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Biomedical subjects

I Nir

Publications and source records attributed to I Nir.

At least 73 records · Page 4Linked to original sources

Insulin-tumour interrelationships in EL4-lymphoma or thymoma-bearing mice. II. Effects of dietary omega-3 and omega-6 polyunsaturated fatty acids.

Male C57BL/65 mice received a basal diet supplemented with 4% soya-bean oil, linseed oil or fish oil, in which the major polyunsaturated fatty acids were linoleic acid, alpha-linolenic acid and long chain omega-3 fatty acids, respectively. Groups of animals were injected into the right flank with EL4-lymphoma cells, others with thymoma cells. Tumour implantation caused a gradual decrease in food consumption with both types of tumour, while body weight increased, especially in the EL4-bearing animals receiving the soya-bean diet. The weight gain was due to body water accumulation and was accompanied by decreases in body fat and minor changes in carcass protein and ash contents. The dietary treatments did not produce significant differences in tumour incidence and mortality, but tumour size was decreased by diets supplying omega-3 fatty acids: in the EL4 mice tumour weight was markedly depressed by linseed oil, compared to soya-bean oil, whereas thymoma tumour weight was lowest in mice receiving fish oil and highest in the soya-bean oil group. Both types of tumour caused pronounced hypoglycaemia and hyperinsulinaemia in the hosts, and the effect was modulated by the diets in the EL4 but not in the thymoma animals: the plasma glucose level was especially low in the linseed oil group and relatively highest in the soya-bean oil treatment. The degree of hyperinsulinaemia depended on the diet only in the thymoma-bearing mice, with linseed and fish oils producing higher insulin levels than soya-bean oil. A slight hyperinsulinaemia was also observed in linseed and fish oil-fed control mice. Serum triglycerides were elevated in tumour-bearing animals, without consistent differences between dietary treatments. Although no clear pattern emerged concerning total cholesterol and LDL levels, HDL values were strongly affected by the type of oil: in the control animals linseed oil caused an increase in HDL-cholesterol compared to the other two oils. The thymoma-bearing mice responded to the linseed and fish oil diets with greatly elevated HDL-cholesterol levels. The results point to important differences in the responses of the two implanted tumours and hosts not only to the omega-6 and omega-3 fatty acids, but also to the type of dietary omega-3 fatty acids, namely alpha-linolenic acid and long chain fish oil polyunsaturated fatty acids.

Animals↗

Utilization of raw or heat-treated starch fed in liquid diet to pre-ruminants. 1. Calves.

Five 7-day-old Frisian bull calves, raised in Israel received twice a day a mixture of 40 g of soybean concentrate (65% protein) and 80 g of one of the following carbohydrates: glucose (G), expanded (heat-treated) (ES) or untreated (US) corn starch. In the afternoon the calves received in addition 400 g of milk replacer. Until weaning at experimental day 25, ES calves showed better growth and food utilization than their counterparts. Daily weight gain for the entire growing period up to slaughter was higher for the starch than for the glucose-fed group (P less than 0.05 for ES vs G). Heat treatment of starch increased its in vitro availability to amylase and its in vivo digestibility. Bypass of the rumen was complete in all G calves. In the ES and US groups, partial diversion of the liquid feed into the rumen was evident. The G group showed hyperglycemia after meals, while almost no increase in blood glucose level was observed after soy-starch meals (either US or ES).

Amylases↗

Effect of dietary concentrations of fat and energy on fat deposition in broilers divergently selected for high or low abdominal adipose tissue.

1. Fat deposition in abdominal, mesenterial, sartorial and gizzard adipose tissues (AT), liver, breast muscle, skin and carcase was studied in male broilers, selected for high (HF) and low (LF) abdominal fat and fed on diets differing in energy density and total fat content. 2. There were no significant differences in body weight in the experimental groups. The relative weight (g/kg body weight) of the dissected adipose tissues was higher in HF than in LF birds. Fat concentration in the AT (sartorial excepted), skin and body was higher in the HF compared with the LF birds. The lines did not differ significantly in liver and breast muscle fat content. 3. Abdominal AT was affected by selection or dietary fat more than other AT and total body fat. 4. In the HF birds increasing energy density from 12.3 to 13.4 MJ/kg (dietary fat kept constant: 5.46 g/MJ) significantly increased the weight of the abdominal, mesenterial and sartorial AT. Increasing dietary fat (at both energy densities) decreased the weight of the AT, whereas increasing both energy and fat did not affect it. In the LF birds, similar but milder and insignificant trends were observed. It is suggested that this interaction has biological significance.

