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1.
Support Care Cancer ; 32(5): 291, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630197

ABSTRACT

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.


Subject(s)
Antiemetics , Colorectal Neoplasms , Pyrrolidines , Thymine , Humans , Trifluridine/adverse effects , Antiemetics/therapeutic use , Prospective Studies , Vomiting/chemically induced , Vomiting/epidemiology , Vomiting/prevention & control , Nausea/chemically induced , Nausea/epidemiology , Nausea/prevention & control , Colorectal Neoplasms/drug therapy , Drug Combinations
2.
Biol Reprod ; 110(3): 465-475, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-37995271

ABSTRACT

The mammalian oviductal lumen is a specialized chamber that provides an environment that strictly regulates fertilization and early embryogenesis, but the regulatory mechanisms to gametes and zygotes are unclear. We evaluated the oviductal regulation of early embryonic development using Ovgp1 (encoding an oviductal humoral factor, OVGP1)-knockout golden hamsters. The experimental results revealed the following: (1) female Ovgp1-knockout hamsters failed to produce litters; (2) in the oviducts of Ovgp1-knockout animals, fertilized eggs were sometimes identified, but their morphology showed abnormal features; (3) the number of implantations in the Ovgp1-knockout females was low; (4) even if implantations occurred, the embryos developed abnormally and eventually died; and (5) Ovgp1-knockout female ovaries transferred to wild-type females resulted in the production of Ovgp1-knockout egg-derived OVGP1-null litters, but the reverse experiment did not. These results suggest that OVGP1-mediated physiological events are crucial for reproductive process in vivo, from fertilization to early embryonic development. This animal model shows that the fate of the zygote is determined not only genetically, but also by the surrounding oviductal microenvironment.


Subject(s)
Fallopian Tubes , Oviducts , Humans , Pregnancy , Animals , Cricetinae , Female , Mesocricetus , Germ Cells , Ovary , Mammals , Glycoproteins
3.
J Obstet Gynaecol Res ; 49(8): 2073-2085, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37317990

ABSTRACT

AIM: Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti-Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti-Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation. METHODS: Thirty-three patients who underwent OTC were divided into the chemotherapy (n = 22) and non-chemotherapy (n = 11) groups; their ovarian tissues underwent histological examination. Pathological ovarian damage induced by chemotherapy was assessed. Ovarian volumes were estimated from weights. We compared the number of follicles at each developmental stage as a percentage of primordial follicles between the groups. The relationship between serum anti-Müllerian hormone level and primordial follicle density was analyzed. RESULTS: The chemotherapy group had a significantly lower serum anti-Müllerian hormone level, ovarian volume, and density of developing follicles than the non-chemotherapy group. Serum anti-Müllerian hormone levels correlated with primordial follicle density only in the non-chemotherapy group. The chemotherapy group had significantly lower numbers of primary and secondary follicles. CONCLUSIONS: Chemotherapy induces ovarian damage and follicle loss. However, serum anti-Müllerian hormone level does not always reflect the number of primordial follicles after chemotherapy, and chemotherapy more significantly affects primary and secondary follicles than primordial follicles. Many primordial follicles remain in the ovary after chemotherapy, supporting OTC for fertility preservation.


Subject(s)
Cancer Survivors , Neoplasms , Female , Humans , Anti-Mullerian Hormone , Ovarian Follicle , Ovary , Cryopreservation , Neoplasms/drug therapy
4.
J Reprod Immunol ; 157: 103930, 2023 06.
Article in English | MEDLINE | ID: mdl-36933475

ABSTRACT

We previously established a spontaneously occurring monoclonal antibody, namely Ts3, that was reactive to sperm from an aged male mouse. The present study investigated the characteristic properties and reproductive functions of Ts3. Immunofluorescent staining revealed that Ts3 reacted to epididymal sperm, and the corresponding antigen was located in the midpiece and principal piece. Immunohistochemistry revealed positive reactions in the germ cells and Sertoli cells in the testis, the epithelial cells in the epididymis and vas deferens. Through western blotting with two-dimensional electrophoresis, we demonstrated that Ts3 reacted with four spots, which were around Mr ∼25,000-60,000 and pI 5-6. MALDI-TOF/TOF mass spectrometry identified outer dense fiber 2 (ODF2) as a candidate for Ts3. ODF2 is a cytoskeletal structural component located in the midpiece and principal piece of the flagella of mammalian sperm. This was validated with the result of immunofluorescent staining, suggesting that ODF2 was the main target antigen for Ts3. Sperm immobilization test showed that Ts3 possessed sperm immobilizing activity. Furthermore, Ts3 impaired early embryo development but not in vitro fertilization. These results suggest that ODF2 plays an important role in both sperm function and early embryonic development.


