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Biomedical subjects

R Henderson

Publications and source records attributed to R Henderson.

At least 19 recordsLinked to original sources
PubMed1992

A system for studying the microstructure of ingestive behavior in mice.

A system for long-term monitoring of mouse eating and drinking behavior with 6-s resolution is described. The apparatus utilizes infrared beams to monitor activity at a single feeding port and electronic contact detector circuitry to record individual licks at two drinking ports. Eight SWR/J mice were monitored using this system and data from the last day of testing with food and water were analyzed. Mice ate an average of 4.54 +/- 0.40 g of powdered food and drank an average of 5.81 +/- 0.65 ml of water. Mice had an average of 36.25 +/- 3.96 food bouts and 32.25 +/- 7.56 water bouts lasting 3.00 +/- 0.48 and 0.88 +/- 0.35 min, respectively. Information regarding the temporal association between eating and drinking and the circadian patterns of ingestion was provided, utilizing customized software that augments the system. Important implications for the use of mice in ingestion pattern research are discussed.

Animals↗
PubMed1992

Image contrast in high-resolution electron microscopy of biological macromolecules: TMV in ice.

It is shown that the contrast in high-resolution electron micrographs of biological macromolecules, illustrated by a study of TMV in ice, falls considerably below the level which should theoretically be attained. The factors which contribute to the low contrast include radiation damage, inelastic scattering, specimen movement and charging. Future progress depends on improved understanding of their contributions and relative importance. Contrast is defined as the amplitude of a particular Fourier component extracted from an image in comparison to that expected by extrapolation from separate electron or X-ray diffraction measurements. The fall in contrast gets worse with increased resolution and is particularly serious at 10 A and beyond for specimens embedded in vitreous ice, a method of specimen preparation which is otherwise particularly desirable because of the expectation that the embedded molecules should be well preserved in a near-native environment. This low contrast at high resolution is the principal limitation to atomic-resolution structure determination by electron microscopy. In spite of good progress in the direction of better images, it remains a major problem which prevents electron microscopy from becoming a simple and rapid method for biological atomic structure determination.

Bacteriorhodopsins↗
PubMed1992

Preliminary examination of the comorbidity of anxiety and depression in Parkinson's disease.

Significant anxiety in combination with depression may represent a specific depressive subtype in Parkinson's disease (PD). To ascertain the prevalence of this symptom complex, we administered a self-report survey and standardized psychological tests that measure anxiety and depression to 164 PD patients and 150 age-matched healthy spouse control subjects. The reporting of depression in combination with panic/anxiety best differentiated the two populations (38% vs. 8%). Depression and anxiety were highly correlated in relationship to clinical features of PD. Our findings suggest that clinically significant levels of depression and anxiety may frequently coexist in PD. The specific neuropathology of PD may predispose to this pattern of behavioral disturbance.

Aged↗
PubMed1992

Lifetime sexual behaviors among predominantly minority male runaways and gay/bisexual adolescents in New York City.

Lifetime sexual behaviors were examined among two samples of predominantly minority, male adolescents in New York City aged 12 to 18 (M = 16.3), believed to be at high risk for HIV infection: 59 runaway males in two residential shelters and 60 males attending a community agency (HMI) for gay and bisexual youths. Interviews regarding psychosexual milestones indicated that 93% of these youths had engaged in oral, anal or vaginal intercourse and/or anilingus, with a median of 11.0 female partners among runaway males and a median of 7.0 male partners among HMI males. Both groups initiated sexual activity at a relatively early mean age of 12.6 years. Each group reported a unique developmental sequence of psychosexual milestones. Consistent condom use was reported by 13% of the youths. One quarter of the youths reported involvement in prostitution. These findings detail the need for AIDS prevention programs for these youths.

Adolescent↗
PubMed1992

An atomic model for the structure of bacteriorhodopsin, a seven-helix membrane protein.