Adipose Tissue↗

Metabolic and anatomical adaptations of heavy-bodied chicks to intermittent feeding. 2. Pancreatic digestive enzymes.

1. Activities of digestive enzymes in meat-type chickens under ad libitum or alternate-day feeding were determined from 14 to 83 d of age. 2. Final body weight of intermittently fed birds attained 75% of that of the ad libitum-fed controls. 3. When compared with the ad libitum-fed counterparts, a marked increase in the relative weight of the pancreas and intestinal contents were found on repletion days. On depletion days the relative weights of the pancreas and of the intestinal contents were about half those found in ad libitum-fed birds. 4. The activity of the digestive enzymes in the pancreas, expressed as U/g pancreas or U/kg body weight, was not affected consistently by the feeding regime. In the small intestine a marked increase in relative activity (U/kg body weight) was observed on repletion days and a marked decrease on depletion days as compared with ad libitum-fed controls. The activities per g intestinal contents following food restoration did not differ significantly from those of ad libitum-fed controls except for trypsin, which was higher in the former. On depletion days the activities per g intestinal contents were lowest, lipase excepted.

Adaptation, Physiological↗

Cyclohexyladenosine reduces MPTP induced tremor in dogs.

Male dogs were injected i.v. with 1 methyl-4-phenyl-1,2,3,6-tetrahydro- pyridine (MPTP) 2.5 mg/kg twice with an interval of 6 days. Twenty minutes after MPTP injection cyclohexyladenosine (CHA) 1 mg/kg i.v. was injected. Ten minutes after CHA injection the MTPT induced tremor, tachycardia and salviation ceased.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Composition of eggs from dwarf and normal chickens before incubation and at hatching in lines selected for 56-day body weight.

Comparisons of egg composition prior to incubation and when the chick had pipped through the shell were made for dwarf (D) and normal (N) chickens from lines selected for high (H) or low (L) body weight. Weight of moisture, ash, and fat decreased and nonlipid organic matter increased during incubation. The pattern for these components was the same on a percentage of egg weight basis except that there was no change in ash. Genotype by line interactions were significant for egg weight, moisture, ash, fat, and nonlipid organic matter before incubation and for all of these characteristics except fat at pipping. The interactions were due to values being lower for D than N in Line L, and D and N were similar in Line H. When egg component weights were expressed relative to egg weight, interactions were not significant prior to incubation but were present for moisture and fat at hatch. These data show that characteristics influenced by the sex-linked dwarfing gene are modified by the background genome.

Alleles↗

Opsin synthesis and mRNA levels in dystrophic retinas devoid of outer segments in retinal degeneration slow (rds) mice.

Opsin gene regulation, as a function of outer segment structure, was studied in normal and mutant retinal degeneration slow (rds) mice. We investigated the level of expression of the opsin gene in the rds mutant to determine if the reduced opsin content observed in this mutation (around 3% of normal) is a consequence of lowered expression of its gene. Normal BALB/c and rds mice were analyzed for levels of opsin mRNA and opsin content by Northern and immunoblot analysis, respectively. The rate of opsin synthesis in isolated retinas was measured by 35S-methionine incorporation in vitro, followed by analysis of the radiolabeled opsin by SDS-gel electrophoresis and autoradiography. Photoreceptor cell loss at various stages of degeneration was determined by quantitation of surviving photoreceptor nuclei. Opsin was localized in the mutant photoreceptors by immunoelectron microscopy of LR gold-embedded retinas using anti-opsin and antibody gold conjugates. The results indicate that 11- and 30-d-old mutant mice have considerable levels of opsin mRNA (60-70% of normal) and opsin synthetic rates (76-92% of normal), after the data from mutant mice are corrected for photoreceptor cell loss. We conclude, therefore, that the very low level of opsin observed in rds mice (approximately 3%) is not a result of greatly reduced expression of the opsin gene. Rather, continuous turnover of newly synthesized opsin as a result of its failure to become sequestered into an intact outer segment appears to account for the low levels of opsin in the rds mutant.

Animals↗

Opsin distribution and synthesis in degenerating photoreceptors of rd mutant mice.

