Relationship between intracellular calcium-dependent process and protein-tyrosine phosphorylation in human platelets: studies of platelets from a patient with defective A23187-induced platelet aggregation

We had postulated that in a patient with defective calcium ionophore (A23187)-induced platelet aggregation, whose platelets showed normal intracellular Ca2+ mobilization in either the presence or absence of extracellular Ca2+ in response to A23187. A defect was present in an intracellular calcium-dependent process. We have now investigated whether the agonist-induced protein-tyrosine phosphorylation (PTP) was altered. Protein-tyrosine phosphorylation (PTP)-induced by A23187 in the patient's platelets was greatly diminished but that induced by thrombin was almost normal. These results suggest that an intracellular calcium-dependent process plays a fundamental role in A23187-induced PTP, whereas it does not in thrombin-induced PTP.     

Ovarian morphology and prevalence of polycystic ovary syndrome in Japanese women with type 1 diabetes mellitus

Aims/Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder including polycystic ovary morphology (PCOM), ovulatory dysfunction and hyperandrogenism. PCOS is frequently associated with type 2 diabetes mellitus; however, it is unknown whether PCOM and PCOS are prevalent in Japanese patients with type 1 diabetes mellitus. The purpose of our study was to determine the frequency of PCOM and PCOS in women with type 1 diabetes mellitus.

Materials and Methods

We evaluated clinical, hormonal and ovarian ultrasound data from 21 type 1 diabetes mellitus patients whose average glycated hemoglobin levels were 7.9 ± 1.5%.

Results

Ultrasound identified PCOM in 11 patients (52.4%) and these patients also had higher levels of the androgen dehydroepiandrosterone sulfate (DHEA‐S) than those without PCOM (P < 0.05). Of the patients with PCOM, five presented menstrual irregularities (45.5%) and three met the Japanese criteria for PCOS (27.2%); whereas all patients without PCOM had a normal menstrual cycle (P < 0.05).

Conclusions

Japanese premenopausal women with type 1 diabetes mellitus had a high frequency of PCOM as well as PCOS. This is the first research of this area carried out in an Asian population.     

Inhibitory mechanism of human platelet aggregation by nafamostat mesilate

We found that nafamostat mesilate (NM) inhibits platelet aggregation induced by all agonists tested, including ADP, collagen, arachidonic acid, thromboxane A analog, A23187, phorbol 12-myristate 13-acetate (PMA), NaF and thrombin. The IC50 values were in the range of 9.3-17.8 microM. NM inhibited agonists-induced aspirin-treated platelet aggregation at >10 microM, suggesting that the action site lies beyond thromboxane (TXA)2 formation. However, NM inhibited thrombin (0.5 IU/ml)-induced TXB2 formation (IC50 = 1.9 +/- 0.6 microM, mean +/- SD). Intracellular Ca2+ mobilization was also inhibited only when platelets were challenged by thrombin, but the effect was found at NM concentrations >50 microM. This finding suggests that NM reduces the responses to thrombin by inhibiting its proteolytic activity on the platelet thrombin receptor (PAR1). NM did not affect the intracellular cAMP concentration or A-kinase activity. Agonists-induced surface expression of activated glycoprotein (GP)IIb-IIIa was inhibited by 10 microM NM and was completely inhibited by 50 microM NM. Since this inhibitory effect was parallel to the inhibition of platelet aggregation, the main inhibitory mechanism of NM against platelet aggregation seemed to be the suppression of activated GPIIb-IIIa expression, which makes it able to bind fibrinogen.     

Morphometrical study on prognosis of stage I pulmonary adenocarcinoma

The prognostic significance of morphometry in stage I pulmonary adenocarcinoma had been examined in Papanicolaou-stained bronchial brushings, using an image analyzer. The data of long-term survivors (LTS), alive for more than 5 years, and short-term survivors (STS), who had died within 5 years, were compared. LTS were found to have a smaller nuclear area, a shorter nuclear perimeter, and a smaller nucleolar area than those of the STS. The nuclear size is considered important in any histological subtypes. The variation index of the nuclear area, the nuclear circularity, and the number of nucleoli did not differ between the two groups. These results would seem to be useful in determining the prognosis and the indication type of adjuvant therapy to be used in surgical operations.     

Magnetic resonance imaging in acute optic neuropathy by sphenoidal mucocele

A 45-year-old man suffered sudden visual loss with Marcus-Gunn pupil anda central scotoma in the right eye as evaluated by visual field examination.The patient's right visual acuity was 0.02 (0.08× - 4.5D).T1-weighted magnetic resonance imaging (MRI) demonstrated a cystic lesion ofhigh intensity in the right sphenoid sinus. Short TI inversion recovery(STIR) images presented a cystic lesion of high intensity in the rightsphenoid sinus. In addition, a ring-shaped high intensity signal was seensurrounding the right optic nerve. Post-contrast fat suppression T1-weightedimages did not demonstrate any enhancement within the right optic nerve.After intranasal sphenoidectomy, good recovery of the right visual acuitywas noted. On subsequent MRI, the cystic lesion in the sphenoid sinusdisappeared. Also, the ring of high intensity surrounding the right opticnerve became unclear. It was thought that the ring of hyperintentisy seen onthe STIR images demonstrated cerebrospinal fluid in the dilated periopticsubarachnoid space. Therefore, these MRI findings suggested that the acutevisual loss resulted from a disturbed blood supply to the optic nerve due tocompression by the sphenoidal mucocele, and not due to an inflammatoryprocess.     

Mechanism of carcinogenesis induced by a veterinary antimicrobial drug, nitrofurazone, via oxidative DNA damage and cell proliferation

Nitrofurazone, a veterinary antimicrobial drug, causes mammary and ovarian tumors in animals. We investigated the mechanisms of carcinogenesis by nitrofurazone. Nitrofurazone significantly stimulated the proliferation of estrogen-dependent MCF-7 cells. Nitrofurazone caused Cu(II)-mediated damage to 32P-5'-end-labeled DNA fragments obtained from human genes only when cytochrome P450 reductase was added. DNA damage was inhibited by catalase and bathocuproine. DNA damage was preferably induced at the 5'-ACG-3' sequence, a hotspot of the p53 gene. These findings suggest that nitrofurazone metabolites are involved in tumor initiation through oxidative DNA damage and nitrofurazone itself enhances cell proliferation, leading to promotion and/or progression in carcinogenesis.     

A case of Klinefelter's syndrome with bilateral absence of the vas deferens

A 33-year-old male presented to the Chiba University Hospital with the main complaint of right flank pain. Bilateral vas deferens were not palpable. Hormonal examination revealed hypergonadotropic hypogonadism and cytogenetic studies a 47,XXY karyotype. The significance of the association of this karyotype with the absence of vas deferens is discussed.     

Hypoosmotic swelling test in patients with varicocele.

The hypoosmotic swelling test is a simple test for measuring the functional competence of human sperm membrane. Thirty-five patients with varicocele were assessed by hypoosmotic swelling test and the results were compared with those in patients with idiopathic infertility. Percentage of swollen sperm in varicocele tended to be lower than that in idiopathic infertility, especially in sperm concentration between 30 x 10(6)/mL and 40 x 10(6)/mL. Varicocele with sperm motility of 40% or more revealed lower percentage of swollen sperm than idiopathic infertility did. The results indicate that varicocele may particularly injure sperm membrane function because hypoosmotic swelling test is a test for measuring functional ability of human sperm membrane. The percentage of swollen sperm recovered after the operation earlier than did the other sperm parameters such as sperm concentration or motility, which indicates that impaired sperm membrane injury by varicocele is reversible.