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A Reiner

Publications and source records attributed to A Reiner.

At least 181 records · Page 10Linked to original sources

[Steroid hormone receptors in mammary carcinoma. Immunohistochemical detection and prognostic significance].

Estrogen and progesterone receptors were immunohistochemically recorded from 426 cases of primary mammary carcinoma. Immunohistochemical detection was based on monoclonal antibodies to estrogen receptor (H222) and progesterone receptor (KD68). Immunohistochemical and biochemical tests were correlated to each other with significance (p less than 0.0001) for either receptor. Some of the histological parameters exhibited relationships with the immunohistochemical receptor status. Receptor positivity of lobular, mucoid, tubular, and papillary carcinomas was more frequent than that of ductal carcinoma, whereas that of medullary carcinoma fell below ductal cases. A straight forward correlation of statistical significance was found to exist between histological tumor grade and steroid hormone receptor status. Receptor positivity of carcinomas with sizeable stroma components proved to be more frequent than that of carcinomas with lower stroma levels. Steroid hormone receptors can be immunohistochemically identified from cytological specimens, as well, though some limiting factors are implied in the latter. Thirteen percent of fine-needle aspirates provided falsely negative steroid hormone receptor findings, as compared to histological biopsy. This problem was encountered primarily in cases of low receptor positivity and high stroma content of carcinoma, factors for which only minor amounts of cell material could be obtained from puncturing. Clinical follow-up checks and evaluation of survival data revealed the immunohistochemically determined steroid hormone receptor status to be of significant importance to prognostication (ER-ICA p less than 0.00001; PgR-ICA p = 0.004). The prognosis of patients with negative estrogen and progesterone receptors was found to be worse than that of patients with positive receptor status. These studies are likely to confirm immunohistochemical determination of steroid hormone receptors, using monoclonal antibodies, to be a reliable method of great prognostic importance.

Adenocarcinoma↗

Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer.

An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.

Adult↗

Distribution and relative abundance of neurons in the pigeon forebrain containing somatostatin, neuropeptide Y, or both.

Immunohistochemical studies in several mammalian species and in red-eared turtles have shown that somatostatin (SS) and neuropeptide Y (NPY) co-occur in a substantial proportion of the telencephalic neurons containing either. To explore further the possibility that telencephalic neurons co-containing SS and NPY may be evolutionarily conserved among amniotes, we determined the distribution and co-occurrence of SS and NPY in forebrain neurons in pigeons. Single-label immunohistochemical studies revealed the presence of overlapping populations of SS+ neurons and NPY+ neurons in most of the major subdivisions of the telencephalon. Double-label immunofluorescence studies revealed that in subdivisions of the telencephalon that are comparable to mammalian cortex (i.e., those dorsal and lateral to the basal ganglia), the vast majority of NPY+ neurons were also SS+, whereas a major and regionally variable percentage of the SS+ neurons were not NPY+. In contrast, within the basal telencephalon (including the basal ganglia and several other structures) neurons labeled only for NPY or only SS were more abundant than those containing both neuropeptides. Outside the telencephalon, the only forebrain cell group containing neurons in which SS and NPY were co-localized was in the lateral hypothalamus. A series of double- and triple-label immunohistochemical studies was undertaken to determine the extent of co-occurrence of SS and NPY in striatal neurons and the relationship of these neurons to striatal neurons containing other neuropeptides. In addition, immunohistochemical single- and double-label techniques were employed in conjunction with retrograde-labeling by fluorogold to determine the projections of SS+ and NPY+ striatal neurons. The results indicate that: 1) a population of striatal interneurons containing both SS and NPY exists in pigeons and constitutes approximately the same fraction of all striatal neurons as reported in mammals, 2) neurons containing NPY (but not SS) form a second, larger population of striatal interneurons, 3) neurons containing SS (but not NPY) form a third population of striatal interneurons that is approximately half as abundant as the NPY+ interneuron population, and 4) one-third of the substance P-containing striatonigral projection neurons also contain SS. The existence in pigeons of a major population of neurons containing both SS and NPY throughout the telencephalon, the existence of a population of neurons containing only SS in cortex-equivalent parts of the telencephalon, and the existence of a population of interneurons containing only NPY in the striatum is consistent with findings in mammals and turtles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization.

