Raised Thyrotrophin-Releasing Hormone, Pyroglutamylamino Peptidase, and Proline Endopeptidase Are Present in the Spinal Cord of Wobbler Mice but Not in Human Motor Neurone Disease

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.     

Glyconeogenic and oxidative lactate utilization in skeletal muscle.

In this article we present a synthesis of recent information concerning the fate of lactate in skeletal muscle. This is important since lactate is continuously produced by skeletal muscle at rest and at all levels of exercise. Therefore, the disposal of lactate as an 'intermediary' metabolite is discussed. The two primary fates of lactate in skeletal muscle are (1) oxidation and (2) glycogen synthesis (glyconeogenesis). From recent evidence it seems relatively clear that glycogen formation in muscle is primarily dependent on glucose, although in fast twitch muscles a considerable proportion of lactate can account for muscle glycogen formation, especially immediately after exercise when circulating lactate levels are elevated. Exactly how lactate is converted to glycogen is not known yet, but an extramitochondrial pathway that is divergent from the hepatic gluconeogenic pathway seems likely. Oxidation of lactate is quantitatively the most important means of disposing of lactate, whether in exercising or nonexercising muscle. The lactate gradient between muscle and blood may be an important factor dictating whether lactate is taken up or released by muscle, independent of whether the muscle is active or not. Finally a novel role for epinephrine is considered that may be important for the mitochondrial oxidation of lactate.     

Production of inositol phosphates in BALB/C 3T3 cells stimulated with basic fibroblast growth factor

When quiescent 3T3 fibroblast cells were pre-labelled with [3H]inositol and stimulated with basic fibroblast growth factor there was a stimulation of the hydrolysis of membrane lipids and the rapid production of [3H]inositol polyphosphates. Rapid and transient peaks of isomers of inositol phosphates with the chromatographic properties of inositol trisphosphates and inositol tetrakisphosphates were detectable by anion-exchange HPLC between 5 and 10 s after stimulation. These data suggest that upon stimulation the receptor for fibroblast growth factor is coupled to a phosphoinositidase C and that one of its signal-transducing pathways involves hydrolysis of inositol lipids and the production of inositol polyphosphates, some of which may act as intracellular signals mediating the cellular response. Chronic stimulation with basic fibroblast growth factor is associated with desensitization of the inositol lipid signaling pathway.     

Delayed formation of neural representations of space in aged mice

Aging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for processing spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Using in vivo two-photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.     

Conklin, Joyce, and the Wannaknów

Verbal play among the Hanunóo of Mindoro is surprisingly similar to that practiced by the Dubliners of Ireland. The similarity invites a comparison of the work habits of their scribes: the ethnographer Harold Conklin and the novelist James Joyce. A Joycean version of an ethnography of the Wannaknow is presented as a textual focus for the comparison.     

Influence of Achlorhydria on Aspirin-induced Occult Gastrointestinal Blood Loss: Studies in Addisonian Pernicious Anaemia

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1·9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4·29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.