Search

Purpose The clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in‐house vaginal suppository formulation of progesterone used between 2006 and 2007 for assisted reproductive technology (ART). Methods We retrospectively evaluated the efficacy and safety of chlormadinone acetate by comparing the pregnancy rates and the incidences of birth defects and hypospadias in frozen‐thawed embryo transfer cycles using the in‐house vaginal progesterone and those using chlormadinone acetate for luteal phase support. Results The pregnancy rates in the frozen‐thawed embryo transfer cycles were 31.2% (259/831) with vaginal progesterone for luteal phase support and 31.6% (4228/13 381) with chlormadinone acetate (no significant difference). In the cycles resulting in live birth following administration of chlormadinone acetate between July 2007 and December 2015, the incidence of birth defects was 2.8% (80/2893), and the incidence of hypospadias was 0.03% (1/2893). Conclusions These results indicate that the pregnancy rate following frozen‐thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.

Purpose To demonstrate the benefits of the freeze‐all strategy for in vitro fertilization treatment based on retrospective analyses. Methods Post‐thaw embryo survival rates of slow‐frozen embryos in 294 cycles and vitrified embryos in 12 195 cycles were assessed. Progesterone (P4) and estradiol (E2) levels per mature oocyte by age category were assessed in 9081 cycles and pregnancy rates with fresh embryo transfer and frozen‐thawed embryo transfer by P4 level were assessed in 1535 cycles. Results The survival rates of frozen‐thawed embryos were 92.5% with slow freezing and 99.1% with vitrification. P4 levels on the day of human chorionic gonadotropin (hCG) injection showed a trend toward an increase with age. The pregnancy rate per mature oocyte with fresh embryo transfer decreased dependently upon P4 level, while that with frozen‐thawed embryo transfer was not affected by P4 level. The pregnancy rates with frozen‐thawed embryo transfer were higher than those with fresh embryo transfer in patients aged 42 years or younger. Conclusions The freeze‐all strategy is a valuable treatment option which allows the separation of an embryo transfer cycle from an oocyte retrieval cycle, especially for patients with high P4 levels at oocyte retrieval and patients of advanced maternal age.

Anti-N-methyl-d-aspartate receptor (NMDAR) limbic encephalitis is the most common form of paraneoplastic encephalitis that is associated with teratomas. Because tumor removal leads to better clinical outcomes, it is essential to reveal the location of the teratomas. This is the first reported case of anti-NMDAR encephalitis associated with teratoma of the fallopian tube. Salpingo-oophorectomy improved neurological symptoms and immunohistochemical examinations indicated the expression of NMDAR on neuroglial cells within the fallopian tube teratoma. Teratomas of the fallopian tube cause anti-NMDAR encephalitis; the imaging analysis and exploratory laparoscopies of the fallopian tube as well as of the ovary should be considered. Surgical removal of both fallopian tubes and ovaries with a normal appearance should be considered for patients in whom immunotherapy is not effective.

Background High performance liquid chromatography and immunological and enzymatic methods are known as the methods for HbA1c measurement. However, the differences in the principles of the methods may cause slight discrepancies, which become problems especially in the regions where hemoglobinopathies that have high HbF concentrations are commonly seen. In this report, we discuss the effect of HbF on the HbA1c measurement by the enzymatic method (BM Test HbA1c) which can be applied to automatic analyzer of high sample throughput. Methods Thirty-five samples (HbF concentration: between 1.4 and 90.1%) and 68 samples (HbF concentration: Results The high and positive correlation coefficient was demonstrated between the enzymatic and International Federation of Clinical Chemistry methods for the samples with normal HbF concentration. The samples with high HbF concentration exhibited high and positive correlation coefficient, although the figure is lower than that of the normal HbF concentration group. Conclusions BM Test HbA1c revealed a high and positive correlation with high performance liquid chromatography and International Federation of Clinical Chemistry reference methods. However, the HbA1c values by BM Test HbA1c and high performance liquid chromatography method were lower than those by International Federation of Clinical Chemistry reference method when the HbF concentration was high. BM Test HbA1c had some deviation from the International Federation of Clinical Chemistry reference method, while no significant interference was seen when the HbF values were less than 15%. When HbF is higher than 15%, however, the interpretation of HbA1c by BM Test may require some special consideration.

