The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

Processes and outcomes of psychotherapists' personal therapy: Replication and extension 20 years later.

In this replication and extension of a national survey of psychotherapists conducted in 1987, American psychologists (n = 219), counselors (n = 191), and social workers (n = 192) reported in 2007 on the processes and outcomes of their personal therapy experiences. Of the 85% who sought therapy at least once, women, men, and members of all three professions were equally as likely to have received personal treatment. Their top reasons for seeking therapy were marital–couple distress (20%), depression (13%), need for self-understanding (12%), and anxiety–stress (10%). Approximately 24% used psychotropic medication in combination with personal therapy. More than 90% of therapists reported positive outcomes across multiple domains. The modal lasting lessons from personal treatment related to therapist reliability, skill, and empathy. The results are tentatively compared with those obtained in 1987, thus chronicling the evolution of personal therapy among psychologists and social workers during the past 20 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Beta-glucuronidase in human mammary carcinomas

The result of prompt squatting is an increase of the venous return and of the arterial resistance. Consequences are increasing of the end-diastolic and systolic chamber pressure, stroke volume, average arterial blood pressure as well as decreasing of the frequency of the pulse controlled by baro-receptors. The regulatory mechanism both change the intensity of heart murmurs of various cardiopathies and of functional heart murmurs in children. Only the systolic murmur of muscular subvalvular aortic stenosis softens. The experiment is most valuable for the recognition of mild insufficiency of semilunar valves.     

The response of Golgi tendon organs to single motor unit contractions

1. Cross-correlation analysis has been used to quantify the responses of cat soleus tendon organs to repetitive twitch contractions of: (a) different motor units within the muscle, (b) single motor units at different muscle lengths, and (c) single motor units when the pulse-train pattern of stimulation delivered to the motor unit axon was altered. 2. Ib afferents were observed which responded to each of several hundred successive motor unit twitches with identical numbers of spikes and with relatively invariant latencies. 3. The present results show that tendon organs are sensitive to subtle alterations in motor unit twitch wave form and amplitude, and that this sensitivity is reflected in the precise timings of their afferent discharge. 4. Examination of these tendon organ responses indicates that the forces produced by single motor units couples to the receptor capsule are well above threshold. Calculations based on these results, and earlier soleus motor unit and muscle fibre data, suggest that the absolute force threshold for tendon organs may be as little as 4 mg, which is less than the estimated minimum twitch force generated by individual soleus muscle fibres. 5. Considering the number of tendon organs in a muscle, and the likelihood that every motor unit is connected with at least one receptor, the sensitivity of tendon organs ensures that every twitch of every motor unit will be reflected in the population of afferent signals projecting to the spinal cord.     

Electrocardiographic abnormalities in hypothyroidism before and after exercise

Eleven men and 50 women with severe hypothyroidism were studied. All patients had a serum PBI less than 3.0 mug/100 ml, 131I 24 hours uptake less than 13% and a a photomotogram contraction and half relaxation time of 380 msec or more. Before exercise the mean +/- SE heart rate was 68.39 +/- 3.26/min, the PR interval 17.08 +/- 0.37 csec, the QRS voltage (sum of the QRS amplitude in leads I, II and III) 16.44 +/- 0.89 mm (10mm = 1.0 mV) and the T wave amplitude 0.06 +/- 0.15 mm. A significant correlation (p less than 0.05) existed between the PBI values and the QRS voltage. Following exercise there was a significant acceleration of the heart rate (+ 23.39/min, p less than 0.001), shortening of the PR interval (-0.66 csec, p less than 0.02) and T wave elevation (+ 0.40 mm, p less than 0.001). ST segment changes were not observed in any case. Replacement treatment in 7 cases resulted in a significant change in the resting heart rate (+ 11.86/min. p less than 0.025), PR interval (-3.28 mm, p less than 0.025) and T wave height (+ 2.50 mm, p less than 0.01). These findings suggest that exercise may be used in the differentiation between hypothyroidism and coronary heart disease. The theoretical importance of these findings is also discussed. An increase in cardiac energy demands during exercise may be the cause for some of the ECG changes observed on exertion.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Atraumatic retrieval of the proximal end of a severed digital flexor tendon

A suction catheter technique is suggested as the next procedure of choice when proximal digital "milking" with wrist flexion fails to deliver the proximal end of the flexor tendon severed within the digital sheath.     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.