Subject(s)
Semen , Spermatozoa , Male , Female , Pregnancy , Animals , Mice , Testis , Autoantibodies , Antibodies, Monoclonal , Mammals , Heat-Shock Proteins
5.
J Biol Chem ; 298(10): 102455, 2022 10.
Article in English | MEDLINE | ID: mdl-36063994

ABSTRACT

Pore-forming proteins perforate lipid membranes and consequently affect their integrity and cell fitness. Therefore, it is not surprising that many of these proteins from bacteria, fungi, or certain animals act as toxins. While pore-forming proteins have also been found in plants, there is little information about their molecular structure and mode of action. Bryoporin is a protein from the moss Physcomitrium patens, and its corresponding gene was found to be upregulated by various abiotic stresses, especially dehydration, as well as upon fungal infection. Based on the amino acid sequence, it was suggested that bryoporin was related to the actinoporin family of pore-forming proteins, originally discovered in sea anemones. Here, we provide the first detailed structural and functional analysis of this plant cytolysin. The crystal structure of monomeric bryoporin is highly similar to those of actinoporins. Our cryo-EM analysis of its pores showed an actinoporin-like octameric structure, thereby revealing a close kinship of proteins from evolutionarily distant organisms. This was further confirmed by our observation of bryoporin's preferential binding to and formation of pores in membranes containing animal sphingolipids, such as sphingomyelin and ceramide phosphoethanolamine; however, its binding affinity was weaker than that of actinoporin equinatoxin II. We determined bryoporin did not bind to major sphingolipids found in fungi or plants, and its membrane-binding and pore-forming activity was enhanced by various sterols. Our results suggest that bryoporin could represent a part of the moss defense arsenal, acting as a pore-forming toxin against membranes of potential animal pathogens, parasites, or predators.


Subject(s)
Bryopsida , Porins , Animals , Amino Acid Sequence , Bryopsida/genetics , Bryopsida/metabolism , Cnidarian Venoms/chemistry , Cytotoxins , Porins/genetics , Porins/metabolism , Sea Anemones/chemistry
6.
Reprod Med Biol ; 21(1): e12477, 2022.
Article in English | MEDLINE | ID: mdl-35814191

ABSTRACT

Background: Some diseases have sex differences. There have been no reports on the relationship between anti-sperm antibodies (ASA) and sex differences. Methods: ASA are detected by sperm-immobilization test using patients' sera in women. In men, the ASA testing is generally performed by direct-immunobead test. Main findings: Sperm-immobilizing antibodies in women inhibit sperm migration in their genital tract and exert inhibitory effects on fertilization. ASA bound to sperm surface in men also show inhibitory effect on sperm passage through cervical mucus. The fertilization rate of IVF significantly decreased when sperm were coated with higher numbers of ASA. For women with the antibodies, it is important to assess individual patients' SI50 titers. In patients with continuously high SI50 titers, pregnancy can be obtained only by IVF. For men with abnormal fertilizing ability by ASA, it is necessary to select intracytoplasmic sperm injection. Production of sperm-immobilizing antibodies is likely to occur in women with particular HLA after exposure to sperm. The risk factors for ASA production in men are still controversial. Conclusion: Attention to sex differences in specimens, test methods and the diagnosis of ASA should be paid. For patients with ASA, treatment strategies have been established by considering sex difference for each.

