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Biomedical subjects

A Imai

Publications and source records attributed to A Imai.

At least 19 recordsLinked to original sources

High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial.

PURPOSE: To improve results for localized prostate cancer, a prospective clinical trial of hyperfractionated Iridium-192 high-dose-rate (HDR) brachytherapy as a monotherapy was initiated. METHODS AND MATERIALS: Between May 1995 and September 1998, 22 implants were performed on 22 patients with localized prostate cancer (T1:T2:T3:T4 = 4:6:9:3) at Osaka University Hospital. Nineteen patients, who had T3-T4 tumors or pretreatment PSA >/= 20.0 ng/mL, received hormone therapy. No patient had external beam radiation. Transperineal needle implants using real-time ultrasound guidance were performed, followed by dose optimization program. Patients were irradiated twice a day, with a time interval of more than 6 h. Total dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Median follow-up time was 31 months. RESULTS: HDR brachytherapy as a monotherapy was well-tolerated. No significant intra- or peri-operative complications occurred. No patient experienced acute toxicity of grade 3 or more. PSA levels normalized in 95% of patients within 20 months after irradiation. Four-year clinical and biochemical relapse-free rates were 95% and 55%, respectively. CONCLUSION: Acute toxicity with this method was acceptable. Further patient accrual and longer follow-up will allow comparison to other techniques.

Aged↗

Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism.

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m2) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p<0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but Gn therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH.

Adolescent↗

Expression, characterization, and localization of Rab26, a low molecular weight GTP-binding protein, in the rat parotid gland.

We investigated the expression of the genes encoding Rab proteins, low molecular weight GTP-binding proteins, in the rat parotid gland by the use of reverse transcription-polymerase chain reaction, and detected cDNAs of Rab3D, Rab4, and Rab26. We further examined the characteristics and localization of Rab26 by western blotting and light and electron microscopic immunocytochemistry. Western blotting using an antibody against the Rab26-specific, C-terminal peptide detected the His-tagged Rab26 protein as a single 27-kDa band. This band also displayed binding to [alpha-32P]GTP. The fraction containing secretory granule membranes in an acinar cell homogenate was immunostained with the antibody. Supporting this, the immunocytochemical reaction for Rab26 was localized immediately around secretory granules in the acinar cells. The immunostaining disappeared from the acinar cells after treatment of rats with isoproterenol. These findings suggest that Rab26 participates in the regulated secretion of granules and functionally belongs to the Rab3 group.

Animals↗

GnRH receptor and apoptotic signaling.

In addition to its hypophysiotropic action, gonadotropin-releasing hormone (GnRH) can modify activity in extrapituitary organs and peripheral tumors. GnRH analogs are the preferred treatment for advanced and even metastatic or recurring carcinomas in vivo and in vitro. Hormone-responsive tumors undergo apoptosis with the appropriate stimulus; GnRH-induced tumor growth arrest may result from stimulated apoptotic cell death. The sensitivity of tumors and normal tissue to GnRH is strongly associated with the possession of receptors for GnRH as well as other hormonal control. Despite the lack of a precise apoptotic signaling cascade through GnRH receptors, biochemical events observed within a plasma membrane appear to constitute the most convincing evidence that the membrane event is primarily stimulated during cell activation by GnRH. GnRH receptors in tumors differ from those in pituitary gonadotrophs in some aspects, in particular with regard to the transmembrane signaling cascade. The intramembranous phenomena that occur independently of the contribution of other organelles upon tumoral GnRH receptor engagement include (i) activation of phosphotyrosine phosphatase and loss of phosphotyrosine from the endogenous membrane protein and (ii) phosphoinositide and perhaps sphingomyelin cleavage producing lipid-originated second messengers. GnRH has also been demonstrated to increase Fas ligand expression within plasma membrane, which is known to promote apoptotic cell death through attack on Fas-positive cells within tumors. The Fas-Fas ligand complex might, at least in part, account for the antiproliferative action of the hormone. An understanding of the relationship between the extracellular (hormonal) stimuli that leads to cell death and the intracellular events regulating growth arrest on GnRH action may fundamentally help clarify the therapeutic approach to all hormone-dependent carcinomas that respond to stimuli that lead to apoptosis. In this chapter, we review the recent literature and the results of our studies on GnRH-induced membrane events and summarize what is currently known about this promising antiproliferative function.

