Biomedical subjects

J W Unger

Publications and source records attributed to J W Unger.

At least 19 recordsLinked to original sources

PubMed1999

Neuromyotonia, myocloni, sensory neuropathy and cerebellar symptoms in a patient with antibodies to neuronal nucleoproteins (anti-Hu-antibodies).

A middle-aged patient presented with subacute muscular stiffness, myocloni of both extremity and facial muscles, gait ataxia and symmetrical distal painful paraesthesias. Electrophysiologically, neuromyotonia was confirmed. High titer anti-Hu antibodies were detected, but no other paraneoplastic antibodies were found. Small-cell lung cancer was diagnosed. Under chemotherapy tumor remission was achieved and, except for minor sensory deficits, neurological symptoms disappeared. This report shows that paraneoplastic syndromes associated with antibodies to neuronal nucleoproteins (anti-Hu antibodies) may be associated with a syndrome including neuromyotonia, sensory neuropathy, cerebellar symptoms and myocloni.

Antibodies, Neoplasm↗

PubMed1998

Glial reaction in aging and Alzheimer's disease.

It is well-established that glial cells play an important role during injury and neurodegenerative processes in the central nervous system. In normal aging, no global glia proliferation is found morphologically, but reactive gliosis has been described in specific areas of the limbic system and neocortex that undergo selective neuronal or synaptic degeneration in nondemented elderly persons. In addition, there is an age-associated increase in the metabolic turnover of cellular proteins, such as glial fibrillary acidic protein, in human brain tissue, even without detectable signs of neurodegeneration. In contrast to the relatively moderate overall glial changes in normal aging, the close association of activated astrocytes and microglial cells with neuritic plaques and cells undergoing neurofibrillary degeneration in Alzheimer's disease (AD), the expression of receptors for complement by glial cells, and the release of soluble cytokines strongly suggest that inflammatory processes may play an important part in the complex pathophysiological interactions that occur in AD. Understanding the role of glia in age-associated neurodegenerative disorders may provide new insights into the neurobiology of glia-neuronal interaction and may allow the development of strategies to alter the disease process. This review aims to summarize some of the important aspects of glial cells in aging and dementia.

Aging↗

PubMed1998

Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord.

A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.

Animals↗

PubMed1998

Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system: a review on morphological findings and functional implications.

Receptors for insulin are widely distributed in the brain and pituitary. The current hypothesis on receptor function in these regions points to a role of insulin as a mediator in the communication of the peripheral endocrine system with the brain via various steps of the neuroendocrine axis. Recent data demonstrate that receptor-positive neurons in the brain, i.e. in the hypothalamus, and secretory cells in the anterior pituitary gland possess specific proteins that are thought to be involved in key steps of post receptor signal transduction, in particular insulin receptor substrate-1 and phosphatidylinositol 3'-kinase (PI3k). PI3k is a critical enzyme of the intracellular signaling pathway that is activated by a number of receptor tyrosine kinases, including receptors for insulin and IGF-1. This information further completes the framework indicating in vivo activity of insulin receptors in central neuroendocrine cells and their involvement in one branch of several physiological mechanisms that control body metabolism and nutritional behaviour.

Animals↗

PubMed1997

Insulin receptors in the pituitary gland: morphological evidence for influence on opioid peptide-synthesizing cells.

Previous investigations have demonstrated that peripheral insulin has a significant influence on brain function and that the interaction of insulin with neuropeptides in neuroendocrine regions may be pivotal for the regulation of body metabolism and energy balance. Since the various levels of interactions are only incompletely known, the focus of the present study has been the adenohypophysis of the rat, in which the presence and localization of insulin receptors and the structurally and functionally closely related insulin-like growth factor-1 (IGF-1) receptor has been investigated by light- and electron-microscopic immunocytochemistry. The two receptors are found on separate subpopulations of secretory cells of the pars distalis with a preponderance of IGF-1 receptors in a postero-lateral portion of large endocrine cells, insulin receptors being more widely dispersed throughout the pars distalis in a population of smaller, irregularly shaped cells. Insulin receptors, but not IGF-1 receptors, are also located in a subpopulation of secretory cells in the intermediate lobe. Phosphotyrosine, a marker for substrates of receptor tyrosine kinases, has been detected in numerous cells throughout the anterior and intermediate lobe, including the cell populations containing insulin or IGF-1 receptors, indicating their ability to transduce biological signals in the pituitary in vivo. Almost 90% of cells containing insulin receptors are also immunoreactive for beta-endorphin. In contrast, IGF-1 receptors are almost exclusively located on cells secreting follicle-stimulating hormone, suggesting a regulatory role of IGF-1 in the pituitary gonadotropin system. The relationship between beta-endorphin and insulin receptors provides further evidence for the hypothesis that peripheral insulin acts as a regulatory hormone in the control of body energy homeostasis via various steps of the neuroendocrine axis, including opioid peptides in the hypothalamus and pituitary known to play an important role in the regulation of feeding behaviour.