7.
Cell Mol Life Sci ; 79(6): 324, 2022 May 29.
Article in English | MEDLINE | ID: mdl-35644822

ABSTRACT

We identified a mushroom-derived protein, maistero-2 that specifically binds 3-hydroxy sterol including cholesterol (Chol). Maistero-2 bound lipid mixture in Chol-dependent manner with a binding threshold of around 30%. Changing lipid composition did not significantly affect the threshold concentration. EGFP-maistero-2 labeled cell surface and intracellular organelle Chol with higher sensitivity than that of well-established Chol probe, D4 fragment of perfringolysin O. EGFP-maistero-2 revealed increase of cell surface Chol during neurite outgrowth and heterogeneous Chol distribution between CD63-positive and LAMP1-positive late endosomes/lysosomes. The absence of strictly conserved Thr-Leu pair present in Chol-dependent cytolysins suggests a distinct Chol-binding mechanism for maistero-2.


Subject(s)
Carrier Proteins , Sterols , Carrier Proteins/metabolism , Cholesterol/metabolism , Endosomes/metabolism , Lysosomes/metabolism , Neuronal Outgrowth , Sterols/metabolism
8.
Support Care Cancer ; 30(5): 4497-4504, 2022 May.
Article in English | MEDLINE | ID: mdl-35113224

ABSTRACT

BACKGROUND: Although pre-emptive therapy with oral tetracycline, moisturizer, sunscreen, and topical corticosteroid is useful for preventing acneiform eruption (AfE) due to epidermal growth factor receptor (EGFR) inhibitors, no studies have examined the efficacy of topical corticosteroids themselves, or investigated the optimal potency of corticosteroid for treating facial AfE (FAfE). PATIENTS AND METHODS: Screened patients with RAS wild-type colorectal cancer started pre-emptive therapy with oral minocycline and moisturizer on initiation of cetuximab or panitumumab therapy. Patients who developed grade 1 or 2 FAfE were randomly allocated to two groups: a ranking-down (RD) group that started with a very strong corticosteroid and serially ranked down every 2 weeks unless FAfE exacerbated; and a ranking-up (RU) group that started with a weak corticosteroid and serially ranked up at exacerbation. FAfE grade, patient quality of life, and adverse events (AEs) with topical corticosteroid were evaluated every 2 weeks. The primary endpoint was the total number of times grade 2 or higher FAfE was identified in the central review of the 8-week treatment period. RESULTS: No significant differences in total numbers of grade 2 or higher FAfE or in AEs caused by topical corticosteroids were observed between groups during the 8 weeks. Incidence of grade 2 or higher FAfE tended to be lower in the RD group during the first 2 weeks. CONCLUSION: Considering the long-term care of FAfE, the RU regimen appears suitable and should be considered the standard treatment for FAfE due to EGFR inhibitor therapy. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000024113).


Subject(s)
Acneiform Eruptions , Colonic Neoplasms , Colorectal Neoplasms , Acneiform Eruptions/chemically induced , Acneiform Eruptions/drug therapy , Acneiform Eruptions/prevention & control , Cetuximab/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , ErbB Receptors , Glucocorticoids/therapeutic use , Humans , Quality of Life
9.
Reprod Med Biol ; 20(3): 321-326, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34262400

ABSTRACT

PURPOSE: In a previous study, a new method was described using the sperm immobilization test (SIT) with computer-aided sperm analysis (CASA). However, obtaining high-quality sperm as needed was a known issue. Here, we compared the results of using frozen-thawed sperm and fresh sperm for the SIT using the CASA method. METHODS: For the frozen-thawed preparation, 500 µL of condensed semen and 500 µL of Sperm Freeze were mixed in a cryovial and cryopreserved in liquid nitrogen. Density gradient centrifugation was used for the collection of motile sperm in both the fresh and frozen-thawed sperm preparations. A total of 50 serum samples were prepared for both the fresh and frozen-thawed sperm with each sample tested containing 10 µL of serum, 1 µL of either fresh or frozen motile sperm suspension, and 2 µL of complement. Sperm motilities were measured using CASA after a 1-hour incubation period for both fresh and frozen-thawed sperm. RESULTS: Both fresh and frozen-thawed sperm reacted similarly when exposed to serum containing sperm-immobilizing antibodies asserting the use of frozen-thawed sperm for the diagnosis of immunological infertility. CONCLUSION: These results suggest the possibility of using cryopreserved sperm for the SIT when fresh sperm is unavailable.

