Search

In a registry-based sample of 361 children with a brain tumor, those whose grandparents and great-grandparents had a history of any kind of tumor were younger at the time of presentation than were those who lacked this family history (p = 0.1). In post hoc analyses, the age difference was most apparent among children with cerebral tumors, and when family history was limited to brain tumors and to great-grandparents. These findings are in keeping with the hypothesis that a familial tumor diathesis contributes to an early age at onset of a brain tumor in some children.

Galanin is a widely distributed regulatory peptide which modulates the pituitary secretion of PRL and GH. Estrogen administration strongly stimulates galanin gene expression in the rat anterior pituitary. In adult female Fischer 344 rats, estrogen also induces hyperplasia of lactotropes. We used immunocytochemical analysis to assess the effects of estrogen on galanin-like immunoreactivity (Gal-IR) in the rat pituitary and hypothalamus during sc diethylstilbestrol (DES) implantation and after its removal at 30 days. In the anterior pituitary, DES implantation increased the portion of Gal-IR-containing cells from less than 2% in the control rats to 18.3% after 3 days of DES and 36% after 30 days. These changes paralleled the lactotrope hyperplasia exhibited in response to DES exposure. Ten and 30 days after removal of the DES capsules, the percentage of Gal-IR-containing cells in the anterior pituitary decreased to 6.3% and 1.5%, respectively. Colocalization studies revealed that Gal-IR-containing cells were predominantly lactotropes. Immunoelectron microscopy demonstrated that Gal-IR was concentrated in the Golgi region of these hyperplastic lactotropes and suggests that little of the synthesized galanin is secreted. The distribution of Gal-IR in the hypothalamus, median eminence, and neurohypophysis was unaffected by DES treatment. These data demonstrate that galanin is synthesized by hyperplastic pituitary lactotropes of Fischer 344 rats and that peptide accumulation is dependent on the presence of circulating estrogens. In contrast, neuronal galanin synthesis in the hypothalamus does not appear to be regulated by estrogen.

Absolute and relative growth of cerebral structures was assessed morphometrically in 34 neurologically normal live-born infants surviving up to 1 year of age, 20 infants with fatal intraventricular hemorrhage, and 4 with periventricular leukomalacia. In the normal brain, cerebral cortex grew 25% faster than white matter throughout infancy. Thus, to achieve the normal adult size and 1:1 ratio of cortex to white matter, white matter must continue to grow for several years after cessation of cortical growth. Brains with intraventricular hemorrhage or periventricular leukomalacia manifested accelerated growth of gray-matter structures compared with controls. In addition, brains with periventricular leukomalacia had markedly depressed rates of white-matter growth compared with controls of similar age, whereas brains with intraventricular hemorrhage had disproportionate hydrocephalus. The findings suggest that (1) gray-matter growth is accelerated in premature infants with intraventricular hemorrhage or periventricular leukomalacia, perhaps reflecting perinatal stress; (2) periventricular leukomalacia is associated with impaired growth of white matter during a critical period; and (3) sequential quantitative assessment of ventricular size following intraventricular hemorrhage may assist in early recognition of progressive posthemorrhagic hydrocephalus.

The factors responsible for the production of prolactin-secreting tumors are obscure. One hypothesis, that chronic loss of dopamine control from the hypothalamus may be associated with prolactinoma formation, was tested. Female adult Fischer 344 rats were subjected to ovariectomy and were then given subcutaneous implants of diethylstilbestrol (DES) Silastic capsules to produce lactotrophic hyperplasia. Sequential studies assessed the neuronal activity of the tuberoinfundibular dopaminergic neurons of the arcuate nucleus of the hypothalamus (A12) during and after this estrogen-induced pituitary growth. Immunocytochemical staining for tyrosine hydroxylase was used as a marker for dopamine synthesis, plasma radioimmunoassay provided plasma prolactin levels, and magnetic resonance imaging and histological studies were performed to examine the structural changes occurring in the pituitary gland. Animals were sacrificed from 3 to 67 days after DES implantation. To determine the reversibility of the estrogen-induced changes, rats were also sacrificed at different time intervals after the removal of 30-, 40-, or 60-day DES implants. After 30 days of DES treatment, plasma prolactin levels increased 40-fold and pituitary weight increased more than threefold. Tyrosine hydroxylase immunoreactivity diminished gradually and was almost completely depleted at 30 days. Pituitary histology revealed marked prolactin cell hyperplasia. These changes were completely reversible; removal of the capsule after 30 days resulted in eventual normalization of plasma prolactin levels and pituitary size and in restoration of tyrosine hydroxylase immunoreactivity in the A12 region. Sixty days of DES treatment produced large hemorrhagic tumors with sustained high plasma prolactin levels and an irreversibly distorted A12 area. These observations suggest that in these animals loss of dopamine regulation secondary to estrogen stimulation initially produces prolactin hyperplasia but that prolonged loss leads to adenoma formation.

