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Biomedical subjects

D M Lawrence

Publications and source records attributed to D M Lawrence.

At least 19 recordsLinked to original sources
PubMed1992

kappa-Opioid binding sites on a murine lymphoma cell line.

As a first step in determining whether any subset of lymphocytes expresses opioid receptors, membranes prepared from mouse lymphoma cell lines were screened for [3H]naloxone binding sites. Membranes from the R1.1 cell line specifically bound [3H]naloxone. The Hill coefficient for [3H]naloxone binding was 0.93 +/- 0.18, and nonlinear regression analysis indicated that a one-site model was the best fit of the [3H[naloxone saturation binding data. Low concentrations of kappa-selective opioids, but neither mu nor delta opioids, inhibited [3H]naloxone binding. Saturation binding studies with the kappa-selective compound [3H]U69,593 revealed a single binding site with a KD value of 0.204 +/- 0.039 nM and a Bmax value of 31.7 +/- 3.1 fmol/mg of membrane protein. The Hill coefficient for [3H]U69,593 binding was 1.03 +/- 0.11, indicative of a single site. Time courses for the association and dissociation of [3H]U69,593 binding at 25 degrees C exhibited properties consistent with a single class of binding sites. Low concentrations of kappa-selective opioids, including dynorphin peptides, inhibited [3H]U69,593 binding, while high concentrations of mu opioids were needed to inhibit binding, and the delta-selective ligands were ineffective at concentrations up to 10 microM. Stereoselectivity of the binding site was demonstrated by the finding that the Ki value for (-)-pentazocine in inhibiting [3H]U69,593 binding was 25 times less than for the (+)-isomer. Based on its high affinity for U69,593, alpha-neo-endorphin, and dynorphin B, the kappa opioid binding site on R1.1 cell membranes belongs to the kappa 1b subtype. As observed with brain kappa opioid binding sites, sodium inhibited [3H]U69,593 binding to R1.1 cell membranes in a concentration-dependent manner. These data demonstrate that the murine lymphoma cell line R1.1 expresses kappa opioid binding sites that are very similar to brain kappa opioid binding sites.

Animals↗
PubMed1992

Changes in vestibulo-ocular reflex (VOR) anticipate changes in vergence angle in monkey.

The axis of head rotation is usually different from the axis of eye rotation. Geometrical considerations show that the eyes translate with respect to visual targets located near the head. In order to accurately stabilize retinal images against this translation, the vestibulo-ocular reflex (VOR) must be modulated inversely with the target's distance. The neural correlate of viewing distance used to modulate the VOR is not known. Since vergence angle is related inversely to viewing distance, an efference copy of instantaneous vergence angle or proprioceptive afferent information from extraocular muscles could be used to adjust the VOR. To examine this hypothesis, we compared the time-course of changes in the VOR with the time-course of changes in vergence angle. The VOR was induced by briefly rotating monkeys about a vertical axis at different times during the execution of vergence eye movements. We found that the amplitude of the VOR changed systematically during the course of a vergence eye movement. On average, the changes in the amplitude of vestibular induced eye movements anticipated changes in vergence angle by 50 msec, but in some instances, up to 200 msec of anticipation was observed. These data suggest that a central command signal rather than an afferent or efferent copy of vergence eye position was used to modulate the VOR.

Animals↗
PubMed1992

Kappa opioid binding sites on the R1.1 murine lymphoma cell line: sensitivity to cations and guanine nucleotides.

The present study describes the characterization of an opioid binding site on membranes prepared from the R1.1 cell line, a murine thymoma. Specific (-)[3H]bremazocine binding was saturable, stereoselective, and limited to a single high affinity binding site with a Kd value of 15.2 +/- 1.6 pM and a Bmax value of 54.8 +/- 6.0 fmol/mg of protein. The kappa-selective alkaloids and dynorphin peptides inhibited (-)[3H]bremazocine binding with Ki values of less than 1 nM, in contrast to mu- and delta-selective ligands. The high affinity of this site for alpha-neo-endorphin and U50,488 suggests that this kappa opioid binding site resembles the kappa 1b subtype. NaCl, as well as other mono- and divalent cations, inhibited (-)[3H]bremazocine binding. In the presence of NaCl, the nucleotides GTP, GDP, and the nonhydrolyzable analog guanylyl-5'-imidodiphosphate (Gpp(NH)p) also decreased (-)[3H]bremazocine binding, suggesting that this kappa opioid binding site is coupled to a G-protein. In summary, R1.1 cells possess a single high affinity kappa opioid receptor that shares many properties with brain kappa 1b opioid receptors.

