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Biomedical subjects

H Kushner

Publications and source records attributed to H Kushner.

At least 73 records · Page 4Linked to original sources

Race differences in stress-induced reactivity in young adults.

The cardiovascular response to the stress of mental arithmetic was studied in young Black and White adults. Stress-induced reactivity was studied before and following 14 days of oral sodium loading (10 gm NaCl per day). Marginal hypertensives, both Black and White, had greater systolic blood pressure (SBP) levels (p less than 0.001) and greater diastolic blood pressure (DBP) levels (p less than 0.01) in response to stress. Whites had a greater SBP level during mental stress than Blacks (p = 0.008) and greater reactivity (change from baseline; p less than 0.001). The prevalence of sodium sensitivity was greater in Blacks (37.3%) than in Whites (18.4%). Sodium loading did not augment the BP reactivity to the mental stress in any of the racial or BP groups. These data demonstrate racial variation in the cardiovascular response to centrally mediated adrenergic stimuli. The results also suggest that mild BP elevation in Blacks may be regulated through changes in vascular resistance.

Adolescent↗

Forearm hemodynamics at rest and stress in borderline hypertensive adolescents.

Cardiovascular adaptations to mild elevations of blood pressure (BP) may occur early in the development of essential hypertension (EH). We used strain gauge plethysmography to study forearm hemodynamics in adolescents. Ten normotensive males (N) were compared to ten males with borderline hypertension (H). Measurements of forearm blood flow (FBF) were obtained after supine rest, during ten minutes of mental stress (mental arithmetic) and five minutes post stress. Mean arterial pressure (MAP) and forearm vascular resistance (FVR) were calculated. The H maintained higher MAP and FVR (P less than or equal to .05) throughout the study. The vascular response patterns were assessed by comparing the slopes of the linear regression equation FBF = a ln FVR + b (where a = slope and b = intercept). From baseline to stress, the N exhibit a significant change in slope (P less than .05), shifting to a decrease in FVR per unit FBF change. However, the H maintain a constant slope and FVR per unit FBF change remains constant. The study suggests that a primary peripheral vascular abnormality may be present even in the young with marginally elevated BP.

Adolescent↗

Models of spinal cord injury: Part 3. Dynamic load technique.

Having previously studied a static load model of cord injury in rats, we report here an evaluation of a dynamic (weight drop) technique. Under general anesthesia, Sprague-Dawley rats were subjected to a laminectomy at T12, after which a 10-g weight was dropped onto a force transducer and impounder resting on the spinal cord; the weight drop distances varied in different groups from 0 (control) in increments of 2.5 cm to a maximal height of 17.5 cm. A strain gauge attached to the force transducer yielded an oscilloscopic wave form from which force of impact (peak force and impulse) was calculated. Eighty-six animals were used in this parametric study. The animals were observed for 4 weeks postinjury with two tests of motor recovery (Tarlov score for locomotion and the inclined plane test). After sacrifice at 4 weeks, the spinal cords were removed and, with the use of preset criteria, qualitative histopathological scoring of the extent of tissue damage was carried out. We found that the variable height of weight drop was capable of producing a graded injury that correlated with the force of injury (as measured by the force transducer) and with the outcome parameters of functional recovery and degree of morphological damage in the spinal cord. Histopathologically, there was a tendency to central cavitation of the cord. Both the static load and the dynamic load techniques seem to be valid models of spinal cord injury. Pathologically, however, the tissue damage after static load injury involved primarily the dorsal half of the cord. By contrast, the dynamic load technique produced central cavitation comparable to that observed in human spinal cord injury. In this respect, the dynamic model seems to be superior and its use is therefore recommended for studies of therapeutic intervention for spinal cord injury.

Animals↗

Development of a nonhuman primate model for spontaneous hypertension. Blood pressures in first-generation offspring.

A breeding colony of two subspecies of African green monkeys has been established in an attempt to develop a strain of nonhuman primates with inherited spontaneous hypertension. Selective breeding of normotensive and hypertensive feral animals has produced over 300 first-generation, colony-born offspring of nine possible types, which were grouped according to parentage. Blood pressures were measured by indirect methods in 335 unanesthetized animals aged 0.5 to 6 years. Analysis of variance and covariance of mean blood pressures of animals aged 0.5 to 6 years indicated significant differences between control and experimental offspring groups (p less than .001) both before and after adjusting for sex, subspecies, age, and body weight. Mean blood pressures of control and experimental (p less than .02) offspring were significantly different from 0.5 to 5 years of age. The slopes of the regression of mean blood pressure on age were significantly different between the control and experimental groups (p less than .001). Multiple linear regression analysis indicated significant differences among blood pressure, body weight, and age (p less than .001) and also between age and weight (p less than .001) between the groups. The relative contributions of age and weight to determining the mean blood pressure differed, however. The results indicate that elevated blood pressures can be detected in offspring with even one parent having elevated blood pressure from as early as 1 year of age and that the tendency to develop elevated blood pressure is transmitted from parent to offspring in this species, thereby providing a strong indication that a hypertensive strain of monkeys can be developed through selective breeding.