Apoptosis↗

Postoperative vesicourethral function after ultrasonic surgical aspirator-assisted surgery of gynecologic malignancies.

OBJECTIVE: The most concerned complication of radical hysterectomy includes the vesicourethral dysfunction. The use of Cavitron ultrasonic surgical aspirator (CUSA) may preserve the blood supply to the urinary tract even during the surgical procedure, prompting us to evaluate the advantage of using the CUSA with the complication. STUDY DESIGN: We analyzed medical profiles of a total of 275 patients with pelvic lymphnode dissection (137 subjects with radical hysterectomy and 138 with modified radical hysterectomy). RESULTS: The use of CUSA in radical (formal or extended) hysterectomy reduced the period for the residual urine to become <50 ml in cases of advanced stages equal and over Ib of uterine cervical cancers. CONCLUSION: The CUSA may be more effective in the prevention of radical hysterectomy for its major complication, vesicourethral dysfunction. The CUSA-assisted surgery may be applicable, primarily, for advanced uterine cancer.

Female↗

Postpartum microangiopathic hemolytic anemia: cases of successful and dismal outcome assisted with plasma therapy.

Microangiopathic thrombosis, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), seem to occur with certain stresses, including pregnancy. This report documents the clinical outcome with or without plasma therapy and dismal outcomes of two cases with postpartum microangiopathic thrombosis. One carried a pregnancy to successful cesarean delivery and suffered from postpartum TTP/HUS followed by plasma therapy-assisted recovery. Another developed postpartum TTP/HUS and was complicated with subarachnoid hemorrhage. Submission to plasma therapy should always be considered in a woman with postpartum microangiopathic thrombosis.

Adult↗

Enhancement of nitric oxide generation by low frequency electromagnetic field.

Oxidative stress is implicated in the intracellular signal transduction pathways for nitric oxide synthase (NOS) induction. The electromagnetic field (EMF) is believed to increase the free radical lifespan [S. Roy, Y. Noda, V. Eckert, M.G. Traber, A. Mori, R. Liburdy, L. Packer, The phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst in rat peritoneal neutrophils is increased by a 0.1 mT (60 Hz) magnetic field, FEBS Lett. 376 (1995) 164-6; F.S. Prato, M. Kavaliers, J.J. Carson, Behavioural evidence that magnetic field effects in the land snail, Cepaea nemoralis, might not depend on magnetite or induced electric currents, Bioelectromagnetics 17 (1996) 123-30; A.L. Hulbert, J. Metcalfe, R. Hesketh, Biological response to electromagnetic fields, FASEB 12 (1998) 395-420]. We tested the effects of EMF on endotoxin induced nitric oxide (NO) generation in vivo. Male BALB/C mice were injected with lipopolysaccharide (LPS) intraperitoneously (i.p.), followed by the exposure to EMF (0.1 mT, 60 Hz). Five hours and 30 min after the LPS administration, mice were administered with a NO spin trap, ferrous N-methyl-D-glucaminedithiocarbamate (MGD-Fe). Thirty minutes later, mice were sacrificed, and their livers were removed. The results were compared to three control groups: group A (LPS (-) EMF(-)); group B (LPS(-) EMF(+)); group C (LPS(+) EMF(-)). The ESR spectra of obtained livers were examined at room temperature. Three-line spectra of NO adducts were observed in the livers of all groups. In groups A and B very weak signals were observed, but in groups C and D strong spectra were observed. The signal intensity of the NO adducts in Group D was also significantly stronger than that in Group C. EMF itself did not induce NO generation, however, it enhanced LPS induced NO generation in vivo.

Journal Article↗

Regulation of ANP-stimulated guanylate cyclase in the presence of Mn2+ in rat lung membranes.

