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Biomedical subjects

M R Chance

Publications and source records attributed to M R Chance.

At least 55 records · Page 3Linked to original sources

Structural and functional significance of inhomogeneous line broadening of band III in hemoglobin and Fe-Mn hybrid hemoglobins.

Near-infrared spectra of hemoglobin and Fe-Mn hybrid hemoglobins have been obtained at cryogenic temperatures. The charge-transfer (a2u(pi)----dzy) transition at approximately 760 nm (band III) has been found to be a conformationally sensitive indicator of the heme-pocket geometry in these species. Temperature, protein tertiary and quaternary structure, chain heterogeneity, and ligand rebinding subsequent to CO photolysis all affect the line width and position of this transition. We conclude that the overall line shape of band III is derived from both subunit heterogeneity and conformational disorder within each subunit. A model is suggested that relates the observed pH dependence of the kinetic hole burning due to ligand rebinding to specific structural parameters of the proximal heme pocket that influence both the peak position and the inhomogeneous line shape of band III.

Binding Sites↗

Ligand binding channels reflected in the resonance Raman spectra of cryogenically trapped species of myoglobin.

Variations in the v2 region of the Raman spectra of cryogenically trapped photoproducts of different liganded myoglobins as a function of ligand (CO, O2, and n-butyl isocyanide) and species (whale, tuna, elephant) are reported. These variations are attributed to differences in the population of "open" (ligand accessible) and "closed" (ligand inaccessible) conformations of the distal heme pocket. Based on these findings and those derived from other spectroscopies including x-ray crystallography, NMR, IR spectra, and ESR, a working model is presented which accounts for how the conformation of the distal heme pocket, the geometry of the bound ligand, the identity of the ligand, and the dynamics of the dissociated ligand are all interconnected.

Animals↗

Linkage of functional and structural heterogeneity in proteins: dynamic hole burning in carboxymyoglobin.

Inhomogeneous broadening of the 760-nanometer photoproduct band of carboxymyoglobin at cryogenic temperatures has been demonstrated with a dynamic hole burning technique. Line-shape changes and frequency shifts in this spectral band are generated by ligand recombination and are shown not to be the result of structural relaxation below 60 K. The observation of dynamic hole burning exposes the relation between the structural disorder responsible for the inhomogeneous broadening and the well-known distributed ligand rebinding kinetics. The findings provide direct evidence for the functional relevance of conformational substrates in myoglobin rebinding. In addition, a general protocol for evaluating the relative contributions of structural relaxation and hole burning to the spectral changes accompanying rebinding in hemeproteins is presented.

Animals↗

Myoglobin recombination at low temperature. Two phases revealed by Fourier transform infrared spectroscopy.

The low-temperature recombination of CO with myoglobin was studied using Fourier transform infrared spectroscopy. The bound state of carbon monoxide myoglobin has two distinct conformers observed at 1926 and 1945 cm-1 with an intensity ratio of 1 to 8. The recombination of these bands after complete photolysis at 10 K followed by a temperature jump shows distinct kinetics for the two bands. Although both bands apparently follow the nonexponential kinetics originally described by Frauenfelder and co-workers (Austin, R., Beeson, K., Eisenstein, L., Frauenfelder, H., and Gunsalus, I. (1975) Biochemistry 14, 5355-5373), the 1926 cm-1 band does not appear appreciably below 70 K. In fact, after 20 min of recombination at 70 K the 1945 cm-1 band is fully recovered, while no detectable amount of the 1926 cm-1 band is present. This is the first association of a spectroscopic marker of protein substructure with reaction kinetics.

Carbon Monoxide↗

Movement of Fe with respect to the heme plane in the R-T transition of carp hemoglobin. An extended x-ray absorption fine structure study.

Carp Hb undergoes a well known change in kinetics over the pH range 6-9. X-ray absorption spectroscopy, in conjunction with refined data analysis procedures, shows no difference in iron-ligand distances when carp HbCO is switched from R (high affinity) to T (low affinity) states. These distances are 2.015 +/- 0.015 A for the average iron-pyrrole nitrogen distance, 2.14 +/- 0.04 A for the iron-nitrogen (of histidine) distance, and 1.89 +/- 0.05 A for the Fe-C (of CO) distance. Examination of the region from 30 to 100 eV above the threshold, called the ligand field indicator region, reveals spectral differences, which when compared to model compounds suggest that the iron and the heme are less coplanar in the T-like forms. These results are consistent with the iron being 0.1 A more out of the mean heme plane in both carp HbCO and carp Hb T states, relative to the R forms, and that the change in iron position on ligation to either T or R state is four times larger than that occurring with the quaternary switch.

Animals↗

Influence of novel male on the social behaviour of a captive group of mature female long-tailed macaques (Macaca fascicularis).

The replacement of a sexually mature, but sexually inactive, male by a novel mature male in a small colony of Macaca fascicularis brought about changes in social behaviour and structure. Particularly striking were the heightened levels of all sexual activity, especially in the females' invitation to the male to copulate. Cohesiveness around the male increased. Increased levels of agonism were noted and changes in the agonistic female hierarchy resulted. The grooming relationships in the colony were also significantly altered.

Aggression↗

Social interaction and the use of space on a ward of long term psychiatric patients.

