Geographical distribution and disease associations of the CD45 exon 6 138G variant.

CD45 is crucial for normal lymphocyte signalling, and altered CD45 expression has major effects on immune function. Both mice and humans lacking CD45 expression are severely immunodeficient, and single-nucleotide polymorphisms in the CD45 gene that cause altered splicing have been associated with autoimmune and infectious diseases. Recently, we identified an exon 6 A138G polymorphism resulting in an increased proportion of activated CD45RO T cells and altered immune function. Here we report a significantly reduced frequency of the 138G allele in hepatitis C Japanese patients and a possibly reduced frequency in type I diabetes. The allele is widely distributed in the Far East and India, indicating that it may have a significant effect on disease burden in a large part of the human population.

Microwave endometrial ablation for menorrhagia caused by large submucous myomas.

AIM: To examine the feasibility of microwave endometrial ablation (MEA), using a curved microwave applicator, in patients with menorrhagia caused by a submucous myoma greater than 3 cm in diameter, which is among the contraindications for conventional endometrial ablation. METHODS: Patients included were refractory to medication, more than 45 years of age, and due to undergo hysterectomy to treat menorrhagia as a result of submucous myomas, although they hoped to avoid hysterectomy. Three patients underwent MEA at 2.45 GHz using a curved microwave applicator and microwave tissue coagulator to treat menorrhagia. Patients 1, 2 and 3 had submucous myoma nodes 4.5, 5.0 and 13 cm in diameter respectively. The applicator was guided under transabdominal ultrasonography to microwave irradiation sites arranged to cover the entire uterine lining based on preoperative magnetic resonance images. MEA was performed under general anesthesia or spinal anesthesia. Microwaves were irradiated at 40 W for 50 s for single irradiation sites. RESULTS: Patient 1 became amenorrheic after the second MEA, which was performed 2 months after the first operation. Patients 2 and 3 became amenorrheic after the first MEA. Postoperative abdominal pain was controllable by a suppository of non-steroidal anti-inflammatory drugs. The patients were discharged the day after the operation. No remarkable complications were encountered during or after surgery. CONCLUSION: Microwave endometrial ablation improves menorrhagia caused by large submucous myomas when the microwave applicator reaches all parts of the uterine cavity.

Microwave power and duration without extrauterine thermal damage in microwave endomyometrial ablation at 2.45 GHz.

AIM: We investigated microwave power and duration of use, which does not affect extrauterine organs, in order to treat organic menorrhagia caused by myomas or adenomyosis. METHODS: Electric fields around a microwave applicator at a frequency of 2.45 GHz were calculated using the finite element method with commercially available software for analysis of electromagnetic fields. Transient temperature distributions around the applicator were obtained by numerically solving the bioheat transfer equation during microwave irradiation for 120 s in the human uterus and swine liver. We compared areas enclosed by the 60 degrees C isotherm obtained using numerical simulations and necrosis areas after microwave irradiation. Postoperative avascular areas in a Gd-enhanced MRI of a uterus enlarged by adenomyosis after clinical microwave endomyometrial ablation were compared with numerical simulations. RESULTS: There was good agreement between the calculated results and the experiments. At 40 W of output power for 50 s of duration and 64.5 W for 100 s, the depth of the necrotized uterine wall did not increase beyond 7 mm and 11 mm, respectively, either in the calculations or the experiments. Generally, the 50 degrees C isotherm was located approximately 2 mm external to the 60 degrees C isotherm in temperature distributions. The Gd-enhanced MRI after the operation depicted avascular areas, which agreed with the results of numerical simulations. CONCLUSIONS: The myometrial portion of a uterine wall > or = 13 mm throughout the uterus irradiated for < or = 64.5 W for 100 s is sufficient to avoid thermal damage of the extrauterine organs during microwave endomyometrial ablation.

Disease associations and altered immune function in CD45 138G variant carriers.

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.

Occlusion of the external cervical os after conization in a postpuerperal amenorrheic woman.