Age Factors↗

Models of spinal cord injury: Part 1. Static load technique.

Testing of potential therapies for spinal cord injury has been significantly hampered by the unavailability of a standardized, reproducible animal model with predictable outcome at a given force of injury (dose-response). The rat was selected in the development of this model in preference to larger animals for economy and availability; this permits use of large numbers of animals to increase statistical validity. In the experiments reported in this article, a static load method (weight placed gently on cord) of inducing cord injury was evaluated. A total of 198 Sprague-Dawley rats were used. Under general anesthesia, a one-level laminectomy was carried out at T-12 with the dura mater intact. Weights varying from 80 to 150 g were lowered onto the dorsal surface of the intact dura mater for durations of 0 to 300 seconds. Recovery of motor function was assessed for up to 8 weeks using two behavioral tests, a modified Tarlov scale and an inclined plane test of hind limb motor function. A statistically significant relationship was found between force of injury and motor recovery as measured by the Tarlov scale, but this did not correlate with inclined plane performance; the duration that the weight rested on the cord did not influence outcome. Pathologically, there was variation in the extent of damage for a given injury load. A semiquantitative pathological assessment of cord injury showed a statistically significant correlation between pathological score and behavioral deficit as measured by the Tarlov scale, but this did not correlate with inclined plane performance. In view of these deficiencies, the static load technique does not seem to be an ideal model for spinal cord injury research.

Animals↗

Models of spinal cord injury: Part 2. A mathematical model.

A mathematical model was constructed to predict motor performance in rats for 8 weeks after spinal cord injury. The model is based on experimental data generated from an investigation of the static-load technique of inducing cord injury and was derived using multiple linear regression. The regression coefficients for weight of the injury-producing load were statistically significant (P less than 0.001), and it was found that the weight of the load contributes over 95% of the posttrauma motor deficit, whereas the time duration of the load resting on the cord contributes less than 5% to the deficit. Sex, pretrauma motor performance, and pretrauma body weight are insignificant covariates. The model may be used to establish expected motor deficits and to derive dose-response curves.

Animals↗

Sodium sensitivity, growth and family history of hypertension in young blacks.

The response to chronic oral sodium loading was studied in young adult (18-23 years) blacks. A representative sample of participants (n=40) from previous longitudinal studies had growth measures at age 6-7 years and 11-16 years. Blood pressure, weight and stress-induced reactivity were measured before and after 14 days of 10 g NaCl daily added to the usual diet. A sodium-sensitive response (SS) was an increase in mean arterial pressure (MAP) greater than or equal to 5 mmHg. A sodium-insensitive response (S) was an increase in MAP less than or equal to 5 mmHg. Family history of hypertension (FH+) was determined by self-report. Fifty-three per cent were SS. There were no difference in age-related BP, weight or height between SS and SI in childhood or adolescence. Those with a family history of hypertension had a greater BP response to stress and greater weight change with sodium load. The group which was both SS and FH+ had the highest weight and MAP stress response after sodium load. These results indicate that sodium sensitivity is high among blacks, but does not correlate with childhood growth variables. Sodium sensitivity and FH+ combined produce the greatest stress-induced BP response.

Adolescent↗

In vitro cloning of tumor stem cells in semi-solid media containing agar and agarose.

The formation of tumor stem cell colonies in vitro has been studied by comparing the growth of three mouse teratocarcinoma derived cell lines and one human teratocarcinoma derived cell line in semi-solid media containing either agar or agarose. We show that agaroses should be used in higher concentrations than agar to obtain comparable results. The maximum number of colonies were obtained in agarose over a broader range of concentrations (1%-4% for SeaPrep and 0.5%-2% for SeaPlaque agarose) than in agar, which allowed anchorage-independent growth of tumor cells only over a narrow concentration range (0.3%-0.5%). Overall, the preparation of media containing agarose was less cumbersome than preparation of agar-containing media, primarily because agaroses gelled more slowly and remained liquid in the physiological temperature range. Furthermore, the transfer of colonies from semi-solid media containing agarose to solid surface tissue culture dishes was much more efficient than the transfer of colonies from agar. The stock solutions of SeaPrep agarose could be kept ready for use for extended periods of time. All these features show that the low melting point agarose has considerable advantages over agar for preparation of semi-solid media for anchorage-independent tumor cell growth.

Agar↗

Lymphocyte function in experimental endemic syphilis of Syrian hamsters.

