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A Tessler

Publications and source records attributed to A Tessler.

At least 55 records · Page 3Linked to original sources
PubMed1993

Electrophysiological responses in foetal spinal cord transplants evoked by regenerated dorsal root axons.

Cut dorsal root axons regenerate into intraspinal transplants of foetal spinal cord (FSC) and establish synaptic connections there. The aim of the present study was to determine whether transplant neurons are driven synaptically in response to electrical stimulation of regenerated dorsal root axons. Adult Sprague-Dawley rats received FSC transplants (E14) into dorsal quadrant cavities at the lumbar enlargement. The cut L4 or L5 dorsal root stump was placed at the bottom of the lesion cavity and secured between the transplant and host spinal cord. Four to ten weeks later the animals were prepared for electrical stimulation and recording. We stimulated regenerated dorsal roots and recorded extracellular single unit post-synaptic activities which were evoked close to the dorsal root-transplant interface. We used intracellular recording to observe several examples of monosynaptic EPSPs in transplant neurons evoked by dorsal root stimulation. These results indicate that the regenerated dorsal root axons establish functional connections with neurons within the transplants and suggest that FSC transplants can be used to reconstruct functional connections between neurons that have been interrupted by spinal cord injury.

Animals↗
PubMed1993

Roles of embryonic astrocytes and Schwann cells in regeneration of adult rat dorsal root axons: qualitative observations.

Transplants of fetal spinal cord support regeneration of severed dorsal root axons and allow synapse formation. To analyze the components of the transplants that provide this favorable environment, we studied whether or not 1) the embryonic spinal cord transplants contain Schwann cells, a major producer of laminin, and 2) whether dorsal roots regenerate into transplants of immature astrocytes. We used calcitonin gene-related peptide (CGRP), laminin and glial fibrillary acidic protein (GFAP) immunocytochemistry to identify regenerated axons, Schwann cells and astrocytes, respectively. CGRP-immunoreactive axons regenerated into embryonic day 14 fetal spinal cord transplants, but the transplant did not contain laminin. Dorsal roots immunoreactive for CGRP also regenerated into suspensions of cultured astrocytes. The transplanted astrocytes also favored the expression of laminin and GFAP. CGRP-labeled axons regenerated and distributed widely into the polycarbonate tubes coated with poly L-lysine and containing medium with or without cultured astrocytes. These results indicate that Schwann cells are not likely to account for dorsal root regeneration into transplants of fetal spinal cord and that astrocytes may in fact induce regeneration. Regeneration may also take place in response to various environments.

Animals↗
PubMed1992

Time course of dorsal root axon regeneration into transplants of fetal spinal cord: I. A light microscopic study.

Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal cord and establish synaptic connections there. The aims of the present study were to describe the progression of dorsal root growth within the transplants and the maturation of transplant morphology and to determine whether the regenerated dorsal root axons persist within the transplants or eventually withdraw. Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the transplants. The morphology of the transplants was examined from 1 day to over 1 year after surgery, and the regenerated dorsal roots were labeled with immunohistochemical methods to study the subset that contains calcitonin gene-related peptide (CGRP). Embryonic spinal cord transplants survived and grew within the host spinal cord in over 90% of the animals. Transplant volume increased and the morphology of the transplants matured over the first 12 weeks and then did not change for 48-60 weeks. During the first week the transplants were composed of dissociated neurons, glia, and hematogenous cells with considerable extracellular space between them. Subsequently, the grafted neurons became densely aggregated, and non-neuronal elements such as inflammatory cells and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to regenerate into the transplants within 24 hours, formed dense bundles by 4 days, and were still present at 60 weeks, the longest survival period examined. Myelination of axons within transplants began at 2 weeks. Quantitative analysis showed that the area of the transplants occupied by CGRP-labeled axons and the distribution area of the labeled axons within the transplants increased until 12 weeks and persisted unchanged for over 48 weeks. These results indicate that regenerated dorsal root axons are permanently maintained within transplants of embryonic spinal cord and suggest that the transplants can contribute to the permanent restoration of damaged intraspinal neural circuits.

Animals↗
PubMed1991

Intraspinal transplants.