10.
Sci Rep ; 11(1): 4547, 2021 02 25.
Article in English | MEDLINE | ID: mdl-33633328

ABSTRACT

Olanzapine has exhibited efficacy as an antiemetic agent when used with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists for patients receiving highly emetogenic chemotherapy. In addition, several studies have reported the efficacy or safety of olanzapine in patients receiving moderately emetogenic chemotherapy, including carboplatin, irinotecan, and oxaliplatin. However, no reports of olanzapine use have focused on patients receiving oxaliplatin-based chemotherapy. Therefore, we analyzed the safety of antiemetic therapy using olanzapine, palonosetron, aprepitant, and dexamethasone in colorectal cancer patients undergoing oxaliplatin-based chemotherapy. This study was a prospective phase II single-institution study of 40 patients (median age 60 years, 23 patients were male). The primary endpoint was the incidence of adverse events, and the exploratory endpoints were the rate of chemotherapy-induced nausea and vomiting. Almost all patients (90%) had a performance status of 0. All patients received the scheduled antiemetic therapy. The most common adverse event was somnolence (n = 7 patients, 17.5%). All adverse events were grade 1. Thirty-six patients were included in the exploratory analysis of efficacy. No patients experienced vomiting during the first 120 h after chemotherapy, and complete response and complete control were both 86.1%. The rate of total control was 55.6% during the same time period. Olanzapine use with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists was safe for colorectal cancer patients receiving oxaliplatin-based chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Combined Modality Therapy , Disease Management , Female , Humans , Male , Middle Aged , Olanzapine/administration & dosage , Oxaliplatin/administration & dosage , Prognosis , Treatment Outcome
11.
Contact (Thousand Oaks) ; 4: 25152564211042456, 2021.
Article in English | MEDLINE | ID: mdl-37366372

ABSTRACT

Sphingomyelin (SM) is a major sphingolipid in mammalian cells. Although SM is enriched in the outer leaflet of the cell plasma membrane, lipids are also observed in the inner leaflet of the plasma membrane and intracellular organelles such as endolysosomes, the Golgi apparatus and nuclei. SM is postulated to form clusters with glycosphingolipids (GSLs), cholesterol (Chol), and other SM molecules through hydrophobic interactions and hydrogen bonding. Thus, different clusters composed of SM, SM/Chol, SM/GSL and SM/GSL/Chol with different stoichiometries may exist in biomembranes. In addition, SM monomers may be located in the glycerophospholipid-rich areas of membranes. Recently developed SM-binding proteins (SBPs) distinguish these different SM assemblies. Here, we summarize the effects of intrinsic factors regulating the lipid-binding specificity of SBPs and extrinsic factors, such as the lipid phase and lipid density, on SM recognition by SBPs. The combination of different SBPs revealed the heterogeneity of SM domains in biomembranes.

12.
Am J Reprod Immunol ; 85(4): e13337, 2021 04.
Article in English | MEDLINE | ID: mdl-32885505

ABSTRACT

Reproductive failures include infertility and recurrent pregnancy loss (RPL). Although the relative importance of immunological factors in human reproduction remains unclear, there may be immune-mediated reproductive failures in a portion of unexplained infertility and RPL. As a cause of immunological factor, anti-sperm antibodies (ASA) are produced both in men and women. There have been reported several antigens in the surface of sperm that are especially foreign to women. The presence of ASA, especially sperm-immobilizing antibodies, in the sera of infertile women has been shown to inhibit sperm migration in the female genital tract. Therefore, the effectiveness of the treatments for infertile women with sperm-immobilizing antibodies by timed intercourse or intra-uterine insemination is limited. Such antibodies can also exert inhibitory effects on various stages of sperm-egg interaction and subsequent embryo development in vitro. It is suggested that ASA testing for infertile women should be performed before proceeding IVF. The manipulation of gametes and embryos from patients having sperm-immobilizing antibodies should be carefully carried out especially to avoid contaminating patient's serum and follicular fluid in the culture medium in order to overcome the immunological causes of female infertility by ASA, and satisfactory results under suitable conditions for gametes and embryos have been obtained. The relationship between ASA and RPL was controversially reported. Increased miscarriage rates in women with ASA were demonstrated by some authors. In contrast, lack of association between ASA and RPL was reported. In this manuscript, we are focusing the roles of ASA in women with reproductive failures.


