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Biomedical subjects

A Heller

Publications and source records attributed to A Heller.

At least 145 records · Page 8Linked to original sources
PubMed1989

The effects of nerve growth factor on the development of septal cholinergic neurons in reaggregate cell cultures.

Recent studies suggest that nerve growth factor is present within the central nervous system where it may exert selective trophic effects on cholinergic neurons. We have measured the effects of nerve growth factor on septal cholinergic neurons in three-dimensional reaggregating cell cultures, a system which closely simulates the cellular environment in situ. Septal cells obtained from 15-day-old mouse embryos were dissociated into a single cell suspension and then allowed to reaggregate in culture in a rotary incubator shaker. After 17 days in culture, half of the reaggregates from a flask were sonicated for measurement of choline acetyltransferase activity, and the remaining reaggregates were processed for acetylcholinesterase histochemistry. Addition of nerve growth factor to medium containing septal reaggregates resulted in greater than a three-fold increase in choline acetyltransferase activity and in the number of acetylcholinesterase-positive cells, as well as an enhancement in the staining of acetylcholinesterase-positive fibers. All of these effects of nerve growth factor could be neutralized by antibodies to nerve growth factor. In order to evaluate the possible role of endogenous hippocampal-derived nerve growth factor, antiserum to nerve growth factor was added to the culture media containing septal-hippocampal coaggregates. After 21 days in culture, the presence of nerve growth factor antibodies did not qualitatively affect the pattern or density of cholinergic fibers observed. Synapse formation between cholinergic axons and hippocampal target cells was still in evidence as revealed by electron microscopy. However, there was a modest decrease in choline acetyltransferase activity (20%) and cholinergic cell number (30%) when compared with coaggregates grown in culture medium either without nerve growth factor antiserum or with non-immune serum. The magnitude of these effects was markedly less than the effects observed when exogenous nerve growth factor was added to septal cells grown alone in reaggregate culture. These results suggest that nerve growth factor may play a role during central cholinergic development, but that additional trophic mechanisms are likely to be required.

Animals↗
PubMed1989

Longitudinal study of progestins, mineralocorticoids, and glucocorticoids throughout human pregnancy.

The maternal adrenal cortex seems to be involved in the adaptation to pregnancy. To study in detail adrenocortical secretion during pregnancy, we measured plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone simultaneously by RIA after extraction and automated Sephadex LH-20 chromatography of 10 normal pregnant women longitudinally throughout pregnancy at weeks 8-10, 14-17, 21-24, 28-32, and 38 as well as at the time of admission to the delivery room. The mean plasma progesterone and 17-hydroxy-progesterone concentrations increased from 37.2 +/- 6.5 (+/- SE) and 8.2 +/- 1.0 nmol/L, respectively, in early gestation to maximum levels of 138.0 +/- 25.7 and 22.8 +/- 2.2 nmol/L at week 38 (P less than 0.01). Plasma glucocorticoid levels rose 2- to 3-fold (P less than 0.01) from weeks 8-10 (corticosterone, 18.5 +/- 5.4; 11-deoxycortisol, 1.9 +/- 0.2; cortisone, 24.2 +/- 4.2; cortisol, 195.5 +/- 37.6 nmol/L) to week 38 (corticosterone, 42.9 +/- 11.2; 11-deoxycortisol, 4.6 +/- 0.5; cortisone, 71.5 +/- 13.6; cortisol, 420 +/- 63 nmol/L). Similarly, plasma mineralocorticoid levels increased 5- to 7-fold (P less than 0.01) from weeks 8-10 (11-deoxycorticosterone, 0.69 +/- 0.12; aldosterone, 0.41 +/- 0.08 nmol/L) to maximum levels at week 38 (5.3 +/- 0.9 and 2.1 +/- 0.3 nmol/L, respectively). At the time of admission to the delivery room, plasma 11-deoxycortisol, corticosterone, and cortisol concentrations were higher (P less than 0.02) than at 38 weeks, but plasma progestin and mineralocorticoid concentrations were not. We conclude that the source of the elevated maternal corticosteroid levels in pregnancy in addition to the estrogen-mediated rise in corticosteroid-binding globulin is the maternal adrenal cortex itself. The peak glucocorticoid levels at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor.

17-alpha-Hydroxyprogesterone↗
PubMed1988

The inheritance of Alzheimer's disease: a new interpretation.

Ninety-one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty-nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one-third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.

Age Factors↗
PubMed1988

Quantitation of neurochemically identified neurons in reaggregate tissue cultures.