Animals↗
PubMed1991

A provider's view of prevention approaches in a prepaid group practice.

Kaiser Permanente's health care delivery system and its efforts to integrate public health preventive medicine and curative medicine are described. The author advocates an increased focus on prepaid delivery systems like Kaiser Permanente as the best vehicle to achieve the full promise of health screening, health education, and life-style modification. Because these systems have brought the proper incentives into alignment, prevention and health promotion have become effective tools to achieve cost containment goals. A number of Kaiser Permanente projects are highlighted that demonstrate integration of public health preventive medicine and curative medicine: the Northern California Region's uniform health appraisal examination, which is linked with health education and counseling; the Colorado Region's breast cancer screening program, which is expected to show a higher rate of early breast cancer detection than in the general population; cooperative efforts with two Northern California towns to reduce smoking through a community-wide project; educational theatre programs aimed at early intervention and education of children before high-risk behaviors have become established life-style; and research projects that are possible because of an integrated program. Also, several forces that could endanger integrated systems including cost control practices of employers and insurers, and public policy such as mandating specific benefits, are noted.

Breast Neoplasms↗
PubMed1987

Amniotic fluid testosterone and testosterone glucuronide levels in the determination of foetal sex.

Unconjugated testosterone levels were assayed in 351 amniotic fluid samples obtained at 15-19 weeks gestation. The median values for unconjugated testosterone in the 166 female foetuses and 185 male foetuses were 137 and 712 pmol/l respectively. Sixteen amniotic fluid samples from male foetuses had unconjugated testosterone levels lower than the highest female unconjugated testosterone value (361 pmol/l). Testosterone glucuronide was measured in amniotic fluid from 48 female and 55 male foetuses. There was a significant sex difference in the median values of testosterone glucuronide between female (median 160 pmol/l, range 64-465 pmol/l) and male (median 817 pmol/l, range 68-3707 pmol/l) amniotic fluid specimens (P less than 0.001). Of the sixteen male foetuses with amniotic fluid unconjugated testosterone levels in the female range, 12 had amniotic fluid testosterone glucuronide levels within the male testosterone glucuronide range of values. Hence used in conjunction with unconjugated testosterone, testosterone glucuronide increased the predictive accuracy of foetal sexing from 95.4 to 98.9%. Testosterone sulphate was measured in 24 female and 25 male amniotic fluid samples. There was no Testosterone sulphate was measured in 24 female and 25 male amniotic fluid samples. There was no significant difference between female (median 2591 pmol/l) and male (median 2964 pmol/l) testosterone sulphate levels.

Amniocentesis↗
PubMed1979

Role of verbal representations in testing recognition of naturalistic sounds.

This paper reports two experiments concerned with verbal representation in the test stage of recognition memory for naturalistic sounds. In Study I 10 subjects produced verbal description to 50 sounds and after a 7-day delay 5 subjects reviewed self-produced verbal descriptions while 5 did not prior to testing for recognition. Review of descriptions increased recognition to 94.4% compared to 88.5% for those with no review. In Study II 16 subjects produced verbal descripitions to 50 naturalistic sounds. After a 7-day delay all subjects reviewed descriptionss of one-half of the items which were "targets" and 8 subjects reviewed description of 25 "non-targeted" items. The latter condition produced interference, observed as a significant decrement in recognition from 90.3% to 86.5%.

Auditory Perception↗
PubMed1979

Comparison of accuracy in auditory and tactile recognition memory for environmental stimuli.

Accuracy rates for auditory and tactile recognition of naturalistic stimuli over a 7-day period are compared. 40 subjects listened to 50, 107, or 194 naturalistic sounds and were tested immediately or after delays of 2 or 7 days. 30 other subjects handled but did not visually inspect 150 common objects and were tested over the same three delay intervals. Recognition accuracy for sounds was 87.5%, 82.5%, and 80.4% while common objects were recognized at 96.0%, 93.8%, and 88.5% rates of accuracy. Tactile recognition memory was superior to auditory recognition memory. The recognition accuracies of both modalities were affected by the delay interval. The number of items inspected had no effect on the recognition memory for sounds. Following a delay of 1 wk., the accuracy of recognition relative to the original level of function was 92% for both modalities.

