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Biomedical subjects

G Mor

Publications and source records attributed to G Mor.

At least 55 records · Page 3Linked to original sources
PubMed1996

Synaptic remodeling in the arcuate nucleus during the estrous cycle is induced by estrogen and precedes the preovulatory gonadotropin surge.

We have shown that the ovarian cycle is accompanied by a fall in the axosomatic synapses on randomly selected neurons of the arcuate nucleus by the morning of estrus, with a return to the preovulatory levels by the morning of metestrus, indicating a possible role in positive feedback. However, it remains to be proven that the circulating estradiol is the actual regulator of this physiological synaptic plasticity, or that estrogen-induced synaptic retraction precedes in the surge of gonadotropins at midcycle. To resolve these questions, we used an estradiol-immunoneutralization protocol and studied arcuate nucleus axosomatic synapses during the critical points of the estrous cycle. In addition to blocking positive feedback, estrogen immunoneutralization abolished synaptic retraction in the arcuate nucleus. As a positive control, the nonbinding estrogen diethylstilbestrol maintained the gonadotropin surge and synaptic retraction in the antiestradiol-treated animals. Furthermore, in the diluent-treated cycling control females, the synaptic retraction was found to precede the preovulatory LH surge. We demonstrated that the midcycle synaptic retraction of arcuate nucleus synapses is induced by the preovulatory estradiol surge, and that these morphological events precede the preovulatory gonadotropin surge. Taken together, these observations strongly suggest that the hypothalamic mechanism underlying the physiological disinhibition of gonadotropins at midcycle (positive feedback) requires estrogen-induced synaptic retraction in the arcuate nucleus.

Animals↗
PubMed1996

Anti-idiotypic antibody as an oestrogen mimetic in vivo: stimulation of creatine kinase specific activity in rat animal models.

Previous studies indicated that the anti-idiotypic antibody (clone 1D5) significantly increased the specific activity of creatine kinase (CK) activity in the rat uterus, and in vitro in skeletal cells capable of responding to oestradiol (E2), suggesting that the antibody has oestrogenic-like activity. Moreover, the F(ab')2 dimer of clone 1D5 acted like an antagonist and completely inhibited the increase in CK specific activity by either E2 or clone 1D5 in these skeletal cells. In the present study, we examined the in vivo effects of clone 1D5 and its proteolytic fragment, the F(ab')2 dimer, E2 and dihydrotestosterone (DHT) on CK specific activity in the epiphyseal cartilage, diaphyseal bone, uterus, prostate, thymus and pituitary of immature or gonadectomized female and male rat animal models. In the intact immature animals, clone 1D5 caused an increase in CK in all organs of the female except in the pituitary. In the diaphyseal bone and prostate of male rats there was no stimulation by 1D5. The CK response in the uterus, epiphysis, and diaphysis of immature female rats was dose-dependent and was blocked by either the anti-oestrogen tamoxifen or the F(ab')2 dimer of clone 1D5. E2, DHT, as well as clone 1D5, stimulated CK specific activity in both the diaphysis and epiphysis of ovariectomized female and castrated male rats, whereas sex specificity in the CK response was observed also in the uterus and the prostate of gonadectomized animals. Collectively, these results suggest that, as in cell culture, an intact antibody is necessary for the observed stimulation of CK specific activity and the F(ab')2 dimer can act as an antagonist. Furthermore, the observed biological effects of clone 1D5 which are absolutely parallel to E2, imply that the anti-idiotypic antibody is able to penetrate the cell and reach the nuclear oestrogen receptor and transduces a signal to the nucleus, by as yet uncharacterized mechanisms.

Animals↗
PubMed1996

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

Aged↗
PubMed1995

Complexity of the cytokine and antibody response elicited by immunizing mice with Plasmodium yoelii circumsporozoite protein plasmid DNA.