Objective To compare follicular fluid and serum concentrations of anti-Mullerian hormone (AMH) as predictors of the outcome of assisted reproduction. Study design This observational study enrolled 58 women who were undergoing IVF or ICSI treatment with the long stimulation protocol. Patients diagnosed as having PCOS were excluded. Serum and follicular fluid AMH levels were assessed as predictors of clinical pregnancy. Results Both the serum and follicular fluid AMH levels were higher in the clinical pregnancy group than in the failed group. A significant correlation was found between the serum and follicular fluid AMH levels, but a discrepancy was observed in some patients with elevated AMH levels in the follicular fluid or serum alone. Assisted reproductive treatment resulted in clinical pregnancy in all of the patients with elevated AMH levels in the follicular fluid (>40 pM) or in the serum (>10 pM). The ROC-AUC for the combination of follicular and serum AMH was 0.772, which was relatively higher than that for either the serum AMH (AUC: 0.691) or follicular fluid AMH (AUC: 0.688) alone. Conclusion(s) Elevated AMH levels in either the serum or follicular fluid appeared to be predictive of clinical pregnancy, even if AMH levels in other fluids were low. This is a pilot study with preliminary data that need further confirmation.

A gate drive printed circuit board (PCB) was developed for a 50-mm-wide modular-design thin power unit that uses two double-sided cooled power modules in an uninterruptible power system (UPS). A conventional gate drive PCB has a concentrated gate power supply circuit that uses a large transformer and has a conventional pulse open-phase detection circuit that occupies a large mounting area. Thus, the gate drive PCB had to be downsized to make it as narrow as the thin power unit. Consequently, two circuit configurations were proposed to reduce mounting area: one was to decentralizes a gate power supply circuit using a pre-driver with a built-in DC/DC controller and a small distributed transformer, and the other was to downsize the pulse open-phase detection circuit. As a result, the gate drive PCB was downsized to 50 mm × 220 mm, 56 % smaller than the conventional one. Thus, a very thin power unit using a 50-mm-wide PCB was accomplished, and a UPS was developed that is 30 % smaller in volume than the conventional one.

This article reports on efforts to overcome common hurdles that were faced during population-based screening for common hemoglobinopathies in the United Arab Emirates. An Internet-based approach was designed and implemented to increase the acceptance of the screening program. The process involved: an awareness campaign, a simple bilingual (Arabic/English) online consent form and registration process, the use of a barcode for sample labeling, an equipment upgrade, electronic communication of a successful registration process, test results, and a counseling process. Before the implementation of the Internet-based system, great concern was noted among the clients in terms of the availability of accurate and timely test results, the need for pretest and post-test counseling, and the way that their personal health information was handled. Lapses in information exchange between the clients who participated in the screening program for the carrier state of inherited disorders and the screening laboratory posed significant challenges. The emphasis on confidentiality and the ease of access to services was instrumental in increasing the level of acceptance of these services in our community. Based on an analysis of > 10,000 samples, we conclude that Internet-based reporting holds much promise for improving the quality of care that clients receive.

コーヒー飲用によるストレス緩和作用についてはよく知られているが, その揮発性成分の効用に着目した研究は数少ない。本研究では, 焙煎したコーヒー豆の揮発性成分とストレスとの関連性を明らかにするために, マウスを用いて種々の行動薬理学的実験を行い, コーヒー揮発性成分のストレス緩和作用について検討した。高架式十字迷路試験において, コーヒー揮発性成分は自発運動量に影響を及ぼすことなく, オープンアームへの滞在時間および進入回数を増加させた。また, ペントバルビタールによる睡眠時間は, コーヒー揮発性成分の曝露により明らかに延長した。オープンフィールド試験および強制水泳試験では, コーヒー揮発性成分の効果は見られなかった。以上より, 焙煎したコーヒー豆の揮発性成分はマウスの覚醒水準を低下させ, 抗不安様のストレス緩和作用を発揮することが示唆された。