The study of cellular interactions during the development of the nervous system is facilitated by the use of the reaggregate tissue culture system. In this system, embryonic neurons are dissociated from one another and allowed to reaggregate in rotatory culture, where they resume their normal differentiation. Reaggregates provide a model for studying neuronal development and cell interactions under conditions which allow for the control of a large number of variables, such as the numbers of cells which are allowed to interact, the presence or absence of appropriate target cells, and the chemical environment in which the neurons develop. For quantitative purposes, it is necessary to estimate the numbers of cells of a given neurochemical or morphologic type. Here we describe a computer-assisted counting system which allows one to determine the numbers of neurochemically identified neurons within reaggregate cultures from the counting of such neurons in a randomly selected sample of thirty 10-micron sections from the reaggregates in a given flask. These sections represent less than 0.5% of the total number of sections derived from the reaggregates in a single flask. In addition, the system allows one to quantitatively compare differences in the numbers of such neurons between experimental flasks utilizing appropriate statistical methods. A comparison of the number of central dopaminergic neurons estimated by this method with the direct counting of such neurons in serial sections of single reaggregates resulted in excellent agreement as to the number of dopaminergic neurons within a given experimental flask.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Ultrastructural evidence for hippocampal target cell-mediated trophic effects on septal cholinergic neurons in reaggregating cell cultures.

We have previously demonstrated at the light microscopic level that when embryonic day-15 septal neurons are co-cultured for 21 days with their target cells from the hippocampus, increased numbers of septal cholinergic neurons are present as compared with co-cultures employing cells from the non-target cerebellum. In addition, fine varicose axon-like cholinergic fibers are found to be associated with the hippocampal cells but not with cerebellar cells. We now provide ultrastructural evidence for hippocampal target cell-enhanced cholinergic neuronal survival, axonal proliferation, and synapse formation in this culture system. Dissociated cell suspensions from septal, hippocampal, and cerebellar areas were obtained from 15-day mouse embryos; and hippocampal and cerebellar cells were internally labeled with rhodamine-conjugated wheat germ agglutinin. Combinations of septal and hippocampal cells, and septal and cerebellar cells were allowed to reaggregate in rotation mediated culture for either 15 or 21 days. The reaggregates were then fixed, embedded, sectioned, and processed for acetylcholinesterase-positive acetylcholinesterase-positive cells and fibers, and under fluorescence to locate rhodamine-labeled cell populations. Representative reaggregate profiles were then re-embedded for electron microscopic examination. In both types of reaggregates, either labeled hippocampal target or cerebellar non-target cells segregated from the septal cells so that areas containing each of the respective cell populations could be studied. In sections of septal-hippocampal reaggregates from 15-day cultures, 571 out of 665 (85%) cholinergic neurons examined were intact, whereas 15% of the cells showed some ultrastructural features of degeneration. Similarly, at day 21, 297 out of 335 (88%) of the cholinergic neurons were intact. In sections of septal-cerebellar reaggregates from 15-day cultures, 473 out of 572 (83%) cholinergic neurons were intact. By day 21 of culture, however, only 15 out of 110 (14%) cholinergic neurons examined were intact from the septal-cerebellar reaggregates. In areas of septal-hippocampal reaggregates occupied by rhodamine-labeled hippocampal cells, profiles of acetylcholinesterase-labeled axons were identified, and synaptic specializations were observed between cholinergic terminals and dendrites as well as somata of hippocampal target cells. In contrast, areas of septal-cerebellar reaggregates occupied by rhodamine-labeled cerebellar cells were devoid of cholinergic fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1988

Expected diabetic control in childhood and psychosocial functioning in early adult life.

This study examined relationships between the extent to which doctors seek to achieve good (i.e., tight) diabetic control during childhood and the frequency of psychosocial problems in later life. A sample of 225 young adults with insulin-dependent diabetes mellitus was studied by use of a systematic interview. A measure of the level of control the doctor was attempting to achieve was developed from questionnaires administered to the doctors who provided most of the patient's care during childhood. The results were compared with scores on three indices of psychosocial functioning based on responses given in structured interviews with the patients. Although potentially important psychosocial problems were found for 10-20%, there was no statistically significant relationship between any of these problems and the doctors' desired levels of control. Thus, efforts to achieve good control during childhood, whether successful or not, may not be followed by psychosocial problems in later life. This finding should help support clinicians' attempts to obtain the levels of control during childhood judged to be essential in preventing serious organic complications.

Adaptation, Psychological↗
PubMed1987

Neurotoxic effects of methamphetamine assessed in three-dimensional reaggregate tissue cultures.