The distribution of opsin and the capacity of photoreceptors to synthesize opsin was studied in retinas of mice bearing the rd (retinal degeneration) mutation and compared to control normal mice. Opsin was localized by means of pre-embedding and post-embedding immunocytochemistry and electron microscopy. Cones were identified with anti-cone antibodies and peanut agglutinin lectin which labels cone matrix sheaths. Opsin synthesis was measured by incorporation of [35S]methionine into opsin which was detected by immunoblots. Immunocytochemistry revealed that degeneration of rod outer segments was accompanied by accumulation of opsin in the plasma membrane enveloping the inner segment, nuclei and synaptic terminals. Rod photoreceptors degenerated faster than cones. By post-natal day 19 (P19), 87% of the remaining inner segments were cones. Opsin synthesis in rd mice could no longer be measured after P15. However, opsin molecules could be detected both by immunocytochemistry and immunoblotting up to P30. Between P20 and P30 all detectable opsin was localized in the plasma membrane which envelopes nuclei and synaptic terminals. Unlabeled surviving nuclei after P30 are probably cones. The opsin which is detected in rod inner segment plasma membranes might be derived, by back diffusion, from degenerating outer segments and represent molecules synthesized at an earlier time. Alternatively opsin accumulation might be a result of low levels of opsin synthesis, undetectable by [35S]methionine incorporation, which continues in the absence of outer segments.

Animals↗

Production of bovine rhodopsin by mammalian cell lines expressing cloned cDNA: spectrophotometry and subcellular localization.

Cloned cDNA encoding bovine rhodopsin has been recombined into an expression vector and cotransfected with an antibiotic resistance plasmid into cultured human embryonic kidney cells. The resulting cell lines produce 100-200 micrograms of bovine opsin per liter of saturated tissue culture medium (10(9) cells). Incubation in vitro with 11-cis retinal produces a photolabile pigment the absorbance spectrum of which is indistinguishable from that of bona fide bovine rhodopsin. Expressed rhodopsin accumulates in the plasma membrane as determined by immunoelectron microscopy.

Animals↗

Diurnal variations in melatonin binding sites in the hamster brain: impact of melatonin.

The distribution of 125I-melatonin binding sites in the male Syrian hamster brain was recorded at 3 times over a 24 h period. The binding in the hypothalamus, hippocampus, medulla-pons and midbrain of the hamsters varied significantly over the 24 h period with different patterns and phases. No such variations were observed in the parietal cortex. Daily morning (10.00 h) or late afternoon (18.00 h) injections of melatonin for 28 days markedly increased the serum concentrations of melatonin at all times recorded. Serum concentrations of testosterone were significantly lower in animals injected with melatonin in the late afternoon than in the untreated controls; no such decrease was observed in animals injected in the morning despite the continuously elevated levels of circulating melatonin. The daily melatonin injections did not significantly affect 125I-melatonin binding in the hypothalamus, parietal cortex and medulla-pons. In the midbrain, 125I-melatonin binding decreased regardless of the time of injection. In the hippocampus, morning melatonin injections caused a marked decrease in 125I-melatonin binding at all times recorded whereas melatonin injected in the late afternoon led to a decrease in 125I-melatonin binding at 10.00 h only. These results indicate diurnal variations in 125I-melatonin binding sites in discrete brain areas of the golden hamster, persisting despite prolonged duration of elevated levels of circulating melatonin. The differential effects of timed melatonin injections on the hippocampal 125I-melatonin binding sites are positively correlated with the counter-antigonadal response produced by morning melatonin injections.

Animals↗

Muscle growth and composition in heavy and light breed chickens adapted to intermittent feeding.

