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Biomedical subjects

I Nir

Publications and source records attributed to I Nir.

At least 19 recordsLinked to original sources

Modification by oxazepam of the diurnal variations in brain 125I-melatonin binding sites in sham-operated and pinealectomized rats.

Sham-operated and pinealectomized male rats were maintained at 14 h light:10 h dark cycles (lights-on 5.00 h) and injected daily, for 14 days, with oxazepam or vehicle. 125I-melatonin binding was recorded in synaptosomes prepared at 10.00, 18.00, and 24.00 h from the hypothalamus, hippocampus and medulla-pons of the rats. In the sham-operated, vehicle treated rats, specific 125I-melatonin binding in all brain areas studied was higher at 18.00 h, whereas in the oxazepam-treated animals, binding was higher at 24.00 h than at the other times tested. In the pinealectomized, vehicle-treated rats, the binding recorded at 18.00 h in all three brain areas, was lower than at the other times of day tested. Oxazepam treatment decreased 125I-melatonin binding at 24.00 h in the hippocampus and medulla-pons of the pinealectomized rats and did not significantly affect the binding in the hypothalamus. These results indicate the ability of oxazepam, pinealectomy and their combination, to manipulate the diurnal variations in 125I-melatonin binding sites in the rat brain.

Animals

Expression of opsin and IRBP genes in mutant RCS rats.

The retinal pigment epithelium of RCS rats bearing the autosomal recessive rdy mutation fails to ingest shed rod outer segment tips. Accumulation of disk debris in the subretinal space of the maturing mutant retina causes a secondary degeneration of photoreceptor cells. Two hypotheses have been offered as possible explanations of the death of photoreceptor cells in this disorder: (1) photoreceptors are starved for amino acids, retinal, oxygen, etc; and (2) that IRBP levels and synthesis may be decreased and interfere with retinal transport and this deficiency is lethal to these cells. To test these hypotheses, we have studied the effect of this mutation on the levels of expression of opsin and IRBP genes, and gene products and on rates of synthesis at various ages in dystrophic RCS p+ rats and compared the results to those obtained with normal Long Evans rats. The mutant rats and normal controls had comparable amounts of opsin and IRBP mRNA transcripts and rates of synthesis up to post-natal day 45 (P45) but opsin transcripts were barely detectable at P60 and thereafter. IRBP mRNA levels were also very low after P62 although somewhat higher than opsin mRNA. Opsin could be detected immunochemically, albeit at lower levels, at all the ages studied up to P310, but IRBP levels fell below detection after P45. We localized opsin and IRBP in the retina by post-embedding EM immunocytochemical procedures and found that opsin is present in the remnants of rod outer segment debris, even at P390, long after detectable opsin synthesis had ceased. These data suggest that expression of opsin and IRBP genes is not influenced by the shape and state of the outer segments, and that the rdy mutation does not influence the expression of the opsin and IRBP in these retinas until the photoreceptor cells are profoundly damaged. Thus, neither hypothesis about the causes of cell death in this disorder is supported.

Aging

Metabolic and behavioral adaptation of light-bodied chicks to meal feeding.

1. Two-week-old male chicks of a light-bodied strain were fed one (1M) or two (2M) 2-h meals per day. An additional group was pair-fed (P1M) the amount consumed by the 1M group on the previous day. 2. After 21 days, final body weight of the 1M and 2M chicks attained 65% and 80%, respectively, of that of the control group fed ad libitum. The weight gain of the P1M chicks was equal to that of the 1M chicks. 3. Food consumption of chicks adapted to meals was not even throughout the feeding period. On day 16 of the experiment, the 1M birds consumed 65% of the meal during the first 30 min. P1M chicks behaved similarly to the 1M ones. The intake of the 2M chicks during each meal was exactly half of their daily consumption, despite the uneven time period between meals. 4. The time during which food remained in the gastrointestinal tract (GIT) was longer under the meal feeding regimes than in the ad libitum-fed groups. 5. Although neither body composition nor metabolisable energy was affected by meal regime, food utilisation was poorer in the 1M and P1M than in the ad libitum and 2M-fed chicks.

