ cell apoptosis and high oxidative DNA damage in testicular fragments cultured at the highest dose of Hx (100 μM) with 11-KT. A total superoxide dismutase (SOD) activity assay showed a decrease in SOD activity in testicular fragments cultured with 11-KT. These data suggest that ROS may directly inhibit spermatogenesis, and that decreased SOD activity renders proliferating spermatogonia susceptible to ROS, hence leading to apoptosis.

A candidate mosquito larvicide, 5-31183, 2-[1-methyl-2-(4-phenoxyphenoxy) ethoxy] pyridine, was highly compatible with other organisms in mosquito-breeding habitats. When 5-31183 was applied at a rate of 0.11 kg (AI)/ha (0.11b/acre) (20 times greater than required for controlling Aedes nigromaculis (Ludlow) larvae) to rice plots, no detectable residues «0.00005 ppm) were found after 2 d in treated water. 5-31183 did not accumulate in soil, there were no residues «0.005 ppm) after 3 d in fish (Lepomis macrochirus Rafinesque), and the residue on rice plants declined to <0.005 ppm after 7 d. Despite slight induction of morphogenetic aberrations in Odonata at adult emergence and minor suppression of reproductive capacity of daphnoid cladocerans and ostracods, 5-31183 was safe to aquatic, nontarget organisms, including mosquito predators.