CRISPR/Cas technique allows precise modification of genome

Exclusive: 'Jaw-dropping' breakthrough hailed as landmark in fight against hereditary diseases as Crispr technique heralds genetic revolution - Science - News - The Independent

• David Adams, a DNA scientist at the Wellcome Trust Sanger Institute in Cambridge, said that the technique has the potential to transform the way scientists are able to manipulate the genes of all living organisms, especially patients with inherited diseases, cancer or lifelong HIV infection.
  
  “This is the first time we’ve been able to edit the genome efficiently and precisely and at a scale that means individual patient mutations can be corrected,” Dr Adams said.

Research shows how medicine for the brain can be absorbed through the nose

Research shows how medicine for the brain can be absorbed through the nose
-University of Southern Denmark. "Research shows how medicine for the brain can be absorbed through the nose." Medical News Today. MediLexicon, Intl., 27 Sep. 2013. Web. 27 Sep. 2013.

Editor's notes:
There may be a wonderful use for nasal administration in the treatment of medically resistant pituitary prolactinomas.  These are commonly treated medically by oral administration of the dopamine agonists cabergoline (CAB) or bromocriptine (BRO).  But in some patients normalization of PRL (prolactin) levels is not achieved with even unusually high doses of CAB or BRO. If CAB or BRO can be delivered effectively to the brain via nasal administration, it may be possible to produce higher therapeutic levels of the drug at the pituitary tumor while avoiding the undesired increased exposure to other systems which may be affected: such as the kidneys, pancreas, and immune system.

Cref: Dopamine -Wikipedia

Mechanical ventilation can cause brain damage through dopamine induced apoptosis in hippocampus

Triggers Hippocampal Apoptosis by Vagal and Dopaminergic Pathways
-Adrián González-López, Inés López-Alonso, et al.
American Journal of Respiratory and Critical Care Medicine, Volume 188, Issue 6, 15 September 2013.
Researchers find why ICU ventilation can cause brain damage
-Medical News Today, 26 September 2013.

Excerpts:

• Patients who have been mechanically ventilated in intensive care units have long been known to suffer some form of mental impairment as a result. Now, researchers have uncovered a molecular mechanism that may explain why this happens.
• In comparison with the control mice, the mice on ventilation showed evidence of neuronal cell death in the hippocampus as a result of apoptosis - the process of programmed cell death. The research team discovered that the apoptosis process was caused by dopamine-induced suppression of Akt - a molecule that usually prevents neuronal apoptosis.
• The research team discovered that the apoptosis process was caused by dopamine-induced suppression of Akt - a molecule that usually prevents neuronal apoptosis.

Post-surgical follow-up of primary hyperparathyroidism associated with MEN1

Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1

-Flavia L. Coutinho, Delmar M. Lourenco, Jr.,I Rodrigo A. Toledo, Fabio L. M. Montenegro, and Sergio P. A. Toledo
Clinics (Sao Paulo). 2012 April; 67(Suppl 1): 169–172.
doi: 10.6061/clinics/2012(Sup01)28. PMCID: PMC3328812

• In patients with hyperparathyroidism and MEN1, parathyroidectomy in most cases "was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation."
  

Diagnosis of MEN1 in a patient with back pain

Diagnosis Of Multiple Endocrine Neoplasia Type 1 In A Patient With Back Pain; Case Report And Review Of Literature
-G Cristina, L Cesar A, L Robert, M Vinuta. Diagnosis Of Multiple Endocrine Neoplasia Type 1 In A Patient With Back Pain; Case Report And Review Of Literature. The Internet Journal of Internal Medicine. 2008 Volume 8 Number 1.

• "Usually MEN1 patients are first diagnosed when they present with hypercalcemia. Our patient’s diagnosis was made only after he presented with back and flank pain, and imaging of his abdomen incidentally noted multiple abdominal tumors."
  

Gut reaction: Mice survive lethal doses of chemotherapy

Gut reaction: Mice survive lethal doses of chemotherapy
-University of Michigan News Service

The study, "Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection," was supported by grants from the National Institutes of Health, and is to be published in Nature.

ref: Slit Robo Signaling and Induction of Intestinal Stem Cells for Colorectal Cancer Therapy

Selective parathyroidectomy: a conservative surgical option for MEN1–primary hyperparathyroidism

Minimally invasive parathyroidectomy provides a conservative surgical option for multiple endocrine neoplasia type 1–primary hyperparathyroidism -Mark Versnick, et al.
Surgery, Volume 154, Issue 1 , Pages 101-105, July 2013

• MIP (minimally invasive hyperparathyroidectomy) "provides an acceptable outcome for patients with MEN1."
  