Gene fusion is a very rare mechanism that produces hemoglobin variants. Less than ten types of β-like hybrid globins have been reported to date. Herein we identified the first hybrid hemoglobin between Gγ- and β-globins in a five-year-old Korean male who had thalassemia minor feature and triplication of the HBA2 gene (αα/αααα). The novel globin originated from a 27,707-base pair deletion spanning from the HBG2 to HBB gene (NG_000007.3:g.42947_70653del). Its protein sequence included 13 N-terminal amino acids from Gγ-globin, five common amino acids from Gγ- and β-globins, and 128 amino acids from β-globin (Gγ through 13; β from 19). Molecular genetic analyses characterized the hybrid DNA and RNA. Mass spectrometry and de novo protein sequencing successfully identified the fusion peptide in the hybrid hemoglobin. We named this novel hybrid Hb Gγ-β Ulsan. The novel hemoglobin constituted 37.0% of the total hemoglobin and showed reduced oxygen affinity.

Glycogen storage disease type Ia (GSD Ia) leads to disturbed glycogenolysis and gluconeogenesis due to a deficiency in the enzyme glucose-6-phosphatase. A patient with GSD Ia showed hypoglycemia and proteinuria without dietary management since early pregnancy. The patient's condition was complicated by hypertension with increase in proteinuria at 22 weeks of gestation. In spite of administration of antihypertensive drugs and dietary management, the disease became more severe with deterioration in the fetal status and inhibition of fetal growth. Thus, a cesarean section was performed at 26 weeks of gestation. The delivered male infant weighing 412 g died at 2 days after birth. The patient's blood pressure had normalized within 3 months after delivery, while proteinuria persisted.

The pollutant lead (Pb-plumbum-black lead) is toxic. Organisms in nature cannot naturally suppres its concentration. Special Capital Region of Jakarta is a metropolitan city with densest highway traffic in the world, especially in and around the Marunda area, which is the location 24-hour non-stop loading and unloading activities of various businesses. With that environmental condition, in the Marunda area of Jakarta lies the Naval base where the Marine Taskforce Personnel are stationed. The environmental condition allows the personnel to be quite frequently exposed to lead. This research aims to detect the ALAD gen mutation in the Marine Taskforce personnel as a mapping of the level of ALAD gene mutation frequency in the Marines of the Jakarta area. The research was conducted in a period of [insert data]. The sampling applied the purposive sampling method with a sample size of 100 Marines. The research results show that there was no ALAD gene mutation in the 100 Marines. This could depict a good energy status of the 100 Marines stationed in the Marunda area. With no mutation found in the ALAD gene, that means the process of oxygen binding with hemoglobin has no disruption in energy synthesis.

Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity and its receptor mRNA have been reported in the supraoptic and the paraventricular nucleus (SON and PVN, respectively) and PACAP has been implicated in the regulation of magnocellular neurosecretory cell function. To examine the site and the mechanism of the action of PACAP in the neurosecretory cells, we measured AVP release from SON slice preparations and the cytosolic Ca2+ concentration ([Ca2+]i) from single dissociated SON neurons. PACAP at concentrations from 10(-12) to 10(-7) M increased [Ca2+]i in dissociated SON neurons in a dose-dependent manner. The patterns of the PACAP-induced [Ca2+]i increase were either sustained increase or cytosolic Ca2+ oscillations. PACAP (10[-7] M) increased [Ca2+]i in 27 of 27 neurons and glutamate (10[-4] M) increased [Ca2+]i in 19 of 19 SON neurons examined, whereas angiotensin II (10[-7] M) increased [Ca2+]i in only 15 of 60 SON neurons examined. PACAP at lower concentrations (10[-10] to 10[-8] M) increased [Ca2+]i in 70-80% of neurons examined. Although the onset and recovery of the PACAP-induced [Ca2+]i increase were slower than those observed with glutamate, the spatial distribution of the [Ca2+]i increases in response to the two ligands were similar: [Ca2+]i increase at the proximal dendrites was larger and faster and that at the center of the soma was smaller and slower. The PACAP-induced [Ca2+]i responses were abolished by extracellular Ca2+ removal, the L-type Ca2+-channel blocker, nicardipine, or by replacement of extracellular Na+ with N-methyl D-glucamine, and were partially inhibited by the Na+-channel blocker, tetrodotoxin. The N-type Ca2+-channel blocker, omega-conotoxin GVIA did not significantly inhibit the PACAP-induced [Ca2+]i responses. Furthermore, PACAP (10[-7] M) as well as glutamate (10[-4] M) increased AVP release from SON slice preparations, and extracellular Ca2+ removal or nicardipine inhibited the AVP release in response to PACAP. These results indicate that PACAP enhances Ca2+ entry via voltage-gated Ca2+ channels and increases [Ca2+]i, which, in turn, stimulates somatodendritic vasopressin release by directly activating PACAP receptors on SON neurons. The results also suggest that PACAP in the SON may play a pivotal role in the control of the neurohypophyseal function at the level of the soma or the dendrites.