1. The effect of intermittent feeding in chickens of heavy breed (HB; meat type) and light breed (LB; egg type) on skeletal muscle growth and composition was studied in adapted and non-adapted chickens. 2. Food intake, relative to body-weight, was similar in both breeds but was higher in ad lib.-fed than in intermittently fed birds. 3. On repletion days the relative growth rate was similar in both breeds, while on depletion the LB chickens lost more weight than the HB chickens. In both breeds, the relative growth was higher in the intermittently fed birds during days of food restoration than in those fed ad lib. 4. The relative weight of the breast muscle was higher in HB birds than in LB birds, but deposition rate on the day of food restoration was similar in both breeds. This growth was more pronounced in chickens adapted to alternate feeding than in chickens exposed to this feeding regimen for one cycle. 5. Protein concentration in breast muscle was not affected by age and was slightly higher in LB chickens than in HB chickens. Soluble protein was markedly reduced on days of repletion, and more at 46 d than at 18 d of age. 6. The RNA:DNA ratio was higher in HB than in LB chickens, and lower on days of food deprivation than on days of food restoration. After repletion this ratio returned to the level of the ad lib.-fed chickens. While in LB chickens cell size (as estimated by DNA concentration) remained constant on repletion and depletion days, in the HB chickens it decreased. 7. The rapid growth of breast muscle in HB chickens was attributed to the higher rate of protein synthesis (estimated by RNA:DNA ratio) compared with LB chickens. This may also explain why the breast muscle of LB chickens was less sensitive to intermittent feeding than that of HB chickens.

Adaptation, Physiological↗

Blood-brain barrier permeability of human gliomas as determined by quantitation of cytoplasmic vesicles of the capillary endothelium and scintigraphic findings.

The number of cytoplasmic vesicles in the capillary endothelium was determined by ultrastructural morphometry and correlated with the uptake of technetium-99m pertechnetate used in brain scintigraphy. Ten gliomas were studied for uptake rates of 99mTc pertechnetate. Three gliomas from the different groups of uptake rates were quantitatively analyzed for cytoplasmic vesicle content. Capillaries of tumors without uptake had a low content of cytoplasmic vesicles, which was similar to that obtained in normal brain control. In tumors with low and moderate uptake rates, the cytoplasmic vesicles content increased significantly (p less than 0.05) by about 300% and 400%, respectively, as compared with that found in impermeable tumor and in normal brain. The correlation found between the cytoplasmic vesiculation of the endothelial cells in gliomas' capillaries and the uptake of 99mTc pertechnetate suggests that pinocytosis might be a factor in the uptake of the radionuclide. The present findings might be applicable to treatment with hydrophilic chemotherapeutic agents in moderate and highly permeable tumors.

Blood-Brain Barrier↗

Immunocytochemical localization of opsin in degenerating photoreceptors of RCS rats and rd and rds mice.

Opsin is normally sequestered predominantly in the outer segment disc and plasma membranes of adult photoreceptors. Absence of opsin from the inner segment plasma membrane in normal photoreceptors is probably not due to the inability of the inner segment plasma membrane to retain opsin. Rather, in the adult mammalian retina, if opsin is inserted at sites in the apical inner segment plasma membrane, in a fashion comparable to the pathway in amphibians, it is rapidly transported predominantly to the outer segment by unknown mechanisms. Dystrophic rds retinas, lacking an outer segment, display newly synthesized opsin throughout the plasma membrane. If opsin is transported to the inner segment plasma membrane as a specific insertional site, diffusion in the plane of the membrane may redistribute opsin throughout the plasma membrane which encloses the nucleus and the synaptic terminal. Alternatively, opsin may be inserted randomly throughout the entire cell's plasmalemma beneath the cilium. Selective transport to the outer segment may preferentially clear the inner segment of most of its opsin and nearly clear the perikaryal and synaptic terminal's plasmalemma in normal cells. In dystrophic retinas, however, as outer segments degenerate or fail to form, opsin is detected readily in the remaining plasma membrane sites. In the rd mouse, some of the opsin molecules in the inner segment plasma membrane might be newly synthesized while others may arise from molecules which reached the inner segment by back-diffusion from the outer segment at least at early stages in the degeneration while outer segments survive. The opsin in the plasma membrane which envelopes the residual rod nuclei and synaptic terminals in dystrophic retinas may account for the persisting light perception in retinas which have lost both the rod outer and inner segments. Dystrophic retinas, such as the rd mouse and RCS rats and possibly human RP retinas, in which cone nuclei survive long after rods disappear, might retain light perception because of cone photo-pigments in the outer nuclear and outer plexiform layers. To explore these questions further, the localization of other components of the transduction cascade and the determination of the efficiency of their coupling in dystrophic cells is necessary. We need to know where the cyclic GMP-sensitive sodium channels lie in these dystrophic cells and the cellular requirements for proximity of these components to generate a signal. Outer segment-free photoreceptors, bearing opsin in their plasma membranes, resemble other cells which have receptor-mediated alterations in membrane permeability to ions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Permeability of blood vessels in experimental gliomas: uptake of 99mTc-glucoheptonate and alteration in blood-brain barrier as determined by cytochemistry and electron microscopy.