Animals↗

PubMed1996

In vivo testing of an experimental endosseous implant design.

PURPOSE: The purpose of this study was to test a new implant system with apically expanding, double-hinged wing stabilizers in dogs before human testing. METHODS: Twenty-seven HA-coated endosseous implants were placed in five dog mandibles. The implants were placed into function for 12-weeks after a 12-week healing period. At the end of this period, the implants were evaluated clinically and radiographically. The animals then were killed, allowing for the implants to be evaluated mechanically and histologically. RESULTS: After the initial healing period, 24 of 27 implants demonstrated osseointegration. Seven of eight implants restored with acrylic resin-fixed partial dentures were stable after the 12-week period of function. However, 17 of 27 implants failed to satisfactorily deploy the apical wing stabilizer system. CONCLUSION: This new implant system has a number of design flaws that must be addressed before testing in humans.

Animals↗

PubMed1996

A retrospective clinical study of resin-bonded cingulum rest seats.

PURPOSE: The purpose of this study was to evaluate the success of the resin-bonded cingulum rest seats (RBCRS) supporting removable partial dentures. MATERIALS AND METHODS: Twenty-six patients who had been treated with RBCRSs were recalled and examined. RESULTS: None of the patients who had RBCRSs placed on their teeth experienced debonding, and none of the teeth showed clinically significant signs of wear to the rest seats. CONCLUSIONS: The use of RBCRSs to support removable partial dentures is a highly successful method of treatment.

Adult↗

PubMed1995

Effect of nerve growth factor on peptide neurons in dorsal root ganglia after taxol or cisplatin treatment and in diabetic (db/db) mice.

In our study we have used morphological and radio-immunological methods for the investigation of calcitonin gene-related peptide (CGRP) and substance P in cervical dorsal root ganglia (DRGs) in mice after administration of taxol or cisplatin and in spontaneously diabetic animals (db/db mice). The results were compared to findings in animals receiving recombinant human nerve growth factor (rhNGF). Morphometric analysis did not reveal any significant changes of cell size distribution in diabetic and taxol-treated mice, whereas cisplatin induced a significant decrease in the number of large- and medium-sized neurons, indicating neuronal atrophy. This finding correlated with a highly significant loss of neuropeptides after cisplatin-application. Measurement of peptide levels in the taxol-treated groups and in diabetic mice demonstrated a decrease predominantly for CGRP. Application of 10 mg/kg NGF caused a significant elevation in peptide-immunoreactivity in control animals and in taxol-treated mice, i.e., statistically significant increase in peptide concentrations and in the number of substance P- and CGRP-immunoreactive DRG-neurons, suggesting a recruitment of additional peptide cells. In diabetic animals a restoration in CGRP-content was observed under NGF-treatment; however, in this model the quantitative parameters did not demonstrate further elevation above control levels. Our data support the hypothesis that NGF exerts a major effect on the metabolism of transmitters associated with nociception and sensation in "healthy" controls and in various models of toxic and metabolic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Prospective clinical evaluation of mandibular implant overdentures: Part I--Retention, stability, and tissue response.

Seventeen subjects with preexisting conventional complete dentures were evaluated in this prospective clinical study. Two implants were placed bilaterally in the anterior mandible. In a crossover experimental design, the conventional dentures were modified, and the retention, stability, and tissue response for conventional dentures were compared with implant overdentures that had O-ring and magnet overdenture attachments for all subjects. The study indicated statistical superiority of the implant overdenture to the conventional denture. The O-ring attachment proved significantly better than the magnet attachment for retention and stability. The soft tissue response showed a slight but significant improvement with implant overdenture therapy.

Cross-Over Studies↗

PubMed1995

Prospective clinical evaluation of mandibular implant overdentures: Part II--Patient satisfaction and preference.

In a crossover experimental design, a prospective clinical study was performed with 17 subjects with existing complete dentures. After data collection, two implants were placed bilaterally in the anterior mandible. Conventional dentures were modified into implant overdentures by use of O-ring and magnet attachments. Each attachment was maintained with each subject for 6 months. Subjects responded to patient satisfaction and preference questionnaires about the conventional denture and each attachment. Subjects were satisfied with both attachment overdentures but showed a strong preference for the O-ring. Both attachments resulted in a significant increase in patient satisfaction when compared with the conventional denture.

