Oestradiol up-regulates oestrogen receptor, cyclophilin, and glyceraldehyde phosphate dehydrogenase mRNA concentrations in endometrium, but down-regulates them in liver

Oestradiol regulates reproductive physiology and cardiovascular health in women. In the endometrium of ovariectomized ewes, previous work demonstrated that a single dose of oestradiol (50 microg) up-regulates oestrogen receptor-alpha (ER) and progesterone receptor (PR) gene expression within 24 h. Here we compared responses to different doses of oestradiol and different dosing regimens in two diverse tissues: endometrium and liver. ER, c-fos, cyclophilin and glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA concentrations were analyzed on replicate RNA slot blots in both tissues, while PR and apolipoprotein AI (apo AI) mRNA concentrations were only analyzed in endometrium or liver, respectively. Along with ER mRNA, oestradiol strongly up-regulated GAPDH and cyclophilin mRNA concentrations in endometrium. In liver, however, oestradiol down-regulated them, along with apo AI mRNA. Responses to different doses and dose regimens, including repeated 50 microg doses, were similar to those evoked by a single 50 microg dose of oestradiol. Thus, oestradiol appears to have all-or-none effects which include up-regulation of ER, cyclophilin and GAPDH gene expression in endometrium and down-regulation of ER, apo AI, cyclophilin and GAPDH gene expression in liver. These results illustrate the sharp contrast between two mammalian tissues in their responses to physiological levels of oestradiol.     

At-line solid-phase extraction for capillary electrophoresis: application to negatively charged solutes

The molecular karyotype of a series of Giardia lamblia isolates representing the two major genotypes (Groups 1 and 3) was generated by assigning 13 genetic markers to chromosomes separated by pulsed-field gel electrophoresis. The co-localization identified five linked groups of genetic markers in Group 1 isolates. For each of the five linkage groups, there were up to four size variants that hybridized with the same genetic markers. Long range physical maps of the regions flanking the low copy number genetic markers indicated that these size variants were homologous chromosomes. The linkage groups were similar in Group 1 and 3 isolates. The core of each chromosome was stable while the subtelomeres were variable. The location of the ribosomal DNA repeats was variable among the different isolates and they were found in the subtelomeric regions of any of the five linkage groups. The data suggest a functional ploidy of at least four. Hypervariable subtelomeric regions of homologous chromosomes provide the structural basis of the chromosome size heterogeneity that is characteristic of G. lamblia.     

Parasolitary nucleus: a source of GABAergic vestibular information to the inferior olive of rat and rabbit

At least two subnuclei of the inferior olive, the beta-nucleus, and the dorsomedial cell column (dmcc), contain vestibularly responsive neurons that receive a dense descending projection that uses gamma-aminobutyric acid (GABA) as the transmitter. In contrast to the GABAergic innervation of other olivary subnuclei, the terminal boutons that terminate on neurons in the beta-nucleus and the dorsomedial cell column remain intact after cerebellectomy, ruling out both the cerebellum and the cerebellar nuclei as afferent sources. By using both immunohistochemical as well as orthograde and retrograde tracer methods, we have identified the source of the GABAergic pathway to the beta-nucleus and dmcc in both rat and rabbit. Under physiologic recording of single olivary neurons to guide electrode placement, we injected the bidirectional tracer, wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the beta-nucleus and dmcc of the inferior olive. These injections retrogradely labeled neurons in the parasolitary nucleus (Psol) near the vestibular complex. Psol neurons were identified as GABAergic with an antibody to glutamic acid decarboxylase (GAD). In the rat, Psol neurons are small (5-7 microm in diameter) and number approximately 1,800. In the rabbit, they are slightly larger (6-9 microm in diameter) and number approximately 2,200. WGA-HRP injections in conjunction with GAD immunohistochemistry double labeled a high percentage of neurons in both the rat and rabbit Psol. Injection of the orthograde tracer Phaseolus vulgaris-leucoagglutinin into the area of the Psol revealed a projection from this region to both the beta-nucleus and dmcc. Subtotal electrolytic lesions of this division of the Psol caused a substantial reduction in GAD-positive synaptic terminals in both the ipsilateral beta-nucleus and dmcc. The location of these GABAergic neurons, bordering both the nucleus solitarius and caudal vestibular complex, emphasizes the importance of the Psol in the processing of both vestibular and autonomic information pertinent to postural control.     

