Relationship between histology,development and tumorigenesis of mammary gland in female rat

The mammary gland is a dynamic organ that undergoes structural and functional changesassociated with growth, reproduction, and post-menopausal regression. The postnataltransformations of the epithelium and stromal cells of the mammary gland may contribute toits susceptibility to carcinogenesis. The increased cancer incidence in mammary glands ofhumans and similarly of rodents in association with their development is believed to bepartly explained by proliferative activity together with lesser degree of differentiation,but it is not completely understood how the virgin gland retains its higher susceptibilityto carcinogenesis. During its developmental cycle, the mammary gland displays many of theproperties associated with breast cancer. An early first full-term pregnancy may have aprotective effect. Rodent models are useful for investigating potential breastcarcinogens. The purpose of this review is to help recognizing histological appearance ofthe epithelium and the stroma of the normal mammary gland in rats, and throughout itsdevelopment in relation to tumorigenic potential.     

STUDY ON THE PROLIFERATIVE STATE OF HAEMOPOIETIC STEM CELLS (CFU)

Hydroxyurea was used to study the proliferation rate of haemopoietic stem cells (CFUJ in normal mice, after irradiation or transplantation into irradiated recipients. It was demonstrated that the proliferation rate of endogenous CFU_S (endo-CFU,) and exogenous CFU_S (exo-CFU_s) are identical. After irradiation (650 R) the surviving endo-CFU_s begin to proliferate immediately. By contrast exo-CFU, transplanted into the irradiated recipient mouse (850 R), begin to proliferate only after about 30 hr. However, injection of isoproterenol (which stimulates adenyl cyclase) or dibutyryl cyclic adenosine 3′,5′-monophosphate shortly after marrow cell graft, triggers the transplanted CFU_S into cell cycle as shown by an almost immediately increased sensitivity to hydroxyurea. Isoproterenol is capable of inducing DNA synthesis also in stem cells of normal mice but it takes about 20 hr before CFU, become to be increasingly sensitive to hydroxyurea.     

The mipafox-inhibited catalytic domain of human neuropathy target esterase ages by reversible proton loss

Aging of organophosphorus (OP)-compound-inhibited neuropathy target esterase (NTE) is the critical event that initiates OP-compound-induced delayed neurotoxicity (OPIDN). Aging has classically been considered to involve side-group loss from phosphylated NTE, rendering the enzyme refractory to reactivation. N,N'-Diisopropylphosphorodiamidofluoridate (mipafox, MIP)-inhibited NTE has been thought to age quickly; however, it can be reactivated under acidic conditions. The present study was undertaken to determine whether MIP-inhibited human recombinant NTE esterase domain (NEST) ages classically by isopropylamine loss. Diisopropylphosphorofluoridate (DFP), the oxygen analogue of MIP, was used for comparison. Kinetic values for DFP against NEST were as follows: k(i) = 17 200 +/- 180 M(-1) min(-1); reactivation t(1/2) approximately 90 min at pH 8.0 and approximately 60 min at pH 5.2; k(4) = 0.108 +/- 0.041 min(-1) at pH 8.0 and 0.181 +/- 0.034 min(-1) at pH 5.2. Kinetic values for MIP against NEST were as follows: k(i) = 1880 +/- 61 M(-1) min(-1); reactivation t(1/2) = 0 min at pH 8.0 and approximately 60 min at pH 5.2; aging was complete at all time points tested at pH 8.0, but no aging occurred at pH 5.2. Mass spectrometry revealed a mass shift of 123.0 +/- 0.6 Da for the active site peptide peak of aged DFP-inhibited NEST, corresponding to a monoisopropyl phosphate adduct. In contrast, the analogous mass shift for aged MIP-inhibited NEST was 162.8 +/- 0.6 Da, corresponding to the intact N,N'-diisopropylphosphorodiamido adduct. Thus, MIP-inhibited NEST does not age by isopropylamine loss. However, because kinetically aged MIP-inhibited NEST yields an intact adduct capable of reversible deprotonation, aging could occur by proton loss. Indeed, MIP-inhibited NEST does not age at pH 5.2 but ages immediately and completely at pH 8.0. Therefore, we conclude that the MIP-NEST conjugate ages by deprotonation rather than classical side-group loss.     

Differential coding of humoral stimuli by timing and amplitude of intracellular calcium spike trains

The ubiquitous Ca2(+)-phosphoinositide pathway transduces extracellular signals to cellular effectors. Using a mathematical model, we simulated intracellular Ca2+ fluctuations in hepatocytes upon humoral stimulation. We estimated the information encoded about random humoral stimuli in these Ca2+ spike trains using an information-theoretic approach based on stimulus estimation methods. We demonstrate accurate transfer of information about random humoral signals with low temporal cutoff frequencies. In contrast, our results suggest that high-frequency stimuli are poorly transduced by the transmembrane machinery. We found that humoral signals are encoded in both the timing and amplitude of intracellular Ca2+ spikes. The information transmitted per spike is similar to that of sensory neuronal systems, in spite of several orders of magnitude difference in firing rate.     

PHOTIC STIMULATION AND LEG MOVEMENTS IN THE CRAYFISH

When Cambarus clarkii is exposed to a source of light so that both eyes are equally illuminated, leg movements of the two sides are equal in frequency and amplitude. On covering one eye and exposing the uncovered eye to light, leg movements on the side of the uncovered eye are more frequent and are of greater amplitude than on the side of the covered eye. On covering the exposed eye also the leg movements on the two sides again tend to become equal in frequency and amplitude. When one eye is lost and the other remains functional, the leg movements on the side of the lost eye will be similar to those on the side of a normal, covered eye.