The number, type, and location of cytokine- and Ab-secreting cells activated in mice immunized and boosted with plasmid DNA encoding the circumsporozoite protein of the malarial parasite Plasmodium yoelii (PyCSP) were monitored. The initial humoral response was localized to the draining lymph nodes and was characterized by production of IgG1 anti-PyCSP Abs and the Th2 cytokine IL-4. In contrast, the secondary response was dominated by IFN-gamma production (a Th1 cytokine) and the secretion of IgG2a anti-PyCSP Abs in the spleen. PyCSP DNA and mRNA were detected only in the quadriceps muscles (sites of plasmid injection), yet these sites lacked either cytokine- or Ab-secreting cells. These findings indicate that circulating lymphocytes encounter plasmid-encoded Ag in the muscle bed, initiate a humoral response in the draining lymph nodes, and then seed distal lymphoid organs. Profound differences were observed between the primary and secondary immune responses induced by plasmid immunization, which may influence vaccine efficacy.

Animals↗
PubMed1995

Phenotype and frequency of cells secreting IL-2, IL-4, IL-6, IL-10, IFN and TNF-alpha in human peripheral blood.

The phenotype and frequency of cells in normal human peripheral blood spontaneously secreting IL-2, IL-4, IL-6, IL-10, IFN and TNF-alpha ex vivo was determined using ELIspot assays. CD4+ T cells were the dominant source of IL-2 and IL-4 while multiple cell types (primarily CD8+ lymphocytes) produced IFN. Fewer than 0.05% of mononuclear cells were spontaneously secreting these T cell derived factors. By comparison, IL-6, IL-10 and TNF-alpha were produced by 0.7-20% of PBMC. The primary sources of the latter cytokines were CD14+ macrophages/monocytes. A significant positive correlation was found in the frequency of cells secreting IL-6, IL-10 and TNF-alpha ex vivo, suggesting that the release of such factors was coordinately regulated. No such correlation was found among IL-2, IL-4 and IFN secreting cells, indicating that the production of predominantly T cell derived cytokines was regulated independently.

Antigens, CD↗
PubMed1995

Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes.

PROBLEM: The clinical significance of the differential expression of estrogen receptor (ER) in human monocytes was evaluated. METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy. In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine. RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes, and an increase in blood monocyte number, which declines following estrogen replacement therapy to values of the young. CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes.

Adolescent↗
PubMed1995

Anti-idiotypic antibody as an oestrogen mimetic: removal of Fc fragment converts agonist to antagonist.

Previous studies indicated that the anti-idiotypic antibody (clone 1D5) caused an increase in uterine creatine kinase (CK) activity when administered in vivo to immature female rats, indicating that the antibody has oestrogenic-like activity. It was, therefore, of interest to investigate the structural requirements of clone 1D5 to act as an oestrogen mimetic in an in vitro model system. In the present study, the effect of clone 1D5 and its proteolytic fragments, F(ab')2, Fab' and Fc on CK activity was examined in cultured skeletal cells having functional oestrogen receptor (ER). Incubation of female-derived calvaria cells or epiphyseal cartilage cells with clone 1D5 (8.33 nM) or oestradiol (E2) (30 nM) for 24 h caused a significant increase in CK activity, indicating that clone 1D5 acted as an agonist. On the other hand, incubation of male-derived calvaria cells devoid of a functional ER with clone 1D5 or E2 did not have any effect on CK activity. Incubation of female-derived calvaria cells with clone 1D5 and E2 did not result in any further increase in CK activity, whereas dihydrotestosterone (DHT) did not alter the response to clone 1D5. The CK response to clone 1D5, in female-derived calvaria cells was time- and dose-dependent and could be inhibited in a dose-dependent manner by the oestrogen antagonist tamoxifen. In contrast, the proteolytic fragments of clone 1D5, the F(ab')2 dimer (12 nM) and the Fab' monomer (24 nM), and the Fc fragment (28 nM) did not have E2-like activity in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Assessment of estrogen receptor distribution in human endometrium by direct immunofluorescence.