Experimental gliomas were induced in rats by prenatal exposure to ethyl nitrosourea. Changes in the blood-brain barrier were determined by the uptake of a water-soluble compound, 99mTc-glucoheptonate. Increased uptake of 99mTc-glucoheptonate was measured in intact tumors and in various sectors of dissected tumors. The extent of 99mTc-glucoheptonate uptake greatly varied among different tumors and among different sectors of the same tumor. Ultrastructural and cytochemical analysis of the capillary endothelial wall revealed major alterations in tight junctions, which became permeable to horseradish peroxidase. In brain tissue around the tumors, uptake of 99mTc-glucoheptonate and ultrastructure of tight junctions were comparable to normal brain capillaries. The results of the present study indicate that altered endothelial tight junctions may provide the main route of transport of 99mTc-glucoheptonate through the endothelial wall.

Animals↗

Circadian variations in melatonin-binding sites in discrete areas of the male rat brain.

The binding of 125I-melatonin to synaptosomes prepared from whole brains of male rats of the CD strain and from the brain, hypothalamus and striatum of male rats of the Sabra-Wistar strain was assessed throughout a 24 h period. The animals were maintained under a daily schedule of 14 h light (05:00-19:00 h) and 10 h darkness. In whole brain preparations the density of binding sites at 18:00 h was higher by about 70% than at 02:00 h with no variations in apparent affinity of the binding sites throughout the daily period. Specific binding of 125I-melatonin was found in both hypothalamus and striatum of the male rat with a distinct diurnal variation in binding site density in the hypothalamus only. The density of 125I-melatonin-binding sites in the hypothalamus was maximal between 10:00 and 18:00 h and dropped sharply after the lights went off. The apparent 125I-melatonin-binding affinities in these regions were constant and very similar to those in whole brain preparations. The daily variations in densities of 125I-melatonin-binding sites in discrete brain areas may represent a diurnal rhythmicity in the responsiveness of the neuroendocrine axis to melatonin.

Animals↗

Effect of age on cadmium-induced metallothionein synthesis in the rat.

Cadmium-induced metallothionein (MT) synthesis was investigated in male rats of three ages, 3, 12 and 24 months. Physiological levels of MT in kidney, liver and lung measured simultaneously in untreated animals were found to be within the same range in all three age groups. Following 3-day treatment with CdCl2 equivalent to 1 mg/kg/day Cd, renal MT increased 10-15-fold in all animals. However, hepatic MT became elevated to 36 times the original value in the youngest (3-month-old) rats and 90 and 74 times, respectively, in the 12- and 24-month-old groups. Lung MT, which responded rather poorly to the cadmium inducer, increased 2-fold in the young group, but about 10 and 8 times, respectively, in the two older groups. High mortality of 75% occurred in the aged (24-month-old) group following cadmium administration, indicating age to be an important sensitizing factor in the toxic hazard of heavy metal exposure. The possible role in this connection of MT is discussed.

Aging↗

Pregnancy outcome in heat-exposed hamsters; the involvement of the pineal.

The effect of high ambient temperature (34 degrees C) on the function of the female reproductive system, on embryonic development and on outcome of pregnancy, was investigated in heat-exposed sham-operated (Sh) and pinealectomized (Px) golden hamsters maintained under short photoperiod. Plasma prolactin levels were reduced in both heat-exposed groups (ShH and PxH) but pituitary prolactin was increased in the pinealectomized groups irrespective of ambient temperature (21 or 34 degrees C). Pituitary weights and LH contents were not affected in any test group. Heat exposure brought about a reduction in the number of corpora lutea and of pups born, the latter being more drastically reduced in absence of the pineal; the depressant effect of heat on ovarian weight was evident only in the pinealectomized animals. Progesterone levels were not affected in any test group and pregnancy was not prolonged, thus, it would seem that pregnant hamsters adapt themselves well to heat. Moreover, high ambient temperature promoted a rise in pineal. HIOMT activity and boosted cortisol levels in presence of the pineal gland only, which, together with the above findings, shows that the pineal can provide protection for pregnant hamsters against adverse effects of high ambient temperature.

Animals↗