A Rare Case of Therapy-Related B-cell Acute Lymphoblastic Leukemia Arising From Acute Myeloid Leukemia.

Therapy-related acute lymphoblastic leukemia (t-ALL) is a rare potential complication of chemotherapy. We describe the case of a 47-year-old male patient who was originally diagnosed with t(8;21) positive acute myeloid leukemia (AML) in 2019, received chemotherapy, achieved remission, and was disease-free for the next two years. During a routine follow-up in 2022, he was found to have developed subclinical pancytopenia, and further studies indicated a diagnosis of pH-negative, near-tetraploid B-cell acute lymphoblastic leukemia (B-ALL) that was positive for a Tier 1 TP53 mutation, consistent with t-ALL.

Acute Effects of Glucagon on Reproductive Hormone Secretion in Healthy Men.

Context: Glucagon increases energy expenditure; consequently, glucagon receptor agonists are in development for the treatment of obesity. Obesity negatively affects the reproductive axis, and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects of glucagon receptor agonism on reproductive hormones is important for developing therapeutics for obesity; but reports in the literature about the effects of glucagon receptor agonism on the reproductive axis are conflicting.

Effects of corticosterone within the hypothalamic arcuate nucleus on food intake and body weight in male rats.

Objective: Obesity is a major cause of morbidity and mortality. Few weight-reducing medications are available, and these have limited efficacy. Cushing's Syndrome (caused by elevated glucocorticoid levels) and obesity have similar metabolic features.

Effects of Glucagon-like Peptide-1 on the Reproductive Axis in Healthy Men.

Context: Glucagon-like peptide-1 (GLP-1) potently reduces food intake and augments glucose-stimulated insulin secretion. Recent animal data suggest that GLP-1 may also influence reproduction. As GLP-1 receptor agonists are currently widely used in clinical practice to treat obesity/type 2 diabetes, it is necessary to determine the effects of GLP-1 on the reproductive system in humans.

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

Background: Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.

Methods: We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.

The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans.

Aims: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans.

Materials And Methods: In 15 healthy men (age: 25.2 ± 1.

Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis.

Aims: To investigate the role of arcuate glucokinase (GK) in the regulation of glucose homeostasis.

Materials And Methods: A recombinant adeno-associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus (arc). GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A.

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

Study Question: Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)?

Summary Answer: A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS.

What Is Known Already: Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS.

Carbohydrate craving: not everything is sweet.

Purpose Of Review: Cravings for carbohydrates have been known about for hundreds of years but the mechanisms behind it were unclear. This review will highlight recent advances in our knowledge of mechanisms to detect carbohydrates in the diet.

Recent Findings: Recent work has begun to identify the physiological mechanisms by which carbohydrates and glucose are detected and how this drives their intake.

Kisspeptin modulates sexual and emotional brain processing in humans.

Background: Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood.

Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels.

Background And Objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women.

Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.

Context: In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS).

Objective: This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

Setting And Design: This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013-2014 at Hammersmith Hospital IVF unit, London, United Kingdom.

Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men.

Study Question: How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion when compared with GnRH in healthy men?

Summary Answer: At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin isoform.

What Is Known Already: Kisspeptin-10 and -54 are naturally occurring hormones in the kisspeptin peptide family which potently stimulates endogenous GnRH secretion from the hypothalamus, so have the potential to treat patients with reproductive disorders. Rodent studies suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.

Neurokinin B administration induces hot flushes in women.

Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes.

Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.

Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA.

Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers.

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously.

The effects of kisspeptin on gonadotropin release in non-human mammals.

The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human mammals. Studies of kisspeptin's effects have included both acute and chronic administration regimens via a number of administration routes.

The effects of kisspeptin in human reproductive function - therapeutic implications.

Kisspeptin is a 54-amino acid peptide which is encoded by the KiSS-1 gene and activates the G protein-coupled receptor GPR54. Evidence suggests that this system is a key regulator of mammalian and human reproduction. Animal studies have shown that GPR54-deficient mice have abnormal sexual development.

Factor X inhibitor: a fulminant presentation and fatal course of a rare syndrome in a 59-year-old male.

Factor X inhibitors are rare. The few cases documented in the literature have occurred after viral prodromes, in association with cancer, or after exposure to antibiotics. Acquired factor X deficiencies are also rare and their etiology is largely unknown.

Modulation of the hepatic expression of the estrogen-regulated mRNA stabilizing factor by estrogenic and antiestrogenic nonsteroidal xenobiotics.

Estrogen-mediated accumulation of apolipoprotein II (apoII) mRNA in the avian liver is due, in part, to its stabilization. This stabilization appears to be due to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF) that is expressed in response to estrogen. The E-RmRNASF protects the mRNA from targeted endonucleolytic degradation (Ratnasabapathy, Cell Mol Biol Res 41: 583-594, 1995).

In vitro characterization of an estrogen-regulated mRNA stabilizing activity in the avian liver.

Estrogen-mediated accumulation of the avian apolipoprotein (apo) II mRNA is in part due to its stabilization. To identify the biochemical activity responsible for this effect, radiolabeled, capped, and polyadenylated apoII mRNA was incubated in vitro in liver cytosolic extracts from roosters who received either estrogen (estrogen-treated extract) or the vehicle (control extract) parenterally. The mRNA was very stable in estrogen-treated extract but was rapidly degraded in control extract.

Characterization of the inducer of short transcripts, a human immunodeficiency virus type 1 transcriptional element that activates the synthesis of short RNAs.

The inducer of short transcripts, or IST, is an unusual transcriptional element located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter. IST activates HIV-1 transcription, but the resulting RNAs are short and end at approximately position +59. IST, therefore, appears to promote the formation of transcription complexes that are unable to elongate efficiently.