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Aims and Background Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition.Methods and Study Design Fifty-seven patients (age range: 32–83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor.Results The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples.Conclusions The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.

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. Microsc. Res. Tech. 60:420–429, 2003. © 2003 Wiley‐Liss, Inc.

We reported finding that apoptosis occurred in skeletal muscle in the early stage after implantation. In the present study, we investigated expression of the apoptosis‐related proteins Bax and Bcl‐2 to determine the mechanism of the apoptosis. In the early stage of tumor bearing, 20 days after implantation, lean body mass (LBM) was reduced by 5.06±1.10% in the tumor‐bearing group, compared with an increase of 4.96±1.26% in the control group. The apoptotic index (AI) of the skeletal muscle in the tumor‐bearing group increased to 40.5±3.20% but was 0% in the control group, and Bax expression was strongly positive in 5 of the 10 rabbits in the tumor‐bearing group, and significantly stronger than in the control group (P=0.0002). In the late stage of tumor bearing, 40 days after implantation, the AI had declined to 0.93±0.96% in the tumor‐bearing group, but was still 0% in the control group. Bax expression was rarely detected in either the tumor‐bearing group or the control group, and there was no significant difference between the two groups (P=0.706). No significant changes in Bcl‐2 were observed in either group. The above results showed that apoptosis via Bax played a role in muscle wasting associated with progression of the malignant tumor. However, the apoptosis and expression of Bax were seen only in the early stage, within 20 days after implantation, not in the late stage. This suggested that the muscle wasting in the early stage might be caused by a different mechanism from that in the late stage.

Haptoglobin (Hp) possesses many functions in the immune system and angiogenesis as well as scavenging released hemoglobin, and thus it is speculated that Hp may also play a critical role in the reproductive process. To investigate the possible involvement of Hp in the outcome of in vitro fertilization and embryo transfer (IVF-ET), the serum Hp of 50 patients who underwent IVF-ET was analyzed by the Western blot method. The results showed a higher pregnancy rate in the patients with the Hp2-2 phenotype (38%) than in those with the Hp2-1 phenotype (16%) (p = 0.08), and the serum α2 subunit levels in the patients who achieved pregnancy within four attempts at IVF-ET were higher than in the others (p < 0.05). The results of this study suggest that Hp is involved in the outcome of IVF-ET.

The crisis frequency of stress incontinence (SI) is known to be high among pregnant women. This preliminary study was performed to determine whether the diagnostic standard of the Q-tip test used in the diagnosis of SI in nonpregnant women is applicable to pregnant women. The Q-tip tests were performed regularly during pregnancy and after parturition on primipara (n = 71) and multipara (n = 55) who were not in SI crisis at any time during the pregnancy. The values measured in multipara were significantly higher than in primipara (p = 0.0001), and the tendency to be higher was more prominent at 2–5 months and 10 months of pregnancy. These findings show that different normal values of the Q-tip test are necessary for primipara and multipara.

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2‐tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situend‐labeling assay. Plasma of the tumor‐bearing rabbits was perfused repeatedly through non‐coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3‐methylhistidine/ creatinine ratio (3‐MH/Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3‐MH/Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but unproved LBM, DNA synthesis, and 3‐MH/Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Vaginal total hysterectomy with vaginal plasty was performed in 107 patients with pelvic organ prolapse. The posterior urethrovesical angle (PUVA) was measured by chain urethrocystography. Bladder capacity, residual and incontinence urine volume were measured before and after surgery, and the data obtained were analyzed in relation to postoperative improvement and recurrence of urinary dysfunction. There were no significant differences between the background of patients with dysuria, incontinence, a mixture of dysuria and incontinence, and neither of these symptoms. Postoperative incontinence and residual urine volume decreased in all groups. However there was no correlation between the preoperative PUVA and either incontinence or residual urine volume. Measurement of PUVA was neither helpful in making the diagnosis nor predictive of the recurrence of urinary dysfunction.