Subject(s)
Abortion, Habitual/immunology , Antibodies/immunology , Infertility, Female/immunology , Spermatozoa/immunology , Animals , Female , Humans , Male , Pregnancy
13.
Reproduction ; 158(6): 503-516, 2019 12.
Article in English | MEDLINE | ID: mdl-31585439

ABSTRACT

Ts4, an autosperm-monoclonal antibody (mAb), reacts with a specific oligosaccharide (OS) of glycoproteins containing bisecting N-acetylglucosamine residues. Ts4 reactivity was observed against epididymal spermatozoa, testicular germ cells, and the early embryo, but not against major organs in adult mice. In mature testis, Ts4 exhibits immunoreactivity with a germ cell-specific glycoprotein, TEX101, whereas the mAb immunoreacts with alpha-N-acetylglucosaminidase in the acrosomal region of cauda epididymal spermatozoa. Thus, Ts4 seems to react against different molecules throughout spermiogenesis via binding to its OS epitope. Since the Ts4-epitope OS is observed only in reproduction-related regions, the Ts4-reactive OS may play a role in the reproductive process. The aim of this study is to investigate the characteristics of the Ts4-reactive molecule(s) during testicular development. Ts4 reactivity was observed in testes from the prenatal period; however, its distribution changed according to the stage of maturation and was identical to that of the adult testes after 29-day-postpartum (dpp). Ts4 immunoreactivity was detected against a protein with 63 kDa in testis from 1 to 29 dpp. In contrast, Ts4 showed reactivity against some other glycoproteins after 29 dpp, including TEX101 at the 5-week-old stage and onward. To identify the Ts4-reactive 63 kDa molecule, we identified NUP62 as the target of Ts4 in 22 dpp testis using liquid chromatography-tandem mass spectrometry analysis. Because NUP62 has been known to play active roles in a variety of cellular processes including mitosis and cell migration, the bisecting GlcNAc recognized by Ts4 on NUP62 may play a role in regulating the early development of germ cells in male gonadal organs.


Subject(s)
Acetylglucosamine/immunology , Antibodies, Monoclonal/immunology , Autoantibodies/immunology , Glycoproteins/immunology , Membrane Glycoproteins/immunology , Membrane Glycoproteins/metabolism , Nuclear Pore Complex Proteins/immunology , Nuclear Pore Complex Proteins/metabolism , Testis/cytology , Animals , Epididymis/cytology , Epididymis/immunology , Epididymis/metabolism , Female , Male , Mice , Mice, Inbred ICR , Spermatozoa/cytology , Spermatozoa/immunology , Spermatozoa/metabolism , Testis/immunology , Testis/metabolism
14.
Breast Cancer ; 26(2): 229-234, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30350259

ABSTRACT

BACKGROUND: Paclitaxel (PTX) is an essential anticancer drug used to treat breast cancer. Because it contains alcohol as a solvent, it is contraindicated in many Japanese breast cancer patients when they are suspected of alcohol intolerance. Aldehyde dehydrogenase 2 (ALDH2) is one of several enzymes that catalyzes dehydrogenation of aldehydes, and plays an important role in ethanol metabolism. Deficiency of this isozyme is believed to be responsible for facial flushing and other unpleasant symptoms following ethanol intake. In this study, we examined the safety of PTX for patients with the ALDH2 GA genotype. METHODS: We performed ALDH2 genotyping on 25 patients with various cancers who were suspected to be intolerant to alcohol based on an interview using a simple question. Ten patients with the ALDH2 GA genotype, including 5 breast cancer patients, underwent chemotherapy containing PTX up to 100 mg/m2 (range 80-100 mg/m2), and were questioned about 16 alcohol-related symptoms at 11 timepoints to evaluate sensitivity to alcohol. RESULTS: All patients completed the first course of planned chemotherapy with either no or grade 1 alcohol-related symptoms. CONCLUSIONS: Our study suggests that PTX up to 100 mg/m2 can be used safely for patients with the ALDH2 GA genotype. To confirm the necessity of a genotyping test for ALDH2, further studies evaluating alcohol sensitivity in response to PTX among patients with the ALDH2 AA genotype are required.