Adaptation, Physiological

Effect of different dietary levels of protein on fat deposition in broilers divergently selected for high or low abdominal adipose tissue.

1. Male broilers selected for high (HF) or low (LF) abdominal fat were fed from 8 to 53 d of age on diets containing different concentrations of protein: according to N.R.C. (1984) recommendations (IP), 14% lower (LP) or 14% higher (HP). 2. The growth of LF birds fed on the LP diet was depressed until 35 d of age, but did not differ from the other groups later on. 3. The HF birds had heavier adipose tissues (AT) (g/kg body weight) than the LF birds. Significant line by diet interactions indicated a difference in magnitude of the response of the lines to dietary protein content. 4. Fat concentration of the AT and skin was higher, and in the tibia lower in the HF than in the LF birds. The fat concentration in liver and in breast muscle was not affected by line or by diet. 5. The ratio of saturated plus monoenoic fatty acids to polyenoic fatty acids, considered as an index of fat synthesis, was higher in the abdominal adipose tissue (AAT) of HF compared with LF birds. In AAT, liver and in breast muscle, this ratio was inversely related to dietary protein content.

Adipose Tissue

S-antigen in rods and cones of the primate retina: different labeling patterns are revealed with antibodies directed against specific domains in the molecule.

S-antigen (arrestin) is a soluble 48 KD protein of the retinal photoreceptor cells. It has been found to have a function in regulation of the phototransduction cascade. Previous labeling experiments with anti-S-antigen (SAg) antibodies have yielded conflicting reports as to the presence of SAg in cone photoreceptor cells. In the present study we employed five monoclonal anti-SAg antibodies (MAb) directed against different known domains in the SAg molecule. MAb A9C6, D9F2, and C10C10 are directed against sequences in the carboxy half of the SAg molecule. MAb 5C6.47 and F4C1 are directed against the amino terminal. Immunoelectron microscopy was used in the localization of SAg in LR Gold-embedded baboon retinas. Green/red and blue cones were identified with MAb COS-1 and OS-2, respectively. MAb A9C6, D9F2, and C10C10 densely labeled rods and blue cones but not green/red cones. MAb 5C6.47 and F4C1 labeled rods and both blue and green/red cones. It appears that, in the baboon retina, different SAg molecules are present in the blue and green/red cones. Whereas the blue cone SAg shares common antigenic determinants with rods, both in the amino and carboxy terminals, the green/red cone SAg contains different antigenic determinants at the carboxy half of the molecule.

Amino Acid Sequence

Effect of dietary polyunsaturated fatty acid concentration on performance, fat deposition, and carcass fatty acid composition in broiler chickens.

The effect of dietary polyunsaturated fatty acid (PUFA) concentration on body fat deposition and composition in broiler chickens was studied. Twenty-day-old birds were fed five isocaloric diets supplemented with different combinations of tallow and vegetable oils. Contents of abdominal adipose tissue (AAT) as well as body fat were determined at 40 days of age. A significant linear effect was observed between dietary PUFA and feed utilization. Fatty acid (FA) profiles in AAT and total body fat were correlated to dietary PUFA content, with the main effect of higher dietary PUFA being a reduction in monoenoic FA (C16:1 and C18:1) and an increase in C18:2. The effect of dietary PUFA on the saturated FA (C16:0 and C18:0) was small and not statistically significant. Increased dietary PUFA modified FA composition such that C18:2, rather than C18:1 became the dominant FA in AAT. In that respect, greater changes were observed in FA composition of AAT, as compared with that on the whole carcass. The deposition of saturated and monoenoic FA in the whole carcass during the experimental period was related to dietary PUFA content in a quadratic manner. However, deposition of C18:2 and C18:3 was not affected by intake and their utilization (deposition:intake ratio) was reduced in a manner parallel to their dietary levels.

Adipose Tissue

Arrestin mRNA expression, biosynthesis, and localization in degenerating photoreceptors of mutant rds mice retinas.

