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Biomedical subjects

E Haus

Publications and source records attributed to E Haus.

At least 55 records · Page 3Linked to original sources

Lymphopenia in primary degenerative dementia.

The central nervous and immune systems share a number of common properties, e.g. neurotransmitter receptors. In contrast to age matched healthy and/or hypertensive controls, the total lymphocyte count in 25 carefully diagnosed and staged patients with primary degenerative dementia were significantly reduced and also correlated with the severity of their dementia. Subjects' age, age of dementia onset, or duration of illness were unrelated. Total leukocyte counts were similar between groups. Nutritional status, ACTH, or plasma cortisol in dementia cohort were also not explanatory of their lymphopenia. These results are potentially significant in light of an immune hypothesis for primary degenerative dementia: Alzheimer's type and/or that population's high concomitant risk of infection.

Adrenocorticotropic Hormone↗

Signal transmission after GLP-1(7-36)amide binding in RINm5F cells.

Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], probably representing an important incretin, binds to receptors on RINm5F cells resulting in an adenosine 3',5'-cyclic monophosphate increase. Guanine nucleotides (GTP, GTP-gamma-S, GDP-beta-S) decreased the binding of GLP-1(7-36)amide to receptors on RINm5F cell membranes. Further analysis revealed that GTP (10(-4) M) decreased the receptor affinity with an increase of the Kd from 2.5 +/- 0.99 x 10(-10) M to 9.43 +/- 2.16 x 10(-10) M. In cross-linking experiments the amount of labeled peptide linked to receptors was reduced in the presence of GTP (10(-4) M). Further studies investigated the involvement of membrane depolarization or changes in the cytosolic free calcium level in the intracellular signaling of GLP-1(7-36)amide-induced insulin secretion. In contrast to fuel and nonfuel secretagogues, GLP-1(7-36)amide did not cause a depolarization of the membrane potential. This was unaffected by various glucose concentrations (0-20 mM) or by previous cell depolarization by D-glyceraldehyde. Similarly, the cytosolic calcium concentration remained unchanged after addition of GLP-1(7-36)amide (10(-12)-10(-8) M). The effect of guanine nucleotides on binding of GLP-1(7-36)amide indicates that the action of the peptide is mediated by the adenylate cyclase system. GLP-1(7-36)amide binding neither changed the membrane potential nor altered the intracellular calcium concentration, making an involvement of the inositol 1,4,5-trisphosphate pathway or an activation of protein kinase C in the postreceptor signaling after GLP-1(7-36)amide binding unlikely.

Adenoma, Islet Cell↗

Circadian hematologic time structure in the elderly.

Twenty-three clinically healthy, diurnally active elderly subjects, 71 +/- 5 years of age were studied over a 24-hr span (six samples). Complete blood counts and differential counts were done (Ortho ELT-8, Wright stained smears). The circadian rhythm parameters of the hematologic variables in the elderly subjects were compared with reference values obtained from a larger group of clinically healthy young adult and adult subjects studied independently. The data were analyzed by cosinor and the Bingham test. Circadian rhythms in the number of circulating formed elements in the peripheral blood persist in the aged. In comparison with the young adult, the elderly subjects show differences in the timing (phase advance) of the circadian rhythms in circulating neutrophil leukocytes and lymphocytes, a decrease in the circadian amplitude of circulating platelets, a decrease in circadian rhythm adjusted mean (mesor) in the red cell count, and in the neutrophil band forms.

Aged↗

Chronobiology, growth hormone and healthy and malignant growth.