Transplants of embryonic central nervous system tissue have long been used to study axon growth during development and regeneration, and more recently to promote recovery in models of human diseases. Transplants of embryonic substantia nigra correct some of the deficits found in experimental Parkinson's disease, for example, by mechanisms that are thought to include release of neurotransmitter and reinnervation of host targets, as well as by stimulating growth of host axons. Similar mechanisms appear to allow intraspinal transplants of embryonic brainstem to reverse locomotor and autonomic deficits due to experimental spinal cord injuries. Embryonic spinal cord transplants offer an additional strategy for correcting the deficits of spinal cord injury because, by replacing damaged populations of neurons, they may mediate the restoration of connections between host neurons. We have found that spinal cord transplants permit regrowth of adult host axons resulting in reconstitution of synaptic complexes within the transplant that in many respects resemble normal synapses. Transplants of fetal spinal cord may also contribute to behavioral recovery by rescuing axotomized host neurons that otherwise would have died. Electrophysiological and behavioral investigations of functional recovery after intraspinal transplantation are preliminary, and the role of transplants in the treatment of human spinal cord injury is uncertain. Transplants are contributing to our understanding of the mechanisms of recovery, however, and are likely to play a role in the development of rational treatments.

Animals↗
PubMed1991

Partial nephrectomy for renal cell carcinoma: indications, results and implications.

Of 52 patients who underwent partial nephrectomy for tumor 44 were found to have renal cell carcinoma. The indications for this parenchyma-sparing procedure were categorized according to the initial status of the contralateral kidney and included bilateral tumors or tumor in a solitary kidney in 16 patients (mandatory indications), unilateral carcinoma with compromise of the contralateral kidney by a benign disease process in 9 (relative indications) and small peripheral tumor with a normal contralateral kidney in 19 (elective indications). There were 4 recurrences that accounted for 3 deaths, all in patients with mandatory indications. All patients who underwent partial nephrectomy for relative or elective indications were without definite evidence of recurrent disease at last followup (over-all mean 36 months). Our results suggest that conservative surgery can often provide effective and advantageous therapy for renal cancer and we encourage further consideration of the role of partial nephrectomy as an alternative to radical nephrectomy in selected patients with small peripheral tumors and normal contralateral kidneys.

Carcinoma, Renal Cell↗
PubMed1990

Regeneration of adult dorsal root axons into transplants of fetal spinal cord and brain: a comparison of growth and synapse formation in appropriate and inappropriate targets.

Cut dorsal root axons regenerate into transplants of embryonic spinal cord and form synapses that resemble those found in the dorsal horn of normal spinal cord. One aim of the present study was to determine whether these axons also regenerate into and establish synapses within transplants of embryonic brain. A second aim was to compare the patterns of growth in embryonic brain and spinal cord transplants. Embryonic spinal cord or brain was transplanted into the lumbar enlargement of adult Sprague-Dawley rats, the L4 or L5 dorsal root was cut, and the cut root was juxtaposed to the transplant. The transplants included whole pieces or dissociated cell suspensions of embryonic day 14 (E14) spinal cord, or whole pieces of E14 neocortex, E18 occipital cortex, E15 cerebellum, or E18 hippocampus. One month later the regenerated dorsal root axons were labeled by immunocytochemical methods to demonstrate calcitonin gene-related peptide (CGRP). CGRP-immunoreactive axons regenerated into all the transplants examined and formed synapses in the neocortex and cerebellum transplants in which they were sought. Synapses were far rarer in neocortex and cerebellum than we had observed previously in transplanted spinal cord, and the patterns of growth differed in transplants of spinal cord and brain. In solid transplants of spinal cord, regenerated axons remained relatively close to the interface with the dorsal root, branched, and formed bundles. Areas of dense ingrowth were separated by regions with few labeled axons. In transplants of brain regions, the regenerated axons were few, unbranched, and appeared as individual fibers rather than in bundles, but they were distributed widely in neocortex transplants. The results of quantitative studies confirmed these observations. The area fraction occupied by regenerated axons in solid spinal cord transplants was significantly larger than in occipital cortex or cerebellum transplants. Distribution histograms of the area occupied in transplants demonstrated that regenerated axons were distributed sparsely but homogeneously in transplants of brain, whereas spinal cord transplants were heterogeneous for regenerated axons and contained areas in which growth was dense or sparse. In contrast, several measurements of axon distribution, including area, longest axis, and length of lateral extension, indicated that CGRP-labeled axons spread more widely in occipital cortex transplants than in solid transplants of spinal cord or cerebellum. The results indicate that embryonic CNS tissues that are not normal targets support or enhance the growth of severed dorsal roots and suggest that the conditions that constitute a permissive environment for regenerating axons are relatively nonspecific.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Ultrastructural organization of regenerated adult dorsal root axons within transplants of fetal spinal cord.