Human seminal plasma allergy in women is uncommon, but causes a variety of serious reactions, including urticaria, dyspnea and vomiting, in those that are affected. Semen barriers, such as condoms, are the most widely advocated method for avoiding these reactions. However, this is not acceptable to couples who wish to have children. We present a case of a woman with human seminal plasma allergy who became pregnant after the eighth cycle of artificial insemination using washed sperm from her spouse.

This paper describes a novel high-Q active inductor circuit configuration composed of an operational transconductance amplifier (OTA) and an input RC network. Due to the phase rotation made by the input RC network, the active inductor circuit provides high-Q inductive impedance at higher frequencies. According to circuit simulation with design-kit of a 90-GHz-fT SiGe HBT technology, an inductance of more than 0.53nH and Q of more than 80 can be obtained at quasi-millimeter-wave frequency, 24GHz. The Q value is tunable by controlling the transconductance of the OTA. These features are also ensured by means of measurements of fabricated active inductor circuit. Since the active inductor circuit needs small chip area, which is 25% of a conventional passive inductor, the proposed active inductor contributes to implement a cost-effective high-Q notch filter for frequencies up to quasi-millimeter-wave frequencies.

Problem Inflammatory changes frequently occur in cases of second trimester miscarriage or pre-term delivery, but little attention has been paid to this association with recurrent miscarriage. As interleukin-6 and interleukin-8 are inflammatory cytokines reported to be associated with bacterial vaginosis, intrauterine infections, and pre-term delivery, we here investigated whether they might have predictive value for spontaneous abortion in recurrent cases. Method of study Cervical mucus and sera were collected at 4–5 weeks’ gestation from a total of 59 patients with a history of two or more unexplained consecutive first trimester miscarriages, and examined by enzyme-linked immunosorbent assay. Patients then were followed up without medication and their pregnancy outcomes were compared with the test results. Results Of a total of 59 patients, 13 (22%) miscarried subsequently. Both IL-6 and IL-8 in cervical mucus were significantly higher in patients who miscarried subsequently than in those who had a live birth. In addition, there was no correlation between cervical mucus and serum concentrations of IL-6 and IL-8 take at the same time, and there was no relation with serum IL-6 and IL-8 levels between the two groups. Conclusion Cervical IL-6 and IL-8 might have predictive value for cases of recurrent miscarriage.

A small modular unit for a power converter system with long lifetime DC-link capacitors is proposed. To reduce the ripple current stress of DC-link capacitors and to improve their lifetime by limiting temperature rises, low phase-to-phase-impedance busbars are selected. Consequently, in a power converter system whose size is 101 L, operating at a rated power of 100 kVA, DC-link capacitors achieve a lower temperature rise of 22 K, which means that the capacitor lifetime can be estimated to be over 15 years.

Based on a modular design concept, 100 kVA uninterruptible power system using double-sided air-cooled power module has been developed. An efficient air-cooling system suitable for the double-sided cooled power module is developed, and the volume of the converter adopted developed double-sided air-cooling system becomes less than half compared to the conventional converter based on single-sided cooling system. The width of the modular unit composing the rectifier, inverter, and chopper is only 50 mm so as to stack some units side by side in a smaller space and higher maintainability is achieved. The volume as well as the footprint of the developed UPS is smaller than the conventional one by 30 %.

Among high power conversion systems, several power modules are often connected in parallel, and ideally should be operated synchronously during their switching. Actually, current imbalances occur due to an asymmetry of current paths on busbars connecting these power modules. This paper deals with the problem of current imbalances between paralleled power modules. First, the general occurrence of imbalanced currents is demonstrated. Next, an original design technique for current equalization in a very thin power conversion unit is presented. Finally, the validity of this proposed principle is shown in simulated results.