A 27-year-old man had X-linked true anophthalmos. No evidence of optic globe, nerves, or chiasm was found. Rudimentary structures suggesting optic tracts were present. Lateral geniculate nuclei were present but gliotic. Calcarine cortex was thinner but had usual lamination. The normal patches of cytochrome oxidase activity in layers II and III of visual cortex were absent.

The effects of hypoglycemia on cerebrovascular permeability to a protein, horseradish peroxidase (HRP), were studied in mice given 3 or 8 units of crytalline zinc insulin intraperitoneally. HRP (10 mg in 0.1 ml saline) was injected intravenously 15 to 20 minutes prior to sacrifice. Both mildly and severely hypoglycemic groups of mice showed a drastic reduction in the normal transit of HRP across cerebral arterioles. The number of normally-stained vessel segments and of HRP-filled endothelial vesicles decreased in insulin-treated mice. In the brains of severely hypoglycemic mice, however, increased parenchymal HRP accumulation occurred. A ruptured blood vessel was found in the center of one-fourth of the focal exudates examined. Electron microscopic examination revealed thrombin, sometimes extending through the vessel wall, and hemorrhage, yet inter-endothelial tight junctions remained intact. Seizures were associated with severe hypoglycemia in 6 out of 10 mice with serum glucose levels below 40 mg/100 ml following 8 units of insulin, but the number of focal exudates per brain was similar in all 10 mice. We conclude that insulin-induced hypoglycemia is associated with decreased HRP transit across cerebral arterioles, and that severe insulin shock is also accompanied by actual rupture of vessel walls and extravasation of blood and HRP into the parenchyma of the brain.

A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was extensively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (beta-lipotropin, beta-endorphin, and alpha MSH). The tumor was composed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual combination of pituitary hormones from a mixed pituitary adenoma.

Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary tumors in which no excess hormone secretion can be identified clinically have been considered as nonfunctioning or null-cell adenomas. Immunocytochemical data presented here suggest that many of these tumors contain subunits of the glycoprotein hormones. Of 160 patients referred for pituitary surgery, 37 (23%) had no evidence of excess hormone secretion on preoperative endocrine evaluation. Immunocytochemical staining of these tumors was carried out using antibodies specific for prolactin, growth hormone, adrenocorticotropic hormone, the beta subunits of luteinizing hormone (beta-LH), follicle-stimulating hormone (beta-FSH), and thyroid-stimulating hormone (beta-TSH), and the alpha subunit. One or more of these pituitary hormones were detected in 73% of cases. The alpha and beta subunits were detected most frequently, being found in 68% of cases; 27% had staining for one or more beta subunits and 37.9% had staining for both alpha and beta subunits. The incidence was: beta-FSH in 58%, beta-LH in 47%, beta-TSH in 33%, and the alpha subunit in 42%. Staining for multiple glycoprotein hormones was common (52%), and mixed glycoprotein hormones and prolactin cell types were found in 16% of cases. These data suggest that most apparently nonfunctioning pituitary tumors contain immunoreactive hormones and the majority of these are subunits of the glycoprotein hormones. Since the glycoprotein hormone beta subunits must combine with the alpha subunit to produce biologically active hormones, the production of the subunits alone may not have endocrine manifestations.