The retinal photoreceptors of the mutant rds mouse are unable to form normal outer segments. Eventually the abnormal cells die in the months following birth. The genetic defect in the rds mouse was recently localized to the peripherin gene that encodes a protein in the outer segment disc margin. Although this mutation may explain the morphogenetic defect, i.e., the failure to form outer segments, the reason for subsequent cell death is not clear. Previously, we demonstrated that the capability to synthesize opsin, an outer segment integral membrane protein, is not compromised by the morphogenetic defect although the opsin steady-state content is considerably reduced, since it is not incorporated into an organized outer segment. We have now studied arrestin, a cytoplasmic protein that is part of the phototransduction cascade and appears to shuttle between the inner and outer segment during the light/dark cycle. Since rds mice lack outer segments, it was of interest to determine the effects of the photoreceptor abnormality on arrestin gene expression. Arrestin mRNA levels and protein synthetic rates were high in young rds retinas. When corrected for cell loss, the steady-state arrestin content per cell in the rds retina was comparable to normal. However, in the absence of an outer segment, the total amount of arrestin is concentrated in the remaining inner segment. Consequently, a relatively high level of arrestin is present in the rds inner segment throughout the light/dark cycle. We suggest that the morphogenetic defect indirectly precipitates secondary effects such as the persistent presence of high levels of arrestin or other soluble proteins in the abnormal photoreceptor inner segment, nucleus, and synaptic terminal. This condition, if toxic to the cells, may compromise photoreceptor viability in the rds retina.

Animals

The effect of environmental photoperiodicity on indole rhythms and locomotor activity in sighted and eye covered chickens.

Direct (via the skull) and indirect (via the eyes) light on the rate of adaptation of circadian rhythms of pineal, retina and serum indoleamines and of locomotor activity was examined by observing photoperiod reversal in eye covered and normally sighted chickens. Eye covering did not affect indoleamine levels nor locomotor activity on the regular light:dark (L:D) cycle. However, following photoperiod reversal, the eye covered chickens showed slower rates of adaptation of retinal melatonin and locomotor activity to the new L:D cycle than did the normal sighted chickens. Pineal and serum indole levels were unaffected by eye covering. Our results in birds indicate that 1) light to the eye has a role in governing retinal melatonin and locomotor activity, 2) the pineal is directly photosensitive, and 3) the endogenous rhythm of pineal melatonin may play a role in the entrainment of the locomotor rhythm in the chicken.

Adaptation, Physiological

Insulin-tumour interrelationships in thymoma bearing mice. Effects of dietary glucose and fructose.

Control (C) or Thymoma (T) implanted male C57BL/6J mice received a basal diet containing 16.5% glucose (G) or fructose (F). Compared to the C-G group, the C-F mice consumed more food and less water, and gained more weight. The blood glucose, insulin and triglyceride levels were higher in the C-F than in the C-G mice. Thymoma implantation into the right flank caused a transient decrease in body weight followed by a steady increase due to tumour growth. Tumours were detected earlier and tumour size was greater in the T-F group than in the T-G mice. Tumour chemical composition was similar in both groups. Blood analysis showed that the T mice had lower glucose and higher insulin and triglyceride levels than the C group. Carcasses from the T groups contained more water and ash and less fat than their C counterparts, but the type of sugar did not affect the body composition of the C or T groups. The results suggest that dietary fructose may enhance the growth of tumour via its hyperinsulinaemic action.

Animals

Growth and development of the digestive organs and some enzymes in broiler chicks after hatching.

1. Body weight and the weight of the digestive organs and activities of some digestive enzymes were determined from hatching to 23 d of age. 2. Relative daily growth rate peaked at 11 d of age (22% gain/d) and then decreased gradually. 3. The vitelline residue was decreased rapidly from 4.6 g at hatching to negligible values from 4 d of age. 4. Maximal allometric growth of the pancreas and small intestine was 4-fold and that of liver 2-fold greater than that of the body. 5. Activities (units/kg body weight) of the digestive enzymes measured in the pancreas and intestinal contents increased with age. In the pancreas maximal values were attained on day 8 for amylase and lipase and 11 for trypsin and chymotrypsin. In the small intestine maxima were attained on day 4 for lipase, 11 for trypsin and chymotrypsin and 17 for amylase. 6. The development of secretion of digestive enzymes in the post-hatched chick could be a limiting factor in digestion and subsequently in food intake and growth.

