Comparative studies on membranes from bovine choroid plexus and rat kidney cortex.

Comparative subcellular fractionation studies on rat kidney and bovine choroid plexus using differential centrifugation and free flow electropheresis were undertaken because of the morphological and functional similarities of the epithelial cells of both tissues. The activities of three enzymes commonly used as markers for brush border membranes in kidney were measured in fractions of each tissue. γ-Glutamyl transpeptidase, alkaline phosphatase, and 5'-nucleotidase copurified in membrane fractions of renal cortex collected by differential centrifugation. Application of a similar fractionation procedure to choroid plexus gave relatively similar results, except for alkaline phosphatase, the yield of which was substantially reduced in a fraction enriched with two marker enzymes. Further fractionation of γ-glutamyl transpeptidase and alkaline phosphatase activities in these membrane fractions was achieved using free flow electropheresis. The two enzymes from kidney exhibited discrete peaks with a small separation, while the electropheretic pattern of γ-glutamyl transpeptidase from choroid plexus was biphasic. Alkaline phosphatase was observed to migrate with the more basic γ-glutamyl transpeptidase peak.     

Impulse pattern generation in a crayfish abdominal postural motoneuron

Journal of Comparative Physiology A - It is concluded that burst formation is endogenous to the motoneuron andnot strongly dependent on patterned presynaptic input.     

Nucleotide sequences of HS-α satellite DNA from kangaroo rat dipodomys ordii and characterization of similar sequences in other rodents

The most common repeated nucleotide sequences of the highly repetitive satellite HS-α fraction from kangaroo rat Dipodomys ordii was determined using ribosubstitution methods. This sequence was α nucleotides long and represented about 25% of the total HS-α satellite DNA, while the remaining DNA was composed of sequence variants related to the most common sequence. The sequences of the commonest of these variants are reported. Furthermore, the most common repeated sequence was identical to that reported for the α satellite of guinea pig Cavia porcellus. The α satellites of guinea pig, Cavia porcellus, pocket gopher, Thomomys bottae and antelope ground squirrel, Ammospermophilus leucurus, are shown to have sequences in common with the kangaroo rat. This implies that the simplest repeated sequences of mammalian satellite DNAs may persist over much longer evolutionary times than previously thought.Attempts to explain the very rapid quantitative changes in satellites whose sequence is strongly conserved have led us to consider that they might have a role in sympatric speciation. Among the novel features of the model presented is that fluctuations in satellites could be due to “speciation genes.” Such genes would confer a strong selective advantage in certain situations, and could explain the many puzzling instances in which large numbers of new related species have appeared over a short evolutionary span.     

Carrier-mediated Uptake of Arginine and Urea by Volvox carteri f. nagariensis

Volvox carteri f. nagariensis takes up arginine via a high affinity, highly specific carrier, whereas carriers for neutral and acidic amino acids cannot be detected (even in nitrogen-starved cultures). Exogenous arginine is accumulated against a steep concentration gradient and is incorporated into protein with high efficiency, but it is not catabolized to any significant extent and will not serve as a nitrogen source adequate to support growth. Urea is also taken up by a saturable carrier, but several lines of evidence indicate that the arginine and urea carriers are distinct and different. Preexposure to arginine suppresses arginine uptake while stimulating urea uptake. The K_i values observed for reciprocal, competitive inhibition of uptake by arginine and urea are orders of magnitude different from the respective K_m values for uptake. The two uptake systems show entirely different patterns of sensitivity to inhibition by structural analogs. Finally, the V_max values for arginine and urea uptake fluctuate independently (but in a regular pattern) during the asexual life cycle. The fluctuations of urea uptake activity are of considerable magnitude and appear to be linked to key phases of the developmental program.     

Retinal illumination produces synaptic inhibition of a neurosecretory organ in the crayfish,pacifastacus leniusculus (Dana)

We have identified a cluster of neurosecretory cells in the crayfish eyestalk that possess dendrites in the second optic neuropil (Medulla) and project axons to the first optic neuropil (Lamina). Illumination of the ipsilateral retina produces a synaptic inhibition of these cells that is mimicked by iontophoresis of gamma-aminobutyric acid within the medullary neuropil. The neurosecretory nature of the cells, the efferent projection of their axons, and the strong inhibition of their spiking activity upon retinal illumination suggest that they may be involved in the feedback control of dark adaptation and/or circadian changes in visual sensitivity.     