The effects on rat cranial nerve growth of removing various amounts of extraocular muscle was studied using morphometric techniques. Growth in the third cranial nerves was found to be severely retarded when most of the muscle tissue was removed. By contrast, removal of the eye alone, leaving extraocular muscles relatively intact, was found to have little or no effect on the subsequent growth of third and sixth cranial nerve fibers and of extraocular muscle fibers. This conclusion could be drawn only through the application of statistical methods which take into account several generally unrecognized facts: frequency distributions of axon circumference and myelin sheath thickness are highly variable from nerve to nerve even in normal rats, which often have more large fibers in left than in right nerves. The bimodal nature of peripheral nerve fiber distributions precludes the use of such parametric tests as the commonly and inappropriately used t-test, but a non-parametric test such as the Kolmogorov-Smirnov test, extensively used in these studies, is inadequate for data comprising several sets of distributions to be compared. The application of the analysis of variance to some of the data and the merits of the procedure are discussed.

Recent evidence indicates that vasoactive intestinal peptide (VIP) may be involved in normal pituitary function. Immunocytochemistry was used to localize VIP in human biopsied pituitary adenomas and postmortem anterior pituitary glands. Paraffin sections were immunostained for VIP with the avidin-biotin-peroxidase technique. Strong VIP-like immunoreactivity (VIP-LI) was observed in 16 of 17 prolactinomas, 12 of 14 growth hormone-secreting tumors associated with acromegaly, four of 12 ACTH-secreting tumors, and 14 of 18 nonfunctioning pituitary adenomas. In most cases, VIP was colocalized with the classical pituitary hormones. Six of the 18 nonfunctioning tumors had no demonstrable hormone immunoreactivity; five of these stained strongly for VIP, whereas one was negative. Of 18 normal anterior pituitaries, 12 showed strong diffuse staining for VIP throughout the gland. One pituitary with VIP-LI came from an individual who had undergone pituitary stalk transection. Double-immunoenzyme labeling and immunoelectron microscopy demonstrated VIP-LI in many lactotrophs, scattered thyrotrophs, corticotrophs, and in an occasional gonadotroph. These results suggest the following: 1) VIP is present in more than one cell type in normal and adenomatous human pituitaries; and 2) VIP may be involved in the function and development of pituitary tumors.

A 19-year-old man was a victim of near-drowning in fresh water. After he was resuscitated, examination showed nystagmus, absent gag reflex, diminished facial sensation, dysmetria of all limbs, and failure of automatic respiration. His intellect was perfectly preserved. Eight months later, he died suddenly, and the essential neuropathologic findings were limited to the lower brainstem. There was marked neuronal depletion bilaterally in the nucleus gracilis, nucleus cuneatus, nucleus of the tractus solitarius, nucleus ambiguus, and nucleus retroambiguus; several other lower-brainstem nuclei showed evidence of damage, but to lesser extent. The neuropathologic findings seem to have been an unusual consequence of anoxia-ischemia and support previous concepts of the anatomical localization of the human respiratory centers.

A patient with a discrete metastasis in the ventral hypothalamus and optic chiasm is reported, who developed an abnormal daily rhythm of oral temperature without alteration of the 24-h mean temperature. This region, its afferents, and its efferents appear to be important in the neural regulation of human circadian rhythmicity.

Axonal regeneration across 64 median nerve grafts in 34 rabbits was studied histologically to determine the optimal conditions for nerve allografting. Axonal regeneration across allografts in cyclosporin A-treated animals was satisfactory, but it occurred more slowly and with more inflammation and fibrosis than in autografts. Without immunosuppression, fresh allografts were rejected. However, in immunocompetent hosts, allografts rendered less immunogenic by predegeneration were not rejected, and axonal regeneration occurred. The combination of cyclosporin A and nerve graft predegeneration produced the most substantial axonal regeneration, comparable to autografts. The observations suggest that nerve allograft survival may be optimally effected by cyclosporin A treatment coupled with reduction in the immunogenicity of the grafts, such as by predegeneration.

