Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.     

Eosinophil chemotactic activity in the supernatant of mononuclear cell culture stimulated with specific antigen

Peripheral blood mononuclear cells (PBMC) separated from patients with asthma who were sensitive to Dermatophagoides farinae (Df) were cultured in alpha-medium for 5 days at 37 degrees C in 5% CO2, in the presence or absence of 10 ng/ml of Df antigen. Eosinophils were purified from the peripheral blood of patients with eosinophilia who were not sensitive to Df. Eosinophil chemotactic activity (ECA) was tested using a modified Boyden chamber method. ECA in the supernatant of PBMC stimulated with Df antigen was detectable after 24 hrs, peaked at 72 hrs and continued throughout the experiment. ECA was not observed in the supernatant of PBMC culture from subjects who were not sensitive to Df, and negligible activity was also observed when PBMC were stimulated with an unrelated antigen. The activity was unchanged by heating at 56 degrees C for 30 min, but was inactivated at 100 degrees C for 10 min. CV-6209, a specific PAF antagonist, failed to inhibit this chemotactic activity. The molecular weight of this eosinophil chemotactic factor (ECF) was greater than 30,000 daltons as determined by an ultrafiltration study. In conclusion, these data suggest that in asthmatic patients sensitive to Dermatophagoides farinae mononuclear cells stimulated with a related antigen produce one of cytokine(s) which possess(es) ECA, and may play an important role in the recruitment of eosinophils in chronic asthma.     

The effects of 5-bromodeoxyuridine and isoproterenol on the postnatal differentiation of rat submandibular gland

The effects of 5-bromodeoxyuridine (BrdU) on the postnatal differentiation of rat submandibular gland and on the isoproterenol-induced changes of differentiation were studied. The rats were injected with BrdU for three consecutive days, beginning at two days of age. The total dose of BrdU was 0.9 mg/g body weight. BrdU caused a severe retardation of growth up to 15 days of age. A rapid growth of the animals between 15 and 22 days indicated a recovery from the effect of BrdU. The growth of the submandibular gland was retarded similarly with a corresponding decrease in DNA, RNA and protein content. Incorporation of tritiated thymidine into the submandibular gland was not altered in the BrdU-treated animals at one and three days after the last injection of the analog. At days 15 and 22 the rate of thymidine incorporation was greater in the submandibular gland of BrdU-treated rats as compared to littermate controls. Isoproterenol stimulated thymidine incorporation into the submandibular glands of two-week-old rats. This stimulation was not observed in rats which received BrdU at age 7–9 days, prior to the administration of isoproterenol. Electron microscopic observations, including a quantitative analysis of the frequency distribution of the various cell types in the terminal tubules and developing acini, indicated a retardation of acinar cell differentiation in the glands of BrdU-treated rats. In addition, there was an increase in the number and size of the secretory granules in the terminal tubule cells. BrdU treatment, however, caused no obvious pathologic alterations in the submandibular gland. Administration of isoproterenol for five days, beginning at five days of age, caused an apparent acceleration of the differentiation of acinar cells. In the glands of isoproterenol-treated rats the acinar cells were enlarged and were filled with homogenous secretory granules. Pretreatment with BrdU partially inhibited the effects of isoproterenol on differentiation and hypertrophy of the submandibular gland. With the given dose of BrdU, approximately 5% of thymine was replaced by bromouracil in the DNA of the submandibular gland. Such a replacement would be consistent with a direct effect of BrdU on the cytodifferentiation in the submandibular gland. However, because of the severe retardation of growth of the BrdU-treated rats, indirect effects can not be excluded.     