The catalytic activity of guanylate cyclase (GCase) coupled to atrial natriuretic peptide (ANP) receptor depends on the metal co-factor, Mn2+ or Mg2+. ATP synergistically stimulates the ANP-stimulated GCase in the presence of Mg2+. We have now shown the ATP regulation of the ANP-stimulated GCase in the presence of Mn2+ in rat lung membranes. ANP stimulated the GCase 2.1-fold compared to the control. ATP enhanced both the basal (basal-GCase) and the ANP-stimulated GCase maximally 1.7- and 2.3- fold compared to the control, respectively, at a concentration of 0.1 mM. The stimulation by ATP was smaller in the presence of Mn2+ than in the presence of Mg2+. The addition of inorganic phosphate to the reaction mixture altered the GCase activities in the presence of Mn2+ with or without ANP and/or ATP. In the presence of 10 mM phosphate, ATP dose-dependently stimulated the basal GCase 5-fold compared to the control at a concentration of 1 mM and augmented the ANP-stimulated GCase, which was 4.2-fold compared to the basal-GCase, 5.5-fold compared to the control at a concentration of 0.5 mM. Protein phosphatase inhibitors, okadaic acid (100 nM), H8 (1 microM) and staurosporin (1 microM), did not alter the activity. Orthovanadate (1 mM), an inorganic phosphate analogue, significantly stimulated both the basal-GCase and the ANP-stimulated GCase, which were inhibited by ATP. It was assumed that phosphate and orthovanadate might interact with the GCase to regulate the activity in the opposite manner. This was the first report that inorganic phosphate and orthovanadate affected the ATP-regulation of the ANP-stimulated GCase in the presence of Mn2+.

Adenosine Triphosphate↗

IgE antibody to fish gelatin (type I collagen) in patients with fish allergy.

BACKGROUND: Most children with anaphylaxis to measles, mumps, and rubella vaccines had shown sensitivity to bovine gelatin that was included in the vaccines. Recently, it was found that bovine type I collagen, which is the main content in the gelatin, is a major allergen in bovine gelatin allergy. Fish meat and skin also contain type I collagen. OBJECTIVE: The present study was designed to investigate IgE antibody to fish gelatin in children with fish allergy. METHODS: Serum samples were taken from patients in 3 groups: (1) 10 patients with fish allergy and specific IgE to fish meat; (2) two patients with allergies to both fish meat and bovine gelatin and specific IgE to fish meat and bovine gelatin; and (3) 15 patients with atopic dermatitis and specific IgE to fish meat. Various fish gelatins (type I collagen) were prepared from fish skin. IgE antibody to fish gelatin was analyzed by using ELISA and immunoblotting. RESULTS: Of 10 patients with fish allergy, 3 had specific IgE to fish gelatin. Of two patients with fish allergy and bovine gelatin allergy, all had specific IgE to fish gelatin. Of 15 patients with atopic dermatitis and specific IgE to fish meat, 5 had specific IgE to fish gelatin. Furthermore, IgE from pooled serum of the patients reacted with both the alpha1 and alpha2 chains of fish type I collagen in immunoblots. There is cross-reactivity among gelatins from various fishes, but there is little cross-reactivity between fish and bovine gelatins. CONCLUSION: Some fish-sensitive patients possessed IgE antibody to fish gelatin. Fish gelatin (type I collagen) might be an allergen in subjects with fish allergy.

Adolescent↗

Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometriosis in vitro.

OBJECTIVE: Impaired sensitivity of endometrial tissue to spontaneous apoptosis in women with endometriosis contributes to the abnormal implantation and growth of endometrium at ectopic sites. Our purpose was to examine the effect of gonadotropin-releasing hormone analog, widely used in the treatment of endometriosis, on the reduced rate of endometrial apoptosis in endometriosis. STUDY DESIGN: Paired ectopic and eutopic endometrial tissue specimens were obtained from 13 patients with endometriosis, and control samples were taken from 8 patients with uterine myoma. Apoptotic cell death was assessed biochemically and morphologically with an enzyme-linked immunoassay and Hoechst No. 33342 staining of deoxyribonucleic acid fragment, respectively. RESULTS: Spontaneous apoptosis was significantly lower in ectopic and eutopic endometrial tissue from patients with endometriosis (0.22 +/- 0.082 in absorbance) than in endometrial tissue from control subjects (0.52 +/- 0.483)(P < 0.001). Incubation with a gonadotropin-releasing hormone analog (1 micromol/L) increased the apoptotic rate of endometrial cells from patients with endometriosis to 0.56 +/- 0.501 (P <.001). The effect of this gonadotropin-releasing hormone revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L; however, the control endometrium was not affected. CONCLUSION: Exposure to gonadotropin-releasing hormone results in changes of the sensitivity of endometriotic endometrium to spontaneous apoptosis; these changes in sensitivity may, in turn, release endometrial cells from resistance to apoptosis and result in reduced survival and growth. This phenomenon could, at least in part, account for the therapeutic action of gonadotropin-releasing hormone analog on endometriosis.