Extrafacial lentigo maligna melanoma: analysis of 71 cases and comparison with lentigo maligna melanoma of the head and neck

We report a retrospective analysis of extrafacial lentigo maligna melanoma (LMM), and a comparison with patients with LMM of the head and neck. Seventy-one patients (22 men, 49 women) with extrafacial LMM were identified from the Scottish Melanoma Group database for January 1979-March 1996. Their mean age (63 years) was significantly less than that of 335 patients with head and neck LMM (mean 72 years, P < 0.001), with a significantly greater difference among women than men. Extrafacial sites comprised 17.5% of LMMs. There was a marked body site distribution difference between the sexes (P = 0. 001): 68% of extrafacial LMMs in men were on the trunk while 80% in women were on the limbs, particularly the lower leg. Extrafacial LMMs were thinner at presentation than head and neck LMMs (P < 0.05) in both sexes, but this was not simply explained by the younger age of these patients as there was no significant correlation between age and tumour thickness at either extrafacial or at head and neck sites. Although the female lower leg is a site of chronic solar exposure in older women, the other extrafacial sites are habitually covered in the temperate Scottish climate. The significantly younger age group of patients with LMM at extrafacial compared with head and neck sites therefore suggests that the relationship between LMM and sunlight is not simply related to cumulative solar exposure. The demonstration that head and neck LMMs were thicker at presentation compared with extrafacial sites, despite being at a more routinely visible part of the body, suggests that there are still opportunities for targeted pigmented lesion public education.     

The effect of 12 months'' treatment with eicosapentaenoic acid in five children with cystic fibrosis

BACKGROUND: The use and indications for laparoscopy have been increasing. As part of this trend, a new algorithm may emerge for pediatric trauma in which laparoscopic techniques are used in hemodynamically stable patients with suspected hollow viscus perforation. CASE REPORT: We present a case in which laparoscopy was successfully used in a pediatric trauma patient as a diagnostic and therapeutic modality. A 4-year-old boy was a back-seat passenger in a head-on collision motor vehicle accident. He was restrained by a lap seat belt. He sustained a concussion, a large forehead laceration and a seat belt abdominal injury. On admission, he complained of abdominal pain. Physical examination revealed a soft, non-distended abdomen with moderate diffuse tenderness. He was hemodynamically stable. Computerized tomography of the abdomen revealed free fluid in the pelvis. No abnormalities were detected in the liver or spleen. Because of clinical deterioration and suspected intestinal perforation, diagnostic laparoscopy was utilized instead of proceeding directly to celiotomy. At laparoscopy a jejunal perforation was found and successfully repaired laparoscopically. Large hematomas were seen in the mesentery, as well as an unsuspected splenic laceration. No active bleeding was found. The patient recovered uneventfully and was discharged 5 days following the surgical procedure. CONCLUSION: This case illustrates the efficacy of using early laparoscopy in children with abdominal trauma when diagnosis is difficult and hollow viscus injury is suspected.     

Effects of a new platelet glycoprotein IIb/IIIa antagonist, SR121566, on platelet activation, platelet-leukocyte interaction and thrombin generation

The effects of SR121566, a new inhibitor of the glycoprotein (GP) IIb/IIIa complex on platelet activation and platelet-leukocyte interactions, as well as on thrombin generation were investigated. SR121566 dose-dependently inhibited adenosine diphosphate (ADP)-induced platelet fibrinogen binding determined either by flow cytometry analysis (IC50=50 nmol/l) or by measuring the binding of 125I-fibrinogen to activated human gel-filtered platelets (IC50=20 nmol/l). Consistent with its inhibitory effects on platelet fibrinogen binding, SR121566 demonstrated a dose-dependent inhibition of collagen-, ADP- or thrombin-induced platelet aggregation with IC50 values ranging between 20 and 60 nmol/l. SR121566, even tested at high concentrations, did not significantly affect ADP-induced platelet-leukocyte aggregate formation. The GPIIb/IIIa antagonist strongly inhibited thrombin generation in both native clotting blood and recalcified whole blood, suggesting that SR121566, by interfering with the platelet-activation events involved in facilitating thrombin generation, may also function as an anticoagulant, an effect which may contribute to its antithrombotic properties in humans.     

Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter

BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.     

Role of macrophages in defective cell mediated immunity in lepromatous leprosy. I. Factor(s) from macrophages affecting protein synthesis and lymphocyte transformation

Macrophages from lepromatous leprosy patients specifically show reduced protein synthesis in the presence of M. leprae. They also produce, as a result of interaction with M. leprae, factor(s) that reduce protein synthesis in normal macrophages as well as block lymphocyte transformation in normal leukocyte cultures in the presence of M. leprae as the antigen. These observations implicate a defective macrophage system in lepromatous leprosy patients.     

Intellectual deficits after transient tyrosinemia in the term neonate

An analysis was made of the obstetric history of 1,360 patients who were delivered in 1971. It involved 3,185 pregnancies. The aim of the study was to evaluate the risk of spontaneous termination of the pregnancy, worked out from its demographic aspect. Several ideas are worthy of consideration. The risk of spontaneous intra-uterine death is cumulative, sharply increased by a repetition of such cessation of pregnancy. The same patients often undergo intentional abortion repeatedly. The respective risks of spontaneous and provoked interruption of pregnancy have been studied in greater detail as a function of parity.