Three-dimensional, rotation-mediated, reaggregate tissue cultures formed from dissociated fetal rostral mesencephalic tegmental (RMT) and corpus striatal (CS) or frontal cortical (FCx) cells were used to study methamphetamine neurotoxicity. Analysis of dopamine (DA), serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels using HPLC techniques revealed decreases in RMT-CS and RMT-FCx reaggregate DA and 5-HT levels after treatment between 14 and 21 days in culture with methamphetamine in concentrations ranging from 10(-6)M to 10(-3)M. Dopamine cell numbers in RMT-CS and RMT-FCx reaggregates were estimated after visualization by histofluorescent techniques. Methamphetamine treatment caused decreases in DA cell numbers which paralleled the decreases in endogenous DA levels. Estimates of the accumulation of exogenous DA by RMT-CS reaggregates treated with methamphetamine showed that the amount of accumulation per cell remained fairly constant despite marked reductions in total DA cell numbers. This suggests that the reductions in endogenous DA levels following methamphetamine were secondary to loss of entire DA neurons rather than of a portion of the terminal axonal fields in the surviving neurons. Reaggregate tissue cultures are a useful tool in the study of potential neurotoxic effects of new or untested psychotherapeutic agents.

Animals↗
PubMed1987

Neurotrophic effects of hippocampal target cells on developing septal cholinergic neurons in culture.

The influence of hippocampal target cells on the development of cholinergic septal neurons was studied in rotation-mediated reaggregating cell cultures. Brain cells from 15-day-old mouse embryos were obtained from: septum, containing cholinergic cells which project to the hippocampus; hippocampus which contains target cells for the septal cholinergic neurons; and cerebellum, containing cells which are not targets for the septal cholinergic cells. The cells were then cultured for 3 weeks in a rotary incubator in the following combinations: septal cells alone; hippocampal cells alone; cerebellar cells alone; septal-hippocampal cells together; and septal-cerebellar cells together. After harvesting, fixation, and embedding, 50 micron sections were cut and processed for visualization of acetylcholinesterase activity. Sections from reaggregates containing either hippocampal or cerebellar cells alone contained only a few acetylcholinesterase-positive cells, but no positive fibers. Sections from septal-hippocampal coaggregates revealed a pattern of well-defined, fine-caliber acetylcholinesterase-positive fibers with extensive arborizations and varicosities suggesting axonal proliferation. In septal-cerebellar coaggregates, acetylcholinesterase-positive fibers appeared to be degenerating and distinct areas were observed which were essentially devoid of acetylcholinesterase fibers. In some experiments, either cerebellar or hippocampal cells were labeled with wheatgerm agglutinin-rhodamine prior to culture in order to identify these cells in the resulting reaggregates. Analysis of sections from these studies showed that acetylcholinesterase fibers were excluded from regions of coaggregates containing cerebellar cells, but were present in regions of coaggregates containing hippocampal cells. Finally, cell counts of acetylcholinesterase-positive cells in the various combinations revealed that these putative cholinergic neurons were significantly more numerous in septal-hippocampal coaggregates (271 +/- 19 per 10(6) septal cells added) than in septal reaggregates (38 +/- 6 per 10(6) septal cells added) or septal-cerebellar coaggregates (85 +/- 29 per 10(6) septal cells added). These results, taken together, suggest that hippocampal target cells influence the development and survival of cholinergic neurons.

Acetylcholinesterase↗
PubMed1987

Arm function after stroke: measurement and recovery over the first three months.

Four short, simple measures of arm function, suitable for use with patients recovering from acute stroke, are described. These tests are: the Frenchay Arm Test, the Nine Hole Peg Test, finger tapping rate and grip strength. Good interobserver and test-retest reliability was demonstrated for all tests, and the Frenchay Arm Test was shown to be valid. Normal values for all tests were established on 63 controls. It was found that the limited sensitivity of the Frenchay Arm Test could be improved using the Nine Hole Peg Test and grip strength. Recovery of arm function has been studied in a sample of 56 patients seen regularly over the first 3 months after their stroke, using these standard measures. The results demonstrated a wide variation in recovery curves between patients. The use of the Nine Hole Peg Test enabled further recovery to be detected after patients achieved a top score on the Frenchay Arm Test. Failure to recover measureable grip strength before 24 days was associated with absence of useful arm function at three months. Measurement of finger tapping rate was not useful.

Aged↗
PubMed1987

Walking after stroke. Measurement and recovery over the first 3 months.

Sixty surviving patients had their walking ability and speed assessed regularly over the first 3 months after an acute stroke. Sixty-four matched controls were studied to allow categorisation of speed as 'slow' or 'normal'. Fourteen patients never had any significant loss of walking speed; fifteen patients never recovered the ability to walk and one patient remained dependent upon verbal support. Of the 30 showing significant recovery, only 10 regained normal speed, and 8 remained dependent upon a physical aid at 3 months. Plotting individual recovery curves of walking speed over time showed the wide range of change which may be expected. It is argued that timing of gait over 10 metres is a valid reliable measure that is currently underused.

Adult↗
PubMed1986

Neuronal properties of clonal hybrid cell lines derived from central cholinergic neurons.