Auditory Perception↗
PubMed1979

Report on blind subjects' tactile and auditory recognition for environmental stimuli.

In two related experiments on recognition-on touch and audition-accuracy rates were obtained from congenitally blind subjects and compared with those for normally sighted subjects. In Exp. 1, 5 blind subjects inspected, i.e., handled, 150 common objects and were tested after a delay of 7 days. In Exp. 2, 9 blind subjects listened to 194 naturalistic sounds and were also tested after a 7-day delay. Accuracy of tactile recognition for the blind was 89.4% while it was 87.9% for the normally sighted. Sound recognition by blind subjects was 76.6% and for the normally sighted it was 78.4%. Neither difference was statistically significant.

Adult↗
PubMed1979

Testosterone concentration in different functional compartments of the male reproductive tract.

The concentration of testosterone in testicular tissue (TT), spermatic vein blood (SVB), cubital blood (CB), and seminal fluid (SF) was estimated using a radioimmunoassay technique in a total of 50 normospermic, oligozoospermic, and azoospermic men. Testosterone was also determined in cauda epididymis-vas deferens ductus wash fluid (WF) in 6 normospermic men. In 2 oligozoospermic men the testosterone concentration in TT was 556 and 725 ng/g tissue, respectively. In 9 normospermic men the mean SVB testosterone concentration was 473 ng/ml. CB and SF concentrations of this steroid were 6.8 and 0.4 ng/ml in normospermic, 6.4 and 0.5 ng/ml in oligozoospermic, and 4.9 and 0.4 ng/ml in azoospermic men, respectively; the difference among the three groups was not significant. The SVB:CB and SVB:SF ratios in normospermic men were 71 and 1549, respectively, while the CB:SF ratio was 18 in normospermic, 18 in oligozoospermic, and 16.6 in azoospermic men. Testosterone could not be detected in individual specimens of WF, but after pooling of samples a concentration of 0.08 ng/ml WF was estimated. These results demonstrate the relative concentrations of testosterone in the different functional compartments of the reproductive tract in man and facilitate a better understanding of its function.

Adult↗
PubMed1978

Pituitary-testicular interrelationships in mumps orchitis and other viral infections.

Leydig-cell function was assessed in 27 men with acute mumps orchitis by measuring plasma testosterone concentrations before and after the administration of human chorionic gonadotrophin (HCG). The test was also performed on groups of patients with other febrile viral infections and mumps without orchitis and on healthy euspermic men. The concentrations both before and after HCG were significantly lower in patients in the acute phase of mumps-but not in those with other viral infections and mumps without orchitis-than in the healthy men. Basal concentrations of follicle-stimulating hormone (FSH) and luteinising hormone (LH) were significantly increased in patients with acute mumps orchitis, while an exaggerated response to LH-releasing hormone was noted in four patients after the acute phase of the disease. Raised plasma LH concentrations were also found in several patients with viral infections, including mumps without orchitis. There appeared to be no particular merit of any of the treatments used (aspirin, prednisolone, and cold baths). In patients reevaluated three to five and 10 to 12 months after the acute phase of their disease the basal testosterone concentrations were similar to those of the healthy men, but several of the patients showed a severely impaired response to HCG. Mean basal FSH and LH concentrations were significantly increased 10 to 12 months after the acute phase, while the mean LH concentration was also raised at three to five months.It is concluded that mumps orchitis impairs Leydigcell function during the acute phase of the disease but may also have a more permanent damaging effect, similar to that found in the germinal epithelium.

Acute Disease↗
PubMed1978

Prolactin and luteal insufficiency.

The relationship between mid-luteal plasma levels of progesterone and prolactin was studied in 75 women with regular menstrual cycles. Eighteen women had normal prolactin (mean 260 +/- 51.7 mU/l) and normal progesterone levels (mean 67 +/- 21.3 nmol/l). Thirty-nine women had elevated prolactin levels (mean 850 +/- 503 mU/l): progesterone levels were normal in all cases (mean 61 +/- 22.3 nmol/l). Eighteen women had evidence of luteal deficiency (mean progesterone 15.3 +/- 7.7 nmol/l); prolactin levels were normal in all cases (mean 243 +/- 106 mU/l). There was no correlation between plasma prolactin and progesterone levels.