Twenty-four cats were divided into two groups and treated with an intravenous infusion of either fluosol DA or dextran. One-half of the animals in each group were ventilated with room air and one-half with 100% oxygen. The right middle cerebral artery was occluded for a period of 4 hours through a transorbital approach. Regional blood flow by the hydrogen clearance method was measured before and after the infusion of fluosol DA or dextran, after oxygenation in the animals on 100% oxygen, three times during the period of ischemia, and after reperfusion. Regional cerebral blood flow increased slightly with the infusion of fluosol or dextran, decreased slightly with hyperoxygenation in the animals so treated, and decreased markedly in the right hemisphere during temporary occlusion of the right middle cerebral artery in all groups. With reperfusion regional flows in the right hemisphere varied considerably, with some animals showing hyperperfusion and others essentially no flow. There was no significant difference in average regional cerebral blood flow between any of the groups. The severity of infarction in all groups was directly related to the decrease in regional cerebral blood flow in the right hemisphere during temporary occlusion. There was also a strong correlation between the regional cerebral blood flow in the right hemisphere after reperfusion and the severity of infarction. In general, the animals showing normal or increased flow after reperfusion had small infarcts and those showing no reflow had large infarcts. Mortality was high in all groups, was not significantly different between any of the groups, and was highly correlated to the size of infarction. In brief, in this study fluosol offered no advantage over dextran, and probably neither agent, in the dose used, offered any protection against cerebral ischemia.

Several aspects of data collection and analyses of peripheral nerve experiments employing light and electron microscopic morphometric techniques have not been adequately discussed in the literature. From statistical tests performed on nerve data, it was found that light compared with electron microscopic morphometry underestimates the number of small fibers. An optimum sampling strategy must take into account a potential bias toward small fibers introduced by measuring fibers from electronmicrographs. It must also take into account a potential bias introduced by the non-random distribution of nerve fibers of different sizes in nerves. These biases are offset by sampling a large enough number of fibers from large enough area electron micrographs. A method is presented for analysing periopheral nerve data using the nested analysis of variance. This requires first dividing the usual bimodal nerve fiber distribution into component normally distributed parts. The number of fibers in the two portions of a bimodal distribution must be considered in data analysis. Knowledge of the variances of parameters to be studied in any particular nerve is necessary for optimum sampling strategies.

A case of cervical diastematomyelia in an adult is reported. The patient first noted sensory and motor symptoms at 34 years of age after two episodes of cervical trauma. Metrizamide computerized tomography myelography of the cervical spine and cord showed the region of diastematomyelia and revealed a spur containing both bone and fat tissue projecting into the spinal canal and cord. The spur arose from the laminae and spinous processes of C-2 and C-3, and was successfully excised. Postoperatively, the patient's deficits gradually improved. The literature concerning adult cervical diastematomyelia is reviewed.

The authors report the first known example of hypoxic-ischemic white matter necrosis limited to one cerebral hemisphere. The patient was a 63-year-old man who developed signs of a stroke following a myocardial infarct after a left carotid endarterectomy and died seven days later. At autopsy, extensive necrosis of centrum semiovale was found only in the cerebral hemisphere supplied by the endoarterectomized carotid artery. A recent thrombus was found at the site of the endarterectomy, and the right common carotid artery was completely occluded by an old thrombus. This observation probably is explained by a well-established collateral blood supply to the right cerebral hemisphere, which protected it from the effects of the hypotension that accompanied the myocardial infarct.

A subacute progressive cerebellar brainstem syndrome developed in a patient with systemic lupus erythematosus in remission. Cerebellar biopsy documented the diagnosis of progressive multifocal leukoencephalopathy (PML). Data from this patient and 10 others in the literature emphasize the need to consider this diagnosis when ataxia develops in any patient with underlying malignancy, chronic infection, or other disease that involves immunological incompetence. Although the ataxic form of PML is not of nosological relevance, early diagnosis may eventually have therapeutic importance.