Abnormalities of hemoglobin (Hb), or hemoglobinopathies, are classified into Hb abnormalities that arise from altered quality induced mainly by amino acid substitution. Furthermore, thalassemia is a quantitative abnormality of normal Hb. Most hemoglobinopathies are inherited disorders. The abnormal Hb known to date comprise more than 210 types in the Japanese population. The rate of thalassemia in Japan is less than that in endemic regions, but the frequencies of β- and α- thalassemias are 1/1,000 and 1/3,500 in the general population, respectively, so not particularly rare. The mutation spectrum is different from that of endemic regions, probably because Japanese have been historically isolated islanders. Japanese hemoglobinopathy generally has minor symptoms, which are different from those in endemic areas where thalassemia exhibits major clinical manifestations. This might be why useful knowledge is obtained in our laboratory which concentrates on detailed observation of clinical data in addition to genetic analysis. We have, in fact, discovered new clinical characteristics and the significance of hemoglobinopathy, especially of minor or intermediate thalassemia. This approach is quite different from that in other countries coping with only the major type. By focusing on this novel approach, we aim to contribute to improving diagnostic technology for patients.

Here we describe a Japanese patient with mild β-thalassemia (β-thal) with an intact β-globin gene but a new missense mutation of c.947G A or p.C316Y in the erythroid Krüppel-Like Factor (KLF1) gene which is strongly associated with the expression of the β-globin gene. The association of the KLF1 mutation with β-thal, is here described. The p.C316Y mutation occurred at one of the cysteines that constitute the second zinc finger motif of KLF1, and would have changed the zinc finger conformation to impair the DNA binding properties or the promoter function of the β-globin gene. Our expression study found that the mutant KLF1 gene had a markedly negative effect on the β-globin gene expression, or 7.0% of that of its normal counterpart. A presumed heterozygous state, or equimolar presence of the mutant and normal KLF1s reduced the expression rate to 70.0% of the normal alone. This degree of the decrease may explain the very mild phenotype of the patient's β-thal. Furthermore, the patient's whole-exome analysis using next-generation sequencing revealed that the β-thal defect is caused by only this KLF1 gene mutation. The Hb A2 and Hb F levels that are frequently elevated in KLF1 mutations were elevated by 4.1 and 1.3%, respectively, in this case. The contribution to their elevation by KLF1: p.C316Y is uncertain.

BACKGROUND: The clinical significance of complement is unclear in patients with unexplained recurrent miscarriage, though low levels of complement 3 (C3) and/or complement 4 (C4) are reported to be associated with the antiphospholipid syndrome (aPS). We therefore investigated whether C3 and C4 have a predictive value for subsequent miscarriages. METHODS: In total, 215 patients with a history of two consecutive first-trimester miscarriages and no abnormal chromosomes in either partner, no uterine anomalies and no antiphospholipid (aPL) antibodies were examined. Blood tests for C3, C4, total haemolytic complement (CH50), immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were performed before subsequent pregnancy. Patients were then followed up without treatment, and their pregnancy outcomes were compared with their previous blood test results. RESULTS: From 215 pregnant patients, 45 subsequently miscarried, whereas the remainder had a live birth. There was no relation with serum CH50, IgG, IgA and IgM levels, but C3 and C4 levels in patients with subsequent miscarriage were significantly higher than in those whose pregnancy was successful. CONCLUSION: In patients with two previous miscarriages, C3 and C4 levels were higher in those women who had a third miscarriage, than in women that went on to have a live birth.