Amylases

Serum melatonin levels in schizophrenic and schizoaffective hospitalized patients.

Conflicting results on changes of the diurnal melatonin rhythms of patients with affective disorders have been reported in the literature. The heterogeneous data may derive from the great discrepancy in the diagnostic criteria of different authors. A study of 12 schizoaffective and chronic schizophrenic psychotic patients found a constant pattern of an obliterated nocturnal melatonin rise only in the latter group. The presence or absence of the nocturnal melatonin rise was determined in drug-free hospitalized patients and remained unchanged despite 2 months of drug treatment including large doses of neuroleptics. This finding, when confirmed in a larger number of patients, could possibly serve as a marker for the type of mental disorder, drug to be applied and response expected.

Adult

Toxic effects of cisplatin alone and in combination with gentamicin in stria vascularis of guinea pigs.

The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs. The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem-evoked response audiometry. The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low-dose cisplatin alone or in combination with gentamicin. Bilateral deafness resulted from high-dose cisplatin combined with gentamicin. The combined treatment produced prominent structural damage in the stria vascularis. The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin.

Animals

Opsin gene expression during early and late phases of retinal degeneration in rds mice.

Opsin mRNA levels, opsin synthetic rates and localization of opsin were studied throughout the photoreceptor's life span in the rds mice. Mutant mice 11 days to 11 months old were investigated. Opsin mRNA levels were studied by means of northern blot analysis. Opsin synthesis was measured by incorporation of [35S]methionine into newly synthesized opsin in vitro. Distribution of opsin in the retina was determined by immunoelectron microscopy. Opsin mRNA was detected in young as well as old retinas, and opsin synthesis could be detected at early phases of degeneration but not in late phases. The absence of opsin synthesis in older rds mice might be due to translational down-regulation or some other defect in the capacity to synthesize opsin. In young mice, opsin was detected in the subretinal space in opsin-laden vesicular membranes: such membranes were absent from retinas of older mice. This disappearance parallels the cessation of opsin synthesis and the consequent failure to deliver opsin to the subretinal space in retinas from older mice. Immunochemical analysis revealed the presence of small amounts of opsin in all retinas up to 11 months of age. Immunoelectron microscopy localized the residual opsin, mostly to the plasma membrane which envelops the nuclei and synaptic terminals. These opsin molecules might be a consequence of very low levels of opsin synthesis, too low to be detected by our assays, or may have been synthesized at an earlier age and retained in the plasma membrane of the old mutant photoreceptors.

Animals

Insulin-tumour interrelationship in EL4 lymphoma or thymoma-bearing mice. I. Alloxan-diabetic or non-diabetic mice.

A study has been carried out in which a comparison was made between EL4 lymphoma (assumed to be an insulin-producing secreting tumour) and thymoma (an insulin-dependent tumour). Tumour development and incidence, 3H-thymidine incorporation and insulin content in tumours, the host's food intake, blood insulin, glucose and cholesterol were determined in non-diabetic and alloxan-diabetic mice. Whereas no significant differences were observed between the diabetic and non-diabetic EL4 tumour-bearing mice, the diabetic, thymoma tumour-bearing mice showed reduced tumour growth and lower tumour incidence as compared with their non-diabetic counterparts. Insulin administration to diabetic tumour bearing mice, enhanced 3H-thymidine incorporation in the thymoma tumour cells only, and the insulin content of the EL4 tumours was found to be higher than that of the thymoma tumours. Rapid diabetes remission was observed in the diabetic, EL4 tumour-bearing mice as compared with the thymoma tumour-bearing mice.

Animals

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