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Biomedical subjects

I Wada

Publications and source records attributed to I Wada.

At least 91 records · Page 5Linked to original sources

Is continuation of a gonadotrophin-releasing hormone agonist (GnRHa) necessary for women at risk of developing the ovarian hyperstimulation syndrome?

A total of 28 women scheduled for in-vitro fertilization used buserelin and human menopausal gonadotrophin (HMG) for ovarian stimulation. One group (I) of 17 women was given human chorionic gonadotrophin (HCG 10,000 IU) to trigger ovulation, but the resulting embryos were electively cryopreserved because of the risk (serum oestradiol greater than or equal to 3500 pg/ml) of developing the ovarian hyperstimulation syndrome (OHSS). Six women continued the buserelin therapy in the luteal phase and eleven did not. In group II (n = 11), the HMG injections were discontinued because of an exaggerated ovarian response and the HCG was omitted. Six of these women continued the buserelin injections until the onset of menses and five did not. In both groups, the ovarian response to induction of ovulation (serum oestradiol concentrations and number of follicles) was similar for those who did or did not continue buserelin therapy. There was no difference in the rate of ovarian quiescence (weekly fall in serum oestradiol concentration following the stimulation) between those women who did or did not continue the buserelin therapy in either group. The serum luteinizing hormone concentrations remained low in all women in both groups. We conclude that the omission of buserelin therapy after discontinuing the HMG in women at risk of developing OHSS does not affect subsequent ovarian quiescence.

Adult↗

SSR alpha and associated calnexin are major calcium binding proteins of the endoplasmic reticulum membrane.

GTP phosphorylation of rough microsomes in vitro is limited to four integral membrane proteins. Two of these, a phosphoprotein (pp90) and a phosphoglycoprotein (pgp35) were purified as a complex with two nonphosphorylated membrane glycoproteins, gp25H and gp25L. The authenticity of this complex was confirmed using two different purification procedures and by coimmunoprecipitation. By immunofluorescence a reticulated cytoplasmic network was revealed for the proteins which was similar to that for Louvard et al. (Louvard, D., Reggio, H., and Warren, G. (1982) J. Cell Biol. 92, 92-107) marker antisera which also recognized purified pp90 on immunoblots. Amino acid sequencing of peptides derived from pgp35 identified this protein as SSR alpha, an endoplasmic reticulum constituent as identified by cross-linking of translocating nascent chains (Görlich, D, Prehn, S., Hartmann, E., Herz, J., Otto, A., Kraft, R., Wiedmann, M., Knespel, S., Dobberstein, B., and Rapoport, T. A. (1990) J. Cell Biol. 111, 2283-2294). The sequence of gp25H was determined from cDNA clones and was identical with SSR beta identified by Görlich et al. (1990) as being tightly bound to SSR alpha. Sequencing of gp25L revealed no similarity of the deduced sequence with other proteins. However, pp90 revealed a high degree of sequence identity with the Ca(2+)-binding protein, calreticulin. 45Ca2+ overlay studies indicated that pp90 bound Ca2+ and the name calnexin is proposed. Surprisingly, pgp25 (SSR alpha) also bound Ca2+ although gp25H (SSR beta) and gp25L did not. Triton X-114 partitioning of the integral membrane proteins of rough microsomes suggested that pgp35 (SSR alpha) and calnexin were major Ca(2+)-binding proteins of the endoplasmic reticulum membrane. We propose that the function of the complex is to regulate Ca(2+)-dependent retention mechanisms for luminal proteins of the endoplasmic reticulum.

Amino Acid Sequence↗

[Clinical evaluation of severe toxicity in two patients with acute lymphoblastic leukemia receiving outpatient methotrexate therapy].

Methotrexate (MTX) is now widely used for the treatment of acute leukemia and non-Hodgkin lymphoma in the pediatric oncology field and is thought to be one of the key drugs for this treatment. A regimen utilizing high dose MTX (HD-MTX) with leucovorin rescue is being investigated as effective chemotherapy in the patients with these kinds of cancer. Relatively large amounts of MTX (225 mg/m2) are given to such outpatients by intravenous push as a course of maintenance therapy. It is said that those amounts will infuse safely. However, we experienced two serious cases-patients T.H. and M.Y.--which developed into severe side effects after this treatment. Both patients showed acute renal failure, severe myelosuppression, erosion around the oral and anal region, and continuous diarrhea. Judging from the serum concentration of MTX, patient T. H. was exposed to more than the maximum allowance serum MTX level for 9.6 days, patient M. Y. for 6.5 days. This suggests physicians must pay attention to the clinical symptoms even after treatment using MTX without HD-MTX.