Apoptosis↗

A gonadotropin-releasing hormone-responsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells.

Lysophosphatidic acid (LPA) mediates pleomorphic effects on multiple cell lineages, including an increased proliferative response of ovarian cancer cells both in vitro and in vivo, at least in part through the novel expression of LPA receptors. Thus, LPA hydrolysis is necessary to limit the duration of LPA's action on multiple cell types, including ovarian cancer cells. We determined the principal mechanism of LPA hydrolysis by ovarian cancer cells and its regulation by GnRH, which is known to have antiproliferative actions on ovarian carcinomas. LPA-hydrolyzing activity in cell membranes of ovarian cancer specimens was assessed by measuring the conversion of exogenous [3H-oleoyl]LPA to [3H]oleic acid or mono[3H-oleoyl]glycerol. Approximately 98% of LPA hydrolysis could be accounted for by the dephosphorylation of LPA to yield monoglyceride, with the deacylation reaction accounting for less than 1% of LPA hydrolysis. The phosphatase activity in the plasma membrane ovarian cancer cells was approximately 2.5- and 8-fold higher than those in microsome and homogenate fractions, respectively. The membrane phosphatase was Mg2+ independent and insensitive to inhibition by N-ethylmaleimide, characteristics suggestive of phosphatidic acid phosphatase activity. Incubation of membranes from GnRH receptor-positive ovarian cancer specimens with the GnRH agonist, buserelin, induced a dose-dependent increase in LPA phosphatase activity, with a half-maximal effect occurring with 30 nmol/L buserelin. The stimulatory action of buserelin could be neutralized by displacement of GnRH from its receptor by the GnRH antagonist, antide. The plasma membranes from GnRH receptor-negative ovarian cancer specimens did not respond to GnRH stimulation. LPA phosphatase activity was also increased when the ovarian cancer cell line Caov-3 was exposed to GnRH agonist in intact cells before assay of cell membranes. These data demonstrate that LPA is hydrolyzed in the plasma membrane of ovarian cancer cells by the action of LPA phosphatase and provide initial evidence for functional coupling of LPA phosphatase to GnRH receptor occupancy.

Adenocarcinoma, Clear Cell↗

Difference by instructional set in stabilometry.

There is no standard for the awareness of standing posture in stabilometry, yet little research addressing the matter has been carried out. In the present study, we evaluated the influence of different instructional sets during a test on stabilometry. Stabilometry was performed on 349 male subjects. Two different instructions were prepared for the subjects regarding the awareness of their standing posture. These instructions were a) "Please relax when you stand" (R-standing), and b) "Please make an effort to minimize your body sway" (E-standing). Subjects were classified into four groups according to the combination of these instructions they received. For the five body sway parameters, a comparison between R-standing and E-standing was performed, controlling for possible confounders such as age, height, body weight, educational history, alcohol consumption, and smoking status. The sway length in E-standing was larger than that in R-standing, even after the adjustment for possible confounders. Our results indicate that the difference in the instructional set caused a significant measurement bias. Thorough-going unification of instructions for the stabilometry should be recommended when stabilometry is performed in an epidemiological investigation.

Adult↗

Radiotherapy of early tongue cancer in patients less than 40 years old.

PURPOSE: To evaluate the results of treatment for early mobile tongue cancer in patients less than 40 years. METHODS AND MATERIALS: Between January 1967 and September 1992, 70 patients less than 40 years old (young age group) with early tongue cancer (T1-2N0M0) were treated with low-dose-rate (LDR) interstitial radiotherapy at the Osaka University Hospital (OUH). All patients had a minimum 2-year follow-up (median: 13 years). External radiotherapy (median: 30 Gy) was combined in 25 cases. The treatment results were compared with those for two older age groups (middle age: 40-64 years old; old age: 65 years old or more). RESULTS: The 5-year probability of cause-specific survival (CSS) rate for the young age group was 80%, which was not significantly different from the two older groups: 81% for middle age and 71% for old age. However, male patients of young age showed significantly worse rates than those of middle and old age (p = 0.02). The 5-year local control rate for the young age group was 78%. It was not significantly different from the two older groups: 81% for middle age and 70% for old age. The incidence of regional lymph node metastasis was 32% for T1, 48% for T2, 56% for males, and 24% for females. The regional failure rate of young males was significantly higher than those of the two older groups: 32% for middle and 22% for old age (p = 0.001). CONCLUSION: The overall treatment results for patients with early tongue cancer less than 40 years old were not worse than those of older age groups. However, male gender was a risk factor for lymph node metastasis and CSS.