Visual and vergence eye movement-related responses of pursuit neurons in the caudal frontal eye fields to motion-in-depth stimuli

The caudal parts of the frontal eye fields (FEF) contain smooth-pursuit related neurons. Previous studies show that most FEF pursuit neurons carry visual signals in relation to frontal spot motion and discharge before the initiation of smooth-pursuit. It has also been demonstrated that most FEF pursuit neurons discharge during vergence tracking. Accurate vergence tracking requires information about target motion-in-depth. To further understand the role of the FEF in vergence tracking and to determine whether FEF pursuit neurons carry visual information about target motion-in-depth, we examined visual and vergence eye movement-related responses of FEF pursuit neurons to sinusoidal spot motion-in-depth. During vergence tracking, most FEF pursuit neurons exhibited both vergence eye position and velocity sensitivity. Phase shifts (re target velocity) of most neurons remained virtually constant up to 1.5 Hz. About half of FEF pursuit neurons exhibited visual responses to spot motion-in-depth. The preferred directions for visual responses of most neurons were similar to those during vergence tracking. Visual responses of most of these neurons exhibited sensitivity to the velocity of spot motion-in-depth. Phase shifts of most of the responding neurons remained virtually constant up to 2.0 Hz. Neurons that exhibited visual responses in-depth were mostly separate from neurons that showed visual responses in the frontal plane. To further examine whether FEF pursuit neurons could participate in initiation of vergence tracking, we examined latencies of neuronal responses with respect to vergence eye movements induced by step target motion-in-depth. About half of FEF pursuit neurons discharged before the onset of vergence eye movements with lead times longer than 20 ms. These results together with previous observations suggest that the caudal FEF carries visual signals appropriate to be converted into motor commands for pursuit in depth and frontal plane.     

Changes of brain serotonin and muricide behavior following chronic administration of theophylline in rats.

Temporal modification of amygdaloid serotonin (5HT) content and the resultant muricide behavior, compared to isolated and olfactory bulbectomized rats, were studied after chronic theophylline administration. Theophylline raised amygdaloid 5HT after Day 28 and amygdaloid 5-hydroxyindoleacetic acid (5HIAA), its deaminated metabolite, after Day 7. Theophylline applied for 29 days elevated 5HT and 5HIAA in the amygdala, the diencephalon and the brain stem, but not in the cortex. Effects of theophylline were reduced latency and maintained tendency to kill, even after overnight muricide test. The 5HT content of the amygdala decreased in bulbectomized rats. Discrepancy between brain 5HT changes and aggressive behavior were discussed.     

Theophylline disrupts diurnal rhythms of humoral factors with loss of meal cyclicity

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at ? 120, ?60 or ?15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.     

The Costello syndrome: Are nasal papillomata essential?

Summary Two patients with the Costello syndrome are presented. One was a 7-year-old girl with a history of infantile hypotonia and feeding difficulties. The other was a 3 5/12-year-old boy with a history of neonatal sepsis and respiratory problems. Both had relative macrocephaly at birth, curly hair, large ear lobes, epicanthic folds, a low nasal bridge, thick lips, a short and wide nose, a short neck, a barrel chest, redundant skin, tight Achilles tendons, and pes equinovarus. Nasal papillomata, as described in Costello's two patients, were absent in both patients. Borochowitzet al. (1992) described five patients with what we interpreted as the Costello syndrome but without nasal papillomata. In view of these findings, nasal papillomata are not likely to be essential in the diagnosis of the Costello syndrome.     

A human recessive neurosensory nonsyndromic hearing impairment locus is a potential homologue of the murine deafness (dn) locus

A locus for recessive neurosensory nonsyndromic hearing impairmentmaps to chromosome 9q13–q21 in two regionally separateconsanguineous families from India. Each family demonstratesa LOD score greater than 4.5 to this region. D9S15, tightlylinked to the Friedreich's ataxia locus, a region that has beendefined with over 1 Mb of YAC contig information and severalexpressed sequences, is one of the flanking markers. In mice,the deafness (dn) locus maps to mouse chromosome 19 and flankingloci are syntenic to human chromosome 9q11–q21. The dnmouse is a potential model for the hearing impairment foundin both these families.