A number of different neuroactive substances have been found in striatal projection neurons and in fibers and terminals in their target areas, including substance P (SP), enkephalin (ENK), and dynorphin (DYN). In a preliminary report on birds and reptiles, we have suggested that SP and DYN are to a large extent found in the same striatal projection neurons and that ENK is found in a separate population of striatal projection neurons. In the present study, we have examined this issue in more detail in pigeons and turtles. Further, we have also explored this issue in rats to determine whether this is a phylogenetically conserved feature of basal ganglia organization. Simultaneous immunofluorescence double-labeling procedures were employed to explore the colocalization of SP and DYN, SP and ENK, and ENK and DYN in striatal neurons and in striatal, nigral, and pallidal fibers in pigeons, turtles, and rats. To guard against possible cross-reactivity of DYN and ENK antisera with each others' antigens, separate double-label studies were carried out with several different antisera that were specific for DYN peptides (e.g., dynorphin A 1-17, dynorphin B, leumorphin) or ENK peptides (leucine-enkephalin, metenkephalin-arg6-gly7-leu8, methionine-enkephalin-arg6-phe7). The results showed that SP and DYN co-occur extensively in specific populations of striatal projection neurons, whereas ENK typically is present in different populations of striatal projection neurons. In pigeons, 95-99% of all striatal neurons containing DYN were found to contain SP and vice versa. In contrast, only 1-3% of the SP+ striatal neurons and no DYN neurons contained ENK. Similarly, in turtles, greater than 75% of the SP+ neurons were DYN+ and vice versa, whereas ENK was observed in fewer than 5% of the SP+ neurons and 2% of the DYN+ neurons. Finally, in rats, more than 70% of the SP+ neurons contained DYN and vice versa, but ENK was found in only 5% of the SP+ neurons and in none of the DYN+ perikarya. Fiber double-labeling in the striatum and its target areas (the pallidum and substantia nigra) was also consonant with these observations in pigeons, turtles, and rats. These results, in conjunction with studies in cats by M.-J. Besson, A.M. Graybiel, and B. Quinn (1986; Soc Neurosci. Abs. 12:876) strongly indicate that the co-occurrence of SP and DYN in large numbers of striatonigral and striatopallidal projection neurons in a phylogenetically widespread, and therefore evolutionarily conserved, feature of basal ganglia organization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Breast cancer in the male. A long-term follow-up study of 55 patients].

Between 1964 and 1988, 55 male patients were treated for breast cancer. Fifty-one patients were treated by radical mastectomy; only four patients underwent a simple mastectomy. Nineteen cases received postoperative radiotherapy, eleven cases chemotherapy, six cases adjuvant hormonal therapy, and one patient was submitted to orchiectomy. The five-year survival rate for tumors with nodal metastases was 37%, as compared with 57% for patients with negative nodes.

Adult↗

Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia.

Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.

Adult↗

HER-2 oncogene amplification and overall survival of breast carcinoma patients.

DNA was extracted from tumour samples of 77 patients with primary breast carcinoma and HER-2 proto-oncogene amplification was assessed. Prognostic indices such as number of positive lymph nodes, tumour size and histological grading were strongly associated with overall survival. No statistically significant correlation between amplification of HER-2 and overall survival was observed. In addition, prognostic indices, HER-2 amplification and disease-free interval was not correlated. Analysis of HER-2 amplification alone is not a useful guide in the management of patients with mammary carcinoma.

Breast Neoplasms↗

Evidence for retinal pathology following interruption of neural regulation of choroidal blood flow: Müller cells express GFAP following lesions of the nucleus of Edinger-Westphal in pigeons.

Choroidal blood flow in pigeons is regulated by the medial part of the nucleus of Edinger-Westphal (EW) via the ipsilateral ciliary ganglion. Interruption of this circuit by unilateral lesions of EW results in pathological modifications in the morphology of retinal photoreceptors in the ipsilateral eye in pigeons housed under 12hr light (400 lux)/12hr dark conditions. In the present study, we examined the effects of unilateral EW lesions on glial fibrillary acidic protein (GFAP) expression by retinal Müller cells in pigeons housed under the same lighting conditions. Since Müller cells in the retina of land vertebrates express increased GFAP during conditions of retinal pathology or stress (e.g. inflammation or hypoxia), this study would enable us to further evaluate the effects of disruption in the neural regulation of choroidal blood flow on the retina. We found that following EW lesions, retinal Müller cells expressed GFAP, with the precise intracellular location of the GFAP dependent on the amount of time elapsed following the lesion. One week after the EW lesions, GFAP labelling was restricted to the Müller cell endfeet in the nerve fiber layer and ganglion cell layer. By two-three weeks, the labelling had extended outward (or sclerad) into the portions of the Müller cells spanning the inner plexiform layer. Finally, by six weeks post-lesion, the entire extent of the Müller cell from the nerve fiber layer to the outer limiting membrane contained GFAP. No GFAP immunoreactivity in Müller cells was observed in the eyes contralateral to the EW lesions or in eyes in which the pupil had been fixed and dilated by lesions of the pretectal region. Our results suggest that the retina is in a state of physiological stress following interruption of the neural regulation of choroidal blood flow by EW lesions. Although the precise mechanisms by which altered choroidal blood flow regulation affects Müller cell GFAP production require elucidation, the results nonetheless highlight the importance of intact neural regulation of choroidal blood flow for retinal health.

