Ubiquitin in motor neuron disease: study at the light and electron microscope.

Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease.     

Urine screening practices in methadone maintenance clinics. A survey of how the results are used

The urinalysis practices of 324 methadone maintenance clinics were surveyed using a brief self-report questionnaire. Results indicate that there is wide variability in collection practices and clinic responses to positive findings. Virtually all clinics provide counseling and revocation of take-home methadone doses as a response to positive urinalysis results. However, increase in urine screening frequency, methadone dose adjustments, contingency contracting, group therapy, and eventual discharge are interventions also used. The implementation of different interventions varied as a function of clinic size, city size, region of the country, and program funding source.     

Intrafollicular blood flow during human ovulation.

Transvaginal ultrasonography with color flow mapping has been used to study changes in intrafollicular blood flow and morphology during follicular rupture and presumed ovulation in one human volunteer. Detailed monitoring started on day 11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13. This event was preceded by a defined rise and peak in the level of immunoreactive serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood vessels were clearly visible in the inner ring of the follicle (the granulosa layer) at the time of the LH peak and part of the granulosa (probably containing the oocyte) started to detach before the follicle ruptured. The maximum value for the peak blood velocity in the inner vessels was observed 10 s after the start of follicular rupture and there was a concurrent increase in the impedance to blood flow, as reflected by the resistance index and the pulsatility index. The follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form about 1 min later. These preliminary data suggest that intrafollicular angiogenesis and changes in blood flow can be monitored by a relatively non-invasive technique. Changes in vascularity might be used to predict imminent ovulation and could possibly be identified or modified biochemically to help achieve or avoid a pregnancy.     

The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards

The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity.     

Reasoning in deluded schizophrenic and paranoid patients. Biases in performance on a probabilistic inference task

An experiment is described in which deluded subjects with a diagnosis of schizophrenia or of delusional disorder (paranoia) were compared with a nondeluded psychiatric control group and a normal control group on a probabilistic inference task. Factors relevant to belief formation and maintenance were investigated. Deluded subjects requested less information before reaching a decision and were more ready to change their estimates of the likelihood of an event when confronted with potentially disconfirmatory information. No differences were found between the two diagnostic groups of deluded subjects. The results are discussed in light of prevailing theories of the importance of abnormal experience rather than reasoning biases in the formation and maintenance of delusional beliefs. It is suggested that a reasoning abnormality is involved, which may coexist with perceptual abnormalities.     

Carnitine, valproate, and toxicity

Carnitine is an important nutrient that is present in the diet (particularly in meat and dairy products) and is synthesized from dietary amino acids. It functions to assist long-chain fatty acid metabolism and to regulate the ratio of free coenzyme A to acylcoenzyme A in the mitochondrion. Carnitine deficiency occurs in primary inborn errors of metabolism, in nutritional deficiency, and in various other disorders including antiepileptic drug therapy. Valproate therapy is often associated with decreased carnitine levels and occasionally with true carnitine deficiency. Some experimental and clinical evidence links valproate-induced carnitine deficiency with hepatotoxicity, but this evidence is limited and inconclusive. Carnitine supplementation has been useful in some studies, but these data are also limited. Young children with neurologic disabilities taking multiple antiepileptic drugs may have the greatest risk for carnitine deficiency. Measurement of carnitine levels appears warranted in these patients and in patients with symptoms and signs of possible carnitine deficiency.     

Isolated azygos continuation of the inferior vena cava. (Absence of the retrohepatic segment of the inferior vena cava)

The isolated azygos continuation of the inferior vena cave is a very rare variation of this organ. It is accompanied by the absence of the retrohepatic segment of the vena cava with two new observations, the literature is revised and the origin discussed.