Electron microscopical findings with special reference to cancer in rats caused by inhalation of nickel oxide

A special exposure system was used for the inhalation of nickel oxide (NiO) aerosol by Wistar male rats. The median aerodynamic diameter and the geometric standard deviation were 1.2 μm and 2.2, respectively. A histopathological study of the rats was performed immediately, and at intervals of 12 and 20 mo after a 1-mo expsoure to NiO. Electron microscopy showed that localization of NiO particles was restricted to the lungs and that each particle had been engulfed by the alveolar macrophages. Type II pneumocytes and nonciliated bronchiolar epithelial cells (Clara cells), as well as numerous tubular myelin (surfactant) in the alveoli were prominent. In rats dissected after 12 mo, clusters of NiO particles were still present within the terminal bronchioli, alveolar walls, and lysosomes of the alveolar macrophages. Pools of tubular myelin were observed in the peribron-chial lymphatics. The Clara cells, which project into the lumen of bronchioli, showed active secretion and were filled with smooth en-doplasmic reticulum (SER) in the apical cytoplasm. In the experimental group sacrificed after 20 mo, one rat had papillary adenocarcinoma and two rats showed adenomatosis in the peripheral portion of the lung, but none in the upper respiratory tract.     

Spontaneous cell-mediated cytolysis by peripheral blood cells obtained from whole-body chronically irradiated beagle dogs

The level of natural killer (NK) activity of continuously gamma-irradiated (whole body) beagle dogs and their nonirradiated controls was studied. For analytical purposes, irradiated dogs were segregated into groups according to their clinical status: clinically normal, hypocellular, or with acute non-lymphocytic leukemia. Since unirradiated control animals exhibited a wide range of NK responses, the data from each irradiated animal were compared to its own age-matched or litter-matched unirradiated control. Of the eight clinically normal irradiated dogs (median = 146% activity of control) only one animal had a NK activity lower than that of its control. The hypocellular group (n = 5, median = 21.8% of control) and the leukemic group (n = 4, median = 52.5% of control) each contained one responder with higher activity than its control. The difference between the percentage of control of the clinically normal and clinically abnormal dogs was found to be significant (P less than 0.05). There is a negative correlation between the NK results obtained and the total accumulated dose of radiation at the time of sampling (correlation coefficient = -0.739, P less than 0.01), suggesting a radiation effect upon natural killer activity, which is evidence by enhancement at lower doses and depression at higher doses of irradiation.     

Detailed profile of prolactin secretion in the immature female rat: evidence for the existence of an ultradian rhythm

The detailed profile of prolactin (PRL) secretion in 22-24 and 29-31 days old female rats was investigated by serial blood sampling through an intracardiac cannula at 15-min intervals for each of the 9 or 10-h periods beginning at 09.00 or 10.00 and 22.00 h. By analysis of the power spectrum and the least squares method the time series of PRL concentrations which were measured by RIA were found to have approximately a 3-h period ultradian rhythm in either sampling period of both the 22-24 and 29-31 days old rats. The peak times calculated based on the acrophase estimated through the calculation of periodicity were concentrated around 12.00, 15.00 and 18.00 h for the sampling period 10.00-19.00, and 24.00, 03.00 and 06.00 h for the sampling period 22.00-07.00 h. However, in more than half of the animals at 22-24 days of age, one secretory episode around 12.00 h, and two secretory episodes around 24.00 and 03.00 h had markedly small amplitudes, making the remaining secretory episodes distinct diurnal and nocturnal surges, respectively. In the animals at 29-31 days of age, the amplitudes of the PRL episodes occurring around 12.00 h were markedly small, making the remaining two episodes as diurnal surges, whereas the amplitudes of PRL secretory episodes during the period 22.00-07.00 h were analogous to each other. These findings indicate that the semicircadian rhythm of PRL secretion is established on the basis of PRL secretion with the 3.0-h period ultradian rhythm.     