Cross-Over Studies↗

PubMed1995

Preparation of the denture-bearing area--an essential component of successful complete-denture treatment.

Success in complete-denture treatment is often directly related to the health and condition of the hard and soft tissues that make up the denture-bearing areas. Surgical alteration of the denture-bearing area is frequently necessary to ensure a morphologically correct form capable of providing adequate support for the prosthesis. A number of these anatomic hard and soft tissue obstacles are discussed, and methods for managing these hindrances to complete-denture treatment are suggested.

Alveolar Process↗

PubMed1994

Neuropeptide Y and somatostatin in the neocortex of young and aging rats: response to nucleus basalis lesions.

Lesions of the nucleus basalis of Meynert (NBM) have been used to mimic, in part, cholinergic deficits occurring in age-related neurodegenerative disorders, i.e., Alzheimer's disease. In our study, the effect of a persistent cholinergic denervation of the fronto-parietal cortex on neuropeptide Y (NPY) and somatostatin (SOM) was examined in young adult (3 months old) and aging (> 18 months old) rats, 1, 3 and 6 months after bilateral stereotaxic NBM lesions with quisqualic acid. In aging, non-lesioned rats a significant decrease in radioimmunologically and immunohistochemically detectable NPY and SOM was found with no further changes after lesions. Morphological markers for these peptidergic populations (cell size and number, NADPH-diaphorase histochemistry, electron microscopy) demonstrated no signs of alterations in both age groups after lesion. Densitometric analysis of peptide fibre networks displayed a heterogeneous response with a significant rarefication in young rats 1 month after the lesion, followed by restoration and a tendency towards increase 6 months post lesioning in individual animals. These findings were confirmed by radioimmunological measurements. Examination of synaptic and cytoskeletal markers, i.e., synaptophysin, GAP-43, MAP-2, Tau-1 and amyloid precursor protein, did not reveal any signs for neuronal reorganization or sprouting. These data are discussed in the context of plasticity and pathology in age-related neurodegenerative disorders with cholinergic impairment.

Acetylcholinesterase↗

PubMed1994

The construction of crowns for removable partial denture abutment teeth.

The construction of crowns for teeth that will serve as abutment teeth for removable partial dentures is an important and technically demanding procedure. The preparation of the tooth itself must include provision for the components and path of placement of the removable partial denture and at the same time conform to all the parameters associated with proper tooth preparation. Some of the factors unique to surveyed crowns that must be considered include the position of the tooth in relation to the proposed occlusal plane with the removable partial denture, the type of facial and lingual tooth contours desired for the direct retainer, the size and suitability of existing restorations, and the proposed path of placement and removal of the removable partial denture relative to the orientation of the abutment tooth as well as to other adjacent teeth if the abutment also is to be used as a fixed partial denture retainer. The design requirements for the removable partial denture must be determined before treatment is initiated, to account for all of these factors.

Crowns↗

PubMed1993

Galanin-immunoreactivity in the nucleus basalis of Meynert in the rat: age-related changes and differential response to lesion-induced cholinergic cell loss.

The neuropeptide Galanin (Gal) is known to play a functional role in the basal forebrain cholinergic system. In our study, the morphology and density of the Gal-immunoreactive (Gal-IR) fiber network within the cholinergic nucleus basalis of Meynert (NBM) was investigated 1, 3 and 6 months after stereotaxic lesion with quisqualic acid in young adult (3 months old) and late middle-aged (20 months old) rats. Quantitative densitometry showed a significantly reduced Gal-IR fiber network in 20-month-old control rats. After lesion-induced cholinergic cell loss, no further changes in Gal-IR were noted in this group of aging rats during the period of investigation. In contrast, young adult animals displayed a significant increase of Gal-IR fiber density 6 months after NBM lesion. However, no hyperinnervation of individual surviving cholinergic neurons was seen. The results obtained in an animal model of cholinergic deficit support the hypothesis of age-related neuroplasticity of specific transmitter and peptide systems. Adaptive changes in Gal may play a role for the modulation of cholinergic function and could be of importance in human age-related neurodegenerative disorders, i.e. Alzheimer's disease.

Aging↗

PubMed1993

The hypophyseal pars tuberalis is enriched with distinct phosphotyrosine-containing proteins not detected in other areas of the brain and pituitary.