Animals↗

Control of choroidal blood flow by the nucleus of Edinger-Westphal in pigeons: a laser Doppler study.

Anatomical studies in birds have suggested that choroidal blood flow may be regulated by a circuit involving the following serially-connected components: the retina-the suprachiasmatic nucleus (SCN)-the medial subdivision of the nucleus of Edinger-Westphal (mEW)-the ciliary ganglion-the choroidal blood vessels. In order to better clarify the role of this circuit, we examined the effects of electrical stimulation of EW on choroidal blood flow in the ipsilateral eye, using laser Doppler velocimetry to monitor choroidal blood flow in the superior pole of the eye. Baseline choroidal blood flow values (144-311.3 mg/min per eye) were found to be comparable to those previously reported in rabbits, cats and primates. Stimulation of EW dramatically increased choroidal blood flow. The increases were current-related and the average maximal increases ranged between 300-700% above baseline values. In contrast, EW stimulation had little or no effect on overall bodily blood flow. All EW stimulation sites were later verified histologically. These results indicate that the SCN-mEW circuit in birds may be involved in mediating increases in choroidal blood flow, possibly in response to the levels of retinal illumination. Such adaptive neural regulation of choroidal blood flow may play an important role in mitigating the potentially deleterious effects of light on the retina.

Analysis of Variance↗

Evaluation of ibuprofen dimethyl aminoethanol octyl bromide and related active metabolites in biological samples.

AF 150 is ibuprofen dimethyl aminoethanol octyl bromide, endowed with antibacterial and antiinflammatory activities. An indirect HPLC analytical method for AF 150 with UV detection, to be used for pharmacokinetic studies, has been validated in terms of linearity, reproducibility, specificity and sensitivity. Using this method the bioavailability of AF 150 and its active metabolite ibuprofen was investigated following parenteral administration and topical application.

Animals↗

Studies of a monoclonal antibody to skeletal keratan sulphate. Importance of antibody valency.

A mouse monoclonal antibody (AN9P1) to keratan sulphate is described. In a competitive-inhibition solution-phase radioimmunoassay employing 125I-labelled intact proteoglycan, it reacts preferentially with keratan sulphate bound to the core protein of adult human articular-cartilage proteoglycan and to a much lesser degree with keratan sulphate purified from this proteoglycan. Proteolytic cleavage of the proteoglycan by pepsin and trypsin has little effect on antibody binding, but treatment with papain decreases binding considerably and more than does treatment with keratanase. An even greater decrease in binding is observed after treatment with alkaline borohydride. A comparison of binding of antibody AN9P1 with that of another previously described monoclonal antibody, 1/20/5-D-4, to keratan sulphate [Caterson, Christner & Baker (1983) J. Biol. Chem. 258, 8848-8854] revealed similar binding characteristics, both showing much diminished binding after papain digestion of proteoglycan and even less with purified skeletal keratan sulphate. Removal of the Fc piece of antibody AN9P1 had no significant effect on the differential binding of divalent F(ab')2 fragment to proteoglycan, to papain-digested proteoglycan and to keratan sulphate, although there was a small decrease in binding to papain-digested proteoglycan. Conversion of the antibody into univalent Fab fragment with removal of the Fc piece resulted in diminished binding to proteoglycan, compared with that observed with IgG, and in enhanced binding to free keratan sulphate and to papain-digested proteoglycan. These results suggest that close proximity of keratan sulphate chains on the core protein of proteoglycans favours preferential reactivity of bivalent antibody with these species through cross-bridging of chains by antibody. Conversely, much decreased binding to keratan sulphate on proteoglycan core-protein fragments and to free keratan sulphate results from a lack of close proximity of keratan sulphate. By using univalent Fab fragment in these assays these differences in binding are minimized by preventing cross-bridging and thereby enhancing detection of smaller fragments without sacrificing too much sensitivity of detection of larger proteoglycan species. The persistent preferential binding of Fab fragment to proteoglycan is probably in part the result of the increased epitope density in the intact molecule compared with keratan sulphate in a more disperse form.

Antibodies, Monoclonal↗

Distribution of mu, delta, and kappa opiate receptor types in the forebrain and midbrain of pigeons.