Chronobiology, the computer-aided science (logos) of life (bios) in time (chronos), provides novel concepts, tools and facts for those concerned with mitosis, growth and growth hormone (GH). GH concentrations in human plasma demonstrate a statistically significant circadian rhythm on a 6h as well as on a 24h rest-activity cycle. On a 24h routine of light (L) and darkness (D), alternating at 12h intervals, and in continuous D, circadian mitotic rhythms in mice persist as a feature of growth or regeneration. A circadian cell cycle commences with an increase in phospholipid labeling, followed by an increase in cytoplasmic RNA formation, preceding, in regular sequences, an increase in nuclear DNA formation and the next mitotic peak in those cells that are dividing in a growing or regenerating (reversibly "post-mitotic') rodent liver. About 5-day (presumably estral) and about 7-day (circaseptan) components as well as circadians are resolved as a spectrum of mitotic rhythms in rodent cornea. The effects of hormones such as GH or a synthetic ACTH analogue, ACTH 1-17, depend upon the circadian cell cycle stages when the agent is administered. No effect or statistically significant effect can be the result only of 1) the timing of a fixed dose of GH or 2) of the timing of the samples taken to investigate any effect. For both the timing of administration and the assessment of effects, a multifrequency spectrum of rhythms, if taken into account, can provide (in lieu of a considerable and often formidable source of variation) a new critical dimension of growth and development.

Adolescent↗

[Blood levels of dehydroepiandrosterone sulfate (DHEA-S) and the risk of breast cancer].

In North American women at low or high risk of developing breast cancer, as assessed by an epidemiologic questionnaire, the plasma concentration of dehydroepiandrosterone sulfate shows a statistically significant circannual variation. In adolescents, in all seasons, circulating dehydroepiandrosterone sulfate is a classifier of the risk of developing breast cancer, a relatively low concentration of this hormone being associated with an increased risk.

Adolescent↗

Peculiarities of the endocrine time structure in noninsulin-dependent adult-onset (type II) diabetes mellitus.

Twenty noninsulin-dependent elderly diabetic patients, ten of whom were treated by oral hypoglycemic agents and ten of whom were regulated by diet alone, and 20 clinically healthy subjects matched for age, sex, height, and weight were examined with six blood and six urine samples at 4-hr intervals over a 24-hr span. Plasma ACTH, cortisol, aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were determined by radioimmunoassay (RIA); epinephrine, norepinephrine, and dopamine in urine were determined by high-pressure liquid chromatography (HPLC); and magnesium in urine was determined colorimetrically on a DuPont ACA. There were a number of changes in some of these functions in type II diabetic patients with and without oral hypoglycemic agents that appear to be of interest. The circadian mean in plasma ACTH concentration in diabetic patients with and without oral hypoglycemic agents is significantly higher than in matched nondiabetic controls. The plasma aldosterone concentration is similar in type II diabetics treated by diet only and in matched controls but is statistically significantly elevated in patients on oral hypoglycemic agents. Correspondingly, the urinary excretion of sodium in type II diabetic patients on oral hypoglycemic agents is lower than in matched controls. The plasma cortisol concentration is unchanged in type II diabetic patients treated by diet alone but shows a slight increase in patients on oral hypoglycemic agents. The circadian means of plasma DHEA-S concentration is slightly higher in diabetic patients with and without oral hypoglycemic agents than in matched controls. This elevation, however, does not quite reach the 95% level of statistical significance. Urinary norepinephrine excretion in type II diabetic patients is similar to that in matched controls. The urinary epinephrine excretion in diabetics with and without oral hypoglycemic agents, however, was lower than in controls, and the urinary excretion of dopamine was higher in the diabetics. The urinary magnesium excretion in type II diabetic patients was lower than in matched controls.

Adrenal Cortex Hormones↗

Circadian reference values for hematologic parameters in several strains of mice.