We have studied the changes in the lymph nodes, spleen and thymus that occur in inbred LSH Syrian hamsters infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis, as well as the B-cell responses of these infected animals to helper T-cell independent and dependent antigens. The lymph nodes increased significantly in weight up to 6 weeks after infection, and contained viable treponemes. No significant changes in the spleen weight were observed, and no viable treponemes could be recovered from the spleen. However, the size of the thymus decreased steadily during the course of the disease. The relative number of Ig+ cells (B cells) increased in the spleen and regional lymph nodes, whereas the relative number of T cells decreased during the course of infection. In both the spleen and lymph nodes, the relative number of macrophages increased initially and decreased thereafter in the form of a bell-shaped curve showing a peak at 4-6 weeks of infection. The ability of splenic lymphocytes from infected hamsters to mount a primary PFC response to pneumococcal polysaccharide type III (SIII), a helper T-cell independent antigen, was elevated throughout the course of infection. However, the splenic PFC response to sheep erythrocytes (SRBC), a helper T-cell dependent antigen, was increased only during the first 4 weeks of infection and progressively decreased thereafter. The PFC responses of infected lymph node lymphocytes to both SIII and SRBC were increased during the first 4 weeks and decreased thereafter. These data suggested that atrophy of the thymus seen in syphilitic infection is accompanied by the complex losses of subsets of T cells and altered B-cell functions. An early loss of suppressor T cells in both the lymph nodes and spleen occurs concomitantly with a loss of T helper cells and heterologous (treponema-unrelated) B-cell functions in the lymph nodes. Helper T cells are lost from the spleen only in the later stages of infection, whereas splenic B-cell functions remain intact throughout the course of the disease. These findings were further tested by in vitro methods where splenic and lymph node lymphocytes from infected hamsters were examined for their ability to respond to Con A in terms of the induction of antigen non-specific suppressor T cells. The mixing of Con A stimulated splenic or lymph node lymphocytes from infected hamsters was unable to inhibit the primary antibody responses of SRBC as compared to the normal control.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effects of regional factors on the growth rate and the differentiation of mouse teratocarcinoma.

Murine embryonal carcinoma cells, the pluripotent stem cells of teratocarcinoma were injected simultaneously into caudal and cranial sites on the back of syngeneic recipients in order to determine whether regional anatomical differences affect their take and growth rate and differentiation. The overall tumour take rate was higher in caudal than cranial sites, but the initial weight of tumours was higher in the cranial than caudal sites. Tumours developing in the two anatomical sites grew at the same rate with a linear increase in volume. At the end of the 4-week experimental period the differences in the size of anterior and posterior tumours were negligible and no histological differences were noted between the two groups. Our data indicate that regional factors significantly affect the take rate and the initial growth of this murine teratocarcinoma, i.e. the establishment of solid tumours from injected stem cells. The growth rate of established tumours was not affected by regional factors.

Animals↗

A harmonic analysis of cardiac response of normotensive and hypertensive adolescents during stress.

In this paper, a statistical analysis is applied to the systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) data of 23 normotensive (NT) and 24 hypertensive (HT) adolescents who underwent a 10-minute mental stress regimen. Readings were measured at one-minute intervals. The harmonic time series analysis is based on the data of an eight-minute interval of the stress phase. The NT group established a statistically significant (p less than .05) rhythmic variation described by a sinusoidal wave about a near pre-stress mean. The HT group exhibits for the three parameters a near constant response about a significantly elevated level. The consistent existence of a rhythmic pattern for the NT subjects under mental stress, in contrast to the constant response for the HT subjects, suggests that mental stress causes a change in the "natural" rhythmic pattern of cardiac response for the HT subject alone.

Adolescent↗

Judgments by children and adults regarding communication skills of esophageal speakers.

The intelligibility and acceptability of esophageal speech were judged by a group of children and a group of adults. Eight esophageal speakers demonstrating a range of speech proficiency and differing vocal characteristics were videotaped reading a children's story. These recordings were played to child and adult judges. Data were analyzed to provide information about within-group and between-group comparisons. Findings indicated that children achieved higher intelligibility scores and employed different values than did adults when listening to esophageal speech.

Adult↗

Cardiovascular characteristics in adolescents who develop essential hypertension.

The risk parameters for the development of essential hypertension (EH) were evaluated in a group of adolescents with borderline hypertension. A population comprised of 50 adolescents with systolic or diastolic blood pressure between the 90th and 95th percentile was compared to a normotensive (less than 90%) family history-negative control population. Evaluative parameters included genetic risk, resting blood pressure, resting heart rate, and cardiovascular response to mental stress. In a follow-up period of up to 41 months, 28 borderline hypertensive adolescents (56%) developed fixed EH. At the time of initial evaluation, these 28 hypertensive adolescents had a strong family history of EH, higher resting heart rate (p less than 0.01) and blood pressure (p less than 0.01), and a greater cardiovascular response to mental stress (p less than 0.001) compared to the normotensive family history-negative control population. Time series analysis of the stress phase also demonstrated a rhythmic cardiovascular response in the normotensive group (p less than 0.05) that was not present in the hypertensive group. These results indicate that adolescents with borderline hypertension displaying these characteristics have a greater risk for EH than previously reported.

Adolescent↗