A three-dimensional map of bacteriorhodopsin has been obtained, at near-atomic resolution, by collecting and analysing electron diffraction patterns and electron micrographs from crystals of bacteriorhodopsin preserved at very low temperatures. The map shows a resolution of 3.5 degrees in a direction parallel to the plane of the membrane, but poorer resolution perpendicular. It shows many features well resolved from the main density of the seven alpha-helices, which we interpret as the bulky sidechains of tyrosine, phenylalanine and tryptophan, as well as a very dense feature, which is the beta-ionone ring of the retinal chromophore. Using these bulky side chains as starting points and taking account of bulges of density for the smaller side chains such as leucine, we built an atomic model for the residues between 8 and 225. There are 21 amino acids from all 7 helices surrounding the retinal and 26 amino acids contributed by 5 helices that form the proton channel. Ten of the amino acids in the middle of the proton channel are also part of the retinal-binding site. The model provides a useful basis for considering the mechanism of proton pumping and in the interpretation of other experimental data. In particular, the model suggests that the pK changes in the Schiff base must act as the means by which light energy is converted to proton pumping through the channel. Asp-96 is on the pathway from the cytoplasm to the Schiff base and asp-85 on the pathway from the Schiff base to the extracellular surface. The experimental map and the building of the model of the structure will be described, as well as our interpretation of the structural basis of the mechanism.

Amino Acids↗
PubMed1991

Donor-recipient age difference--an independent risk factor in cyclosporin-treated renal transplant recipients.

Whilst HLA matching is routine in renal transplantation the possible benefits of matching donor to recipient age have not been previously explored. The simultaneous effect on graft survival of donor and recipient age was therefore investigated for 274 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression in two centres. The overall graft survival was 77%, and was not significantly different between the two centres. Individually there was no significant effect of donor or recipient age but taken together, the difference in age significantly affected graft survival (P less than 0.01) regardless of the mode of failure. The 1-year graft survival for all failures was 66.2% when the donor was 5 or more years older. 84.5% when the donor was 5 or more years younger and 71.7% when the donor was within 5 years of the recipient's age. Multivariate analysis, taking into account other variables (HLA matching, dialysis time and type, donor/recipient sex, local/imported kidneys, sensitivity, operation time, total ischaemic time, pre-operative transfusions) indicated that age difference was the single most important variable (P less than 0.01). The only other important covariate risk factor in improving graft survival was HLA-DR matching (P less than 0.05). Donor-recipient age difference is a potentially important recipient selection criterion in cyclosporin-treated renal transplant patients.

Adolescent↗
PubMed1991

Daunomycin treatment prevents clinical expression of experimental autoimmune myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease, characterized by muscle weakness and electrophysiological abnormality. No treatment which would reliably induce permanent clinical remission of MG is yet available. The therapeutic efficacy and toxic effect of daunomycin (Dm), an antibiotic of the rhodomycin group, was evaluated in murine experimental autoimmune MG. Low dosage Dm treatment effectively prevented the development of muscle weakness and its associated electrophysiological abnormality, without inducing detectable toxicity and global immunosuppression.

Animals↗
PubMed1991

A side-entry cold holder for cryo-electron microscopy.

A side-entry cold holder for cryo-electron microscopy has been constructed which can be used with no loss of image resolution or contrast at 3.4 A resolution compared to the normal room-temperature holder. A description is presented of some of the ideas and tests which we have developed during its construction and are included in the design, together with a briefer outline of the remaining limitations.

Cryopreservation↗
PubMed1991

An electronic image drift compensator for electron microscopy.

Image drift frequently occurs when temperature-controlled specimen holders are used or when there is a malfunction of the electron microscope. A simple circuit is presented which supplies a noise-free linear ramp of increasing or decreasing current suitable for manual drift compensation. It has been tested extensively with several side-entry cold stages in a Philips EM420 electron microscope equipped with a low-dose kit. The compensator does not interfere with the use of the low-dose kit and requires no modifications to the microscope.

Electric Conductivity↗
PubMed1991

Effect of visual display unit use on blink rate and tear stability.

