Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice

1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.     

Effects of long-term phasic electrical stimulation on denervated soleus muscle: guinea-pig contrasted with rat

Guinea-pig soleus muscles were denervated and electrically stimulated for periods of 43 to 66 days. Stimuli were in 1 s bursts of 40 Hz pulses, repeated every 5 min. Other guinea-pigs were denervated for 82 days without stimulation and, in a third group, the soleus muscle was necrotized and allowed to regenerate without reinnervation for 13-15 days. Isometric and isotonic recordings were made in vivo. Denervated guinea-pig muscles were embedded in epoxy resin for light and electron microscopy. Chronic stimulation of denervated guinea-pig soleus had no effects on the prolonged twitch or on reduced maximal shortening velocity, maximal rate of rise of tension and tetanic force. This contrasts with the slow-to-fast conversion produced by denervation and denervation-stimulation of rat soleus. Loss of force was much greater in rat than guinea-pig after denervation, and chronic stimulation increased force in rat to the same level as in guinea-pig after denervation (with or without stimulation). Eighty-day denervated guinea-pig soleus did not reveal those morphological signs of fibre breakdown and regeneration which are prominent in denervated rat soleus muscles. Those changes in rat resembled aneurally regenerated muscles in several aspects, especially the increased incidence of fibres with internal myo-nuclei which did not appear in guinea-pig soleus after denervation. Aneurally regenerated guinea-pig soleus became fast like aneurally regenerated rat muscle. Our data are compatible with the hypothesis that slow-to-fast transformation of denervated rat soleus is not directly brought about by chronic stimulation but by de-novo formation of fast-contracting regenerated fibres. The persistence of fibrillation in guinea-pig but not rat after denervation may account for the species difference.     

Event-related potential correlates of linguistic information processing in schizophrenics

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.     

Normal left ventricular ejection fraction in older persons with congestive heart failure

STUDY OBJECTIVES: To investigate in older patients with congestive heart failure (CHF) associated with prior myocardial infarction or hypertension the relationship between normal left ventricular (LV) ejection fraction and age, gender, hypertension, prior myocardial infarction, and atrial fibrillation. DESIGN: A prospective study was performed in 572 older patients (age >60 years) with CHF associated with prior myocardial infarction or hypertension and technically adequate two-dimensional echocardiograms for measuring LV ejection fraction. SETTING: A long-term health-care facility. PATIENTS: One hundred seventy-seven men and 395 women, mean age 82+/-8 years, with CHF associated with prior myocardial infarction or hypertension. MEASUREMENTS AND RESULTS: Normal LV ejection fraction (> or = 50%) occurred in 66 of 177 men (37%) and in 221 of 395 women (56%) (p<0.0001). Multiple logistic regression analysis showed that independent risk factors for normal LV ejection fraction in patients with CHF were no prior myocardial infarction (p=0.0001; odds ratio=3.048), female gender (p=0.0004; odds ratio=1.978), and age (p=0.016; odds ratio=1.029). CONCLUSIONS: Normal LV ejection fraction occurred in 50% of 572 older patients with CHF associated with prior myocardial infarction or hypertension. Independent risk factors for normal LV ejection fraction in patients with CHF were no prior myocardial infarction, female gender, and age.     

Neural encoding of single-formant stimuli in the ventral cochlear nucleus of the chinchilla

Responses of the principal unit types in the ventral cochlear nucleus of the chinchilla were studied with a single-formant stimulus set that covered fundamental frequency (f0) from 100 Hz to 200 Hz and formant center frequency (F1) from 256 to 782 Hz. Temporal coding for f0 and F1 was explored for 95 stimulus combinations of f0 (n = 5) and F1 (n = 19) in primarylike, onset and chopper unit categories. Several analyses that explored temporal coding were employed including: autocorrelation, interspike interval analysis, and synchronization to each harmonic of f0. In general, the representation of f0 is better in onset and chopper units than in primarylike units. Nearly all units in the cochlear nucleus showed a gain in phase locking to the envelope (f0) of the single-formant stimulus relative to the auditory nerve. The fundamental is represented directly in neural discharges of units in the cochlear nucleus with an interval code (also Cariani and Delgutte, 1996; Rhode, 1995). The formant is represented in the temporal domain in primarylike units, though some chopper and onset units also possess the ability to code F1 through discharge synchrony. Onset-I units, which are associated with the octopus cells, exhibited the strongest phase locking to f0 of any unit types studied. The representation of f0 and F1 in the temporal domain is weak or absent in some units. All-order-interspike interval distributions computed for populations of units show preservation of temporal coding for both f0 and F1. Results are in agreement with earlier amplitude modulation studies that showed nearly all cochlear nucleus unit types phase lock to the signal envelope better than auditory nerve fibers over a considerable range of signal amplitudes.     

