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Biomedical subjects

R Newcomb

Publications and source records attributed to R Newcomb.

At least 37 records · Page 2Linked to original sources
PubMed1993

Profiles of extracellular amino acid changes in focal cerebral ischaemia: effects of mild hypothermia.

Mild hypothermia has been recently proposed as a therapeutic approach for ameliorating ischaemic cerebral damage. The protective potential of mild hypothermia, however, may be dependent on its ability to reduce the efflux of potentially excitotoxic amino acids and the severity of ischaemia. In this study, we examined the effects of mild brain hypothermia (33 degrees C) in a rabbit model of permanent focal ischaemia. In vivo microdialysis was used to measure extracellular amino acids in central and peripheral regions of the ischaemic cortex. In normothermic ischaemia (n = 7), glutamate, alanine, taurine, and phosphoethanolamine increased above baseline levels by about 2 h post-ischaemia. Mild hypothermia (n = 7) reduced glutamate efflux only in the central regions and increased alanine efflux in the peripheral regions of ischaemia. There were no significant differences in other amino acid levels between the two temperature groups. Haematoxylin-eosin histology did not demonstrate hypothermic protection in the ischaemic hemisphere. The lack of neuroprotection in this study may correspond with the sustained release of glutamate in the peripheral regions of ischaemia even with lowered brain temperature. These results suggest that hypothermic reduction of excitotoxic perturbations may be more important in the ischaemic periphery than the core.

Amino Acids↗
PubMed1990

Subcellular fractionation of prohormone processing products in the bag cell neurons.

Multiple biologically active peptides arising from a common prohormone are sorted into distinct classes of dense core vesicles within the bag cell neurons of Aplysia californica. In this study, pulse-chase analysis, combined with subcellular fractionation on Percoll gradients, are used to define the location of the prohormone processing events within the secretory pathway. Initial cleavage of the prohormone occurs in a light cellular compartment associated with the Golgi apparatus. The amino-terminal processing intermediate then accumulates in a denser compartment containing small dense cores enclosed in membranous sacs, as well as larger immature vesicles. After 4 h, amino-terminal products are found primarily in a much denser compartment which consists of large and small dense core vesicles. These large and small vesicles can be separated from each other using Percoll gradient centrifugation and are found to be enriched in amino- and carboxy-terminal products, respectively. Lastly, membrane association experiments suggest differential binding to membranes, or integral membrane proteins, as a possible mechanism for sorting of amino- and carboxy-terminal products.

Animals↗
PubMed1988

Multiple neuropeptides derived from a common precursor are differentially packaged and transported.

The ELH prohormone is proteolytically processed into at least nine peptides which govern egg-laying behavior in Aplysia. Quantitative immunocytochemistry demonstrates that peptides derived from the prohormone are packaged into distinct vesicle classes. Further experiments suggest the segregation occurs via a rapid initial proteolytic cleavage of the prohormone followed by sorting at the trans Golgi. Egg-laying hormone (ELH) immunoreactivity is localized to the cell body and processes, while bag cell peptide (BCP) immunoreactivity is greater in the cell body. Steady state levels of the amino-terminal set of peptides including the BCPs are 3- to 8-fold lower than the carboxy-terminal cleavage products, such as ELH. Thus, intracellular packaging and routing of the peptides cleaved from a single prohormone regulate their localization and levels in these neurons.

Animals↗
PubMed1988

Processing of the egg-laying hormone (ELH) precursor in the bag cell neurons of Aplysia.

Egg laying in Aplysia is mediated by a battery of neuropeptides released from the bag cell neurons. Predominant intermediates in the proteolytic processing of the Aplysia egg-laying hormone neuropeptide precursor were characterized using biochemical and immunological techniques. Following removal of the signal peptide, a rapid cleavage at the tetrabasic sequence Arg-Arg-Lys-Arg separates the amino and carboxyl regions of the prohormone. Processing of the carboxyl-terminal portion of the precursor then proceeds rapidly via two further cleavages at dibasic residues, resulting in a well defined product mixture within 4 h of chase. By contrast, processing of the amino-terminal side of the molecule proceeds only partially to completion after 20 h of chase and a well defined set of intermediates is not observed. Molecular genetic, physiological, and behavioral studies in conjunction with the biochemical investigations presented here are defining the information flow which governs the egg-laying behavior of Aplysia.