OBJECTIVE: To use a direct immunofluorescence technique employing a fluorescein labeled anti-idiotypic antibody that recognizes the estrogen receptor (ER) order to assess the distribution of ER in the uteri of normal women throughout the normal menstrual cycle and of a woman exposed prenatally to diethylstilbestrol (DES). SUBJECTS: Included in the study were 25 women aged between 35 and 50 years and an amenorrheic patient diagnosed as "DES Syndrome". LOCALIZATION: Localization of ER expression in frozen sections of uterine tissue was achieved by direct immunofluorescence using a fluorescein labeled anti-idiotypic antibody that interacts with ER. RESULTS: Analysis of the immunofluorescence staining indicated that in the normal human endometrium the intensity of ER staining varied according to the phase of the cycle as well as according to the cell type. On the other hand, endometrial ER evaluation of the patient with DES syndrome showed minimal expression of ER and after treatment with conjugated estrogens, endometrial biopsy revealed a significant increase in ER expression. CONCLUSIONS: These findings indicate that the fluorescein labeled anti-idiotypic antibody can be used to detect ER in normal and pathological human endometrium and to monitor changes in ER expression in the endometrium during hormonal therapy.

Adult↗
PubMed1993

Localization of estrogen receptors in long bones and vertebrae of human fetuses.

In order to investigate the possible role of estrogen in the development of cartilage and bone we studied by immunofluorescence immunohistochemistry and autoradiography 26 human embryos and fetuses 7-22 weeks in gestational age associated with pregnancy interrupted for non-medical reasons. In order to demonstrate the presence of estrogen receptors (ERs) in human fetal cartilage, cryostat sections of long bones and lumbar and thoracic vertebrae were prepared for (1) fluorescent immunocytochemistry using an antiidiotypic monoclonal antibody to anti-estradiol receptor monoclonal Ab labeled with fluorescein isothiocyanate (FITC), (2) immunohistochemistry using monoclonal antihuman estradiol receptor antibody, labeled with strept. A-B immunoperoxidase, and (3) autoradiographic localization of estradiol using labeled (3H) 17 beta estradiol. In fetuses aged 10 weeks or older, intranuclear and perinuclear localization of ER was demonstrated by all methods, mainly amongst chondrocytes of the proliferating and higher hypertrophic zones of the epiphyses and in the cartilage of vertebral bodies. These data suggest that estrogen acts directly on chondrocytes of human fetuses through an ER-mediated mechanism.

Antibodies, Monoclonal↗
PubMed1992

Characterization of an antiidiotypic antibody mimicking the actions of estradiol and its interaction with estrogen receptors.

The ability of a monoclonal antiidiotypic antibody (clone 1D5) directed against the binding site of a monoclonal antiestradiol antibody to interact with the estrogen receptor (ER) was investigated. The following lines of evidence indicate that clone 1D5 has the capacity of mimicking the actions of estradiol, and recognizes ER: 1) in binding experiments, clone 1D5 inhibited the binding of [3H]estradiol to porcine cytosolic 32-kilodalton ER fragment in a dose-dependent manner; irrelevant antibody had no effect; 2) in sucrose gradient density analysis, clone 1D5 abolished the specific peak of the [3H] estradiol-ER complex in the 4S region; 3) in immunoprecipitation experiments, clone 1D5 interacted with unoccupied ER, but not with estradiol-occupied ER; 4) in direct immunofluorescence studies clone 1D5 stained the nuclei of cultured rat epithelial cells and recognized estrogen binding sites in nuclear cryostat sections prepared from human, rat, and mouse estrogen-responsive tissues; and 5) When clone 1D5 was injected to immature female rats, it caused 46% increase in uterine creatine kinase activity, suggesting that clone 1D5 may possess estrogenic like activity. Under the same experimental conditions, estradiol caused 58% increase in creatine kinase activity. Collectively, these results suggest that clone 1D5 interacts with the steroid binding site of ER. Therefore, clone 1D5 can serve as a tool in the study of function and structure relationship of ER and to detect changes of ER levels in target cells of various species.

Animals↗
PubMed1988

Neurogenic stimuli alter preoptic area and amygdala unit activity: central effects of olfactory projections on paraventricular nucleus units.

