Ovarian function in three female patients with McCune-Albright syndrome with persistent autonomous ovarian activity

Autonomous ovarian activity persists throughout adolescence in some patients with McCune-Albright syndrome (MAS). There have been few studies of longitudinal assessment of ovarian function in these patients. We investigated the first morning voided urinary gonadotropin and ovarian steroid levels consecutively in three patients aged 3 to 7 years after withdrawal of therapy for precocious puberty. They had the triad of MAS with onset of menses within the first 3 years of life. Excessively elevated urinary estrogen levels with one or two peaks per cycle were found in all patients. In two patients, café-au-lait spots and dysplastic bones were located unilaterally. These two patients showed significantly increased urinary pregnanediol levels, suggesting ovulation, with low levels of gonadotropins in one patient and moderately low levels with an LH surge in the other. Thus, only a unilateral ovary was anticipated to be mutated with persistent autonomous ovarian activity. In the remaining patient with bilateral involvement of tissues, relatively high LH and low FSH levels throughout a cycle were found with no rise in urinary pregnanediol.     

Regulatory T cells for tolerance

Regulatory T cells (Tregs) are critical mediators of immune homeostasis and hold significant promise in the quest for transplantation tolerance. Progress has now reached a critical threshold as techniques for production of clinical therapies are optimised and Phase I/II clinical trials are in full swing. Initial safety and efficacy data are being reported, with trials assessing a number of different strategies for the introduction of Treg therapy. It is now more crucial than ever to elucidate further the function and behaviour of Tregs in vivo and ensure safe delivery. This review will discuss the current state of the art and future directions in Treg therapy.     

Relationship between Plasma Fibrinogen Levels and Pulmonary Function in the Japanese Population: The Takahata Study

Background:Plasma fibrinogen is considered a biomarker of respiratory disease, owing to the relationship between plasma fibrinogen and pulmonary function established in Western populations. However, such a relationship has not yet been confirmed in an Asian population. We assessed this relationship in the general Japanese population.Methods:Totally, 3,257 men and women aged ≥40 years who participated in a community-based annual health checkup in Takahata, Japan, from 2004 to 2006, underwent spirometry, and their plasma fibrinogen levels were determined.Results:We found an inverse relationship between spirometric measures (percent predicted forced vital capacity [%FVC] and forced expiratory volume in 1s [%FEV₁], and FEV₁/FVC) and plasma fibrinogen levels in men, but not in women. The plasma fibrinogen levels were significantly higher in subjects with restrictive, obstructive, and mixed ventilatory disorders than in those with normal spirometry results. Multiple linear regression analysis revealed that in men, plasma fibrinogen levels were predictive for %FVC and %FEV₁ (independent of age, body mass index, and cigarette smoking) but not for FEV₁/FVC.Conclusions:Plasma fibrinogen was significantly associated with pulmonary function in Japanese men, and as such, plasma fibrinogen might be a potent biomarker for pulmonary dysfunction in men.     

The positive rate of lupus anticoagulant according to the each understanding disease in our hospital

We investigated positive rate of lupus anticoagulant (LA) according to the each understanding disease in our hospital. 596 cases (F/M 477/149, 7-87 y.o.) were examined from 2003 to 2004 years. LA tests were performed using 2 methods such as kaolin clotting time (KCT) mixing test and dilute Russell's viper venom time (dRVVT). The LA tests were most frequently ordered in dermatology, and the most common purpose of LA test was the check of existence of antiphospholipid (aPL) in patients with collagen diseases. The LA positive rate was the highest in patients with SLE among the collagen diseases, and in patients with cerebral infarction among the thrombotic diseases. The LA positive rate exceeded 40% in ITP and livedo reticularis. Moreover, LA positive rate was 16% in preoperative tests of the orthopedic patients without any physical diseases. Thus, it was suggested that there were considerable numbers of the asymptomatic LA positive persons. The LA positive cases based on KCT only accounted for about 60% of all the LA positive cases. Among the thrombotic patients, there were not the DVT/PE patients with only KCT positive. On the other hands, the KCT positive rate was higher than the dRVVT positive rate in patients with cerebral infarction. There were not dRVVT single positive cases in patients with recurrent abortion and ITP, but KCT single positive case accounted for about 90%. From these results, it is suggested that there is a difference in KCT and dRVVT about detecting aPL, and that care should be taken to interpret the LA test.     

Cholera Toxin Production by the El Tor Variant of Vibrio cholerae O1 Compared to Prototype El Tor and Classical Biotypes