In the literature, there is evidence supporting the notion that visual display unit (VDU) use decreases the blink rate and possibly reduces the stability of the precorneal tear film. In this investigation the blink rate and tear stability were measured using noninvasive techniques, in relation to VDU use. In normal healthy subjects, the results show an average 5-fold drop in blink rate during VDU use but tear stability appears to be unaffected. During VDU use a significant relation was found to exist between the interval between blinks and the stability of the precorneal tear film.

Adolescent↗
PubMed1991

Patients avoiding surgery. Pathology and one-year life status follow-up.

Patients were selected for a research study to determine the outcome of patients who had demonstrated enough pathology to have been viewed as surgical candidates and had chosen to avoid surgery. The purpose of the study was to identify the diagnostic categories and to obtain follow-up data on these patients. The patient population consisted of 66 patients with the following pathologies: disc disruption (one and two levels), disc disruption (three levels), stenosis, spondylolisthesis, instability, and herniated nucleus pulposus. The patients were followed for a period of 1 1/2 years and rated on the following lifestyle status categories: Returned to Work, Retired, Retraining, Able to Increase Activity Level, or No Change from Initial Status. Of the nonoperative patients, 18% returned to work. Twelve patients (18%) were retired. Eleven patients (16%) were placed in retraining programs. Twenty patients (29%) were able to increase activity level. Eleven patients (16%) fell under the category of no change.

Activities of Daily Living↗
PubMed1991

Voluntary blood pressure control by biofeedback: relationship to psychological characteristics.

1. Psychological characteristics were studied in 25 hypertensives (mean and standard deviation of blood pressure 150/95 +/- 12/5 mmHg), who received blood pressure (BP) biofeedback (BFB). Personality factors and success in BFB-BP modifying ability were correlated and the predictive value of psychological factors was estimated. 2. Questionnaires consisted of a Locus of Control of Behaviour (LCB) scale, the Spielberger state trait anxiety inventory and the Framingham Type A personality inventory. 3. BP was monitored continuously from the finger by volume clamp plethysmography during eight BFB sessions, each with three trials of raising, ignoring and lowering systolic blood pressure (SP). 4. SP was raised/lowered by 12 +/- 11/6 +/- 9 mmHg and heart rate (HR) increased by 10 +/- 3.9/+ 1 +/- 6.1. Ten subjects were able to lower SP by greater than or equal to 5 mmHg (15 +/- 7.5) and raise it by 17 +/- 11. The others achieved no decrease in SP and were also less successful at raising (8 mmHg, P = 0.04). 5. Changes in LCB and trait anxiety correlated with DP rise, whereas type A and pre-study state anxiety correlated with rising HR. Lowering of SP correlated weakly with change in LCB (r = 0.47, P = 0.06). 6. Combinations of psychological factors had independent predictive value for BP and HR change: trait anxiety (P = 0.03) and change in LCB (P = 0.009) with rise in diastolic blood pressure (DP); type A (P = 0.009), pre-study LCB (P = 0.02) and pre-study state anxiety (P = 0.01) with HR rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Biofeedback, Psychology↗
PubMed1990

Electron cryo-microscopic analysis of crystalline cytochrome oxidase.

The structure of cytochrome oxidase from beef heart mitochondria has been analysed by cryo-electron microscopy of vesicle crystals of the space group p22(1)2(1), with cell dimensions a = 102 A, b = 123 A, gamma = 90 degrees. Several methods of specimen preparation were applied to the vesicular two-dimensional crystals in the electron microscope, to ensure that the structure was preserved to the maximum resolution. The two most informative density maps were from specimens embedded in ice and from negative staining in a 1:1 mixture of glucose and uranyl acetate. The three-dimensional structure of the ice-embedded molecule shows a single, well resolved, but convoluted density, which represents in size and shape one cytochrome oxidase dimer. At the bottom of the molecule, a substantial part of the protein is embedded in the lipid bilayer of the vesicle. The molecule then extends upwards, out of the bilayer, into the internal space within the vesicle. Here, the structure first passes through a region within the molecule containing a hollow cavity that lies roughly at the centre of mass of the dimer, and then branches into two well-resolved halves at some distance from the membrane. The negatively stained structure, in contrast, shows a stain-excluding region in the centre of the vesicle at the level of the cavity in the ice-embedded structure, but otherwise has a similar overall external shape. In addition, there is a small rotation of the whole molecule by approximately 25 degrees relative to the orientation of ice-embedded specimens. We interpret these differences to mean that the central cavity seen in the ice-embedded structure is too small to allow the stain to penetrate during the drying process and that the drying process causes the rotation. The structures described here are consistent with one another and allow an interpretation at higher resolution than from previous work.