It has previously been demonstrated that the severed central branches of adult mammalian dorsal root ganglion cells regenerate into transplants of fetal spinal cord. The aim of this study was to determine whether these regenerating axons form synapses, and, if they do, to characterize them morphologically. Embryonic day 14 or 15 spinal cord was transplanted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and then juxtaposed to the transplant. One to 3 months later the regenerated dorsal roots were labeled by anterograde filling with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or by immunocytochemistry for calcitonin gene-related peptide (CGRP). Dorsal root labeling with WGA-HRP demonstrated that regenerated axon terminals made synaptic contacts within transplants, and stereological electron microscopic analysis demonstrated that CGRP-immunoreactive axon terminals occupied an average of 9% of the neuropil within 2 mm of the dorsal root-transplant interface. The majority of synapses were axodendritic, but a significant percentage were axosomatic or axoaxonic. Since axoaxonic synapses were observed in transplants in which both pre- and postsynaptic profiles of axoaxonic synapses were labeled for CGRP, some regenerated axons apparently form synapses with each other. Approximately 90% of synaptic contacts were simple, 9% were complex, and 25% of the complex terminals were immunopositive for CGRP. Glia occupied 25% of the neuropil within 1 mm of the dorsal root-transplant interface, but only 6% of the neuropil 1-2 mm from the interface. We also performed a stereological analysis of the neuropil in lamina I. The area fractions of neuropil occupied by myelinated axons, perikarya, and dendrites were similar in transplants and in lamina I. However, the area fraction occupied by unmyelinated axons was significantly smaller in transplants, and the area fraction occupied by axon terminals was significantly larger in transplants compared with lamina I. Regenerated CGRP-immunoreactive synaptic terminals in transplants were significantly larger than in normal lamina I, and their synaptic contact length was also increased, suggesting that a compensatory mechanism for increasing synaptic efficiency might occur within the transplants. Synaptic density, however, was significantly reduced in transplants, indicating a smaller number of synaptic terminals per unit area. In lamina I, as in the transplant, most synapses were axodendritic, but the percentage of axosomatic and axoaxonic terminals was lower in lamina I than in the transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy.

The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post-operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post-operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy.

Animals↗
PubMed1989

Death of some dorsal root ganglion neurons and plasticity of others following sciatic nerve section in adult and neonatal rats.

Newborn animals recover from neurological injury to a greater extent than adults in spite of the greater vulnerability of developing neurons to retrograde or transneuronal degeneration (Kennard, '42; Goldman, '74; Prendergast and Stelzner, '76; Bregman and Goldberger, '82, '83). The cellular mechanisms underlying this "infant lesion effect" are incompletely understood (Bregman and Goldberger, '82). The dorsal root ganglion (DRG) is an excellent model in which to compare the developing and adult nervous system with respect to the effects of axotomy on cell survival and cellular function. We studied the survival of L5 DRG neurons after section-ligation of the sciatic nerve of adult and neonatal rats and used qualitative and quantitative immunocytochemical methods to examine changes in intraspinal substance P immunoreactivity (SPIR). Retrograde transport of wheatgerm agglutinin-horseradish (WGA-HRP) peroxidase applied to the sciatic nerve of adult or neonatal rats demonstrated that 70% of the neurons in the normal L5 DRG project into the sciatic nerve at the site of transection. In adults 20% of all L5 DRG neurons died between 10 and 60 days postoperative; in newborns 50% of the neurons died between 5 and 10 days. These results indicate that 30% of axotomized neurons in adults and 75% in neonates die after sciatic nerve section and that neuron loss is both more rapid and more extensive in neonates. No cell death was observed in the L5 DRG of neonates after dorsal rhizotomy, thus suggesting that at this stage of development the survival of DRG neurons depends on the peripheral but not the central process. SPIR in laminae I and II of both adult and newborn operates decreased and then recovered, but the time course and extent of the recovery differ. In adults SPIR was depleted in the medial portion of the L5 segment ipsilateral to surgery by 10 days postoperative and remained depleted for at least 2 months. By 1 year partial recovery occurred, but remained incomplete even at the longest survival time studied (15 months). SPIR, which is present in the dorsal horn at birth, was diminished in ipsilateral laminae I and II by 4 days after nerve section on the day of birth. Between 30 days and 60 days, the density of SPIR in the dorsal horn ipsilateral to surgery became virtually indistinguishable from that on the contralateral, intact side, suggesting a more rapid and complete recovery than in adults.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1989

Differentiation of substantia gelatinosa-like regions in intraspinal and intracerebral transplants of embryonic spinal cord tissue in the rat.

