Hypercalcemia in infants presenting with apnea.

To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy.     

Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9. Received: 20 January 1997 / Accepted: 5 November 1997     

Retrograde Traffic Out of the Yeast Vacuole to the TGN Occurs via the Prevacuolar/Endosomal Compartment

A large number of trafficking steps occur between the last compartment of the Golgi apparatus (TGN) and the vacuole of the yeast Saccharomyces cerevisiae. To date, two intracellular routes from the TGN to the vacuole have been identified. Carboxypeptidase Y (CPY) travels through a prevacuolar/endosomal compartment (PVC), and subsequently on to the vacuole, while alkaline phosphatase (ALP) bypasses this compartment to reach the same organelle. Proteins resident to the TGN achieve their localization despite a continuous flux of traffic by continually being retrieved from the distal PVC by virtue of an aromatic amino acid–containing sorting motif. In this study we report that a hybrid protein based on ALP and containing this retrieval motif reaches the PVC not by following the CPY sorting pathway, but instead by signal-dependent retrograde transport from the vacuole, an organelle previously thought of as a terminal compartment. In addition, we show that a mutation in VAC7, a gene previously identified as being required for vacuolar inheritance, blocks this trafficking step. Finally we show that Vti1p, a v-SNARE required for the delivery of both CPY and ALP to the vacuole, uses retrograde transport out of the vacuole as part of its normal cellular itinerary.     

Hormonal adaptation determines the increase in muscle mass and strength during low-intensity strength training without relaxation

The study was designed to test the hypothesis that, during strength training, a restricted blood supply to the working muscles stimulates the secretion of anabolic hormones and an increase in the muscle mass and strength can be achieved with significantly lower training loads. During eight weeks, three times a week, 18 young, physically active males trained their leg extensor muscles. Nine subjects (group I) worked at 80% of the maximal voluntary contraction (MVC), whereas the rest (group II) performed their exercise without relaxation and at a lower load (50% MVC). The total training load in group II was significantly lower than in group I (77 ± 5 vs. 157 ± 7 kJ, respectively). The eight-week training of both groups significantly increased the mean maximum strength (by 35 and 21% in groups I and II, respectively) and volume (by 17 and 9%, respectively) of the muscles trained (however, the differences between the groups with respect to these changes were nonsignificant). Group I displayed a higher increase in the blood level of creatine phosphokinase than group II, while group II showed a greater increase in the blood concentration of lactate. In contrast to group I, group II displayed a significant increase in the blood concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), and cortisol. Hence, the suggestion that the secretion of metabolic hormones is triggered by a metabolic, rather than mechanical, stimulus from working muscles seems plausible.     

Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects.     

Efficacy of intermittent or continuous administration of GnRH in inducing ovulation in early and late seasonal anoestrus in the Père David's deer hind (Elaphurus davidianus)

Père David's deer hinds were treated with GnRH, administered as intermittent i.v. injections (2.0 micrograms/injection at 2-h intervals) for 4 days, or as a continuous s.c. infusion (1.0 micrograms/h) for 14 days. These treatments were given early (February-March) and late (May-June) in the period of seasonal anoestrus. The administration of repeated injections of GnRH increased mean LH concentrations from pretreatment values of 0.54 +/- 0.09 to 2.10 +/- 0.25 ng/ml over the first 8 h of treatment in early anoestrus, and from 0.62 +/- 0.11 to 2.73 +/- 0.49 ng/ml in late anoestrus. The mean amplitude of GnRH-induced LH episodes was greater (P less than 0.01) in late (4.03 +/- 0.28 ng/ml) than in early (3.12 +/- 0.26 ng/ml) anoestrus, but within each replicate (early or late anoestrus), neither mean LH episode amplitude nor mean plasma LH concentrations differed significantly between the four periods of intensive blood sampling. On the basis of their progesterone profiles, 6/12 hinds had ovulated in response to treatment with injections of GnRH (1/6 in early anoestrus and 5/6 in late anoestrus), and oestrus and a preovulatory LH surge were recorded in all of these animals. Oestrus and a preovulatory LH surge were also recorded in one other animal treated in early anoestrus in which progesterone concentrations remained low. The mean times of onset of oestrus (91.0 +/- 1.00 and 62.4 +/- 0.98 h) and of the preovulatory LH surge (85.8 +/- 3.76 and 59.4 +/- 0.25 h) both occurred significantly earlier (P less than 0.001) in animals treated in late anoestrus. Continuous infusion of GnRH to seasonally anoestrous hinds resulted in an increase in mean plasma LH concentrations, but this response did not differ significantly between early (2.15 +/- 0.28 ng/ml) and late (2.48 +/- 0.26 ng/ml) anoestrus. Ovulation, based on progesterone profiles, occurred in 2/7 hinds in early anoestrus and in 4/6 hinds in late anoestrus. Oestrus was detected in all except one of these hinds. The mean time of onset of oestrus occurred earlier in animals treated in late anoestrus (66.2 +/- 0.32 h and 46.7 +/- 0.67 h, P less than 0.01). The administration of GnRH, given either intermittently or continuously, will induce ovulation in a proportion of seasonally anoestrous Père David's deer. However, more animals ovulate in response to this treatment in late than in early anoestrus (75% compared with 23%).     

The role of N-quinones in the regulation of glucose-6-phosphate metabolism

In experimental (white rats, rabbits) and clinical (erythrocytes, blood plasma) studies on 29 healthy subjects and patients it has been demonstrated that primary or secondary n-quinone deficiency is accompanied by increased tissue activity of glycolysis enzymes (aldolase, PGmutase) and aerobic pentose phosphate shunt (6 GPDH). Parallel rise in the amount of glycolysis metabolites (pyruvate and lactate) in the blood and the decline in blood plasma glucose level were observed. The changes in glucose-6-phosphate metabolism are, probably, secondary and reflect tissue structure alterations in the development of K and E avitaminosis.     

Immunoenzyme analysis of the fertility alpha 2-microglobulin in the blood serum of men and women

It has been found that fertility alpha 2-microglobulin content in male and female serum does not exceed 20 ng/ml and 40 ng/ml, respectively. A high level of fertility alpha 2-microglobulin was found in the serum in early pregnancy, with its concentration decreased by parturition.