Accuracy of measurements for the revised NIOSH lifting equation

Twenty-seven non-ergonomists who participated in a one-day training session on the use of the NIOSH lifting equation (NLE) were subsequently tested on a simulated lifting task eight weeks later to determine their accuracy in measuring the variables. Analysis of the results indicate that (1) inter-observer variability was small, especially for the most important factor (i.e. horizontal distance); (2) individuals can be trained to make measurements with sufficient accuracy to provide consistent recommended weight limit and lifting index values; and (3) measurement of the coupling and asymmetric variables were the least accurate.     

Association of plasma renin activity and echocardiographic left ventricular hypertrophy with frequency of new coronary events and new atherothrombotic brain infarction in older persons with systemic hypertension

In older hypertensive persons, male gender, prior coronary artery disease, prior atherothrombotic brain infarction (ABI), and echocardiographic left ventricular (LV) hypertrophy are independent risk factors for new coronary events; age, prior ABI, and echocardiographic LV hypertrophy are independent risk factors for new ABI. The data suggest that high plasma renin activity in hypertensive older persons is associated with a high risk of new coronary events and of new ABI through its association with echocardiographic LV hypertrophy.     

The effects of reactive centre loop length upon serpin polymerisation

Our rapid method of microwave-mediated saponification for preparing lysoglycosphingolipids from their parent glycosphingolipids was also able to prepare lysogangliosides or modified lysogangliosides, which were identified by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometric (DE MALDI-TOF MS) analysis. When GM3, GM2, and GM1 isolated from adult human brain gangliosides were subjected to the saponification, GM3 was found to give rise to only lyso-GM3 containing de-N-acetylneuraminic acid (de-N-acetyl lyso-GM3), whereas the GM2 produced both lyso-GM2 and the de-N-acetyl compound, and GM1 also gave both lyso-GM1 and the de-N-acetyl compound. In the saponification of GM1 and GDla, isolated from rat brain gangliosides, GM1 similarly produced both lyso-GM1 and the de-N-acetyl compound, but GDla was found to give rise to both dehydrated de-N-monoacetyl and dehydrated de-N-diacetyl lyso-GDla. However, the saponification of the GM1 fraction isolated from porcine brain gangliosides gave rise not only to both lyso-GM1 and the de-N-acetyl compound, but also unexpectedly to both lyso-fucosyl GM1 and its de-N-acetyl compound. The untreated GM1 fraction was examined by TLC and DE MALDI-TOF mass spectrometry, and proved to contain fucosyl-GM1. The DE MALDI-TOF MS analysis of the prepared lyso-gangliosides showed that their long chain bases consisted of d18:1 and d20:1 sphingosines in various ratios reflecting those of the different mammalian brain gangliosides.     

The functional neuroanatomy of episodic memory: the role of the frontal lobes, the hippocampal formation, and other areas

Because it allows direct mapping of synaptic activity during behavior in the normal subject, functional neuroimaging with the activation paradigm, especially positron emission tomography, has recently provided insight into our understanding of the functional neuroanatomy of episodic memory over and above established knowledge from lesional neuropsychology. The most striking application relates to the ability to distinguish the structures implicated in the encoding and the retrieval of episodic information, as these processes are extremely difficult to differentiate with behavioral tasks, either in healthy subjects or in brain-damaged patients. Regarding encoding and retrieval, the results from most studies converge on the involvement of the prefrontal cortex in these processes, with a hemispheric encoding/retrieval asymmetry (HERA) such that the left side is preferentially involved in encoding, and the right in retrieval. However, there are still some questions, for instance, about bilateral activation during retrieval and a possible specialization within the prefrontal cortex. More expected from human and monkey lesional data, the hippocampal formation appears to play a role in both the encoding and the retrieval of episodic information, but the exact conditions which determine hippocampal activation and its fine-grained functional neuroanatomy have yet to be fully elucidated. Other structures are activated during episodic memory tasks, with asymmetric activation that fits the HERA model, such as preferentially left-sided activation of the association temporal and posterior cingulate areas in encoding tasks and preferentially right-sided activation of the association parietal cortex, cerebellum, and posterior cingulate in retrieval tasks. However, this hemispheric asymmetry appears to depend to some extent on the material used. These new data enhance our capacity to comprehend episodic memory deficits in neuropsychology, as well as the neural mechanisms underlying the age-related changes in episodic memory performances.     

Hemopoietic growth factor receptor abnormalities in leukemia

Growth factor and cytokine control of hemopoiesis, the process of blood cell development, is mediated by specific interactions with cell-surface receptors. Hemopoietic growth factor receptors belong to two major families, the transmembrane protein tyrosine kinases and the hemopoietin receptors. Ligand binding stimulates receptor aggregation and activation resulting in transduction of signals that induce diverse cellular responses including proliferation, maturation, prevention of apoptosis and/or functional activation. Deregulation of hemopoiesis can result in leukemia, the malignant transformation of blood cells, or the development of other hemoproliferative disorders. As hemopoietic growth factor receptors are integral to blood cell regulation, it is feasible that receptor abnormalities may contribute to leukemia by circumventing normal growth factor control or altering the balance of proliferation and differentiation. Although considerable experimental evidence has clearly established the leukemogenic potential of mutated growth factor receptors, studies to date suggest that such abnormalities contribute only rarely to human disease.