Unit responses were recorded in the preoptic area and amygdala of conscious male rats during exposure to stressful neurogenic stimuli. Olfactory stimulation elicited increases in preoptic area activity on all occasions and also increased activity in the intercalating, medial, and basomedial nuclei of the amygdala, but not in other regions. Acoustic stimulation had less specific effects, even inhibiting unit activity in the central amygdala. A separate series of experiments using urethane-anesthetized rats was carried out to examine the effects of electrical stimulation of the medial amygdala and olfactory tubercle on single-unit activity within the hypothalamic paraventricular nucleus. Inhibition was the predominant response following olfactory tubercle stimulation while excitatory responses predominated following stimulation of the medial amygdala. This was the case particularly for those paraventricular nucleus units identified as projecting to the median eminence (P less than 0.005 vs unidentified cells). The results obtained may be related to the neural regulation of adrenocortical activity as well as higher central nervous activity and have been discussed within these contexts.

Acoustic Stimulation↗
PubMed1987

Neural pathways that mediate the effects of afferent stimuli on paraventricular nucleus multiunit activity in freely moving rats.

The direct involvement of the hypothalamic paraventricular nucleus (PVN) in the control of adrenocortical secretion is now generally accepted. In order to contribute to our understanding of the electrical activity of cells in this region during adrenocortical activation, we have recorded multiunit electrical activity (MUA) in response to acute neural stimuli in freely moving male rats and have examined the pathways involved. Photic, acoustic, olfactory, and sciatic nerve stimulation all increased PVN MUA by between 130% and 250%. These responses were selectively blocked, according to the stimulus modality tested, by radiofrequency lesions of central neural structures. Thus PVN responses to photic stimulation were blocked by lesions of the suprachiasmatic nuclei and reduced by mammillary peduncle lesions but were unaffected by lesions of the bed nuclei of the stria terminalis. Responses to acoustic stimulation were blocked by lesions of the mammillary peduncles but not by those placed in the suprachiasmatic nuclei, the septum, or the bed nuclei of the stria terminalis. Lesions of the septum blocked the response to sciatic nerve stimulation but did not affect the response to olfactory stimulation with amyl acetate fumes, which was blocked by lesions of the bed nuclei of the stria terminalis. The data confirm those obtained in endocrine studies concerning the neural pathways involved in the transmission of neural stimuli that produce adrenocortical activation.

Acoustic Stimulation↗
PubMed1987

Evaluation of the annual activity of a continuing medical and home care unit.

This report presents the annual activity of a home care unit which operates as an extension of a regional hospital into the community. This 'intermediate-care' (between hospitalization and ambulatory care) was developed because of the demographic and health characteristics of the urban population served and in response to their specific health care needs (immediate availability and accessibility of care). During this period, 471 patients were under care, 85% of whom were 65 years old and over. Forty percent were referred with a diagnosis of a malignant disease, about 20% with a diagnosis of a cerebral event and 15% with cardiac and vascular problems. The average period of stay in the program was three months, with less than 10% remaining under supervision for more than a year. In about 50% of the patients involved the care goals were attained and in an additional 25% (terminal cases) the patients were cared for at home until death. The service was found to be an important factor in the interim phase between acute hospitalization and the continuation of care provided by the family physician. The multidisciplinary team care approach was found to be effective in providing services to that group of patients characterized by old age, multiple medical problems and being homebound. The concerned service is continuously developing in compliance with the changing and growing needs of particular groups of patients such as advanced malignant disease, complex cardiovascular problems and multiple (simultaneous) diseases.

Adult↗
PubMed1987

Multiunit electrical activity in conscious rats during an immune response.

Mechanisms by which the central nervous system may be influenced during the course of an immune response probably exist but remain obscure. In an attempt to determine any neurophysiological changes during such responses, we have employed a conscious animal model bearing chronically implanted recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Rats were sensitized to sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) increased significantly to a maximum 5 days after SRBC injection and correlated with the initial appearance of anti-SRBC serum antibodies. Significant decreases in PO/AH MUA were recorded on Days 3 and 8 following the sensitization. PVN MUA decreased significantly for the first 3 days following immunization and then returned to a basal rate before increasing on Day 6. On the ninth and tenth days following the SRBC injection, both PO/AH and PVN MUA levels had returned to those recorded before immunization. A further group of animals was examined for PO/AH MUA changes during induction of a secondary response to SRBC. Firing rates increased significantly between Days 4 and 9 following the injection, the maximum increase being on Day 6. The profile of this response was different from that recorded during the first response, with no decreases recorded. The results are discussed in terms of neuroimmunomodulatory mechanisms such as those influencing neuroendocrine secretory function.