Naturalistic observations were made on 24 chronic schizophrenic patients in order to determine whether patterns of spatial behavior in a ward setting resembled those reported by Esser et al. for similar population. Patients were ranked in a social interaction hierarchy. Interactional categories included altruistic, verbal, and assertive behavior, and behavior surrounding the exchange of cigarettes. Patient space use was analyzed on a group and individual basis according to preferences for particular chairs or particular areas of the ward. Groups were formed by dividing the interactional hierarchy into thirds: top, middle, and bottom. Results showed that patients who interacted the most (i.e., top interactors) tended to sit in the areas closet to the front of the ward. Middle interactors preferred the areas furthest from the front, and bottom interactors exhibited no preference for any area. Preferences remained stable over a 1-year period. More patients in this study (100 per cent) than in Esser's study (50 per cent) met the criterion of territoriality, as defined by Esser. These findings are inconsistent with those of Esser et al. Possible sources of discrepancy are discussed.

Adult↗

An ethological perspective on social behavior in long stay hospitalized psychiatric patients.

Ethological methods were employed to gather normative data on social behavior in long stay male inpatients in the ward environment. Most were diagnosed schizophrenic. Social bheavior was categorized into four main types: altruistic, assertive, cigarette, and verbal. Patients (N = 24) were divided into three groups on the basis of the amount of social interaction (top, middle, and bottom thirds of the interactional scale). With the use of these divisions, results indicated: a) marked variability between thirds in the amount of social behavior exhibited; b) differences in the kinds of social behavior utlized by each third--the top was predominantly verbal whereas the middle and bottom were predominantly nonverbal; c) differences in the modes of interaction between thirds--verbal behavior characterized interactions between the top and top, and top and bottom, whereas assertive behavior characterized interactions between the top and middle, middle and middle, middle and bottom, and bottom and bottom; and d) correlative relationships between various social and nonsocial parameters, the most noteworthy including the positive relationship between head up, eyes open, and high rate of social interaction, and the positive relationships between altruistic, cigarette, and verbal behavior. Discussion focused on issues of variability between patients, stability of behaviors over time, behaviors indicative of bonding and social attentiveness, profiles of behavior characteristic of each third of the interactional scale, and the ethological constructs of dominance and attention structure.

Adult↗

An ethological analysis of long stay hospitalized psychiatric patients. Senders and receivers in social interaction.

Ethological methods were employed to monitor social interaction among 24 long stay male patients on a psychiatric ward. Most were diagnosed as schizophrenic. Analysis was made using four molar behavioral groupings: assertive, altruistic, cigarette, and verbal. Within each grouping social behavior was divided into two categories: sending and receiving. Patients were ranked in an interactional scale and divided into three groups on the basis of the amount of social interaction: top, middle, and bottom third. Results showed that individuals in the top third tended to be senders of social behavior, whereas individuals in the middle and bottom thirds tended to be receivers. Individuals in the middle received relatively large amounts of assertive behavior. In addition, correlative relationships indicated positive associations between send and receive verbal and send and receive cigarette. No associatiociation existed between send and receive verbal and send and receive assertive. Findings are discussed in terms of a) sending and receiving profiles characteristic of each third of the interactional scale; b) the value of dividing social behavior into components of sending and receiving; and c) the role assertive behavior plays in the social organization of hospitalized groups.

Adult↗

Factors influencing nursing in Macaca fascicularis.

Nursing by two mother-infant pairs in a caged colony of Macaca fascicularis was monitored at 1-min intervals for 8 h beginning 8:30 a.m. BST, once a week for 3 months in the summer of 1973. Nursing occupied about 210 min in 8 daylight hours for the infants at 10 weeks of age, and the time spent nursing decreased at the average rate of 9.4 min per week until the infants were about 6 months old. The time spent nursing by the infants studied here resembles closely the times spent nursing by some other macaques and by baboons. In the course of a day the amount of time spent nursing varies significantly with a diurnal peak. If nursing by one mother-infant pair is independent of nursing by the other pair, then the time the two pairs spend nursing together would be a function of the product of the frequencies of nursing by each pair. The expected times for the pairs nursing together based on the hypothesis of independent events were significantly less than the observed times the pairs nursed together. Nursing, therefore, involves a positive influence or imitation of one nursing pair by the other. Nursing sessions involving both mother-infant pairs were longer on the average than sessions involving only one pair.

Age Factors↗

Behavioural changes in laboratory mice during cannabis feeding and withdrawal.

The effects of feeding cannabis at a level of 0.4% in the diet has been studied by an ethological analysis of encounters between male mice. Administration of cannabis to dominant males resulted in a reduction of non-social activity and an increase in flight and in social and sexual investigation when compared with untreated controls, but the behaviour of subordinate males was not significantly altered by cannabis. One week after withdrawal of cannabis, the behaviour of diminant males showed a rebound effect with increase in aggression. Nevertheless, by a preference feeding test it was demonstrated that the treated mice were not dependent on the cannabis-containing diet but consumed the control diet in preference.

Aggression↗

Effects of cannabis resin on social behaviour in the laboratory mouse.

The effects of several dose levels of cannabis have been studied by an ethiological analysis of encounters between male mice injected with the drug and partners injected with Tween-saline. The duration of immobility was directly related to the logarithm of the dose of cannabis given. The ratio of flight in the treated animals to aggression in those mice with which they were paired showed a progressive increase as the dose of cannabis was raised from 4-50 mg/kg. A straight line relationship was found to exist between the logarithm of flight/aggression and logarithm of the dose of cannabis administered. Non-social activity and social investigation were decreased by the administration of cannabis; this was due to the time spent by the treated animals in immobility. Aggression was not significantly altered. Many mice given doses of 25-100 mg cannabis/kg showed an ataxic gait and the Straub tail reaction.

Aggression↗