Amino Acid Sequence↗
PubMed1987

Proteolytic processing of the Aplysia egg-laying hormone and R3-14 neuropeptide precursors.

A number of animal behaviors are influenced by the actions of neuropeptides that arise from the processing of complex protein precursors. In this report we investigate the proteolytic processing of neuropeptide precursors expressed in the Aplysia californica bag cells, which govern egg-laying, and neurons R3-14, which mediate aspects of cardiac output. Peptides were purified by fractionation on 2 high-pressure liquid chromatography systems followed by determination of amino acid compositions. Most of these compositions are indicative of processing products derived from the egg-laying hormone (ELH) and R3-14 precursors by cleavage at basic residues. We characterized 9 peptides that arise from the ELH precursor by cleavage of the signal sequence, as well as 7 out of 8 dibasic residues and at least 1 single Arg residue. The peptides range in size from 5 to about 60 amino acids. The R3-14 neuropeptide precursor is cleaved at 2 internal dibasic residues in addition to the signal sequence, resulting in 3 peptides. Shortened forms of several peptides probably result from amino- and carboxy-terminal peptidase action. It is likely that the complex mixtures of neuropeptides arising from these single protein precursors are co-secreted.

Amino Acid Sequence↗
PubMed1985

Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist.

In 9 young subjects with mild asthma, we investigated the possibility that chronic daily administration of an inhaled muscarinic antagonist (ipratropium bromide) might increase the response of muscarinic receptors in airway smooth muscle to agonist stimulation caused by receptor upregulation. Subjects inhaled 60 micrograms of ipratropium 4 times daily for 3 wk. Methacholine bronchoprovocation (with or without acute pretreatment with ipratropium) was performed before (control period) and during 3 wk of daily ipratropium therapy (medication period). At the end of the medication period, subjects returned at 12, 24, 48, and 72 h after the last dose of ipratropium (withdrawal period) to determine the provocative concentration of methacholine producing a 20% decrease in FEV1 (PC20). During the medication period, there was no significant diminution of the acute bronchodilator response to ipratropium or of the protective effect of ipratropium against methacholine-induced bronchospasm when compared with the control period. During the withdrawal period, mean in PC20 was significantly less (increased airway responsiveness) at 24 h than during the control period (p less than 0.01) and returned to the control period value within 48 to 72 h. We conclude that daily administration of ipratropium to mildly asthmatic subjects for 3 wk does not produce tolerance to either the bronchodilator effect of ipratropium or to its inhibition of methacholine-induced bronchospasm but does induce transient supersensitivity of airway cholinergic receptors to muscarinic stimulation.

Adult↗
PubMed1984

Subjective response to cigarette smoking following airway anesthetization.

Subjective response to cigarette smoking was assessed after partial blockade of upper and lower airway sensations by the topical application of lidocaine. Pack-a-day smokers were given one cigarette after each of four conditions: (1) mouth anesthesia, obtained by rinsing the mouth with 2% lidocaine; (2) mouth and pharyngeal anesthesia, in which subjects rinsed their mouths and gargled with 2% lidocaine; (3) upper and lower airway anesthesia, in which subjects rinsed their mouths and gargled with a 2% lidocaine solution, and inhaled a mist containing 4% lidocaine (60 breaths); and (4) saline control, in which all solutions (rinse, gargle and inhalation) were saline. A significant linear decline in cigarette craving occurred with increasing anesthesia, and desirability ratings over the first several puffs were also reduced by anesthesia. These results suggest that sensory cues are important factors in smoking satisfaction, and their influence can be analyzed with the use of local anesthetics.

Adult↗
PubMed1980

Non-surgical transfer of bovine eggs: investigation of some factors affecting embryo survival.

In an investigation on the effect of position of deposition of the egg within the uterus, surgical transfer of single eggs to the tip of the horn resulted in a significantly higher pregnancy rate than transfer to the base. To determine embryo survival at differing times after transfer single eggs were transferred non-surgically to the base of the uterine horn. The highest pregnancy rate occurred in a group of heifers slaughtered 16 to 17 days after oestrus followed by heifers slaughtered on days 24 to 26. The lowest pregnancy rate occurred in a group where pregnancy diagnosis was on day 42 by rectal palpation. The pregnancy rates of the highest and the lowest groups were significantly different. The pregnancy rate was increased in a group of heifers which were treated with human chorionic gonadotrophin from day 13 to 24 and palpated per rectum on day 42 to determine pregnancy. The presence or absence of penicillin and streptomycin in the medium and of passing differing volumes into the uterus after non-surgical transfer of single eggs using a glass pipette had no effect on pregnancy rate and there was no significant difference in pregnancy rate and there was no significant difference in pregnancy rate between the groups using different volumes of transfer media. The position of the egg within the uterine lumen after transfer contributes to the reduced pregnancy rate achieved after nonsurgical transfer when compared with the surgical method. The greatest proportion of embryonic death after non-surgical transfer occurs after day 17 and there is some evidence that human chorionic gonadotrophin treatment can improve embryo survival. The use of comparatively small volumes of medium to eject the egg into the uterus may be preferable to achieve maximum pregnancy rates.

Animals↗
PubMed1980

Investigation of factors affecting superovulation and non-surgical embryo recovery from lactating British Friesian cows.

Factors affecting the success of superovulation and embryo recovery were examined in two groups of 16 lactating Friesian cows which were superovulated twice at five to six week intervals in a 24 factorial experiment. There were no differences in ovarian response using pregnant mare serum gonadotrophin or human menopausal gonadotrophin. A total of 3000 iu human chorionic gonadotrophin given intravenously at the first insemination significantly (P less than 0.01) affected embryo recovery rate. A single intramuscular treatment with releasing hormone had no effect. A lower proportion of unfertilised eggs was recovered after insemination with semen from a bull of above average fertility than with semen from a bull of below average fertility (P less than 0.03). Insemination routines affected both the proportion of unfertilised eggs (P = 0.06) and embryo recovery rate (P less than 0.03). Antibacterial treatment given when insemination was carried out after the end of oestrus did not affect success. The three-way circulation system of embryo and fluid recovery was significantly (P less than 0.01) more efficient than the two-way to-and-fro system at day 7 after oestrus, but this appeared to alter at day 8 in favour of the two-way system. A more efficient fluid recovery was achieved with the three-way system (P less than 0.001). Catheter location, catheter size, interval from calving and condition of the donor did not affect success, but embryo recovery rate from younger cows (less than 4.5 years) was lower than from older animals (4.5 to 7 years) (P less than 0.05).

Animals↗
PubMed1980

Fetal survival rate after the surgical transfer of two bovine embryos.

Single embryos were bilaterally transferred on Day 7 to the tip of the uterine horn ipsilateral to the corpus luteum and to the tip of the opposite horn, to the tip and contralateral base, base and tip and base and base (20 recipients/group). Ten of the recipients in each group were treated with 1000 i.u. hCG daily from Days 13 to 35 after oestrus. At 42 days, pregnancy rate (N.S.) and fetal survival rate (P < 0.05) were greater when an embryo had been transferred to the tip rather than to the base of the ipsilateral horn, but the twin pregnancy rate was not improved. Treatment with hCG had no effect on these rates but the corpora lutea of treated animals were heavier (P < 0.02). Unilateral transfers of 2 embryos were made both to the tip of the ipsilateral uterine horn or one to the tip and one to the base (20 recipients/group). The pregnancy rate, fetal survival and twin pregnancy rate in each group were the same, but in the latter one of the embryos had migrated to the other horn in 5/9 animals with twin fetuses. The location of fetuses did not influence their rate of development as determined by fetal measurements. It is concluded that the tip of the ipsilateral uterine horn is the optimal site for fetal survival and that to ensure a high twin fetal survival one embryo must be in this site.

Animals↗
PubMed1980

Prevalence of asteroid bodies in a VA optometry clinic.

One thousand, five hundred and fifty-nine consecutive optometry clinic records at the Birmingham Veterans Center (BVAMC) were reviewed in an attempt to determine the prevalence of asteroid bodies in the vitreous. A review of the pertinent literature was conducted and a higher prevalence was found in our population than that reported in the literature. The difference was statistically significant at the 0.05 level.

Adolescent↗
PubMed1979

Surgical and non-surgical transfer of bovine embryos.

Methods of transferring one bovine embryo to the ipsilateral uterine horn have been compared. In heifers mid-ventral surgical laparotomy under general anaesthesia (n=22) was compared with flank surgery with paravertebral anaesthesia (n=21). Pregnancy rate was higher with a midventral approach (P less than 0.05) (77.3 per cent of 42.9 per cent respectively). In heifers mid-ventral surgery (n=36) was compared with two methods of non-surgical transfer either using the Cassou insemination gun (n=36) or a modification of it (n=39) with embryos collected on days 7, 8 or 10 after oestrus. There were no differences in pregnancy rate between methods or different ages of embryos (methods: 55.6, 55.6, 43.6 per cent respectively; Day: 48.8, 55.8, 48.1 per cent respectively) but the condition score of recipients affected success (P less than 0.05). Of 10 cows which each received an embryo using the modified Cassou gun eight became pregnant.

Anesthesia↗
PubMed1979

Ovulation rate and egg recovery in cattle treated repeatedly with pregnant mare serum gonadotrophin and prostaglandin.

Fourteen heifers were superovulated five to 10 times using pregnant mare serum gonadotrophin (PMSG) and prostaglandin in a standardised regime which resulted in a mean interval of 42.1 days (SEM +/- 0.97) between treatments. There was a significant (P less than 0.02) fall in the mean ovulation rate at the second treatment when compared with the first but no significant difference between mean ovulation rate at the second and subsequent treatments. No significant difference between treatments in mean egg recovery rate or in the percentage of normal eggs recovered was demonstrated. Four heifers treated 10 times continued to respond with multiple ovulations on most occasions. At the end of the experiment 13 of the 14 heifers were inseminated and 12 conceived, requiring a mean of 1.67 services per pregnancy.

Animals↗
PubMed1979

Influence of dose, repeated treatment and batch of hormone on ovarian response in heifers treated with PMSG.

The effect of two dose levels (1000 and 2000 i.u.) of three different commercially available batches of PMSG on the ovarian response (ovulations and follicles greater than 10 mn) of 42 heifers was examined in a randomized incomplete block experiment. Each animal was subjected to two consecutive but different treatments. A significant effect of dose was observed and there were fewer ovulations, but no reduction in the number of follicles, after the second PMSG treatment. There was no evidence that the ovarian response was affected by the PMSG batch used.

Animals↗
PubMed1979

Embryo survival in heifers after transfer of an egg to the uterine horn contralateral to the corpus luteum and the effect of treatments with progesterone or hCG on pregnancy rates.

Day 7 eggs (oestrus = Day 0) were surgically transferred singly to the uterine horn contralateral to the CL and heifers were either slaughtered on Day 24-26 (Group 1) or palpated per rectum on Day 42 (Group 2) to determine the presence of a developing conceptus and a maintained corpus luteum. There was a fall in pregnancy rate of the control heifers in Groups 1a (6/10) and 2a (2/10) (P = 0.085). Pregnancy rate was unaffected by progesterone treatments from Day 13 to the day before slaughter in Group 1b (8/10), or to Day 23 in Group 2b (2/10). Two of the conceptuses recovered in Group 1b were developing in the presence of regressed corpora lutea. There was, however, an increase in pregnancy rate in Group 2d (6/10) compared with Group 2a (2/10) when heifers were treated with hCG from Days 13 to 35 (P = 0.085). The results indicated that embryonic death is occurring after Day 24 and suggest that a change in the nature of the embryonic signal may be occurring at this time.

Animals↗
PubMed1978

The Sacrewell project: an on farm demonstration of the potential of egg transfer.

A surgical demonstration of the potential use of egg transfer for converting a herd of cattle from one breed to another (Jersey to Friesian) was undertaken on farm. Friesian donors were non-lactating but 50 per cent failed to respond adequately (greater than 3 ovulations) to treatment with PMSG (1500 to 3000 iu). Heifers yielded more ovulations and eggs than cows, but recovery rate was higher from cows (80 per cent cf 60 per cent). Fertilised eggs were recovered from old (13 years) cows, some of which had ceased to breed normally. Pregnancy rate after transfer of these eggs was normal. Purebred Friesian calves out of Jersey recipients were Friesian weight (male, 44.8 kg; female, 37.4 kg) and contrary to experience with crossbreds caused severe dystocia problems. Severity of dystocia was related to birth weight and sex of calf.

Animals↗