The circadian rhythms in the numbers of circulating formed elements in the peripheral blood were studied in 712 CD2F1, 188 BDF1, and 250 Swiss Webster mice kept under a lighting regimen of LD 12:12 (L 0600 to 1800 hr), a room temperature of 21 +/- 1 degree C, and food and water available ad libitum. The circadian rhythms were evaluated by the single cosinor procedure. The rhythm parameters--mesor, amplitude, and acrophase--the percentage of total variability attributable to the circadian rhythm, and the extent of the circadian rhythm are presented as guidelines for experimental design and evaluation. Under the conditions of this study, the mice of all three strains and both sexes show circadian variations, which are similar in their timing, in their red and white cell parameters. The percent of the total variance attributable to the circadian rhythms of each function varies between the strains studied in our laboratory being lowest in the Swiss Webster female mice. The extent of the circadian variation as expressed by the double amplitude as percent of mesor is similar in the three strains and between males and females. In relation to rest and activity spans, the hematologic circadian time structure in the nocturnally active mouse is different from that in diurnally active human subjects. The red-cell parameters show an acrophase in the middle of the rest span instead of the middle of the activity span as in human subjects. The lymphocytes and eosinophils in the mouse show an acrophase during the rest span that is similar to human subjects. In contrast to human subjects, however, neutrophils and monocytes show their acrophase in the first half of the rest span rather than during the second half of the daily activity span. The circulating formed elements in the peripheral blood thus follow a different circadian timing in the mouse than in human subjects; this has to be kept in mind when the time structure of the two species is compared, e.g., in models for experimental chemotherapy.

Animals↗

Circaseptan rhythm in sodium and potassium excretion in salt-sensitive and salt-resistant Dahl rats.

Six salt-sensitive (S) and six salt-resistant (R) male Dahl rats were housed in metabolic cages under LD 12:12 (L 0600-1800). High-salt (8%) and low-salt (0.4%) diets were available to half the S and R rats, respectively for 4 hr during a 24-hr span (feeding 1800-2200). Urine was collected at 4-hr intervals for 30 days. Sodium and potassium were determined by ion-specific electrode. Apart from circadian rhythmicity, a circaseptan rhythm in sodium and potassium excretion came to the fore in the rats on the high-salt diet only, with a phase difference of about 180 degrees between sodium and potassium. These rhythms were not detectable in the animals eating their usual-low salt diet. The ability to induce circaseptan variations in renal function may lend itself to the chronotherapeutic utilization of such cycles in achieving optimal therapeutic effects or minimizing undesirable side effects of different forms of treatment.

Animals↗

Circadian urinary characteristics of adolescents: sensitive dynamic indices complement mean values as new physiologic endpoints.

To introduce the study of physiologic urinary rhythms into secondary education, six girls and 11 boys, 14-18 years of age, collected urine at about 3-hr intervals for 24 hr. The volume and the excretion in urine of creatinine, potassium, and sodium were determined. Blood pressure was measured during the same 24-hr span to teach the students some elements of chronobiologic sampling and analysis in the context of evaluating the risk of developing a high blood pressure later in life. Herein, we examine on urinary excretory rates whether dynamic chronobiologic endpoints such as the amplitude (A) and/or acrophase (phi) may complement the more static mesor (M) in distinguishing groups of adolescents. In a comparison of the two sexes, dynamic characteristics of the urinary excretion of sodium and of the ratio of sodium/potassium do not separate the two groups, while the M does so. The reverse holds true for the excretion of potassium. In the case of urinary creatinine, the circadian A in itself is an index suggesting a "sex" difference; whereas in urinary volume, the M alone, and to a lesser extent the combination of (M, A, phi), yields a P value below the 5% level. The groups are rather small and heterogeneous; a study of ethnicity is beyond our scope. These qualifications notwithstanding, results indicate the need for testing multiple chronobiologic characteristics in comparing groups whether one's interest in the future relates to ethnicity, sex, or other factors. Such studies of urinary rhythms of high-school students serve for instruction and research and to instill responsibility for self-help in preventive health care.

Adolescent↗

Circadian and circannual variations of thyroid function in children 11 +/- 1.5 years of age with and without endemic goiter.