Intermittent cisplatin (CDDP) administration as consolidation therapy for stage-III ovarian cancer was studied. No patients with residual disease at surgery or at second-look operation or patients with <8 U/ml of CA125 after remission induction chemotherapy were enrolled in this study. Fifteen subjects received intermittent chemotherapy, and 10 control patients did not. CDDP of 20 mg/m2 for 5 days was administered every 3–4 months for 5 years. A significant increase in 5-year survival rate was found in the intermittent chemotherapy group when compared with the control group. Side effects from the intermittent chemotherapy were controllable. Intermittent CDDP therapy seems to be an effective consolidation therapy for stage-III ovarian cancer patients.

Changes in total body fat and the metabolic and morphologic characteristics of adipose tissue were sequentially investigated in individual rabbits implanted with VX2 tumors to elucidate the pathology of the fat reduction in animals with malignant tumors as compared with that of diet‐restricted rabbits. Lipogenesis in normal, VX2–implanted, and diet‐restricted rabbit groups on day 40 after the start of the experiments was 19.1±2.9, 13.3±3.5, and 41.7±6.0×l05cpm/g/h, respectively, and glycerol liberation by their adipose tissue was 199±21, 528±94, and 301±45 nmol/g/h, respectively. In addition, apoptotic cells were noted in the adipose tissue of VX2–implanted rabbits on days 20–30 after implantation, but not in diet‐restricted rabbits. The results showed clear differences between the total body fat reduction profiles of VX2–implanted rabbits and diet‐restricted rabbits, suggesting a characteristic lipid metabolism with enhanced lipolysis and diminished lipogenesis in VX2–implanted rabbits. The results strongly suggest that adipocyte apoptosis might be involved in these phenomena.

Adenoma malignum (minimum deviation adenocarcinoma) is a rare neoplasma of the uterine cervix, the diagnosis of wich cannot be determined by cervical smear. Recently, magnetic resonance imaging (MRI) was reported as useful for its diagnosis, but differentiation of adenoma malignum from deep-seated nabothian cysts remains problematic. We report here a case of adenoma malignum of the uterine cervix, for which MRI findings could not neglect deep-seated nabothian cysts. However, transvaginal power Doppler ultrasonography clearly showed richness of small vessels, whose arterial flow had higher velocity in the diastolic phase, around the cystic lesion of the uterine cervix. These findings indicate that, at least in the case reported here, transvaginal power and pulsed Doppler ultrasonography is a useful tool for the diagnosis of adenoma malignum of the uterine cervix.

Dynamic osmotic fragility of erythrocytes in cord blood and its changes during the neonatal period were studied by means of a coil planet centrifuge system. The starting-point for hemolysis in the newborn become similar to that of adult blood after approximately a week, while the shift of the end-point to the adult range required one month or more.

AbstractA simple formula (1.536 × TOBEC + 475.146 = LBM, where TOBEC is total body electrical conductivity and LBM is lean body mass) to estimate LBM in grams was developed on the basis of the total body fat data obtained by ether extraction and TOBEC in normal rabbits. The formula was also applicable to rabbits with cachexia induced by inoculation of VX2 carcinoma or by starvation. We were able to assess the losses of body fat in the rabbits with cachexia at 10‐day intervals by using TOBEC.

Rabbits implanted with VX2 carcinoma and treated by cyclic plasma perfusion showed lower weight loss and longer survival than untreated rabbits. The urinary 3‐methylhistidine/creatinine ratio was less elevated in the treated rabbits than in the untreated rabbits. Myoblasts from untreated rabbits with VX2 carcinoma showed lower proliferation than those from normal rabbits, while those from rabbits treated by cyclic plasma perfusion showed intermediate proliferation. Furthermore, the DNA synthesis rate of myoblasts from treated rabbits was much better maintained than in the case of untreated rabbits.

Composition of the amylase isozymes in the amniotic fluid and their transition with fetal age were studied by means of thin-layer acrylamide gel electrophoresis. The results indicate that amylase isozymes in the amniotic fluid were composed of a pancreatic type faint major isozyme and several salivary type isozymes consisting of an intense major and a few less intense minor bands. Characteristic changes in the pattern of these isozymes with fetal age consisted of a marked increase of the salivary type isozymes rather than of the pancreatic type isozyme. A densitometric analysis of the isozyme patterns proved that the ratio of the pancreatic type isozyme to the salivary type major isozyme was highly correlated with fetal age regardless of levels of amylase activity.

