Spontaneous pregnancy after full recovery from hypopituitarism caused by lymphocytic hypophysitis

Lymphocytic hypophysitis (LyH) has been known to be associated with pregnancy. We herein report the case of a 33-year-old woman who underwent vaginal delivery without massive bleeding at 40 weeks of gestation. Because of the presence of headache and terrible fatigue after childbirth, she visited our hospital. Severe hyponatremia (Na, 118 mEq/L) and visual field abnormality was noted upon examination. MRI revealed pituitary enlargement with a swollen pituitary stalk, albeit at low signal intensity. Basal pituitary hormone levels were all reduced and remained low after exogenous administration of hypothalamic-releasing hormones. She was diagnosed with LyH and was started on prednisolone 60 mg/day. A month later, her pituitary function had gradually improved together with a decrease in pituitary enlargement and recovery of her visual field. The dose of prednisolone was gradually reduced and finally withdrawn 27 months later. After prednisolone withdrawal, her pituitary function remained normal despite the absence of any hormonal replacement. A year later, she became pregnant without medication and delivered a second baby without LyH recurrence. Thereafter, her pituitary function has been normal for more than 5 years. Two valuable observations can be highlighted from the case. First, the patient completely recovered from LyH through prompt prednisolone therapy during its initial phase and had almost normal pituitary function. Second, after recovery from LyH, she was able to undergo spontaneous pregnancy and deliver a baby. We believe that reporting incidences of spontaneous pregnancy after complete normalization of pituitary function in patients with LyH is of great significance

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Hyponatremia Associated with Heart Failure: Pathological Role of Vasopressin-Dependent Impaired Water Excretion

An exaggerated increase in circulatory blood volume is linked to congestive heart failure. Despite this increase, reduction of the “effective circulatory blood volume” in congestive heart failure is associated with decreased cardiac output, and can weaken the sensitivity of baroreceptors. Thereafter, tonic inhibition of the baroreceptor-mediated afferent pathway of vagal nerves is removed, providing an increase in non-osmotic release of arginine vasopressin (AVP). In the renal collecting duct, the aquaporin-2 (AQP2) water channel is regulated by sustained elevation of AVP release, and this leads to augmented hydroosmotic action of AVP, that results in exaggerated water retention and dilutional hyponatremia. Hyponatremia is also a predictor for worsening heart failure in patients with known/new onset heart failure. Therefore, such a dilutional hyponatremia associated with organ damage is predictive of the short- and long-term outcome of heart failure

Is Exaggerated Release of Arginine Vasopressin an Endocrine Disorder? Pathophysiology and Treatment

Exaggerated release of arginine vasopressin (AVP) is profoundly involved in impaired water excretion and related hyponatremia. Such disorders underlie syndromes of inappropriate secretion of antidiuretic hormone (SIADH) and edematous diseases, such as congestive heart failure and decompensated liver cirrhosis. All the causes are fundamentally from non-endocrine diseases. AVP-induced water retention could produce hyponatremia, and further accelerate poor long-term outcome of edematous diseases. Administration of AVP V2 receptor antagonists verifies how much AVP is involved in the pathogenesis of the impaired water excretion. The present paper demonstrated that exaggerated release of AVP plays a crucial role as an accessory endocrine disorder in pathological states of water retention and dilutional hyponatremia in non-endocrine disorders