Vibrio cholerae O1 El Tor variant strains produced much more cholera toxin than did prototype El Tor strains. The amount of cholera toxin produced by El Tor variant strains both in vitro and in vivo was more or less equivalent to that produced by classical strains.Vibrio cholerae O1 is classified into classical and El Tor biotypes. Among other genetic, biochemical, and physiological differences, each biotype has unique gene sequences encoding cholera toxin B subunit (CTB), that is, classical ctxB and El Tor ctxB. Besides these two prototype biotypes of V. cholerae O1, Nair et al. (9) in 2002 in Bangladesh isolated strains that possess phenotypic properties of both classical and El Tor biotypes carrying classical ctxB. The same group also isolated El Tor strains that had classical ctxB (10). For these new types of strains of V. cholerae O1, we have recently proposed the designations of hybrid and El Tor variants, respectively (13). Subsequent to the isolation of the El Tor variant in Bangladesh by Nair et al. (10), El Tor variant strains were isolated from several countries and areas in Asia and Africa (1, 11, 15-18). In Kolkata, India, we showed that El Tor variant strains appeared in 1990 and that a complete replacement of prototype El Tor strains by El Tor variant strains has occurred since 1995 (14).In this study, we investigated the amount of cholera toxin (CT) produced both in vitro and in vivo by V. cholerae O1 El Tor variant strains isolated in Kolkata during a period from 1996 to 2007. It was found that El Tor variant strains produced a much larger amount of CT than did prototype El Tor strains and that the amount of CT produced by El Tor variant strains was more or less equivalent to that produced by classical strains.V. cholerae O1 strains used in this study are listed in Table ​Table1.1. AKI (3) and Syncase medium (2) were used for culturing the test strains. The rationale for selecting these media was that AKI preferentially supports the production of El Tor CT (3) while Syncase medium is reported to be the best medium supporting the production of CT by the classical biotype (2). Measurement of CT concentration produced by V. cholerae O1 strains was carried out as follows. Each strain was cultured either in AKI medium at 37°C for 20 h without shaking or in Syncase medium at 37°C for 20 h with shaking, and the optical density of the culture was measured at 600 nm (OD₆₀₀). After centrifugation, the supernatants were collected and the concentration of CT (ng/ml/OD₆₀₀) in the samples was measured by bead enzyme-linked immunosorbent assay (ELISA). The method of the bead ELISA employed was essentially that described by Oku et al. (12). In brief, a polystyrene bead (6.5 mm in diameter) was coated with anti-CT IgG and used as a solid phase. The coated bead was first incubated with the sample and then incubated with anti-CT IgG [F(ab′)]-horseradish peroxidase conjugate. Peroxidase activity was determined colorimetrically with 3,3′,5,5′-tetramethylbenzidine as the substrate. The absorbance at 450 nm (OD₄₅₀) was linear between 0 and 0.5, representing CT concentrations of 0 to 20 ng/ml. The sample prepared as described above (the supernatant of the culture of the strain) was appropriately diluted so that the OD₄₅₀ fell in the range of 0.1 to 0.5, and the amount of CT produced by the strain was expressed as ng/ml/OD₆₀₀.

TABLE 1.

V. cholerae O1 strains used

Expression of hepatic thrombopoietin mRNA in primary cultured hepatocytes and in rats with acute liver injury or bone marrow suppression with or without cirrhosis

BACKGROUND AND AIMS: The main causes of thrombocytopenia in cirrhosis are thought to be platelet destruction and the reduction of thrombopoietin (TPO) expression in the liver. The mechanisms by which levels of TPO mRNA are regulated in cirrhosis have not been elucidated. In this study, we investigated some possible mechanisms. METHODS: We used three experimental models: bone marrow suppression, acute liver injury and primary cultured hepatocytes. We used northern blots to assess the kinetics of TPO mRNA expression in the livers of irradiated rats (with and without cirrhosis) in acute liver injury and in primary cultured hepatocytes treated with hepatotoxin or cytokines. RESULTS: Although the bone marrow was hypocellular, there was no apparent enhancement of TPO mRNA expression in the irradiated rats with cirrhotic livers compared with the unirradiated rats with cirrhotic livers. There were no conspicuous changes in hepatic TPO mRNA expression between the livers of the control rats and the three models of acute liver injury. There were no conspicuous changes in the levels of TPO mRNA between control hepatocytes and hepatocytes treated with hepatotoxin or cytokines. CONCLUSIONS: Our results suggest that bone marrow is not a regulator of hepatic TPO production in cirrhosis. The reduced TPO mRNA expression found in cirrhotic rats may not result merely from serious cellular damage; it may be associated with cirrhosis-specific regulatory mechanisms for the expression of the TPO gene. Further studies are needed to search for other factors that may induce reduced TPO expression.     

Metastatic squamous cell carcinoma of the paranasal sinuses from a primary squamous cell carcinoma of the urinary bladder

Metastatic tumours of the paranasal sinuses from primary lesions of the urogenital tract are rare, with about 50 cases so far being reported in the literature. The most frequent primary lesions is a renal carcinoma. We have experienced a case of paranasal sinus malignancy. There were no symptoms of urinary tract carcinoma preceding those in the paranasal sinuses. This case was later revealed at autopsy to be a metastasis from a diverticulum of the urinary bladder.     

Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced in vivo by heterocyclic amines

Cumulative effects of chromosome aberrations and sister chromatidexchanges (SCEs) were studied in hepatocytes of F344 rats exposedin vivo to 2-amino-3-methylimidazo[4,5-fIquinoline (IQ) at dosesof 12.5,25 or 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f quinoline (nitro-IQ) at doses of 12.5, 25 or 50 mg/kg bodywt/day. Hepatocytes were isolated 24 h after 1, 7,14 or 28 repeateddoses (once a day) by gastric intubation and allowed to proliferatein Williams' medium E supplemented with epidermal growth factor.Cells were fixed after a culture period of 48 h. Multiple treatmentwith IQ or nitro-IQ induced significant chromosome aberrationstime- and dose-dependently, the maximum frequency of chromosomeaberrations in metaphase cells being 39 and 33% respectively,while that in controls was 1.1%. Single treatment with IQ ornitro-IQ induced significant SCEs dose-dependently, the maximumfrequency being 0.83 and 0.79 per chromosome respectively, whilethe control value was 0.51. Multiple treatment with nitro-IQinduced significant SCEs to a plateau level of 0.90 per chromosome.Cytogenetic damage in the liver by IQ was greater than thatby nitro-IQ. These results show that this assay of chromosomeaberrations and SCEs in rat liver in vivo without partial hepatectomyor mitogen treatment in vivo is a sensitive method for evaluatingthe cumulative tumor-initiating activities of carcinogenic heterocyclicamines at low doses and should be useful for the detection ofunknown hepatocarcinogens.