A group of 194 children 11 +/- 1.5 years of age from Tirgoviste, Romania, an endemic goiter area, were studied over a 24-hr span (six blood samples at 4-hr intervals) during all four seasons. One hundred thirty-four of the children had some clinical evidence of endemic goiter, and 60 had none. Total and free T3 and T4, reverse T3, thyroglobulin, thyroxin-binding globulin (TBG; three seasons only), and TSH were studied. The circadian rhythms were analyzed by cosinor and the circannual variations by ANOVA. Children with and without endemic goiter showed circadian rhythms in all functions studied except free T4 for which no statistically significant rhythm was detected in the children with goiter. There were differences in the acrophase of total T3, free T3, and TBG, with phase advance in the children with goiter in total T3 and free T3 and a phase delay in TBG. Mesor and amplitude showed no differences except in total T4 for which the amplitude in the children with goiter was statistically significantly lower than in the children without goiter. Children with and without endemic goiter showed seasonal variations in total T4 and free T4 as well as total T3, free T3, and reverse T3, with the highest values in the fall; in thyroxin-binding globulin the highest values were in the winter; and in TSH the highest values were in the summer. There was no significant seasonal variation in thyroglobulin. There was no difference in the circannual variation between children with and without endemic goiter.

Child↗

Circannual variations in blood pressure, urinary catecholamine excretion, plasma aldosterone, and serum sodium, potassium, calcium, and magnesium in children 11 +/- 1.5 years of age.

A total of 194 clinically healthy children 11 +/- 1.5 years of age were studied during different seasons. Systolic and diastolic blood pressure were determined by auscultatory endpoints, and blood and urine were collected at 4-hr intervals over a 24-hr span. Urinary norepinephrine, epinephrine, and dopamine were determined by HPLC, plasma aldosterone by RIA, serum sodium and potassium by ion-specific electrode, and calcium and magnesium by colorimetry. The circadian means showed statistically significant circannual variations in all variables except epinephrine. The highest circadian means of systolic and diastolic blood pressure and of urinary norepinephrine occurred during winter; the highest values of plasma aldosterone, serum potassium, and urinary dopamine were found in fall, those of serum calcium and magnesium during the summer, and that of serum sodium in spring. Circannual rhythms characterize functions related to blood pressure regulation in children. The circannual elevation of blood pressure (within the usual range) and of norepinephrine were both found to occur in winter. This time relation may have a functional significance, although a causal relationship is not proven by the temporal coincidence of two rhythms.

Aldosterone↗

Chronobiology of catecholamine excretion in different age groups.

Urine was collected at 4-hr intervals over a 24-hr span in 87 boys and 106 girls 11 +/- 1.5 years of age and over one or several 24-hr spans in 62 elderly men and in 85 elderly women 77 +/- 8 years of age. Epinephrine, norepinephrine, and dopamine were determined by HPLC. The data were analyzed by cosinor and by one-, two-, and three-way ANOVA. Children and elderly subjects showed circadian rhythms of urine volume and of the excretion of norepinephrine, epinephrine, and dopamine. While the urine volume was higher in the elderly subjects than in the children, norepinephrine, epinephrine, and dopamine excretion in the girls and epinephrine in the boys showed a statistically significantly higher mesor than in the elderly subjects of the same sex. There was a sex difference, with lower values in all variables in the girls and women compared to their male counterparts; the circadian amplitudes of norepinephrine, epinephrine, and dopamine in the girls and of epinephrine in the boys were higher than the circadian amplitudes in the elderly subjects. The circadian timing in urinary excretion between the elderly subjects and the children was different, with a consistent phase delay; the acrophase of the circadian rhythm in the elderly subjects moved in the night hours. In contrast, there was no age difference in the acrophase of norepinephrine and epinephrine excretion or in dopamine in the females. In the males, the circadian rhythm in dopamine excretion in the elderly subjects did not quite reach statistical significance at the P less than 0.05 level. Circannual variations with high values in winter and low values in spring and summer were found in norepinephrine excretion in boys, girls, and elderly women, but not in elderly men. In neither age group was there a statistically significant seasonal variation in epinephrine. Only in girls was a statistically significant circannual rhythm in dopamine excretion found, with highest dopamine values in the fall and lowest values in winter and spring.

Age Factors↗

Circannual rhythms of laboratory measurements in serum of elderly subjects.