Acute Kidney Injury↗

Use of condoms as contraceptive and disease preventive measures among residents of Jos, northern Nigeria.

The effectiveness, acceptability and protective aspects of condoms as both contraceptive and disease control measures was evaluated in 168 male residents of Jos in Nigeria. They were aged between 15 and 40 years and were attending the Family Planning Clinic of the Jos University Teaching Hospital. The results showed that the majority (87.5%) of our patients were in the 21 to 30 years age group and most of the clients had used condoms for between 1 to 5 years. A good number of our clients (40.5%) used condom because it protects them against venereal disease while others felt it was safe and effective. The Family Planning Clinic was the main source of knowledge of the condom among our clients (42.9%), and the condom was rated as good or excellent by 137 (81.5%) clients. The only side effect of condom usage which featured prominently among our clients was reduced sexual excitement. The results were compared with studies carried out elsewhere. It was concluded that the condom could be an acceptable and effective form of contraception in this population. The users must, however, be highly motivated so as to use it during every act of coitus for optimal efficacy.

Adolescent↗

Changes in circulating inhibin levels during pregnancy and early lactation in the Japanese monkey.

Changes in immunoreactive (ir-) inhibin concentrations in serum throughout pregnancy and early lactation up to one month after parturition were characterized in 6 Japanese monkeys (Macaca fuscata fuscata) by a heterologous radioimmunoassay (RIA) based on a bovine RIA. Serum levels of FSH, LH/monkey chorionic gonadotropin (mCG), estradiol-17 beta, and progesterone were also monitored for the entire period. Ir-inhibin levels in the serum were low (under 0.5 ng/ml) before conception. Three marked increases in serum ir-inhibin levels were found during pregnancy. The first increase was noted during early pregnancy, with a peak (2.2 +/- 0.2 ng/ml) at Day 22 of pregnancy (Day 0 = day of LH surge). The second increase was noted after Day 38 until Day 72 of pregnancy, when a peak value was noted (19.0 +/- 1.4 pg/ml). Plateau levels were maintained until late pregnancy, and a final rise was evident near the term with a peak (36.7 +/- 3.8 ng/ml) at Day 158 of pregnancy, 5 days before parturition. After parturition, ir-inhibin levels in the serum plummeted to nonpregnant levels within one day, and were maintained during early lactation. The first rise in serum inhibin during pregnancy was parallel to the rise of mCG and estradiol-17 beta, and the second and third rise were well correlated with serum estradiol-17 beta. Serum FSH was maintained at low levels throughout pregnancy, followed by a slight increase after parturition when serum inhibin decreased abruptly. Both bioactivity and immunoreactivity of inhibin were detected in the placental homogenates obtained at 120 days of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ligand-mediated internalization, recycling, and downregulation of the epidermal growth factor receptor in vivo.

EGF receptor internalization, recycling,a nd downregulation were evaluated in liver parenchyma as a function of increasing doses of injected EGF. The effect of ligand occupancy in vivo on the kinetics and extent of internalization was studied with changes in the receptor content of isolated plasmalemma and endosome fractions evaluated by direct binding, Scatchard analysis, and Western blotting. For all doses of injected EGF, receptor was lost from the plasmalemma and accumulated in endosomes in a time- and dose-dependent fashion. However, at doses of injected EGF equivalent to less than or equal to 50% surface receptor occupancy (i.e., less than or equal to 1 microgram/100 g body weight), receptor levels returned by 120 min to initial values. This return was resistant to cycloheximide and therefore did not represent newly synthesized receptor. Neither was the return due to replenishment by an intracellular pool of low-affinity receptors as such a pool could not be detected by Scatchard analysis or Western blotting. Therefore, receptor return was due to the recycling of previously internalized receptor. At doses of injected EGF greater than 50% receptor occupancy, net receptor loss-i.e., downregulation-was observed by evaluating the receptor content of total particulate fractions of liver homogenates. At the higher saturating doses of injected EGF (5 and 10 micrograms/100 g body weight), the majority of surface receptor content was lost by 15 min and remained low for at least an additional 105 min. As the kinetics of ligand clearance from the circulation and liver parenchyma were similar for all doses of EGF injected, then the ligand-mediated regulation of surface receptor content and downregulation were not a result of a prolonged temporal interaction of ligand with receptor. Rather, the phenomena must be a consequence of the absolute concentrations of EGF interacting with receptor at the cell surface and/or in endosomes.