1 To determine the binding characteristics of a highly potent agonist for protease-activated receptor-2 (PAR2), 2-furoyl-Leu-Ile-Gly-Arg-Leu-amide (2-furoyl-LIGRL-NH(2)), whole-cell binding assays were performed utilising a radioactive ligand, [(3)H]2-furoyl-LIGRL-NH(2). 2 Specific binding of [(3)H]2-furoyl-LIGRL-NH(2) was observed in NCTC2544 cells, dependent upon PAR2 expression, and competitively displaced by the addition of unlabeled PAR2 agonists. Scatchard analysis of specific saturation binding suggested a single binding site, with K(d) of 122+/-26.1 nM and a corresponding B(max) of 180+/-6 f mol in 3.0 x 10(5) cells. 3 The relative binding affinities of a series of modified PAR2 agonist peptides obtained from competition studies paralleled their relative EC(50) values for Ca(2+) mobilisation assays, indicating improved binding affinities by substitution with 2-furoyl at the N-terminus serine. 4 Pretreatment of cells with trypsin reduced specific binding of [(3)H]2-furoyl-LIGRL-NH(2), demonstrating direct competition between the synthetic agonist peptide and the proteolytically revealed tethered ligand for the binding site of the receptor. 5 In HCT-15 cells endogenously expressing PAR2, the binding of [(3)H]2-furoyl-LIGRL-NH(2) was displaced by addition of unlabeled ligands, Ser-Leu-Ile-Gly-Lys-Val (SLIGKV-OH) or 2-furoyl-LIGRL-NH(2). The relative binding affinity of 2-furoyl-LIGRL-NH(2) to SLIGKV-OH was comparable to its relative EC(50) value for Ca(2+) mobilisation assays. 6 The binding assay was successfully performed in monolayers of PAR2 expressing NCTC2544 and human umbilical vein endothelial cells (HUVEC), in 96- and 24-well plate formats, respectively. 7 These studies indicate that [(3)H]2-furoyl-LIGRL-NH(2) binds to human PAR2 at its ligand-binding site. The use of this radioligand will be valuable for characterising chemicals that interact to PAR2.

Protease-activated receptor 2 (PAR2) belongs to the PAR family (PAR1 to PAR4), which is activated by serine proteases (trypsin, tryptase, etc.). In this study, we evaluated the role of PAR2 in allergic inflammation of airways using PAR2-deficient (PAR2−/−) mice. In wild-type mice, infiltration of eosinophils and high eotaxin content were found in bronchoalveolar lavage fluid (BALF) after ovalbumin (OA) sensitization and following challenge. In contrast, both OA-induced infiltration of eosinophils and increase of eotaxin content were abrogated in BALF from PAR2−/− mice. The activation of PAR2 might be essential in the production of eotaxin and consequential allergic inflammation in airways. Keywords:: protease-activated receptor 2, eosinophil, eotaxin

We report a Japanese woman with 46,XX,dup(16)(p13.11p13.3), who closely resembled the phenotype of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM # 301040). Although she never had alpha-thalassemia, she showed characteristic clinical features including severe mental retardation, characteristic facies and behavior. ATR-X is caused by mutations of the ATRX gene. Although the function of ATRX protein has remained unclarified, it is thought to be involved in the regulation of several genes. The only target gene identified so far is the alpha-globin gene at 16p13.3. Clinical similarity among patients with ATR-X and dup(16)(p13.11p13) may indicate that some target genes regulated by ATRX reside in the duplicated region between 16p13.11 and 16p13.3, and that these genes are abnormally upregulated in ATR-X differently from the alpha-globin gene.

A new GγAγ(δβ)0-thalassemia (thal) was found in six unrelated Japanese individuals, and characterized by a method employing only polymerase chain reaction (PCR) and direct sequencing. This GγAγ(δβ)0-thal mutation has removed a fragment of about 27 kb of DNA, that starts approximately 2.8 kb downstream of the Aγ-globin gene and ends in the L1 repeat sequence, 7.0 kb downstream of the β-globin gene. The 5′ breakpoint is similar to that of the previously reported Japanese GγAγ(δβ)0-thal (called here Jpn type 1 for convenience). However, the 3′ endpoint is quite different. This new Japanese δβ-thal, designated as Japanese type 2 (Jpn type 2), shows a deletion rather similar to Turkish type 3 δβ-thal but with 5′ and 3′ breakpoints located inside the deletion of Turkish type 3. A mutation-specific gap PCR was designed to diagnose patients with the Jpn type 2 GγAγ(δβ)0-thal. The identified carriers exhibited a thalassemia minor.