Animals↗
PubMed1990

Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy.

The light-driven proton pump bacteriorhodopsin occurs naturally as two-dimensional crystals. A three-dimensional density map of the structure, at near-atomic resolution, has been obtained by studying the crystals using electron cryo-microscopy to obtain electron diffraction patterns and high-resolution micrographs. New methods were developed for analysing micrographs from tilted specimens, incorporating methods previously developed for untilted specimens that enable large areas to be analysed and corrected for distortions. Data from 72 images, from both tilted and untilted specimens, were analysed to produce the phases of 2700 independent Fourier components of the structure. The amplitudes of these components were accurately measured from 150 diffraction patterns. Together, these data represent about half of the full three-dimensional transform to 3.5 A. The map of the structure has a resolution of 3.5 A in a direction parallel to the membrane plane but lower than this in the perpendicular direction. It shows many features in the density that are resolved from the main density of the seven alpha-helices. We interpret these features as the bulky aromatic side-chains of phenylalanine, tyrosine and tryptophan residues. There is also a very dense feature, which is the beta-ionone ring of the retinal chromophore. Using these bulky side-chains as guide points and taking account of bulges in the helices that indicate smaller side-chains such as leucine, a complete atomic model for bacteriorhodopsin between amino acid residues 8 and 225 has been built. There are 21 amino acid residues, contributed by all seven helices, surrounding the retinal and 26 residues, contributed by five helices, forming the proton pathway or channel. Ten of the amino acid residues in the middle of the proton channel are also part of the retinal binding site. The model also provides a useful basis for consideration of the mechanism of proton pumping and allows a consistent interpretation of a great deal of other experimental data. In particular, the structure suggests that pK changes in the Schiff base must act as the means by which light energy is converted into proton pumping pressure in the channel. Asp96 is on the pathway from the cytoplasm to the Schiff base and Asp85 is on the pathway from the Schiff base to the extracellular surface.

Bacteriorhodopsins↗
PubMed1990

Analysis of high-resolution electron diffraction patterns from purple membrane labelled with heavy-atoms.

Progress in the structure determination of bacteriorhodopsin, the protein component of purple membrane from Halobacterium halobium has been limited by the lack of three-dimensional phase information between 6 and 3 A resolution. By analogy with X-ray methods, it is possible that heavy-atom labelling of the membrane crystal may provide heavy-atom derivatives that can be used for phasing by the multiple isomorphous replacement method. This paper describes the screening of heavy-atom compounds as potential derivatives, and the evaluation of the data collected from these heavy-atom-labelled membranes. Improvements in the methods for collecting electron diffraction data and analysing and merging the data are presented. Diffraction patterns of purple membrane samples were taken at -120 degrees C to minimize radiation damage. About 30 heavy-atom compounds were tested for use as potential derivatives. The diffraction patterns from labelled membranes were analysed by examining 6.5 A difference Fourier maps. Two heavy-atom compounds were selected for three-dimensional data collection at 3 A resolution. In addition, a full set of native data at -120 degrees C was collected to 2.7 A resolution. The intensity merging, heavy-atom derivative evaluation, heavy-atom refinement and the calculation of phases are presented. Phases are compared to those determined by electron microscope imaging, and limitations of the method are discussed. It is concluded that, with the present accuracy of data collection and the present magnitude of delta F/F available for the derivatives, the phasing power is too small. The phases that are obtained are not sufficiently accurate to provide a reliably interpretable map. It may be possible, however, to use the heavy-atom derivative data in difference Fourier calculations in which the presence of a peak would confirm the phases calculated from a model or obtained by electron microscope imaging.

Bacteriorhodopsins↗