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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 361 records · Page 20Linked to original sources
PubMed1994

Inflammation after axonal injury has conflicting consequences for recovery of function: rescue of spared axons is impaired but regeneration is supported.

Neural injury leads to tissue damage beyond that caused by the initial lesion, mainly as a result of a chain of autodestructive events triggered by the trauma. These events apparently include the activation of immune-derived cells and their products, as treatment with anti-inflammatory agents, such as corticosteroids, limits the damage and thus improves recovery. On the other hand, immune-derived substances, such as cytokines, are thought to play an important role in post-traumatic axonal regeneration. Thus, the need to reduce inflammation to limit the spread of damage appears to be in conflict with the need to permit inflammation to promote regeneration. Comprehension and resolution of this apparent conflict may lead to the development of treatment protocols aimed at rescuing axons spared by the initial injury, without hampering the potential regeneration of directly and indirectly injured axons. In this study, carried out on rats with crushed optic nerves, daily intraperitoneal injections of dexamethasone commencing prior to the injury significantly attenuated the injury-induced decrease in electrophysiological activity and reduced the area of tissue damage. On the other hand, dexamethasone treatment reduced the permissiveness of the injured nerves to neural adhesion and regrowth in vitro. This latter phenomenon was also observed in injured peripheral nerves. Results are discussed with respect to the possible establishment of an appropriate protocol for corticosteroid treatment of nerve injuries aimed at promoting neuronal rescue without compromising neuronal regeneration.

Adrenal Cortex Hormones↗
PubMed1994

The enigma of myelin-associated growth inhibitors in spontaneously regenerating nervous systems.

Recent results shed new light on how some nervous systems can regenerate after injury while others cannot. Until recently, it was widely believed that the main difference between systems that regenerate and those that do not lies in the normal state of their permissiveness to the regenerating axons. Thus, while nonregenerative systems, such as the rat optic nerve, were shown to contain myelin-associated growth inhibitors, regenerative systems, such as the fish optic nerve, were thought to have no such inhibitors. However, it has now been demonstrated that spontaneously regenerating systems do contain growth inhibitors, though their levels seem to be lower than in nonregenerative systems. The main difference, however, appears to reside in the system's response to injury. This article discusses the involvement of myelin-associated growth inhibitors in the spontaneously regenerating nervous system of fish, traces the apparent discrepancy, and shows how it has been resolved recently.

Animals↗
PubMed1994

Linear dimeric interleukin-2 obtained by the use of a defective herpes simplex viral vector: conformation-activity relationship.

An interleukin-2 dimer, produced enzymatically by a nerve-derived transglutaminase in vitro, is cytotoxic to oligodendrocytes, unlike the immune-derived monomeric interleukin-2. The object of this study was to establish a way to produce a dimer of interleukin-2 in quantities, by means of genetic engineering, and to confirm that the structure of the resulting molecule is critical for its function. A defective herpes simplex virus vector was utilized for overproduction of a dimeric interleukin-2. The resulting linear dimer, which is a translational product, differs from the enzymatically produced dimer, which is a posttranslational modification of interleukin-2. The linear dimer, while retaining the known interleukin-2 activity of monomeric interleukin-2 with respect to mitogenicity on T cells, was not cytotoxic to oligodendrocytes. This finding suggests that the lack of cytotoxicity of the linear dimeric interleukin-2 is not caused by a loss of activity during its preparation but is related to its conformational structure, which evidently does not meet the requirements for cytotoxicity. This study opens the way to the design at the transcriptional level of modified proteins and their efficient production, provided that the new transcript encodes for the desired modification in the protein at the appropriate sites.

Animals↗
PubMed1994

CSF inositol in schizophrenia and high-dose inositol treatment of schizophrenia.

Inositol is a key metabolite in the phosphatidylinositol cycle, which is a second messenger system for serotonin-2 receptors that have been implicated in the pathophysiology of schizophrenia. Cerebrospinal fluid inositol levels were measured in 20 schizophrenic patients and 19 age- and sex-matched controls and no difference was found. However, the patients were all neuroleptic-treated. A controlled double-blind crossover trial of 12 g daily of inositol for a month in 12 anergic schizophrenic patients, twice the dose given before in schizophrenia, did not show any beneficial effects. However, the number of patients studied was small and the length of time of inositol administration may not have been sufficient.

Adult↗
PubMed1994

Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients.

The recent isolation of the complete open reading frame of the choroideremia (CHM) gene and the characterization of the exon-intron boundaries has paved the way to mutation detection in patients with classical choroideremia. We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization and the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) technique. Causative mutations in the CHM gene were detected in at least 12 families, indicating that a substantial part of the mutations can be identified by this approach. In four of these families deletions of different sizes were found. Thus, in one patient, the deletion resulted in the absence of only one exon, while in another the deletion comprised the entire CHM gene. Mapping of the deletion endpoints in these four patients and in another 11 male patients with sizeable deletions enabled us to construct a very detailed map of intervals 2 and 3 of Xq21. In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR-SSCP analysis and direct sequencing. Interestingly, all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Cross talk between the immune system and the nervous system in response to injury: implications for regeneration.