Adult↗
PubMed1978

The treatment of mild adrenal hyperplasia and associated infertility with prednisone.

Thirty patients with mild post-pubertal adrenal hyperplasia, characterized by raised urinary 17-oxosteroid levels and variable combinations of irregular menses, hirsuties, infertility, and spontaneous abortion, were treated with 2.5 to 10 mg of prednisone per day and all conceived (55 pregnancies). With this treatment, regular, ovulatory cycles occurred immediately in 25 patients, and after two to six months, in the rest. Treatment reduced raised 17-oxosteroid levels to normal and brought about some improvement in hirsuties and acne. Forty-seven pregnancies ended in the birth of liveborn infants; one of these died of prematurity and another had congenital emphysema. One pregnancy was terminated, two were of unknown outcome and five (9.4%) ended in abortion. Before treatment, 20 out of 22 pregnancies (91%) had ended in abortion.

17-Ketosteroids↗
PubMed1978

Influence of active encoding on tactile recognition memory for common objects.

Active tactile recognition memory for common objects is compared with passive touch. The recognition memory test occure after a delay between inspection and test of seven days. Three groups of five each have the following conditions and results: Group I manipulated objects at both inspection and test to obtain a recognition rate of 87.9%; Group II manipulated objects at inspection but not at test, i.e., passive touch, to produce a recognition rate of 80.7%; Group III manipulated objects at test but not at inspection to perform at a 72.5% accuracy rate. Object manipulation had a significant effect and the group means were all significantly different (p less than or equal to .05), with the largest performance decrement due to passive touch at encoding. Generally, the findings implicated the importance of object identity in tactile recognition memory which, in turn, is supportive of the depth-of-processing approach to memory.

Discrimination, Psychological↗
PubMed1978

Cross-modal utilization of information: recognition memory for environmental stimuli.

In a study of cross-modal recognition memory for vision and audition photographs were matched for meaningful content with naturalistic sounds. Fifteen subjects inspected pictures and were tested with sounds and for 15 other the procedure was reversed. The two cross-modal groups were further divided into subgroups of 5 to test at one of three delays: immediate, 2 days, or 7 days. Accuracies for recognition of vision-audition for the respective retention intervals were 88.0%, 81.8%, and 75.4% and for audition-vision 87.9%, 85.1%, and 76.7%. Delay interval significantly affected cross-modal recognition. There was no interaction. Vision-audition recognition accuracy did not differ from audition-vision. The cross-modal recognition for both was high. Neither differed from a comparable intra-modal recognition memory for naturalistic sounds (Lawrence, 1974).

Auditory Perception↗
PubMed1977

Hypogonadal men treated with oral testosterone undecanoate.

Three hypogonadal male subjects with very low plasma testosterone levels were given testosterone undecanoate orally (120 mg daily for 3 weeks) as a replacement therapy. Normal adult male testosterone plasma values were rapidly reached and attained throughout the therapy. Similar elevations of plasma androstenedione were noted. A reduction in sex hormone binding globulin following the therapy was observed. Satisfactory clinical responses were reported by the patients. We thank Organon Laboratories Ltd. for supplying TU and financial help with this project.

Administration, Oral↗
PubMed1976

Plasma testosterone and androstenedione levels during monitored induction of ovulation in infertile women with 'simple' amenorrhoea and with the polycystic ovary syndrome.

Twenty-seven infertile patients with 'simple' amenorrhoea-oligomenorrhoea and eighteen with the polycystic ovary (PCO) syndrome were treated for induction of ovulation with clomiphene, human menopausal gonadotrophin and human chorionic gonadotrophin. The treatment was monitored by plasma oestradiol, testosterone, androstenedione and progesterone estimation. Women with PCO had significantly higher plasma androgen levels than women with 'simple' amenorrhoea (P less than 0--1 to P less than 0-001) both before treatment and during induction of ovulation. When ovulation was induced the pregnancy rate for women with the PCO syndrome with elevated androgens was 21% while for those with uncomplicated amenorrhoea it was 75%. It is concluded that high levels of circulating androgens might be a factor preventing conception in some patients in whom ovulation is apparently successfully induced.

Adolescent↗