Milk lipid digestion in the neonatal dog: the combined actions of gastric and bile salt stimulated lipases

Intragastric lipolysis may be particularly important for the digestion of milk lipid since milk fat globules are resistant to pancreatic lipase without prior disruption; milk bile salt stimulated lipase (BSSL) may supplement further intestinal hydrolysis. Previous information on gastric lipolysis has been based primarily on in vitro studies using artificial lipid emulsions containing a single component fatty acid and have focused on the preferential release of medium-chain fatty acids. The actual contribution of these enzymes to overall fat digestion in vivo on natural substrates has rarely been studied, however. The neonatal dog is an excellent model in the study of lipid digestion because, like the human, milk lipids are high in long-chain unsaturated fatty acids, milk contains BSSL and gastric lipase is the predominant lipolytic enzyme acting in the stomach. We used a combination of in vivo studies with in vitro incubations to investigate digestion of milk lipid by gastric and milk (BSSL) lipases in the suckling dog. In the first 4 weeks postpartum, 14-41% and 42-60% of milk triacylglycerol was hydrolyzed to primarily diacylglycerol and free fatty acid (FFA) in the first 30 and 60 min in the stomach, respectively. Milk lipid contained high levels (63%) of long-chain unsaturated fatty acids, which were preferentially released as FFA during in vivo gastric lipolysis, consistent with the actions and stereospecificity of gastric lipase. While levels of hydrolysis in gastric aspirates were significantly different (by age and time in stomach) at the start of in vitro studies, total hydrolysis in all incubation systems plateaued at about 65%, suggesting product inhibition by the long-chain FFA, but to a much lesser degree than previously expected from in vitro studies. The magnitude of in vivo intragastric lipolysis was 3- to 6-times greater than that predicted by in vitro assays using either milk lipid or labeled emulsion as substrate, respectively. Prior exposure to intragastric lipolysis resulted in 30% hydrolysis by BSSL compared to 5% hydrolysis without prior exposure. We suggest that previous in vitro studies have largely underestimated the actual degree of intragastric lipolysis that can occur and its activity on long-chain fatty acids; this study indicates the importance of the combined mechanisms of gastric lipase and BSSL to fat digestion in the suckling neonate.     

Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays

Female mice were exposed to varying absorbed doses (108–504 rad) of X-rays and mated at different intervals after irradiation (1–7, 8–14, 15–21 and 22–28 days). Uterine contents were examined at late pregnancy in order to detect early fetal deaths (dominant lethality) and malformations in the live fetuses.Two trends were apparent from data on abnormal fetuses. At each weekly interval, the incidence of abnormalities tended to rise with increase in dose, and, at any given dose, the incidence tended to increase with time after irradiation. Dwarfism and exencephaly were the two most common malformations found.The changes in incidence of dominant lethality and of abnormal fetuses with time and with dose follow each other closely, the highest incidence for both being reached in week 3 (59±4.7% for dominant lethals and 12.5±3.1% for abnormal fetuses, after 504 rad) indicating increased radiosensitivity of less mature oocytes. These results parallel those obtained from known genetic effects reported by other workers and suggest that testing for incidence of congenital malformations among offspring of treated animals may prove a useful means of assessing genetic hazards of radiation of chemicals.     

Combination v. sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer.

The results of a national clinical trial to compare combination and sequential chemotherapy for stage III or IV ovarian cancer are reported. Of the 253 patients from 16 centres across Canada who were admitted to the trial 13 were excluded from the analysis. All the patients were observed for 2 to 5 years from entry into the trial. There were no differences in response to therapy or in survival between the patients treated with melphalan followed by 5-fluorouracil and then by methotrexate in high dosage and the patients treated with the same agents in combination. Patients with minimal residual disease after resection of stage III ovarian cancer had a good prognosis. Other favourable prognostic factors were age (less than 55 years), performance status (90% or 100% on the Karnofsky scale) and histologic grade of the tumour.