Effect of gamma-aminobutyric acid on excitability of tubero-infundibular neurons in rat hypothalamic slices

The effect of gamma-aminobutyric acid (GABA) on antidromically identified tubero-infundibular (TI) neurons was examined in hypothalamic slices of ovariectomized female rats. Twenty antidromically evoked spikes were obtained in the medial basal hypothalamus, including the arcuate and ventromedial nuclei, by electrical stimulation of the median eminence. Sixteen of them had a notch in the rising phase and fractionation of the initial segment (IS)- and somatodendritic (SD)-spikes was elicited by repeated stimulation at frequencies higher than 10 Hz. The application of 0.5-1.5 mM GABA to the incubation medium inhibited SD spikes in 7 of these 16 neurons. The latency, amplitude and threshold of IS spikes were not affected by GABA except for one spike whose latency fluctuated. On the remaining 9 neurons having the notch, no effect of 5-10 mM GABA was discernible. Four of 20 antidromically evoked spikes, which had a smooth rising phase and a shorter duration, were not inhibited by 5-10 mM GABA, but a fluctuation of the latency was observed in one neuron. Fifteen neurons having spontaneous unit activity were also obtained in the arcuate nucleus and its adjacent area and tested with GABA. In 10 of the 15 neurons, spontaneous unit activity disappeared following 0.1-1.5 mM GABA perfusion, while the firing rate in the remaining 5 neurons was not affected by 5-10 mM GABA. These results provide evidence for a direct inhibitory effect of GABA on TI neurons and support the involvement of GABAergic neurons in regulating neuroendocrine functions.     

The actin domain of Gardner-Rasheed feline sarcoma virus inhibits kinase and transforming activities.

The transforming gene product, P70gag-actin-fgr, of Gardner-Rasheed feline sarcoma virus (GR-FeSV) is a single polypeptide composed of regions derived from cellular and viral genes. Gamma actin and c-fgr genes are the two known cellular components of the GR-FeSV genome. In the present study, sequences representing each cell-derived gene were deleted and the resulting constructs were tested for transforming activity by transfection of NIH 3T3 cells. Constructs lacking a portion of the c-fgr proto-oncogene failed to induce focus formation, demonstrating the essential nature of this component for GR-FeSV oncogenic activity. In contrast, the construct lacking the actin domain was more active than GR-FeSV DNA in transformation assays. Protein specified by the actin deletion mutant possessed a 2.4-fold greater specific protein-tyrosine kinase activity compared with that of the wild-type gene product. Furthermore, the actin domain had no detectable effect on the ability of the fgr kinase to associate with cytoskeleton or to phosphorylate unique cellular proteins on tyrosine. Our findings demonstrate that the actin domain inhibits focus formation and impairs protein-tyrosine kinase activity.     

Identification of Mutations in the Pigment Cell-Specific Gene Located at the Brown Locus in Mouse

The pigment cell-specific gene, located at the brown (b)-locus in mouse, encodes the protein that determines the type of melanin synthesized. This protein is known as tyrosinase-related protein, but here we tentatively term it b-locus protein to avoid confusions with the related sequence cross-hybridizing to the tyrosinase gene. In order to identify the mutation at the b-locus, we have cloned and characterized the b-locus protein gene of BALB/c mouse (b/b, c/c). The gene is about 18 kb long and organized into 8 exons and 7 introns. Sequence analysis of the b-locus protein gene reveals four base changes within the protein-coding regions: two missense mutations and two silent mutations. Two missense mutations result in the Cys to Tyr substitution at position 86 (codon 110) and the Arg to His substitution at position 302 (codon 326) of a b-locus protein molecule. Using allele-specific amplification, we confirmed that these missense mutations are actually present in the genomic DNA of two b-mutant strains examined, BALB/c and DBA/2 (b/b, C/C) mice, suggesting that these mutations are specific for the mutant mice at the b-locus. Moreover, we are able to show that the b-locus protein containing Tyr 86 is not reactive with the anti-b-locus protein monoclonal antibody, TMH-1, in transient expression assays.     

biparous:A Novel bHLH Gene Expressed in Neuronal and Glial Precursors inDrosophila

Genetic studies have uncovered many genes that are involved in the first steps of neuronal development inDrosophila.Less is known about the intermediate steps during which individual precursor cells follow either the neuronal pathway or the glial pathway. We report the identification of a novel bHLH gene,biparous,expressed in neuronal and glial precursors inDrosophila.Unlike most bHLH genes,biparousexpression continues to the final stages of neurogenesis in the embryo. Expression ofbiparousis not observed in end stage postmitotic neurons and precedes the expression ofrepo,a gene activated in later stages of glial differentiation. The bHLH domain is sufficiently different from previously described bHLH domains to imply a novel function.