• "It is accepted that recurrent disease is inevitable in these patients; however, such recurrence may take decades to occur and may be able to be dealt with by a further focused procedure."

Menin -today's growth promoter, tomorrow's tumor suppressor

Elucidating the Role of Menin During Islet Cell Development in the Human Fetal Pancreas
-Dubrick, Jessica L., (2013).  
University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 1287.
http://ir.lib.uwo.ca/etd/1287

editor's notes:

Menin functions as a tumor suppressor in adult endocrine cells, but in the fetal pancreas promotes cell survival and proliferation.  At first glance these roles seem very different, almost opposite.  But are they really opposed?

If menin promotes the proliferation of healthy pancreas cells -in particular, cells with at least one functional MEN1 gene- then it would seem that these cells will proliferate faster than those unable to produce menin.  So, cells that are unable to produce menin will represent a decreasing fraction of the cell population. Therefore, even during fetal development, menin's role as a growth promoter offers a tumor suppressive advantage to the developing pancreas, by reducing the percentage of cells that later may pose a tumorigenic risk due to their inability to express menin.

Unless I've got that wrong.

Link discovered between MEN1 and much-studied Hedgehog signal pathway

Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
-Xianxin Hua, MD, PhD, Buddha Gurung, PhD, Perelman School of Medicine, University of Pennsylvania
Cancer Research April 15, 2013 73:2650-2658; Published OnlineFirst April 15, 2013;

Link discovered between MEN1 and much-studied cell pathway
A research team led by Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, report in Cancer Research that menin suppresses signaling in the much-studied Hedgehog pathway in endocrine organs.

• "This study uncovered a new layer of regulation of pro-proliferative genes by menin via the Hedgehog signaling pathway," Hua says.
  
• "These pro-replication genes are regulated through GAS1 and PRMT5."
  
• The GAS1 protein promotes Hedgehog signaling.
  
• Menin interacts with the methylating enzyme PRMT5, and binds to the promoter of the Gas1 gene, inhibiting Gas1 gene transcription.
  
• By inhibiting Gas1 expression, menin and PRMT5 inhibit the pathway's tendency towards cell proliferation.
  
• Mutant menin proteins are impaired in their ability to interact with PRMT5, and lead to increased Hedgehog signaling and cell proliferation.
  
• Hua's team found that treating a mouse model of human MEN1 with a Hedgehog pathway inhibitor called Erivedge reduced proliferation of tumor cells and blood insulin levels. Hua says that this suggests a potential new treatment for MEN1 patients.
  

Men1 mouse studies claim pre-clinical proof-of-concept for gene replacement therapy in pituitary NETs.

Clinical and pre-clinical studies of neuroendocrine tumours (NETs) in multiple endocrine neoplasia type 1 (MEN1), and evaluation of MEN1 gene replacement therapy for MEN1-associated NETs.
-Gerard Walls, Paul Newey, et al.
Endocrine Abstracts (2013) 31 YEP1.1 | DOI:10.1530/endoabs.31.YEP1.1

Hyperprolactinemia and Macroprolactinemia

Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays.
-B Cavaco, S Prazeres, et al.
J Endocrinol Invest. 1999 Mar;22(3):203-8.

"Macroprolactinemia, i.e. sustained hyperprolactinemia where the predominant circulating form of prolactin (PRL) is of large molecular weight, is a common phenomenon comprising up to one-fourth of all cases of hyperprolactinemia."

"we suggest that the routine measurement of PRL should be done with methods that are only minimally affected by the presence of macroprolactin."

Hyperprolactinemia or pseudohyperprolactinemia?

Reporting of Post–PEG Prolactin Concentrations: Time to Change
-T Smith, M Fahie-Wilson
Clinical Chemistry March 2010 vol. 56 no. 3 484-485

Measurement of serum prolactin levels can be exagerated by the presence of biologically inactive "big prolactin" or "macroprolactin", aka "big big prolactin".

"The polyethylene glycol (PEG) precipitation test is widely used to detect pseudohyperprolactinemia caused by big prolactin and/or macroprolactin. Current best practice recommends that all sera with increased total prolactin concentrations be subfractionated by PEG precipitation to measure the bioactive monomeric prolactin concentration, a more clinically meaningful variable."

MEN1 -overview and treatment

Multiple endocrine neoplasia type 1 (MEN1)
-Richard W. Carroll
Asia-Pacific Journal of Clinical Oncology,Wiley Online Library, 2012
doi: 10.1111/ajco.12046