INTRODUCTION: Complete occlusion of the cervical canal following conization is an uncommon complication. CASE REPORT: We encountered a case in a woman with lactation amenorrhea who after conization to treat cervical intraepithelial neoplasia (CIN) 3 developed hematometra and did not resume menstruation. This case was diagnosed early by ultrasonic tomography and magnetic resonance imaging (MRI). CONCLUSION: Postpuerperal amenorrheic women should be managed with care because of the increased risk of occlusion of the cervical duct after conization.

The importance of studying pressure-flow for predicting postoperative voiding difficulties in women with stress urinary incontinence: a preliminary study that correlates low Pdet x Qave with postoperative residual urine.

We evaluated the parameters of preoperative pressure-flow for predicting the postoperative voiding difficulties in women with stress urinary incontinence. The preoperative urodynamic study records of 14 women treated using the tension-free vaginal tape (TVT) procedure were retrospectively analyzed. Of the patients treated with the TVT procedure, urinary retention occurred in one patient, and three had a residual urine volume of more than 30 ml. All patients became completely free of stress urinary incontinence postoperatively. The lowest Pdet max (5 cmH(2)O) in the preoperative pressure-flow study was found in a patient with a remarkable postoperative residual urine volume of more than 50 ml. The second lowest Pdet max value (8 cmH(2)O) was seen in a patient with postoperative urinary retention, whose residual urine volume, however, decreased to almost zero 1 year after the operation. The preoperative Pdet max x Qave values were remarkably low for these three patients, including the one with the lowest Pdet max, with a post-void residual urine volume of more than 30 ml. The plots of Pdet max x Qave versus the age of patients show that the Pdet max x Qave values tend to decrease with aging. The preoperative Pdet max x Qave value can be an important parameter for predicting increased residual urine after TVT sling surgery.

Successful microwave endometrial ablation in a uterus enlarged by adenomyosis.

Adenomyosis can cause severe menorrhagia, which is a common indicator of the need for hysterectomy. None of the ablative techniques developed over the last two decades are of use in treating menorrhagia in a uterus enlarged by deep adenomyosis. Using a curved microwave applicator specifically developed for enlarged uterine cavities, microwave endometrial ablation at a frequency of 2.45 GHz was successfully applied in the treatment of menorrhagia in a patient with adenomyosis and an enlarged uterine cavity 12 cm in length. Two weeks after the operation, the patient experienced a menstrual period of ten days with no flooding. Menstrual duration gradually decreased to six days over the following six months. The quality of life score recovered to within the normal range six months after the operation. The post-operative sub-endometrial low signal intensity zone on the T2-weighted magnetic resonance images, which corresponds to the region of necrotic tissue, vanished 12 months after the operation. Although microwave endometrial ablation using the curved applicator could not treat bleeding from deep adenomyosis lesions, it improved menorrhagia in the uterus, which would conventionally require a hysterectomy.

Microwave endometrial ablation for an enlarged uterus.

INTRODUCTION: An enlarged uterus of more than 12 cm in cavum length with a distorted cavity is a contra-indication for conventional ablative techniques. It is difficult to perform satisfactory endometrial ablation in a large uterus with submucosal myomas using straight instruments. A new curved microwave applicator 4 mm in diameter was developed for microwave endometrial ablation (MEA) for uteri with an enlarged distorted uterine cavity. METHOD: For three patients of menorrhagia due to submucosal myomas with cavum lengths 13 to 15 cm, MEA was performed using the curved applicator. RESULTS: Menorrhagia was improved in each case. No complications were encountered. CONCLUSION: A large number of hysterectomies could be avoided using the new curved microwave applicator.

A high-frequency polymorphism in exon 6 of the CD45 tyrosine phosphatase gene (PTPRC) resulting in altered isoform expression.

CD45 (leukocyte common) antigen is a hemopoietic cell-specific tyrosine phosphatase essential for antigen receptor-mediated signaling in lymphocytes. The molecule undergoes complex alternative splicing in the extracellular domain, and different patterns of CD45 splicing are associated with distinct functions. Lack of CD45 leads to severe combined immunodeficiency, and alterations of CD45 splicing, because of a polymorphism in exon 4, have been associated with altered immune function. Here we describe a polymorphism in exon 6 (A138G) of the gene encoding CD45 that interferes with alternative splicing. The polymorphism results in an amino acid substitution of Thr-47 to Ala in exon 6, a potential O- and N-linked glycosylation site. This exon 6 A138G variant is present at a frequency of 23.7% in the Japanese population but is absent in Caucasoids. Peripheral blood T cells from individuals carrying the A138G variant show a significant decrease in the proportion of cells expressing the A, B, and C CD45 isoforms and a high frequency of CD45R0+ cells. These phenotypic alterations in the A138G carriers may lead to changes in ligand binding, homodimerization of CD45, and altered immune responses, suggesting the involvement of natural selection in controlling the A138G carrier frequency.

Granulated metrial gland cells in the murine uterus: localization, kinetics, and the functional role in angiogenesis during pregnancy.

Granulated metrial gland (GMG) cells are a major immune cell population in the murine pregnant uterus, and contribute to the maintenance of pregnancy by functioning as uterus-specific natural killer (NK) cells. In order to reveal their kinetics, activation, and functional roles in pregnancy, we conducted quantitative and immunohistochemical analyses in normal and immuno-modulator-treated mice. Under a light microscope, GMG cells were identified by red cytoplasmic granules in periodic-acid-Schiff (PAS)-stained sections. They progressively increased in number and size with the peak at day 12-14 of pregnancy in the decidua and metrial gland. New vessel formation was most prominent around day 8, and the total vascular area reached the peak at day 13. GMG cells were often located near the blood vessels, and expressed vascular endothelial growth factor (VEGF), suggesting their possible inducing role in angiogenesis during the development of decidua/metrial gland. While blood vessels in the non-pregnant uterus were negative for vascular cell adhesion molecule (VCAM)-1, those in the pregnant one were positive. Treatment with neutralizing antibody against VCAM-1, however, did not decrease the number of GMG cells. On the other hand, mitosis of GMG cells was frequently observed. These data suggest that the increment of GMG cells during pregnancy may largely result from local proliferation in the uterus rather than an increased influx of precursor cells. Although we attempted to induce in vivo activation of GMG cells by administration of interleukin-12 (IL-12) or alpha-galactosylceramide, a potent activator for natural killer-T (NK-T) cells, the number of GMG cells did not appreciably increase. The present study has demonstrated that GMG cells locally proliferate in the pregnant uterus, not being related to VCAM-1 expression by the uterine vasculature or systemic activation of NK cells and NK-T cells, and seem to be involved in angiogenesis in the pregnant uterus through VEGF production.

Local erythematous dermatitis after intravenous docetaxel.

We report the case of a patient who developed a local skin eruption over the vein following intravenous infusion of docetaxel at 4-week intervals. The skin lesions were limited to an area of the forearm proximal to the site of infusion. They appeared 1 week after the infusion and were diagnosed as erythema multiforme (mixed-type) based on the histological findings.

Female urinary incontinence: diagnosis, treatment and patients' concerns.

We developed a simple and accurate method of diagnosing urinary incontinence by means of a 15-item questionnaire that helps physicians evaluate a patient's incontinence status more easily than conventional diagnostic procedures. The results of using the questionnaire showed a total improvement rate of more than 80% among urinary incontinence patients treated in our clinic. Surgical treatment for stress urinary incontinence has improved in terms of both effectiveness and patient quality of life after introduction of a tension-free vaginal tape procedure. Our research on the prevalence of urinary incontinence among a large number of Japanese women showed that, overall, 26.8% complained of some symptoms of incontinence and, the percentage increased with age, reaching more than 40% among women over 40 years of age. However, very few of the women (4%) wished to consult a physician, with shame in the young population and resignation in the old population being the major reasons for not seeking treatment. Women need to be provided with correct information about urinary incontinence in order to improve their quality of life.