Thalassemia is relatively rare in Japan. Of 387 β-thalassemia cases of Japanese, homozygotes for β + - and β 0 -thalassemias were twenty-two (5.7%) and one (0.26%), respectively. The rest (94%) were of β - thalassemia trait. Ten different kinds of β-thalassemia mutations comprised about 80% of all cases. Half of these "common" mutations were unique to Japanese and another half were possibly from abroad. Sixty-nine α -thalassemia cases were analyzed, in which HbH and α - thalassemia trait comprised nineteen and fifty, respectively. Most of the α o - and α + -thalassemia chromosomes were of Southeast Asian type (--SEA) and -α 3.7 type, respectively. The frequency of α + - thalassemia as well as triplication of α -globin gene was high in northern Japan. Recent increase in the number of immigrants from Southeast Asia seems to raise the number of α -thalassemia found in Japan. They comprise at least 20% of the α -thalassemia. Six mutants classified into dominant-type β-thalassemia were found. All of them exhibited moderate anemia and marked anisopoikiocytosis. Heinz body varied in degree from copious to rare or even absent. Any mutation at initiation codon demonstrated marked microcytosis and erythremia. The breakpoint determination for large deletion-type thalassemia became feasible by estimation of gene dosage and PCR. Thus, the precise breakpoints for Filipino-type α o -thalassemia (--FIL) and Japanese type-2 δβ-thalassemia were disclosed. The genetic diagnosis for these thalassemias are now readily conducted by gap PCR. The characterization of several new large deletions is being carried out.

We describe a 6-year-old girl and her mother with dominant β-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115,\(G\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{C} C[Ala] \to G\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{A} C[Asp]\)). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at β-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant β-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.

We encountered two patients with abnormally low glycohemoglobin levels in spite of normal plasma glucose levels. Since the presence of an abnormal hemoglobin was suggested by high-performance liquid chromatography (HPLC), gene analysis of these two patients was conducted by single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing, and Hb Kamakura with one base substitution (beta3 Leu --> Val) in the beta globin gene was detected in both patients. There was been only one report of Hb Kamakura in Kanagawa Prefecture, and our patients represent the second and third cases, respectively.

Summary. We identified a Japanese family with a β-thalassaemia trait and hereditary elliptocytosis (HE). We studied five members of this family. One was normal, one had only the β-thalassaemia trait, one had heterozygous HE, and two had compound heterozygous β-thalassaemia trait and HE. The last two had already undergone splenectomy. The molecular profile of β-thalassaemia was consistent with that of Hb Gunma: codon 127/128CAGGCT(Gln–Ala) CCT(Pro). Analysis of erythrocyte membrane proteins revealed a partial deficiency of protein 4·1 in all those with HE, whereas the spectrin content was within the normal range. Each heterozygous family member with either the β-thalassaemia trait or HE was asymptomatic, whereas the two with both β-thalassaemia and HE had marked red blood cell deformities and haemolysis. The abnormalities of the red blood cells in patients with the β-thalassaemia trait might be enhanced by association with HE owing to a protein 4·1 deficiency.

To study the effects of maxillary advencement surgery, morphological changes were evaluated on the basis preoperative and postoperative cephalograms at rest position in 11 patients with maxillary hypoplasia associated with cleft palate (cleft palate group) and were compared with those in 11 patients with maxillary hypoplasia without cleft palate (control group).1. The amount of advancement in the cleft palate group (4.6±1.4mm) did not significantly differ from that in the control group (5.1±1.0mm).2. The length of the soft palate (PNS-Uv) increased slightly in both groups; however, the mean difference between before and after surgery, in the cleft palate group (2.8mm) was slightly but not significantly less than that in the control group (3.9mm).3. The depth of the pharynx increased in both groups after surgery. There was a significant difference between the control group (5.5mm) and the cleft palate group (2.9mm).4. The inclined angle of the soft palate (∠ANS-PNS-Uv) increased in almost all patients in both groups (5.0 degrees in the cleft palate group and 5.8 degrees in the control group).5. There was no significant difference between the two groups in the change in the shortest distance between the soft palate and the posterior pharyngeal wall after surgery (-0.7mm in the cleft palate group and -0.6mm in the control group).