Subject(s)
Aldehyde Dehydrogenase, Mitochondrial/genetics , Antineoplastic Agents/adverse effects , Ethanol/adverse effects , Paclitaxel/adverse effects , Adult , Aged , Antineoplastic Agents/chemistry , Asian People/genetics , Breast Neoplasms/genetics , Breath Tests , Ethanol/analysis , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/genetics , Paclitaxel/chemistry , Paclitaxel/therapeutic use
15.
Reprod Med Biol ; 17(4): 449-453, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30377398

ABSTRACT

PURPOSE: Sperm cryopreservation is the gold standard for maintaining fertility in male survivors of cancer. In order to help increase the future success of fertility preservation in these patients, the present state of sperm cryopreservation was examined at the current institution and its challenges were discussed. METHODS: Between January, 2004 and February, 2017, 31 male patients with cancer were introduced to the center for fertility preservation. The ages and semen characteristics of these patients were examined and compared between those whose sperm were cryopreserved before (the pretreatment group) and after (the post-treatment group) cancer treatment. RESULTS: The mean sperm concentration of the pretreatment group was significantly higher than that of the post-treatment group. Normozoospermia was found in eight and three patients in the pretreatment and the post-treatment groups, respectively, albeit this difference was not significant. In contrast, the prevalence of azoospermia was higher in the post-treatment group (five patients) than in the pretreatment group (one patient). CONCLUSION: As many patients possibly suffer from infertility following chemotherapy, it is necessary to provide fertility preservation opportunities to young male patients with cancer prior to the commencement of cancer treatment.

16.
Am J Reprod Immunol ; 79(3)2018 03.
Article in English | MEDLINE | ID: mdl-29350445

ABSTRACT

PROBLEM: Since the 1970s, anti-sperm antibodies have been studied as a pathogenic factor contributing to infertility. The complement-dependent sperm-immobilization test (SIT) and quantitative SIT have been used as effective tools for detecting anti-sperm antibodies in clinical settings. These tests have been carried out traditionally by manually counting the number of motile sperm through eye estimation. METHOD OF STUDY: In this study, we developed a novel method using computer-aided sperm analysis. The results were compared with those obtained by the traditional method. RESULTS: The results were identical and 25 of 78 samples tested were positive and 53 samples were negative for sperm-immobilizing (SI) antibodies based on both methods. For SI-positive samples, the values of SI50 obtained using the two methods correlated closely with high co-efficiency. CONCLUSION: Using the novel method, manually counting the number of motile spermatozoa becomes unnecessary. The novel method presented here will increase the objectivity and convenience of using the SIT as a clinical indicator.


Subject(s)
Infertility, Male/diagnosis , Serology/methods , Spermatozoa/immunology , Adult , Autoantibodies/metabolism , Automation, Laboratory , Cells, Cultured , Diagnosis, Computer-Assisted , Humans , Male , Middle Aged , Sperm Motility/immunology
17.
Semin Cell Dev Biol ; 73: 188-198, 2018 01.
Article in English | MEDLINE | ID: mdl-28751253

ABSTRACT

Lysenin, which is an earthworm toxin, strongly binds to sphingomyelin (SM). Lysenin oligomerizes on SM-rich domains and can induce cell death by forming pores in the membrane. In this review, the assembly of lysenin on SM-containing membranes is discussed mostly on the basis of the information gained by atomic force microscopy (AFM). AFM data show that lysenin assembles into a hexagonal close packed (hcp) structure by rapid reorganization of its oligomers on an SM/cholesterol membrane. In case of a phase-separated membrane of SM, lysenin induces phase mixing as a result of pore formation in SM-rich domains, and consequently its hcp assembly covers the entire membrane. Besides the lytic action, lysenin is important as an SM marker and its pore has the potential to be used as a biosensor in the future. These points are also highlighted in this review.