A total of 160 elderly subjects 77 +/- 8 years of age were studied in 201 24-hr profiles consisting of six blood samples collected at 4-hr intervals. The sampling sessions were spread over all four seasons. The circadian means were analyzed (one-way ANOVA) for the presence of circannual variations. Statistically significant circannual variations were found in the serum concentrations of albumin, bilirubin, calcium, chloride, CPK, globulin (calculated), glucose, LDH, potassium, sodium, triglycerides, uric acid, and total protein. The data presented indicate that many chemical constituents commonly measured in human serum and urine show seasonal variations in elderly subjects, some of which are large enough to present potential diagnostic problems. Others may not pose diagnostic problems in today's practice of laboratory medicine, but indicate seasonal changes in metabolic functions or, if endogenous in nature, circannual rhythms that may be of physiologic and pathobiologic importance. There is a need to quantify certain of these rhythms as a predictable portion of variability in laboratory values and presumably as an indicator of human health.

Aged↗

Individualized principal component analysis of endocrine circannual variability.

The technique of principal component (PC) analysis (PCA) of multivariate observations is a method that allows dimension reduction of multivariate data for further analysis. It is here introduced as a means of selecting chronobiologically important variables that can be further studied by an analysis of variance. The use of PCA is illustrated for a study of major temporal sources of human endocrine variability. Contributions to temporal variability by seven steroidal and six nonsteroidal hormones are compared in samples available at 100-min intervals for 24 hr in three seasons for each of three clinically healthy individuals: an adolescent woman, a menstrually cycling woman, and a postmenopausal woman. On an individualized basis, it is ascertained that the first principal component, a new variable, is primarily determined by steroids and that PCA can single out variables displaying interseasonal (circannual) differences validated as statistically significant by a subsequent analysis of variance. The variables here scrutinized and identified as contributing to the PC, however, need not all differ with statistical significance along the scale of the seasons. The steroids contributing the first principal component are DHEA-S and an estrogen in all three individuals studied, cortisol and aldosterone in two of them, and 17-OH progesterone in one case.

Adolescent↗

Endocrine factors of blood pressure regulation in different age groups.

Systolic and diastolic blood pressures were measured and blood and urine were collected at 4-hr intervals over a 24-hr span in 194 diurnally active children 11 +/- 1.5 years of age and in 278 elderly subjects 77 +/- 8 years of age. Plasma aldosterone and cortisol were determined by radioimmunoassay, serum calcium and magnesium on a Dupont ACA, and urinary epinephrine and norepinephrine by high-pressure liquid chromatography. In the children, there was a slight but statistically significant positive correlation between the circadian means in systolic blood pressure and norepinephrine excretion and serum calcium, and between diastolic blood pressure and norepinephrine excretion and serum calcium and magnesium. In the elderly subjects, there was a positive correlation between the circadian mean in diastolic blood pressure and aldosterone. In contrast to the findings in the children, however, the elderly subjects showed a negative correlation between the circadian means in norepinephrine excretion and in systolic and diastolic blood pressures. These investigations indicate differences in the regulation of the blood pressure within the "usual range" between children and elderly subjects. This has to be kept in mind in the study of essential hypertension, a syndrome that may be caused by different mechanisms in different age groups.

Age Factors↗

Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation.

Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.

Adenocarcinoma↗

Circadian characteristics of urinary melatonin from clinically healthy young women at different civilization disease risks.

Rhythm characteristics in the about-daily (circadian) and about-yearly (circannual) frequency ranges were assessed for urinary melatonin. Clinically healthy women in Minnesota, USA, and Kyushu, Japan, were sampled around the clock once in 1-4 seasons. Possible differences that could reflect the large difference in breast cancer incidence in these two geographic locations were investigated. Each subject's risk of developing breast cancer, cardiovascular diseases resulting from an elevated blood pressure, and emotional conditions was numerically evaluated according to epidemiologic questionnaires. A prominent circadian rhythm characterizes urinary melatonin in both populations, peaking in the middle of the night. The American women exhibit a larger circadian rhythm-adjusted mean (mesor) than do the Japanese women. A circannual rhythm is also apparent in the North American women, but not in the Japanese women. The circadian mesor of urinary melatonin correlates negatively with the risk score of emotional depression and positively with that of developing cardiovascular diseases.

Adolescent↗