Animals↗

[Primary osteogenic sarcoma of the breast. Report of a case].

Primary osteogenic sarcoma (POS) of the breast is very rare. Only eleven cases have been previously reported in Japan. In this paper, we report an additional case of POS. A 30 year old female was admitted to our hospital with chief complaint of rapidly growing mass of the right breast. She was diagnosed carcinoma of the right breast and underwent a radical mastectomy (Br + Ax + Mj + Mn). Histological findings of the resected tissues revealed POS of the breast. After three months from the operation, local recurrence was demonstrated by an incisional biopsy. One more months later, chest X-P revealed bilateral lung metastases. Irradiation with 60Co for recurrence and chemotherapy using vincristine, methotrexate for distant metastases were not effective. However, cisplatin caused the necrosis of local recurrent tumor. She died nine months after operation. At autopsy, extended metastasis of tumor cells diffusely to the pleura, lungs, liver, adrenal glands, pancreas, peritoneum, fifth lumbar vertebra, skull, dura mater and left pulmonary hilar lymph nodes was observed.

Adult↗

[A case of congenital retinoschisis in a 34-week gestation female infant].

At age one month a female infant was referred for a fundus examination because she was delivered after a 34-week gestation and her birth weight was 1908 g. Fundus examination revealed a brown granular pigmentary deposition surrounding the foveola in the macular region and a large highly ballooning retinoschisis occupying almost the lower half of the fundus in each eye. There was slight hemorrhage in the vitreous body and the retinoschisis cavity, and no retinal hole. The anterior border of the retinoschisis did not extend to the ora serrata. The almost negative ERG response showed an abnormal b-wave amplitude. Over the course of about one year, the vitreous hemorrhage developed and cleared. The ballooning feature of the retinoschisis also developed and disappeared. On examination of the infant's family her father and elder sister had no abnormal findings but her mother had chorioretinal degeneration with macular yellow pigmentary deposition, visual defect and negative ERG. These abnormal findings of her mother were suggested to have been derived from congenital retinoschisis. Therefore, this is a very rare case because of the different hereditary form, the common sex-linked recessive inheritance, the 34-week gestation and female infant.

Female↗

Ureteral urine transport: changes in bolus volume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs.

An experimental model which permits independent changes in ureteral peristalic frequency and bolus volume was employed to explore the effects of autonomic agonists on ureteral bolus volume, peristaltic frequency, intraluminal pressure and flow volume in the dog. Norepinephrine caused an increase in ureteral peristaltic frequency, an elevation in intraureteral baseline and contractile pressure and a decrease in bolus volume, with a resultant decrease in the rate of fluid transport. Isoproterenol caused a decrease in ureteral peristaltic frequency, and a fall in intraureteral baseline and contractile pressure, or it completely abolished peristalsis and bolus formation. These changes were accompanied by an increase in the rate of fluid transport. Acetylcholine caused an increase in ureteral peristaltic frequency, an elevation of intraureteral baseline pressure but no change in contractile pressure, and a small decrease in bolus volume with a resultant small decrease in the rate of fluid transport. These data suggest that the autonomic nervous system may affect urine transport through the ureter by not only regulating peristaltic frequency but also by influencing bolus volume.

Acetylcholine↗

5'-Nucleotidase in rat liver lysosomes.