Subject(s)
Microscopy, Atomic Force , Sphingomyelins/chemistry , Sphingomyelins/metabolism , Toxins, Biological/chemistry , Toxins, Biological/metabolism , Sphingomyelins/pharmacology , Thermodynamics , Toxins, Biological/pharmacology
18.
Endocr J ; 65(2): 203-211, 2018 Feb 26.
Article in English | MEDLINE | ID: mdl-29162783

ABSTRACT

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.


Subject(s)
Galactorrhea/diagnosis , Galactorrhea/epidemiology , Hyperprolactinemia/diagnosis , Hyperprolactinemia/epidemiology , Prolactin/blood , Adult , Blood Chemical Analysis/methods , Blood Chemical Analysis/standards , Female , Galactorrhea/blood , Genital Diseases, Female/blood , Genital Diseases, Female/complications , Genital Diseases, Female/epidemiology , Humans , Hyperprolactinemia/blood , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Prevalence , Prolactin/analysis , ROC Curve , Reference Values , Retrospective Studies
19.
Science ; 358(6369): 1431-1434, 2017 12 15.
Article in English | MEDLINE | ID: mdl-29242345

ABSTRACT

Necrosis and ethylene-inducing peptide 1-like (NLP) proteins constitute a superfamily of proteins produced by plant pathogenic bacteria, fungi, and oomycetes. Many NLPs are cytotoxins that facilitate microbial infection of eudicot, but not of monocot plants. Here, we report glycosylinositol phosphorylceramide (GIPC) sphingolipids as NLP toxin receptors. Plant mutants with altered GIPC composition were more resistant to NLP toxins. Binding studies and x-ray crystallography showed that NLPs form complexes with terminal monomeric hexose moieties of GIPCs that result in conformational changes within the toxin. Insensitivity to NLP cytolysins of monocot plants may be explained by the length of the GIPC head group and the architecture of the NLP sugar-binding site. We unveil early steps in NLP cytolysin action that determine plant clade-specific toxin selectivity.


Subject(s)
Arabidopsis/parasitology , Cytotoxins/metabolism , Host Specificity , Phytophthora/metabolism , Plant Diseases/parasitology , Pythium/metabolism , Sphingolipids/metabolism , Toxins, Biological/metabolism , Binding Sites , Crystallography, X-Ray , Cytotoxins/chemistry , Ethylenes/metabolism , Sphingolipids/chemistry
20.
Eur J Obstet Gynecol Reprod Biol ; 211: 146-149, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28260688

ABSTRACT

OBJECTIVE: To evaluate the vascularity of the myometrium after laparoscopic myomectomy sutured by two different methods using contrast-enhanced Magnetic Resonance Imaging. STUDY DESIGN: Twenty-eight women who had symptomatic leiomyomas and underwent laparoscopic myomectomy between June 2013 and July 2014 were included in the present study. In the first half period, continuous sutures were used in 12 patients, and in the latter half period, single interrupted sutures were used in 16 patients. Contrast-enhanced Magnetic Resonance Imaging was used 3 or 6 months after surgery to evaluate vascularity after laparoscopic myomectomy. We defined avascularity index as the percentage of avascular area after surgery to cross sectional area of myoma before surgery. The Wilcoxon rank-sum test was applied to compare avascularity indeces in the two study groups. RESULTS: At 3 months after surgery, avascularity index in continuous sutures group was significantly higher than that in single interrupted sutures group (median 5.0 vs.1.2, p<0.001), suggesting a poorer vascular recovery of the myometrium sutured continuously. CONCLUSION: Simple interrupted suturing might be superior to continuous suturing in terms of vascularity evaluated using contrast enhanced Magnetic Resonance Imaging.


Subject(s)
Myometrium/diagnostic imaging , Myometrium/surgery , Suture Techniques , Uterine Myomectomy/methods , Adult , Female , Humans , Magnetic Resonance Imaging , Myometrium/blood supply , Sutures , Treatment Outcome
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