Adult↗

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors.

PURPOSE: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. CONCLUSION: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases.

Adolescent↗

A kuroko-type polymetallic sulfide deposit in a submarine silicic caldera

Manned submersible studies have delineated a large and actively growing Kuroko-type volcanogenic massive sulfide deposit 400 kilometers south of Tokyo in Myojin Knoll submarine caldera. The sulfide body is located on the caldera floor at a depth of 1210 to 1360 meters, has an area of 400 by 400 by 30 meters, and is notably rich in gold and silver. The discovery of a large Kuroko-type polymetallic sulfide deposit in this arc-front caldera raises the possibility that the numerous unexplored submarine silicic calderas elsewhere might have similar deposits.

Journal Article↗

A novel sex-determining region on Y (SRY) nonsense mutation identified in a 45,X/47,XYY female.

OBJECTIVE: To determine whether an SRY mutation participated in the phenotypic outcome in the case of a 45,X/47,XYY female. DESIGN: Analysis of genomic DNA for mutations in SRY. SETTING: An academic teaching hospital. PATIENT(S): A family that included one phenotypic female with 45,X/47,XYY mosaicism. INTERVENTION(S): Extraction of DNA, polymerase chain reaction analysis, nucleotide sequencing, and restriction enzyme analysis. MAIN OUTCOME MEASURE(S): Comparison of control and subject DNA sequences. RESULT(S): The patient demonstrated one nucleotide (thymine, T) deletion at position 422, leading to a frame-shift mutation. This mutation changes the codon for Tyr (TAT) to a stop codon (TAG) within the open reading frame just upstream of a conserved DNA-binding motif. Neither other mutations nor nucleotide mosaicisms were found in the remaining regions of the gene. This mutation was not present in the patient's normal father. CONCLUSION(S): The mutant SRY may be assumed to induce a nonfunctional SRY-coded protein that lacks a DNA-binding motif. These results explain the phenotypic female and the gonadal dysgenesis in the 45,X/ 47,XYY sex-reversed offspring.

Amino Acid Sequence↗

IgE reactivity to alpha1 and alpha2 chains of bovine type 1 collagen in children with bovine gelatin allergy.

BACKGROUND: Anaphylactic reactions to measles, mumps, and rubella vaccines, including gelatin as a stabilizer, have been reported. It had been found that most of these reactions to live vaccines are caused by the bovine gelatin included in these vaccines. Gelatin mainly includes denatured type I collagen, which consists of alpha1 and alpha2 chains. OBJECTIVE: The current study was designed to investigate the IgE reactivity to alpha1 and alpha2 chains of bovine type I collagen in gelatin-sensitive children. METHODS: Serum samples were taken from 10 children who had anaphylaxis to the vaccines and high levels of specific IgE to bovine gelatin. Bovine type I collagen was isolated from bovine skin and then separated to alpha1 and alpha2 chains by column chromatography. IgE reactivity to denatured type I collagen and its alpha1 and alpha2 chains was analyzed by immunoblotting, ELISA, and histamine release from the mast cells passive sensitized with IgE antibodies in pooled serum of the children. RESULTS: All children had specific IgE to bovine type I collagen. Furthermore, IgE antibodies in their sera reacted with the alpha;2 chain but not with the alpha1 chain. Similarly, the mast cells sensitized with pooled sera in the children showed alpha2 chain-specific histamine release but not alpha1 chain-specific histamine release. CONCLUSION: In gelatin allergy denatured bovine type I collagen is a major allergen and IgE-binding sites exist in the alpha2 chain of type I collagen.

Anaphylaxis↗

Brain metastasis as first manifestation of ovarian cancer.

Brain metastasis from ovarian cancer, a rare and highly dismal event, develops mostly during or after postoperative chemotherapy. This report documents the clinical findings and magnetic resonance imaging of an uncommon case who presented signs of increased intracranial pressure as a first manifestation. Histologic examination of removed brain lesion demonstrated ovarian origin, while no evidence of a locally invasive lesion was found at exploratory laparotomy ('tentative' surgical stage Ia). The possibility of ovarian origin should be always considered in a woman with brain involvement.

Adult↗