The differentiation of intracerebral and intraspinal transplants of fetal (E14-E15) rat spinal cord was studied to determine the extent to which myelin-free zones in these embryonic grafts exhibit cytological features and immunocytochemical characteristics of the substantia gelatinosa (SG) of the normal spinal cord. Immunocytochemical staining with antiserum to myelin basic protein (MBP) revealed myelin-free areas of varying proportions within fetal spinal cord grafts. These regions were identified in both newborn and adult recipients regardless of whether donor tissue was grafted to heterotopic (intracerebral) or homotopic (intraspinal) sites. As in the SG of the intact spinal cord, the myelin-free regions consisted mainly of small (7-15 microns) diameter neurons. At the ultrastructural level, these cells were surrounded by a neuropil composed of numerous small caliber, unmyelinated axons and intermediate-sized dendrites. Synaptic terminals in these areas were primarily characterized by the presence of clear, round vesicles, although granular vesicles were occasionally found within these terminals. Immunocytochemical staining demonstrated met- and leu-enkephalin-, neurotensin-, substance P-, and somatostatin-like immunoreactive elements within these myelin-free areas. Thus, regions within embryonic spinal cord grafts undergo some topographical differentiation which parallels that of the normal superficial dorsal horn. The presence of SG-like regions illustrates the potential capacity of fetal spinal cord transplants for replacing some intraspinal neuronal populations at the site of a spinal cord injury in neonatal and adult animals. These graft regions may serve as a source of intersegmental projection neurons or establish an extensive intrinsic circuitry similar to that seen in the normal SG. In addition, the definition of these areas provides a useful model to study the innervation patterns of host axons that typically project to the substantia gelatinosa of the normal spinal cord.

Animals↗
PubMed1988

Regeneration of adult dorsal root axons into transplants of embryonic spinal cord.

Transplants of the embryonic rat spinal cord survive and differentiate in the spinal cords of adult and newborn host rats. Very little is known about the extent to which these homotopic transplants can provide an environment for regeneration of adult host axons that normally terminate in the spinal cord. We have used horseradish peroxidase injury filling and transganglionic transport methods to determine whether transected dorsal roots regenerate into fetal spinal cord tissue grafted into the spinal cords of adult rats. Additional transplants were examined for the presence of calcitonin gene-related peptide-like immunoreactivity, which in the normal dorsal horn is derived exclusively from primary afferent axons. Host animals had one side of the L4-5 spinal cord resected and replaced by a transplant of E14 or E15 spinal cord. Adjacent dorsal roots were sectioned and juxtaposed to the graft. The dorsal roots and their projections into the transplants were then labeled 2-9 months later. The tracing methods that used transport or diffusion of horseradish peroxidase demonstrated that severed host dorsal root axons had regenerated and grown into the transplants. In addition, some donor and host neurons had extended their axons into the periphery to at least the midthigh level as indicated by retrograde labeling following application of tracer to the sciatic nerve. Primary afferent axons immunoreactive for calcitonin gene-related peptide were among those that regenerated into transplants, and the projections shown by this immunocytochemical method exceeded those demonstrated by the horseradish peroxidase tracing techniques. Growth of the host dorsal roots into transplants indicates that fetal spinal cord tissue permits regeneration of adult axotomized neurons that would otherwise be aborted at the dorsal root/spinal cord junction. This transplantation model should therefore prove useful in studying the enhancement and specificity of the regrowth of axons that normally terminate in the spinal cord.

Animals↗
PubMed1988

In situ hybridization of mRNA for beta-preprotachykinin and preprosomatostatin in adult rat dorsal root ganglia: comparison with immunocytochemical localization.

In situ hybridization histochemistry was used to identify neurons in rat dorsal root ganglia that contained mRNAs encoding beta-preprotachykinin and preprosomatostatin. The distribution of these neurons was compared with the distribution of neurons containing tachykinins or somatostatin, identified using immunocytochemical techniques. Neurons labelled for beta-preprotachykinin mRNA constituted 20% of the total neuronal population and belonged to the small cell class. Neurons labelled for preprosomatostatin mRNA with either RNA or DNA hybridization probes constituted approximately 10% of the total cells and comprised a small cell group that differed in average size from the beta-preprotachykinin labelled population. The distribution of cells containing tachykinin- or somatostatin-like immunoreactive material was identical to the distribution of cells containing the respective mRNAs and, in addition, individual somata in adjacent sections contained both the mRNA precursor and the peptide. These results suggest that for these neuropeptides the sensitivity of the two methods is equivalent and the respective mRNAs and peptides are co-localized in the same neurons.