The central nervous system has long been regarded as an immunologically privileged site. Accumulating evidence suggests, however, that the privilege is not total, and that certain immune functions involving immune components and resident glial cells can operate in the central nervous system. The nervous and immune systems interact during normal development, but in the mature brain their interaction is restricted mainly to cases of pathogenic infections and traumatic lesions. The focus of this review is on bidirectional interactions between immune and neuroglial components in response to nerve injury. The macrophage is the most ubiquitous of the immune-derived cell types associated with injury. Its role, as in any other organ, is tissue remodeling and promotion of healing. Macrophage activities include removal of dead tissue and debris by phagocytosis, lipid recycling, and secretion of a wide spectrum of cytokines possessing trophic, mitogenic, and chemotactic properties. These activities affect the behavior of resident cells in the vicinity of the wound. We discuss the possible association of these cytokines with the ability of injured nerves to regenerate. Finally, we consider the apparently conflicting effects of posttraumatic inflammation on the recovery of function.

Animals↗
PubMed1994

GM-CSF activates regenerative epidermal growth and stimulates keratinocyte proliferation in human skin in vivo.

Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.

Cell Differentiation↗
PubMed1994

Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506.

Long-term renal function was compared in 49 liver recipients [25 patients received cyclosporin (CyA) and 24 patients received FK 506] followed for a period of 1 year. Creatinine (CR) and glomerular filtration rate (GFR) pretransplantation (pre-Tx) and at 1, 3, 5, and 12 months post-Tx were recorded, as well as incidences of hyperkalemia, post-Tx hypertension, and insulin-dependent diabetes mellitus (IDDM) in the two groups. At 1 year post-Tx, the mean Cr had risen from baseline by 56% and 60% in the FK and CyA groups, respectively; the mean GFR had dropped by 32% in FK patients and by 27% in CyA patients. Acute nephrotoxicity occurred in 7/25 CyA patients (2/7 required dialysis) and 9/26 FK patients (7/9 required dialysis; 2/7 were switched to CyA). None remained on dialysis at 3 months. Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity (CyA, 4; FK, 3) and in 3 of the remaining 36 pts (P < 0.001). Hyperkalemia occurred in 4/25 CyA, and in 12/24 FK patients (P < 0.025), post-Tx hypertension occurred in 15 CyA, and 7 FK patients (P < 0.05), and IDDM occurred in 4 CyA and 7 FK patients (P = ns). FK 506 and CyA, thus, exerted similar chronic renal effects. Although acute renal insufficiency improved upon dose reduction, renal impairment was permanent in some cases.

Creatinine↗
PubMed1994

Age differences of visual field impairment and mutation spectrum in Danish choroideremia patients.

Visual prognosis is a crucial theme in the counselling of individuals affected by a progressive retinal dystrophy. Unfortunately prognostic predictions are hampered by large interindividual differences in disease courses even within well defined nosological entities. Ten patients from 8 families affected by choroideremia were studied. The clinical signs in our patients were rather uniform. Deterioration of the peripheral visual fields typically began in the second decade of life, and progressed during the following one or two decades. Esterman transformation of peripheral visual field measurements was chosen as the best single indicator of visual impairment. Noticeable age differences in residual visual fields among patients were demonstrated. The age difference between the mildest and the severest cases amounted to 25 years. One of the expectations of the exploration of disease genes, is the potential predictive value of mutation identification with regard to phenotypic variability. Different presumed causative mutations were identified. Nevertheless, all the mutations are predicted to cause premature stops during translation, resulting in a non-functional or missing protein. Consequently, the observed age variation in the photopic visual field degradation must be due to still unrecognized factors, either constitutional and/or environmental.

Adolescent↗
PubMed1994

Tracheobronchomegaly.

We report two cases of tracheobronchomegaly with differing presentations. The radiologic, fiberoptic bronchoscopic, and clinical findings as well as management of this rare condition are reviewed.

Aged↗
PubMed1994

Clinical indications for the radiosurgical treatment of brain tumors.

Recently there has been an exponential growth in the use of radiosurgery in the treatment of brain tumors. Although a place for radiosurgery in the management of benign disorders, especially arteriovenous malformations (AVM) is established, its role in the treatment of brain tumors continues to be defined. This paper reviews the results of recently-published studies of the use of radiosurgery for brain metastases, acoustic neuromas, primary brain tumors and tumors at the base of skull. An attempt is made to identify a number of clinical questions that need to be addressed before radiosurgery can be advocated as the treatment of choice.

Brain Neoplasms↗
PubMed1994

[Idiopathic intracranial hypertension and tetracycline].

Idiopathic intracranial hypertension (IIH, pseudotumor cerebri) was diagnosed in 4 patients who had been treated with tetracycline. The main symptom was headache, and in all there was papilledema. Symptoms and signs improved after tetracycline was discontinued and acetazolamide treatment started. When a patient receiving tetracycline develops IIH, the medication should be stopped as it may be the cause of the IIH, as appeared to be the case in our 4 patients.

Acetazolamide↗