Ligands that are highly specific for the mu, delta, and kappa opiate receptor binding sites in mammalian brains have been identified and used to map the distribution of these receptor types in the brains of various mammalian species. In the present study, the selectivity and binding characteristics in the pigeon brain of three such ligands were examined by in vitro receptor binding techniques and found to be similar to those reported in previous studies on mammalian species. These ligands were then used in conjunction with autoradiographic receptor binding techniques to study the distribution of mu, delta, and kappa opiate receptor binding sites in the forebrain and midbrain of pigeons. The autoradiographic results indicated that the three opiate receptor types showed similar but not identical distributions. For example, mu, delta, and kappa receptors were all abundant within several parts of the cortical-equivalent region of the telencephalon, particularly the hyperstriatum ventrale and the medial neostriatum. In contrast, in other parts of the cortical-equivalent region of the avian telencephalon, such as the dorsal archistriatum and caudal neostriatum, only kappa receptors appeared to be abundant. Within the basal ganglia, all three types of opiate receptors were abundant in the striatum and low in the pallidum. Within the diencephalon, kappa and delta binding was high in the dorsal and dorsomedial thalamic nuclei, but the levels of all three receptor types were generally low in the specific sensory relay nuclei of the thalamus. Kappa binding and delta binding were high, but mu was low in the hypothalamus. Within the midbrain, all three receptor types were abundant in both the superficial and deep tectal layers, in periventricular areas, and in the tegmental dopaminergic cell groups. In many cases, the distribution of opiate receptors in the pigeon forebrain generally showed considerable overlap with the distribution of opioid peptide-containing fiber systems (for example, in the striatal portion of the basal ganglia), but there were some clear examples of receptor-ligand mismatch. For example, although all three receptor types are very abundant in the hyperstriatum ventrale, opioid peptide-containing fibers are sparse in this region. Conversely, within the pallidal portion of the basal ganglia, opioid peptide-containing fibers are abundant, but the levels of opiate receptors appear to be considerably lower than would be expected. Thus, receptor-ligand mismatches are not restricted to the mammalian brain, since they are a prominent feature of the organization of the brain opiate systems in pigeons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. An immunohistochemical study.

The number of proliferating cells was determined by Ki-67 antibody in 107 primary breast carcinomas. These results were compared with transferrin receptor (TrfR) expression, estrogen receptor (ER) status, histologic type, tumor grade, size and axillary lymph node status. The percentage of Ki-67-positive cells ranged from 0.9 to 26.4%. The proportion of Ki-67-positive cells was highest in medullary carcinomas. Immunoreactivity of Ki-67 in relation to TrfR expression showed significant correlation (p = 0.0001). An inverse relationship between ER status and Ki-67 positivity existed (p = 0.0001). 88 cases were subjected to histologic grading. There was a significant relationship showing an increase of Ki-67 immunoreactivity with decrease of tumor differentiation (p = 0.0001). The distribution of Ki-67 reactivity in relation to tumor size and nodal status of the axilla revealed positive correlations (p = 0.02; p less than 0.05). In conclusion, the use of Ki-67 monoclonal antibody as a marker for cell proliferation represents a method to get kinetic data inhering prognostic value.

Antibodies, Monoclonal↗

High-performance liquid chromatographic evaluation of salicyloyl pyridixol and systemic metabolites in biological samples.

An high-performance liquid chromatographic analytical method, which allows quantitative evaluation of both salicyloyl pyridixol and its metabolite salicylic acid, is reported. This method has demonstrated to possess the required specifications in terms of linearity, sensitivity, extraction recovery, reproducibility and specificity for pharmacokinetic investigations in both human subjects and experimental animals. The results obtained from an investigation on the rat are briefly discussed.

Animals↗

Immunohistochemical study of the telencephalon of the spiny dogfish, Squalus acanthias.

The paucity of experimental data and the differences in telencephalic organization between sharks and other jawed vertebrates have complicated telencephalic comparisons. The distribution of neuropeptides has been extremely useful in recognizing and comparing major subdivisions of the telencephalon among vertebrates. Immunohistochemical techniques were therefore used to study the distribution of substance P (SP), leucin-enkephalin (LENK), and serotonin (5HT), as well as tyrosine hydroxylase (TH), an indicator of catecholamines, in the telencephalon of the spiny dogfish. The distribution of SP and LENK provides a clear distinction between pallial and subpallial portions of the telencephalon. Two regions of the ventrolateral telencephalon, area superficialis basalis and area periventricularis ventrolateralis, exhibit histochemical similarities to the pallidal and striatal subdivisions, respectively, of the basal ganglia in amniotes. Lower densities of LENK+ and SP+ perikarya and fibers occur in the medial pallium and the pars centralis of the dorsal pallium. Similar histochemical traits characterize the sensory thalamorecipient telencephalic structures in amniotes. The lateral pallium in dogfishes is distinguished by the presence of large numbers of TH+ neurons with radially oriented processes. The presence of these distinctive cells also in the medial wall of the rostral telencephalon suggests that the lateral pallium has a medial extension that is situated ventral to the medial pallium. Neurons containing TH were widely distributed in the telencephalon of spiny dogfish and were particularly abundant in the dorsal pallium, olfactory pallium, and area superficialis basalis. It is currently unclear whether these TH+ telencephalic neurons are, in fact, catecholaminergic or merely contain a TH-like substance unrelated to catecholamine synthesis.

Animals↗