β-Thalassemia (β-thal), especially β-thalassemia major (β-TM), is reported to be related to reactive oxygen species (ROS) and enhanced oxidation status. It is reflected by increased malondialdehyde (MDA), by membrane lipid peroxidation and decreased by the newly developed total antioxidant capacity (TAC). However, there is less evidence for β-thal minor and Hb H (β4) disease on its association with oxidation status. On the other hand, hemolysis by glycerol lysis time (GLT50) is invariably prolonged in thalassemia. The reason for the prolongation of GLT50 is not well understood. The aim of this study was to investigate the oxidation state in β-thal minor and Hb H disease and to find out the association of the oxidation with the prolongation of GLT50. Blood samples from 39 subjects (33 with β-thal minor, six with Hb H disease) were collected from individuals living in Japan. The clinical screening tests and molecular identification of the thalassemias were performed. Malondialdehyde and TAC were measured using spectrophotometric analyses. In β-thal minor and Hb H disease, the plasma MDA level was significantly elevated and the TAC reduced. A highly reversed correlation between MDA and TAC was noted. Their GLT50 levels were evidently prolonged, and the GLT50 has significant correlations with MDA and TAC. β-Thalassemia minor and mild Hb H disease are evidently in a milieu of reduced redox state, and GLT50 prolongation in β-thal minor and Hb H disease has a close correlation with the oxidation state, possibly by oxidative impairment of the membrane protein of the red cell.

The levels of polyamines, N-acetylpolyamines, and GABA in the cerebral cortex and brainstem of rat brain after completion of pentylenetetrazol (PTZ)-induced kindling were investigated. Pretreatment with the polyamine oxidase inhibitor MDL72527 caused an accumulation of N1-acetylspermidine and N1-acetylspermine in normal rats. After a kindling seizure, the levels of N-acetylpolyamines were elevated, particularly in the cerebral cortex, indicating activation of polyamine interconversion. The levels of putrescine and GABA were lower in kindled rats pretreated with MDL72527. In addition, pretreatment with MDL72527 enhanced the seizure susceptibility to PTZ in normal rats. These results suggest that the polyamine interconversion pathway is involved in brain excitability, probably through the regulation of putrescine and GABA levels.

The effects of intracerebroventricular (i.c.v.) administration of adrenomedullin (AM) on plasma oxytocin (OXT), c-Fos protein (Fos), and c-fos messenger RNA (mRNA) in the paraventricular (PVN) and supraoptic nuclei (SON) of the rat were investigated using RIA for OXT, immunohistochemistry for Fos, and in situ hybridization histochemistry for c-Fos mRNA. Central administration of AM caused a significant increase in the plasma OXT level. Intracerebroventricular administration of AM caused a marked induction of Fos-like immunoreactivity (LI) in the PVN and in the dorsal parts of the SON. In the PVN and SON, OXT-LI cells predominantly exhibited nuclear Fos-LI in comparison with arginine vasopressin-LI cells. In situ hybridization histochemistry revealed that the induction of c-fos mRNA in the PVN and SON was increased in a dose-related manner 30 min after i.c.v. administration of AM. This induction was reduced by pretreatment with the AM receptor antagonist, human AM-(22-52)-NH2. These results suggest that central AM is responsible for activating the neurosecretory cells in the PVN and SON via selective AM receptors, and that AM stimulates the secretion of OXT by activating hypothalamic OXT-producing cells.

Obwegeser II method was applied to an 18-year-old male patient with severe progenia and open bite.The reasons for selecting this method were as follows;1. His lateral cephalometric analysis revealed only excessive mandibular protrusion without any maxillary abnormality.2. It was necessary for the mandible to be set back 14 mm posteriorly to obtain the ideal intermaxillary occlusion.3. The anteroposterior width of his mandibular ramus was bilaterally narrow.4. Furthermore, severe open bite still remained at the end of pre-surgical orthodontic treatment.Postoperative cephalometric analysis revealed both skeletal stability and harmonious balance.One of the advantages of this method is that a bigger contact area can be obtained between the two separated bone segments compared with that of sagittal split ramus osteotomy when the width of the mandibular ramus is narrow. In addition, it was suggested that a longer distance between the mandibular second molar and the anterior edge of the mandibular ramus could be a good indication for this operation.