Mice transplanted with a cachexia-inducing colonic adenocarcinoma (MAC16) show a progressive decrease in liver glycogen in direct proportion to the loss of body weight. Such tumours elaborate a lipid mobilizing factor (LMF), which produces a dose-dependent stimulation, not only of adipocyte adenylate cyclase, but also of heptocyte adenylate cyclase in a GTP-dependent manner. These results suggest that LMF has the capacity to initiate hepatic glycogenolysis through an increase in cyclic AMP.

Leiomyomas of the deep soft tissue are extremely rare. We report a case of a deep soft tissue leiomyoma that was difficult to differentiate from a uterine leiomyoma. A 48-year-old woman was diagnosed with a uterine leiomyoma, but surgical and pathological findings revealed a deep soft tissue leiomyoma and normal uterus.

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.

Cirsoid aneurysm, an uncommon abnormal either congenital or acquired arteriovenous communication, is described. As massive life-threatening bleeding can be a consequence, diagnosis is very important. Earlier, angiography was the only imaging method available for visualizing vascular lesions and recent developments in imaging techniques have made diagnostic imaging of cirsoid aneurysms possible using ultrasonography, color flow mapping, magnetic resonance imaging and magnetic resonance angiography. In this report, a patient with intrapelvic cirsoid aneurysm posthysterectomy who died 8 h after she had been kicked in the abdomen is described and the results obtained by various imaging techniques are discussed.

Endometrial stromal sarcoma of low-grade malignancy (ESSL) is a rare neoplasm, and neither preoperative diagnostic procedures nor standard therapy have yet been established. We treated 3 cases of ESSL in the past 27 years, and we report here one of these cases that was classified as stage III (according to the FIGO classification of endometrial carcinoma). Postoperative radiotherapy was used to treat a residual tumor, and the patient showed a complete response.

We developed a method of endocervical staining with toluidine blue solution during cervicoscopy that clearly discriminates between the endocervical region and the endometrium and allows easy detection of superficial cervical invasion by endometrial carcinoma. Toluidine blue staining cervicoscopy was used for preoperative histological diagnosis in 10 cases of endometrial carcinoma. The staining permitted a correct diagnosis in 3 cases in which conventional diagnostic methods were practically useless. Endocervical staining with toluidine blue is highly useful for diagnosis of superficial cervical invasion by endometrial carcinoma.

A premenopausal woman with vaginal agenesis underwent surgery for leiomyomas in rudimentary uterine horns. Immunohistochemical study of surgical specimens revealed that progesterone receptors are distributed in the nuclei of a majority of the leiomyoma cells and in the nuclei of a minority of the myometrial cells. Estrogen receptors are not detected in the surgical specimens.

Despite confirmation or the placental location by ultrasound examination, bloody tap during diagnostic and therapeutic amniocentesis may occur. If the blood originates from the fetus, such unfavorable complications as fetomaternal transfusion or maternal sensitization may result. Thus, it is necessary to determine immediately the origin of the blood by the presence of fetal hemoglobin (HbF) in the specimen. To meet an urgent demand for a simpler and faster method for measuring HbF within a few minutes at bedside without requiring complicated procedures or instrumentation, a method has been developed which uses the alkali denaturation technic.

We report a case of a perforated sigmoid diverticulum abscess that was difficult to differentiate from an ovarian tumor. A 53-year-old woman was diagnosed with an ovarian tumor, but laparotomy revealed a perforated sigmoid diverticulum abscess and appendicitis, with normal ovaries.

We report a case of chronic myelocytic leukemia (CML) in which the initial manifestation of blastic crisis was massive genital bleeding. The bleeding was diagnosed as being caused by CML metastasis to the uterus on the basis of the magnetic resonance imaging findings.