Estrogen inhibition of a Mr 39,000 glycoprotein secreted by human breast cancer cells

We have identified a secreted glycoprotein with an apparent molecular weight of 39,000 that is inhibited by estrogens and stimulated by antiestrogens in the MCF-7 human breast cancer cell line. The protein was detected within 24 h of hormone treatment with inhibition occurring at concentrations as low as 10(-11) M estradiol and stimulation occurring with antiestrogens. When phenol red, which has been found to have estrogenic activity, is removed from the tissue culture medium, no inhibition of cell growth or induction of the Mr 39,000 protein is seen with antiestrogens. A 6-fold decrease in the amount secreted in the presence of estrogens is seen under these conditions. The induction was specific in that growth inhibition by several other means did not induce expression of the Mr 39,000 protein. The Mr 39,000 protein has been identified as a glycoprotein complex that can be resolved into four polypeptides with two major components that migrate in the pH range of 5.5 to 6.3 by two-dimensional gel electrophoresis. This protein is the first evidence that estrogens inhibit a specific protein and it may prove useful as a marker of antiestrogen-induced growth arrest in breast cancer.     

Alpha-methyltyrosine blocks the expression of rotation classically conditioned with apomorphine.

Rats with unilateral 6-hydroxydopamine lesions of substantia nigra rotate (circle) when placed, undrugged, in the environment in which they have previously been treated with apomorphine. This conditioned rotation, like the unconditioned rotation which acutely follows the administration of apomorphine, is directed away from the side with the lesion, i.e., the rotation is contralateral. Here, rats that had been administered apomorphine weeks earlier were tested, in a crossover design, for the expression of conditioned rotation following treatment with saline and with alpha-methyltyrosine. When administered four hours prior to testing, 100 mg/kg alpha-methyltyrosine significantly antagonized the expression of classically conditioned rotation. In a second group of animals, alpha-methyltyrosine had no effect on the unconditioned rotation induced by 0.05 mg/kg apomorphine.     

Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial

BACKGROUND: The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze. METHODS: A prospective, randomised, partially blinded, controlled trial was designed at two secondary care centres. Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children's ward or attendance at an accident and emergency department or children's (emergency) assessment unit (A&E/CAU) with a primary diagnosis of acute severe asthma or wheezing were recruited. 101 children were randomised into the control group and received usual care and 99 were assigned to the intervention group and received: (1) a pre-school asthma booklet; (2) a written guided self-management plan; and (3) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s) and child. Subjects were assessed at 3, 6, and 12 months. The main outcomes were GP consultation rates, hospital re-admissions, and attendances at A&E/CAU. Secondary outcomes included disability score, caregivers' quality of life, and parental knowledge of asthma. RESULTS: There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures. CONCLUSIONS: These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months.     

Truncus Arteriosus With Patent Ductus Arteriosus and Normal Aortic Arch

In hearts with a common arterial trunk (truncus arteriosus), there is almost always an inverse development of the aortic arch and the ductus arteriosus. Truncus with a normal aortic arch and a patent ductus is a rare echocardiographic and surgical finding. In this report, we describe 2 neonates in whom truncus arteriosus with a normal aortic arch and a medium or large patent ductus was diagnosed by preoperative echocardiography (without catheterization) and confirmed intraoperatively.     

Chronic recurrent multifocal osteomyelitis and psoriasis—A report of a new association and review of related disorders

In summary, we have described two patients with CRMO and psoriasis, and have reviewed the musculoskeletal manifestations associated with pustular eruptions of the palms and soles. In view of the frequent occurrence of PPP in patients with CRMO, we suggest that the occurrence of psoriasis in our two patients is more than coincidence, and that noninfectious, inflammatory lesions of bone may be another musculoskeletal manifestation of psoriasis. This rare association, as well as the association of PPP with disorders associated with new bone formation, may shed new insights on the relatively common finding of periosteal elevation associated with psoriatic arthritis and the occasional severe juxta-articular osteolytic destructive bone lesions seen in psoriatic arthritis.     

Strangulation of the Colon Complicating Acute Pancreatitis

We report a patient with alcohol-induced necrotizing pancreatitis who developed a severe ileus followed by incarceration of a portion of the transverse colon within a ventral hernia. Laparotomy 9 days after the onset of symptoms revealed infarction of the transverse colon and infection of the pancreas. This is the first report of a case of acute pancreatitis that led to a strangulated ventral hernia of the colon. We believe that the enteric organisms that infected the pancreas originated in the incarcerated transverse colon.     

Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss.

The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction.     

3-alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents.

Recently we showed that 3-alkyl-4-aminobutanoic acids are in vitro activators of brain L-glutamic acid decarboxylase (GAD) that show anticonvulsant activity. Since activation of GAD leads to increased concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in vitro, these compounds could represent a new class of anticonvulsant agents. Here it is shown that 3-alkylglutamic acid analogues also activate GAD and that all of the compounds in both series are active anticonvulsant agents against low intensity electroshock in mice. The most active compound, 3-isobutyl GABA, was tested further against maximal electroshock in mice and was shown to be very potent after both intravenous and oral administration without causing ataxia. It is not known if brain GABA levels are elevated in vivo by administration of these compounds or if the mechanism of anticonvulsant activity is related to their ability to activate GAD.