Animals↗
PubMed1987

A neurophysiological correlate of an immune response.

In order to examine possible neurophysiological changes during an immune response, we have recorded neural activity in a conscious animal bearing chronic recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Male rats were sensitized with sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) was recorded as 14.7 +/- 2.1 Hz prior to sensitization and was seen to increase significantly to a maximum of 33.1 +/- 6.0 Hz (p less than 0.005) five days after SRBC injection. This increase correlated with the initial appearance of anti-SRBC serum antibodies at a mean antibody titer of 1:32. Also recorded were decreases in PO/AH MUA on days 3 and 8 after the sensitization (8.2 +/- 2.4 Hz, p less than 0.005); 7.1 +/- 3.3 Hz, p less than 0.005, respectively). Basal PVN MUA was recorded as 14.7 +/- 2.4 Hz. It decreased significantly for the first three days after immunization, and then returned to a basal rate before increasing to 25.9 +/- 8.4 Hz (p less than 0.005) on day 6. On the ninth and tenth days after SRBC injection PO/AH and PVN MUA levels returned to those recorded before immunization.

Animals↗
PubMed1986

Inhibition by corticosterone of paraventricular nucleus multiple-unit activity responses to sensory stimuli in freely moving rats.

In order to determine possible electrophysiologic correlates of negative feedback influences of glucocorticoids upon neuroendocrine secretory activity, the effects of various doses of corticosterone on paraventricular nucleus multiple-unit activity responses to neural stimuli were examined in conscious, freely moving male rats. In control animals, photic and acoustic stimulation significantly increased multiple-unit activity of the paraventricular nucleus by increments of 75% and 117% (P less than 0.005), respectively. Doses between 0.1 and 5.0 mg of corticosterone produced a dose-dependent inhibition of responses to photic stimulation with a high correlation coefficient (r = -0.990). Corticosterone also caused an inhibition of paraventricular multiple-unit activity in response to acoustic stimulation, which was more effective than for photic stimulation, with complete blockade of response occurring with a dose of 1 mg corticosterone. These electrophysiologic findings, within a region of the hypothalamus known to contain corticotrophin-releasing factor cell bodies, may be related to reduced secretion of the hormone in response to the neurogenic stimuli employed, following glucocorticoid administration.

Acoustic Stimulation↗
PubMed1986

Exposure to Legionella in geriatric institutions.

A study of seroreactivity to six Legionella species (L. pneumophila, L. longbeachae, L. micdadei, L. gormanii, L. dumoffii and L. bozemanii) performed in two geriatric hospitals, a day club for the aged and a group of aged with independent life styles revealed a high prevalence of seropositivity in the hospitals. A titer of 1:256 to at least one antigen was obtained in 30.5% of the patients and 35.7% of the staff members from one hospital, 12.1% of the patients and 17.2% of the staff members from a second hospital, 9.1% of the day club attendants, and in none of the 26 old people living in their own households. A second study of the possible source of Legionella spp. in three geriatric hospitals was performed. Three strains of L. pneumophila [serogroup (SG) 1, 3 and 6] were isolated from water, one water sample was positive for L. pneumophila SG 1-4 (pool), by direct immunofluorescence staining only. In a survey of seroconversion to Legionella antigens, 105 new patients were investigated on their arrival day and over a 2-year period; 24% of the patients who could be followed up significantly seroconverted to at least one of the Legionella antigens. Although the findings proved that Legionella existed on the premises of two hospitals, and the high prevalence of seropositivity to Legionella spp. indicated intramural exposure to the agents of legionellosis at one hospital, we found no evidence linking these agents to patient illness.

Aged↗