Animals↗
PubMed1986

Characterization of forms of immunoreactive somatostatin in sensory neuron and normal and deafferented spinal cord.

In order to determine the contribution made by primary sensory afferents and supraspinal projections to the immunoreactive somatostatin (IRS) content of the spinal cord, measurements were made of the concentration of IRS in the dorsal and ventral halves of the cord in cats subjected to unilateral lumbosacral dorsal rhizotomy (L1-S3) alone or combined with spinal cord transection. The molecular forms of IRS (characterized by gel chromatography) in L7 lumbar spinal cord, L6-S1 dorsal roots, ventral roots and dorsal root ganglia, and sciatic nerve were also determined. S14 was the predominant form in all tissues examined, but two additional molecular forms corresponding to S28 and S11.5 kdalton were present in dorsal root ganglia and spinal cord; S28 but not S11.5 kdalton was detected in both dorsal roots and sciatic nerves. These results indicate that S14 and S28 are transported along the central and peripheral processes of dorsal root ganglia, but that spinal cord S11.5 kdalton originates in the central nervous system. IRS in the dorsal horn was reduced by ca. 40% following dorsal root section. Neither disruption of descending pathways by spinal transection nor surgical isolation of the lumbar segments lowered cord somatostatin content below that produced by dorsal root section, indicating that most of the somatostatin within the cord arises from the dorsal root and from neurons in local spinal segments. Although the total content of IRS in the dorsal horn was reduced by ca. 40% following dorsal rhizotomy, the pattern of molecular forms was not changed accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1986

Renal cell carcinoma: survival and prognostic factors.

Three hundred twenty-six patients treated at New York University from 1970 to 1982 were studied for survival in relationship to surgical stage, type of therapy, and pathologic characterization of the primary tumor. At the time of diagnosis 25.5 per cent of tumors were Stage I, 15 per cent Stage II, 28.5 per cent Stage III, and 31 per cent Stage IV. The retrospective study showed that patients with tumor confined within the capsule achieved the highest five- and ten-year survivals of 88 per cent and 66 per cent, respectively. Survivals decreased as tumor invaded perirenal fat (67% and 35%) or regional lymph nodes (17% and 5%). Tumor invasion into the renal vein alone did not significantly change five-year survival (84%) but lowered ten-year survival to 45 per cent. Patients with metastases at the time of nephrectomy did poorly regardless of site of metastases or kind of adjuvant therapy, except for those managed by surgical extirpation of the secondary lesion. Certain tumor characteristics were associated with a better prognosis, e.g., size below 5 cm in diameter, lack of invasion of collecting system, perirenal fat or regional lymph nodes, and predominance of clear or granular cells growing into a recognizable histologic pattern.

Carcinoma, Renal Cell↗
PubMed1986

Radiotherapeutic prophylaxis of estrogen-induced gynecomastia: a study of late sequela.

Radiation therapy is an effective means of preventing the development of hormone-induced gynecomastia in men with cancer of the prostate. The efficacy and morbidity of this type of radiation was studied in a retrospective analysis of 87 patients referred for treatment from 1972 to 1982. Patients receiving DES as treatment for prostate carcinoma were treated with irradiation to the breast tissue. Patients were treated with 4 MV, 60Co superficial X rays. Doses range from 1200 to 1500 cGy in 3 fractions. The majority of patients had satisfactory results in terms of prevention of gynecomastia and mammalgia. There were few acute reactions noted and no evidence of long term sequela.

Aged↗
PubMed1986

Aggressive treatment of metastatic renal cancer.

Radical nephrectomy and excision of metastases were performed in 21 patients with metastatic renal cell carcinoma. Followup was 12 years. Eight patients had metastases at the time of diagnosis and survived an average of 54 months, with 50 per cent alive 5 years postoperatively. Metastases developed after nephrectomy for localized disease in 13 patients. After extirpation of the secondary lesions these 13 patients survived an average of 38 months and 25 per cent were alive at 5 years. Survival varied with the length of time free of disease. Patients in whom metastases developed later than 2 years after nephrectomy survived 55 months compared to only 22 months for those in whom metastases developed earlier. Survival also was influenced by tumor aggressiveness (reflected by prognostic index number) and completeness of surgical excision of the secondary lesion.

Carcinoma, Renal Cell↗