Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly

Treadmill User Centering

The goal of team CENTREAD was to design a device to allow a person with a visual disability to run efficiently and effectively on a treadmill without fear of falling off or injuring themselves. The customer wished for the device to be small, lightweight, and have an easy, autonomous setup, while providing feedback to the user wirelessly for them to correct their own movement. The ultimate goal of the device is to allow the user to be comfortable, safe, and free while using it in order to ensure they have the best running experience. The device utilizes ultrasonic sensors in housings to detect distances of objects using sound wave pulses. These sensors send signals out and detect the amount of time it takes for the signal to return to the same place, taking that time and converting it into a distance. These distances are sent directly into a microcontroller, where the microcontroller collects and analyzes the data. While analyzing the data, the microcontroller looks for data points that are within the boundaries set as not safe zones. These data points are then assigned a value and are sent over to a wireless transmitter to communicate with its sister receiver. The receiver detects a signal sent from the relative transmitter and sends the signal to another microcontroller to be processed. This process takes the value sent from the transmitter and assigns that value to a pin to activate a voltage to. This pin contains a small eccentric weighted motor that vibrates when a voltage is applied. This vibration is then interpreted by the user to move in the opposite direction of the vibration, correcting their location. This device utilizes two housings, one along the length axis of the treadmill belt and one along the width axis of the treadmill belt. These boxes interpret backwards distance from the front edge of the belt and left and right distance from the inside face of the right treadmill arm, respectively. These housings each contain their own microcontroller and transmitter that communicate with the receiver. The receiver is contained with a belt that the user wears, and collects signals from both housings. The microcontroller interprets these signals and applies a voltage to the respective motor. These motors are located on the left, right, and back of the belt and are there to correct the user to the right, left, and forwards respectively. This feedback system ultimately serves the purpose for solving the users problem and is an effective way of helping them get back to running confidently and safely again

Pergolide As Primary Therapy for Macroprolactinomas

The objective of this study is to determine whether pergolide therapy is an effective modality for the de novo treatment of patients with macroprolactinomas. Twenty-two consecutive patients with macroprolactinomas were included in the study and followed prospectively. These included 16 men and 6 women in whom pregnancy was not of concern. Pergolide was administered once or twice a day depending on the patient's preference. Ten patients received 0.1 mg daily as a maintenance regimen and in the others the daily dose ranged from 0.05 to 0.5 mg. Eight patients reported minor but tolerable side effects. One patient had to be switched to cabergoline because of intolerable nausea. After a mean of 12 months (range, 3–36), mean PRL levels declined from 3,135 ng/ml (range, 126–31,513) to 50 ng/ml (3–573), representing a mean PRL suppression of 88% (range, 0–99). PRL levels became normal in 15 patients and decreased to 25–40 ng/ml in 3 others. The mean tumor volume shrinkage was 25% or greater in 19 patients (86%), 50% or greater in 17 patients (77%), and 75% or greater in 10 patients (45%). Visual abnormalities were reversible after pergolide therapy in all but 1 of 12 patients with initially abnormal formal visual testing. Two out of 4 premenopausal women did not normalize PRL levels and had persistent oligomenorrhea. Testosterone was low in 14 men at presentation and normalized in 3 with pergolide therapy. We conclude that pergolide is a safe, inexpensive, and generally well-tolerated dopamine agonist for the treatment of macroprolactinomas in men and women in whom pregnancy is not of concern. In these specific populations, pergolide may become the first-line therapy for treatment of macroprolactinomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47496/1/11102_2004_Article_382165.pd

Rapid Re-expansion of a Macroprolactinoma After Early Discontinuation of Bromocriptine

Prolactin (PRL)-secreting pituitary adenomas are the most common functioning pituitary tumors. Medical treatment with dopamine agonists is the therapy of choice for macroprolactinomas (≥10 mm). Withdrawal of bromocriptine after weeks or months of uninterrupted therapy has been associated with rapid tumor re-expansion as evidenced by x-ray and CT scanning of the pituitary region. We report a patient with a giant macroprolactinoma who had a dramatic response to bromocriptine (tumor volume shrinkage of 53% within a month) but rapid re-expansion to its original dimensions one week after discontinuation of bromocriptine. To our knowledge, this is the first time that the rapid shrinkage/re-expansion of a macroprolactinoma has been documented with serial MRI scans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47493/1/11102_2004_Article_324060.pd

Somatotropinoma Infarction During Octreotide Therapy Leading to Bilateral Cavernous Sinus Syndrome

The cyclic somatostatin analog, octreotide, forms the mainstay of medical treatment for acromegaly. In addition to lowering circulating growth hormone levels and shrinking tumor size, octreotide may provide symptomatic relief of headaches associated with growth hormone secreting tumors. The majority of reported complications of octreotide therapy are gastrointestinal and metabolic. The present case illustrates the development of acute bilateral cavernous sinus syndrome with loss of eye movement bilaterally during octreotide therapy. Serial MRI examination suggest tumor infarction as the etiology. The symptoms resolved over 2 months as the tumor shrunk in size and growth hormone was dramatically reduced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47491/1/11102_2004_Article_324058.pd

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure