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Biomedical subjects

J D Newman

Publications and source records attributed to J D Newman.

At least 55 records · Page 3Linked to original sources
PubMed1986

Benactyzine increases alarm call rates in the squirrel monkey.

The effects of benactyzine (0.01-3.0 mg/kg) were examined on the frequency of alarm calls of squirrel monkeys in a laboratory setting. Under baseline conditions, few calls occurred, and neither saline nor a low dose (0.01 mg/kg) of benactyzine increased calling. Higher doses (0.03-3.0 mg/kg) of benactyzine significantly increased call rate (to 1-2 calls per s) in a dose-dependent manner. The rate-increasing effect of benactyzine on alarm calls appears to be related to a central antimuscarinic effect, as it could be partially blocked by 0.01 mg/kg physostigmine, completely blocked by 0.1 mg/kg physostigmine, but was not blocked at all by 0.1 mg/kg neostigmine. Neither of these cholinomimetics increased call rates when given alone. These findings show that benactyzine can increase alarm call rates in squirrel monkeys under defined laboratory conditions, and may serve as a useful pharmacological probe to study neurochemical mechanisms mediating the production of this type of vocalization. In the squirrel monkey, one such mechanism apparently involves a cholinergic substrate.

Animals↗
PubMed1986

An atypical insulin receptor with high affinity for insulin-like growth factors copurified with placental insulin receptors.

Insulin receptors purified from human placenta by sequential affinity chromatography on wheat germ lectin-agarose and insulin coupled to 1,1'-carbonyldiimidazole-activated agarose (CDI-agarose) retained full binding activity but bound a greater than predicted amount of 125I-labeled insulin-like growth factor I (IGF-I). IGF-I and multiplication-stimulating activity (MSA; the rat homologue of IGF-II) were equipotent in displacing either 125I-labeled IGF-I or 125I-labeled MSA from the purified receptors; insulin was 5-15 times more potent. Competitive binding studies indicated that this IGF binding activity could not be explained by cross-reaction with classical insulin receptors or by coelution of IGF-I or IGF-II receptors. Instead, it was due to a minor population of discrete atypical insulin receptors (6-18% total insulin receptors) with moderately high affinity (Kd = 2-4 X 10(-9) M) for IGF-I and MSA. These receptors were not an artifact of insulin-CDI-agarose chromatography, since they were present in wheat germ lectin-agarose-purified preparations and could also be purified from insulin-succinyldiaminodipropylamino-agarose. Affinity labeling with 125I-labeled MSA revealed that these atypical receptors had the same binding subunit (Mr 140,000) as classical insulin and IGF-I receptors. They displayed intermediate reactivity with polyclonal and monoclonal antibodies to the insulin and IGF-I receptors. It is therefore likely that insulin receptors purified by immunoadsorption would also contain atypical insulin receptors. The finding of more than one type of insulin receptor might relate to the slight variations in the cDNA nucleotide sequences and the multiple mRNA species reported for the insulin receptor [Ebina, Y., Ellis, L., Jarnagin, K., Edery, M., Graf, L., Clauser, E., Ou, J.-H., Masiarz, F., Kan, Y. W., Goldfine, I. D., Roth, R. A. & Rutter, W. J. (1985) Cell 40, 747-758].

Affinity Labels↗
PubMed1985

Homogeneous bivalent insulin receptor: purification using insulin coupled to 1,1'-carbonyldiimidazole activated-agarose.

A novel affinity gel, consisting of insulin coupled to 1,1'-carbonyldiimidazole-activated agarose (CDI-agarose), was used to purify insulin receptors from human placenta to homogeneity. This affinity gel is reproducibly prepared and is reported to have a number of advantages over the standard cyanogen bromide activated supports, such as ease and simplicity of coupling and minimal ligand leakage and non-specific binding. Insulin receptors in Triton X-100-solubilized microsomal membranes were purified 2,000-fold by sequential affinity chromatography on wheat germ lectin-agarose and insulin-CDI-activated agarose. They have one of the highest specific insulin-binding capacities (6 nmol/mg protein) reported and can be calculated to have a binding valence of two on the basis that the molecular weight of the oligomeric receptor is 300-350,000.

Chromatography, Affinity↗
PubMed1985

A simple, rapid method for the preparation of plasma membranes from liver.

A method for the preparation of plasma membrane fractions from liver is described. A crude membrane fraction, substantially free of mitochondria and nuclei, is collected by centrifuging liver homogenate over a pad of 1.45 M sucrose. This interfacial fraction is further purified by isopycnic centrifugation in a self-generating density gradient of Percoll. All steps are carried out in buffered, isotonic solutions. Membrane prepared in this way is enriched in marker enzymes associated with plasma membrane, while marker enzymes for cellular components other than plasma membrane are diminished. Contamination by mitochondrial components is very much less than for membrane prepared from hypotonic liver homogenates. The membrane fraction also shows specific insulin binding, and negligible degradation of insulin. The procedure is rapid, uses simple equipment, and can be completed within 3 h.

Adenylyl Cyclases↗
PubMed1985

Multiple forms of synthase D phosphatase and phosphorylase a phosphatase in liver and regulatory effects of metabolites on their activities.

The smooth endoplasmic reticulum (ER) and cytosol fractions of liver homogenates exhibit phosphoprotein phosphatase activity towards glycogen synthase D and phosphorylase a. The following observations suggest that liver contains multiple forms of these phosphatases. Synthase phosphatase activity in either fraction was more readily inactivated by heating than phosphorylase phosphatase activity. Both synthase phosphatase and phosphorylase phosphatase activities in smooth ER were non-competitively inhibited by Mg2+, but were activated by this ion in the cytosol. Synthase phosphatase activities in cytosol and smooth ER were stimulated by a number of sugar phosphates, particularly glucose-1-phosphate, galactose-6-phosphate and fructose-6-phosphate. Erythrose-4-phosphate stimulated synthase phosphatase activity in the cytosol, but inhibited the microsomal enzyme. Phosphorylase phosphatase activities in either fraction were inhibited by most sugar phosphates. Adenosine mono-, di- and tri-phosphates inhibited phosphatase activities in both fractions. Low concentrations of AMP and ADP inhibited phosphorylase phosphatase activities to a greater extent than synthase phosphatase activities. Chromatography of the smooth ER fraction on DEAE-cellulose resulted in the separation of synthase phosphatase from phosphorylase phosphatase, as soluble proteins. The elution profile for the microsomal phosphatase was different from that for the cytosol enzymes. It is concluded that: both synthase phosphatase and phosphorylase phosphatase in liver have at least two isoenzyme forms; synthase phosphatase and phosphorylase phosphatase are separate enzymes; the different behaviour of microsomal and cytosol phosphatases towards divalent cations and sugar phosphates provides a potential mechanism for the differential regulation of these activities in liver.

Adenine Nucleotides↗
PubMed1985

Assay of insulin mediator activity with soluble pyruvate dehydrogenase phosphatase.

The putative mediator of intracellular insulin action has been assayed quantitatively by its ability to increase the activity of solubilized pyruvate dehydrogenase (PDH) phosphatase. Conversion of soluble beef heart PDH b to PDH a by PDH phosphatase increased when incubation was carried out in the presence of a crude insulin mediator fraction generated from insulin-treated adipose tissue or liver plasma membranes. Increased PDH phosphatase activity was proportional to the concentration of added insulin mediator. Mediator generation was rapid, with a half-time of approximately 45 sec and was insulin dose dependent. Half-maximal mediator activity was produced at 0.3 nM added insulin, with maximal activity being generated at approximately 3 nM insulin. Mediator activity was significantly decreased at 7 nM insulin, but was increased 4-fold after ethanol extraction. Mediator behaved as an activator of PDH phosphatase, apparently by abolishing the inhibitory effects of ATP on phosphatase activity, but had no effect on PDH kinase activity. The assay of insulin mediator activity described here can be carried out under standardized conditions, in contrast to previously described methods using particulate mitochondrial preparations.

Adenosine Triphosphate↗
PubMed1983

Structural variability in primate vocalizations and its functional significance: an analysis of squirrel monkey chuck calls.

Sound spectrograms of vocalizations recorded from 'Gothic arch' squirrel monkeys were examined for shared structural characteristics. A rapidly descending element, the 'mast', was found to be diagnostic for a group of variable but structurally similar vocalizations called chucks. In addition to the mast, a variable FM element ('flag') and a terminal noisy element ('cackle') formed a basic 3-element structural unit. A review of functional studies suggests that this flag-mast-cackle structure is used by the squirrel monkey and a variety of other New World primates in circumstances involving close social contact.

Animals↗
PubMed1983

Effects of reproductive state on vocalizations in squirrel monkeys (Saimiri sciureus).

Vocalizations and behavior of a group of 6 squirrel monkeys, 2 males and 4 females, were recorded during the nonbreeding and breeding seasons. Behavioral and physical criteria were used to determine the presence of estrus. During the breeding season the types of vocalizations uttered by estrous females changed, and the adult male increased his rate of vocalizing. Err vocalizations by estrous females were associated with increased following and initiation of affiliative behavior with the adult male, and may have functioned to facilitate these interactions. Errs appeared to be related to changes in female reproductive state rather than to the behavior of others. The adult male increased vocalizations associated with sexual and aggressive behavior (squeals and cackles), primarily in response to the estrous females' persistent initiation of interactions with him. We concluded that certain vocalizations in Saimiri reflected changes in the reproductive state of males and females, and functioned to mediate changes in social bonding during the breeding season.

Animals↗
PubMed1982

Effects of tegmental lesions on the isolation call of squirrel monkeys.

The present study is concerned with identifying brain mechanisms underlying a basic mammalian vocalization known as the isolation call. The call serves to reestablish contact of separated individuals. Adult squirrel monkeys were used as experimental subjects because the isolation call in these animals has been shown to be stable, well-defined, and readily elicited under experimental conditions. Bilateral, symmetrical electrocoagulations in certain parts of the tegmentum and core gray matter of the thalamus and midbrain variously altered the character and production of isolation calls, but had no apparent effect on other vocalizations. In respective cases the changes were characterized by: (1) reduction in number of calls; (2) calls with abnormal structure; and (3) calls of infantile character. As opposed to earlier investigations on mammals, the present study has shown that damage to certain brain structures may not only affect the production of a vocalization but also its physical characteristics.

Animals↗
PubMed1982

Statistical discrimination among vocalizations of individual squirrel monkeys (Saimiri sciureus).

Discriminant analysis was used to distinguish statistically between the chuck vocalizations of individual squirrel monkeys. A unique combination of values of six structural parameters characterized the chucks of each of 5 individuals, permitting reliable identification of sources of chuck vocalizations on the basis of chuck structures alone. Certain parameters were found to be nearly invariant within individual monkeys, while others were quite variable within and between individuals. We propose that this technique be used in retrospective classification of vocalizations by source, when observational identification of the sources of all vocalizations in a rapid sequence is not possible.

Animals↗
PubMed1980

Anatomical and physiological evidence for a relationship between the 'cingular' vocalization area and the auditory cortex in the squirrel monkey.

With the aid of the autoradiographic tracing technique the projections from cortical limbic vocalization areas to the auditory cortex in the superior temporal gyrus were studied in the squirrel monkey. The vocalization areas were identified by exploring the anterior limbic cortex with moving electrodes until a site was found where electrical stimulation yielded vocalization. Projections from the region around the cingulate sulcus and supracallosal anterior cingulate gyrus have their terminal fields in the lower part of the superior temporal gyrus (STG) and upper bank of the superior temporal sulcus. Injections just in front of the genu of the corpus callosum and in the subcallosal gyrus and gyrus rectus lead to terminal fields in the middle part of STG. No projections were found in the upper part of STG, i.e. the primary auditory cortex. To test the functional properties of this pathway, action potentials of single neurons in the auditory cortex were recorded during electrical stimulation of the cingular vocalization area. From a total of 135 STG neurons, an effect on spontaneous activity was seen in 27 cells. All except one of these neurons also reacted to acoustic stimuli. In most cases, stimulation of the cingular area caused a decrease in the discharge rate of the STG neurons. In 4 neurons, stimulation of the vocalization area had an influence on the acoustic reactivity of the STG neurons. The results provide evidence that during phonation the 'cingular' vocalization area exerts a predominantly inhibitory influence on auditory cortex neurons. This effect probably is mediated via the extreme capsule. Its possible function is discussed.

Animals↗
PubMed1980

Neural processing of vocalizations and artificial stimuli in the medial geniculate body of squirrel monkey.

The responses of 256 single neurons in the medial geniculate body of awake squirrel monkeys have been examined with a variety of acoustic stimuli. Both traditional artificial sounds and tape-recorded tokens of species-specific vocalizations were employed, and one goal of the study was the comparison along a number of response parameters of these two classes. Unit responses to the first group (clicks, tone bursts and noise bursts) revealed a level of responsivity approaching 100% in the principal nucleus. Responses to tone and noise were sustained in about half the cells, and characteristic frequencies could be identified in 81%. Responses to vocal stimuli were also very prevalent, approaching 100% in this sample. A comparison of absolute thresholds, response vigor, rate-level functions, binaural interactions, and spectral composition of effective stimuli confirmed that MGB cells process vocal stimuli and artificial stimuli in similar ways. Selectivity of MGB cells to vocal stimuli was quite low, suggesting that processing of communication sounds in MGB is relatively simple and preliminary when compared to auditory cortex.

Acoustic Stimulation↗
PubMed1978

On the activities of glycogen phosphorylase and glycogen synthase in the liver of the rat.

A procedure was developed for determination of glycogen synthase and phosphorylase activities in liver after various in vivo physiological treatments. Liver samples were obtained from anaesthetised rats by freeze-clamping in situ. Other procedures were shown to stimulate the activity of phosphorylase and depress the activity of glycogen in the liver. The direction of glycogen metabolism appears to be regulated by the relative proportions of the two enzymes, as shown by a strong positive correlation between total activities and active forms of phosphorylase and synthase. The enzyme activities responded as expected to stimuli such as insulin and glucose, which depressed phosphorylase and increased synthase activity, and glucagon, which increased phosphorylase and decreased synthase activity. In fasted animals approximately 50% of each enzyme was in the active form, which suggests the existence of a potential futile cycle for glycogen metabolism. The role for such a cycle in the regulation of glycogen synthesis and degradation is discussed.

Animals↗
PubMed1978

Effects of part sequences of human growth hormone on in vivo hepatic glycogen metabolism in the rat.

Acute effects of two part sequences of human growth hormone on the in vivo activity levels of hepatic glycogen synthase and glycogen phosphorylase were examined. The peptide corresponding to residues 6 to 13 of the hormone (hGH 6--13) decreased the percentage of phosphorylase in the active form without affecting synthase activity. This action was indirect and dependent upon insulin. The peptide hGH 177--191 decreased the level of the active form of synthase without affecting phosphorylase activity. This effect was also observed with analogous peptides containing the sequence hGH 178--191 (i.e., hGH 172--191 and hGH 178--191), whereas the peptide hGH 179--191 was inert. The onset of these effects was rapid, and maximum changes in activity were produced in 5 min by both peptides. The effect for hGH 177--191 was short-lived, and synthase activity had returned to normal levels by 15 min, whereas the action of hGH 6--13 was of longer duration and was still quite marked at 60 min. Both peptides showed a linear dependence of response to the log dose of peptide injected over the range 0.1--250 microgram hGH 6--13 per kg body weight and 0.05--25 microgram hGH 177--191 per kg body weight. Hepatic 3',5'-cyclicadenylic acid levels were not affected by either peptide. Incorporation of glycerol carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH 177--191. This is discussed in terms of a futile cycle between glycogen and hexose phosphate in the liver, as the basis for a control mechanism for hepatic glycogen metabolism. The present observations are consistent with other in vivo and in vitro actions of these and related peptides.

Amino Acid Sequence↗
PubMed1978

Perception of sounds used in species-specific communication: the auditory cortex and beyond.

The auditory cortex, located in the superior temporal gyrus, has been studied in squirrel monkeys with respect to its role in detecting species-specific vocalizations. Single neurons tested with selected vocalizations from the species' repertoire have been grouped into seven functional categories. Each category reflects a different level of processing with regard to vocalizations and artificial sounds. It is argued that, while the auditory cortex has the capability to detect and distinguish species-specific vocalizations, the interpretation of their biological significance likely takes place elsewhere.

Animal Communication↗
PubMed1976

Single unit analysis of auditory processing in squirrel monkey frontal cortex.

Clicks, tone bursts and species-specific vocalizations were used to test 315 units isolated in the dorsolateral prefrontal cortex. Acoustic responses were detected in about 20% of the units. Responsive units were scattered throughout the explored area, although more units responsive to vocalizations were found in the vicinity of sulcus principalis. Vocalizations were effective stimuli, driving 68% of the acoustic units. However, only 19% responded exclusively to vocalizations. Clicks were effective for 65% of the acoustic units, 27% of which responded only to clicks. Tones activated 39% of the acoustic units. Units generally responded to tones over a wide frequency range. Responses to tones, clicks and vocalization were similar, both within the same unit and between units. The biggest difference related to the background activity of the unit: Low rate cells produced a small number of relatively well-timed discharges per stimulus; high rate cells produced a longer, more poorly-timed response. Vocalizations differed in their effectiveness according to their physical structure. Noisy calls elicited 69% of all responses, although they accounted for only one-third of the test vocalizations. We conclude that frontal acoustic units are involved with at least two functional mechanisms, one related to attending to a large class of sounds, the other related to the detection of sounds with high motivational significance.

Acoustic Stimulation↗