5'-Nucleotidase was found in purified rat liver tritosomes. When tritosomes were subfractionated into the membrane and soluble contents fractions, 73% of the total 5'-nucleotidase activity was found in the membrane fraction and 24% in the soluble contents fraction. Immunoblotting using specific polyclonal antibodies against the rat liver plasma membrane 5'-nucleotidase showed that the mobilities on SDS-polyacrylamide gel electrophoresis of both 5'-nucleotidases in the membrane and contents fractions were identical to that of the enzyme in the plasma membranes (Mr = 72,000). 5'-Nucleotidases in the membrane and contents fractions were sensitive to neuraminidase and converted into a form that was 4 kDa smaller after digestion, as observed in the case of plasma membrane enzyme. 5'-Nucleotidases, both from the membrane and contents fractions, were purified using immunoaffinity chromatography, and the isoelectric points, heat stability, and oligomeric structure of the purified enzymes were compared. Isoelectric focusing and the heat stability test indicated the resemblance of the soluble enzyme to the membrane-bound enzyme. However, the membrane-bound enzyme aggregated in the absence of Triton X-100, whereas the soluble enzyme behaved as a dimer. The topography of 5'-nucleotidase in the tritosomal membranes was studied using antibodies against 5'-nucleotidase and neuraminidase treatment. The inhibition of 5'-nucleotidase were not observed in the intact tritosomal fraction until the tritosomes had been disrupted by osmotic shock. These results show that the active sites and the oligosaccharide chains of 5'-nucleotidase are located on the inside surface of the tritosomal membranes.

5'-Nucleotidase↗

Comparison of DT-diaphorases purified from the liver cytosol of untreated, and 3,4,5,3',4'-pentachlorobiphenyl- and 3-methylcholanthrene-treated rats.

DT-Diaphorase purified from the liver cytosol of rats treated with a highly toxic PCB congener, 3,4,5,3',4'-pentachlorobiphenyl (PenCB), was compared to those from 3-methylcholanthrene (MC)-treated and untreated rats. Treatments with PenCB and MC resulted in about 8- and 7-fold increases of cytosolic DT-diaphorase activity, respectively. Purification of the enzyme preparations from untreated, and PenCB- and MC-treated rats were conducted by using DE-52, DEAE-Sephadex A-50, hydroxylapatite, and Bio-Gel P-150 column chromatographies. Both Sephadex G-100 gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that all of the final preparations from the three origins were homogeneous and had the same molecular weight of 59,000, consisting of two subunits with molecular weights of 30,000. Further studies on amino acid composition, Km value, optimum pH, and catalytic activities for various substrates also indicated that both PenCB- and MC-inducible DT-diaphorases were identical with that from the untreated rats. All three DT-diaphorases contained about 2 mol of FAD per mol of enzyme. Partial digestion of the enzymes by trypsin and subsequent analysis by HPLC revealed that the three preparations were indistinguishable. The identity among the three purified DT-diaphorases was finally confirmed by Ouchterlony immunodiffusion employing anti-serum raised against each enzyme preparation.

Amino Acids↗

Urinary retention due to idiopathic megacolon.

A 58-year-old man with neurogenic bladder dysfunction was hospitalized with chief complaints of urinary retention and abdominal distention. He had been treated for neurogenic bladder due to cerebral infarction for 3 years. The pelvic CT scan and excretory urogram revealed an obstruction of the neck of the bladder due to an abundant stool, which was found to have resulted from adult idiopathic megacolon. A permanent colostomy with sigmoid resection was established. The postoperative urodynamic examination demonstrated improvement of micturition.

Constipation↗

Characterization of alpha-adrenoceptor subtypes involved in regulation of ureteral fluid transport.

Experiments were carried out in the dog by the use of experimental procedure which permits to assess independently changes in uretheral peristaltic frequency, bolus volume and intraluminal pressure and flow volume in order to characterize alpha-adrenoceptor subtypes involved in regulation of ureteral urine transport. Norepinephrine caused an increase in ureteral peristaltic frequency, an elevation in intraureteral baseline and contractile pressure and a decrease in bolus volume, with a resultant decrease in the rate of fluid transport. Phenylephrine (alpha 1-agonist) and clonidine (alpha 2-agonist) caused the effects similar to those of norepinephrine on peristaltic frequency, intraureteral baseline and contractile pressure, and bolus volume. Phentolamine (non-selective alpha-antagonist) and prazosin (alpha 1-antagonist) caused a decrease in ureteral peristaltic frequency, and a fall in intraureteral baseline and contractile pressure, and yohimbine (alpha 2-antagonist) abolished peristalsis and bolus formation. These changes were accompanied by an increase in the rate of fluid transport. These data suggest that the ureteral urine transport is controlled by activation of both alpha 1- and alpha 2-adrenoceptors through regulation of peristaltic frequency and bolus volume.

Animals↗