Clonal cell lines derived from specific types of central neurons can be used to identify and characterize properties specific to those neurons. With somatic cell fusion techniques, nine clonal hybrid cell lines have been developed from the septal region of the mouse basal forebrain. Two lines express characteristics typical of cholinergic neurons--choline acetyltransferase activity and immunoreactivity, neurite formation with neurofilament protein immunoreactivity, and aggregation in rotation-mediated cell culture. These cell lines may be useful for studying the trophic interactions that support the development and maintenance of central cholinergic connections.

Animals↗
PubMed1986

[Incidence of pollinosis in Switzerland. Results of a representative demographic survey with consideration of other allergic disorders].

In a survey carried out between January and April 1985 covering all of Switzerland except the Canton of Ticino and including 2524 males and females (49% and 51% respectively) aged 15 to 74 years, the subjects were interviewed regarding pollinosis symptoms during the pollen season of 1984 and in previous years, and questioned about other allergic symptoms. Individuals with pollinosis or with family members suffering from pollinosis received an additional questionnaire. This first extraterritorial survey of Switzerland showed that every tenth Swiss aged 15 or over suffers from hay fever (incidence 9.6%). In addition, 3% had suffered from pollinosis previously. In the 15-24 age group the incidence was 16%. It fell with advancing age and was only 4.2% in the over-60 age group. No statistically significant differences were found between incidences in town (9%) and country (10%) and between the sexes. Hay fever morbidity in individuals with higher education (14.5%) and in certain occupations (student, apprentice - 21%) and among job levels "manager, senior civil servant, senior employee" (13.8%) was higher than in other categories. This representative survey confirmed that in Switzerland hay fever is commoner than in 1926 and 1958. The symptoms of pollen allergy are known: symptoms predominate in May (53%) and June (62%) including rhinitis in 94%, conjunctivitis in 82% and asthma in 24%. In 11% pollen allergy was already manifest in the first four years of life, in 62% before puberty and in 80% before the age of 20.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect.

A metabolic bone disease characterized by a mineralization defect, low plasma 1,25(OH)2D, and hypercalciuria has been described in patients receiving prolonged total parenteral nutrition (TPN). Because the practice of TPN differs from center to center, we investigated 13 home TPN patients to determine whether they had similar or different bone abnormalities. They had received TPN for a mean period of 51 +/- 38 mo. Bone pain occurred in six patients and two had multiple vertebral and rib fractures (with trauma in one patient). Bone pain was mild to moderate and not incapacitating. Bone histomorphometry showed reduced bone volume, reduced osteoid with normal resorption and calcification rates. These abnormalities were associated with hypercalciuria, but the plasma levels of 1,25(OH)2D were normal. Abnormalities in bone metabolism in this group of patients suggest a fundamental decrease in bone matrix-formation rather than a mineralization defect as the underlying mechanism.

Adult↗
PubMed1985

Birth defects and psychosocial adjustment.

A one-year prospective study was conducted to examine the extent to which type of disability, severity, and family functioning serve to predict maladjustment. One hundred forty children, aged 4 to 13 years, born with cardiovascular disorders, cleft lip or palate, or hearing defects were assessed using the Child Behavior Checklist at two points in time. The results suggest that the type of disorder and severity are associated with remaining or becoming maladjusted. Deaf girls and boys with cardiac problems were most likely to be affected, followed by boys with clefts and boys with hearing problems. A direct relationship is found with severity assessed by the Functional Status Measure. Family functioning, however, is not significantly related to maladjustment. These findings provide a framework for better understanding factors contributing to the increased risk of maladjustment for some children with birth defects.

Adaptation, Psychological↗
PubMed1985

Serum interferon as a biological marker in malignant tumors.

A total of 745 serum interferon (IFN) determinations were carried out on the serum of 332 cancer patients with a variety of tumors. Disease activity was defined as either 'active' or 'nonactive' as based on clinical examination, the results of laboratory tests and radiological criteria. IFN levels were estimated for both disease activity and mode of treatment. A statistically significant higher level of IFN in the serum of active, as compared to that of nonactive disease, was established. Furthermore, a slight increase in the IFN level was observed in patients before initiating chemotherapy as compared to untreated patients, followed by a decrease in those patients undergoing chemotherapy. These differences between groups were not found to be statistically significant. However, in the cases of rectum, prostate and female genital cancers, a significant elevated level of serum IFN was observed at a late stage of the disease, followed by a decrease after chemotherapy treatment. In addition, a significant lower level of serum IFN was detected in breast cancer patients shortly after radiotherapy as compared to those before radiotherapy. We conclude that IFN, known to play a role in the control mechanisms of developing malignant processes, can be determined in the serum and used to monitor disease activity in individual patients. The inhibition of IFN release depends in part on therapy and can be used for monitoring treatment schedules along the course of disease.

Antineoplastic Agents↗