The regulation of cell activity, growth and metabolism by a number of growth factor receptors and proto-oncogene products involves tyrosine kinase activity resulting in autophosphorylation of the receptors and production of phosphorylated tyrosine-containing protein substrates. The identification and precise localization of phosphotyrosine (PY)-containing proteins are first steps in elucidating the functional role of tyrosine kinases in the modulation of the central nervous system and related areas. In the present report, we describe PY-containing proteins in the median eminence and adjacent pars tuberalis of the rat adenohypophysis by immunocytochemistry using light and electron microscopy, and by Western blotting analysis. PY-immunoreactivity was found to be most intense throughout the cytoplasm of a population of epithelial pars tuberalis cells. Polyacrylamide gel electrophoresis and Western blotting of tissue extracts from various brain and pituitary regions demonstrated a general pattern of 4 major bands of PY-proteins, with an additional dense band representing a 44 kDa protein that was highly phosphorylated on tyrosines and that was exclusively found in the pars tuberalis. Additional investigation for the presence of insulin receptors, a tyrosine kinase previously correlated with the distribution of PY-proteins, demonstrated a receptor localization in axons and nerve terminals in the external and internal zone of the median eminence. However, the large amount of different PY-proteins present in the secretory cell population of the pars tuberalis could not be attributed to the insulin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Antibodies raised against synthetic peptides react with choline acetyltransferase in various immunoassays and in immunohistochemistry.

Antisera were raised in rabbits against five synthetic peptides. These peptides have been identified as potentially antigenic epitopes from the sequence of porcine choline acetyltransferase (ChAT) using primary and secondary structure analysis. All five antisera recognized immunoaffinity-purified antigen from porcine brain in an ELISA and on western blots. Four antisera recognized ChAT on dot blots, and another four antisera reacted with native and degraded enzyme in a sandwich ELISA using monoclonal antibodies as the capture antibody. One peptide antiserum was of similar avidity in this sandwich ELISA as a polyclonal antibody raised against immunoaffinity-purified ChAT. The same antiserum reacted with the enzyme from human placenta in an ELISA and on western and dot blots and recognized ChAT in rat, primate, and human neurons. Thus, a single peptide (amino acids 168-189) provides the means for easy, reliable, and reproducible generation of antibodies against ChAT suitable for replacing conventional polyclonal and monoclonal antibodies.

Animals↗

PubMed1993

Phosphotyrosine-containing proteins in the CNS of obese Zucker rats are decreased in the absence of changes in the insulin receptor.

The location and quantity of the insulin receptor and its associated tyrosine kinase activity have been examined in the forebrains of lean (Fa/?) and obese (fa/fa) Zucker rats using immunocytochemistry (ICC) and biochemical procedures. These studies were performed in conjunction with ICC and Western blot analysis of phosphotyrosine-containing proteins (PY-proteins). The results from ICC show a similar distribution and content for the insulin receptor among forebrain regions of lean and fatty Zucker rats. Biochemical analysis of the receptor was conducted on the hippocampus. Insulin binding studies using lectin-purified receptor extracts demonstrated similar receptor number and comparable hormone binding affinity for lean and obese animals. Autophosphorylation studies with the receptor extracts from the two groups did not find any differences in the tyrosine kinase activity of insulin receptors. In contrast to the normal findings with the insulin receptor, an abnormality in the obese animals was evident in the content of PY-proteins detected by ICC in the hippocampus, piriform cortex and olfactory bulb. Neurons in these brain regions showed a reduction in staining by an antibody against PY-proteins. Furthermore, Western blots of hippocampal extracts from obese rats demonstrated a reduction in phosphotyrosine content of two proteins of Mr 180 and 130 kD. These findings point to a previously unrecognized alteration in the CNS of the obese, insulin-resistant Zucker rat.

Amino Acid Sequence↗

PubMed1992

Neuropeptide Y-like immunoreactive neurons in the suprachiasmatic-subparaventricular region in the hedgehog-tenrec.

The distribution of the neuropeptide Y (NPY) was studied in geniculate and peri-chiasmatic regions in the lesser hedgehog-tenrec, Echinops telfairi (Insectivora). Only few neurons demonstrated NPY-like immunoreactivity in the ventral lateral geniculate nucleus. In contrast, NPY-immunoreactive perikarya were clearly present in the suprachiasmatic nucleus (SCh) and dorsal and caudal to it. The latter region might correspond to the subparaventricular zone (SPV), recently identified in the rat as an additional area involved in processing circadian rhythms. While the distribution of a distinct cell population across nuclear boundries in both SCh and SPV might conform to the present idea of processing circadian rhythms, the presence of NPY-like immunoreactive neurons in these areas is rather unusual. In mammals, such neurons have only been demonstrated so far in the mentioned insectivore as well as in man.

Animals↗