The monoclonal antibody Hy2D4 was found to label a previously undescribed subset of rat and human anterior pituitary cells. The antibody binding site appears to be a carbohydrate moiety previously named "X hapten." Double-label immunofluorescence studies in both normal rat and postmortem human pituitaries showed that this antigen is distributed on a subset of adrenocorticotropic hormone (ACTH)-positive cells, but is not detectable in cells immunoreactive for growth hormone, prolactin (PRL), thyroid-stimulating hormone, or luteinizing hormone. Since X hapten labeling revealed a biological subdivision of corticotroph cells, it was expected that some ACTH-positive tumors would be immunoreactive, but that tumors of other hormonal types would be negative. Instead, in 21 surgical specimens examined, tumors of all hormonal types were found to show immunoreactivity. To determine whether experimental proliferative changes in the pituitary could explain the shift in the cell type expressing the antigen, PRL-cell hyperplasia was induced in rats through chronic (8-week) exposure to diethylstilbestrol. The fraction of X-positive cells increased in these hyperplastic glands almost ninefold and, as in human adenomas, many non-corticotroph cells expressed the X marker in this model. However, the non-corticotroph cells expressing X were predominantly growth hormone cells, not the proliferative PRL cells. Thus, expression of the antigen does not necessarily imply that a cell is in a proliferative mode. While it is not known what role an altered expression of this antigen might play, the antibody offers a probe into cellular biology of human and experimental pituitary tumors.

The histopathological and immunopathological features of peripheral neuropathy were investigated in 21 patients with the acquired immunopathological syndrome (AIDS) or AIDS-related complex (ARC). Clinical syndromes observed in the 11 (52%) symptomatic patients included distal symmetrical polyneuropathy (DSPN) and chronic inflammatory demyelinative polyneuropathy (CIDP). Specimens from 19 of 20 patients (95%), both symptomatic and asymptomatic, had histopathological evidence of moderate or severe demyelination (79%), axonal degeneration (36%), and mononuclear cell inflammation (37%). Nerves from patients with CIDP and DSPN showed similar degrees of demyelination and axonal degeneration, but inflammation was more intense in CIDP. Immunohistochemical staining identified the majority of inflammatory cells as T lymphocytes or macrophages, with a predominance of CD8+ cytotoxic/suppressor cells. Diffuse immunostaining for human leukocyte antigen (HLA)-DR was present on endothelial cells, mononuclear inflammatory cells, and Schwann cells, and variable patchy immunostaining for HLA-DR was present on nerve fibers. Control nerve specimens showed staining for HLA-DR limited to endothelial, and a few mononuclear cells. The patterns of immunostaining were similar for AIDS and ARC patients. Human immunodeficiency virus (HIV) was cultured from peripheral nerve in 3 patients, but HIV antigen was not detected by immunohistochemical staining of 8 specimens. The findings implicate HIV infection in nerve, with T cell- and macrophage-mediated tissue destruction as the pathogenetic mechanism of the AIDS/ARC neuropathy.

A patient with two intracerebral glioblastomas of differing histology with metastases to the liver in the absence of surgery is reported. The gliomatous nature of the lesions was confirmed by staining for glial fibrillary acidic protein. Histological and immunohistochemical evidence suggests that the metastases arose from the more poorly differentiated of the intracerebral tumors. One of the intracerebral tumors had enhanced expression of the ras p21 oncogene as compared to the other tumors and as compared to nonmalignant brain tissue from this patient.

The periodicity of the myelin sheath in glutaraldehyde carbohydrazide (GACH) embedded tissues from three 10-day-old and two 43-day-old mice was investigated with the electron microscope. The mean repeat period and number of repeats per fiber was measured in 31-89 fibers in the trapezoid bodies, olfactory tract and sciatic nerves. The mean period of the myelin sheaths in both the peripheral and the central nervous systems of the 10-day-old mice (15.1 +/- 0.07 nm (S.E.M.) and 13.4 +/- 0.09 nm respectively) are smaller (rho less than 0.001) than those of the adult mice (15.9 +/- 0.08 nm and 14.7 +/- 0.06 nm respectively). These differences may be related to the known differences in chemical composition of immature and mature myelin.

The spinal cord and brain of a man who died 18 years after a crush injury of lumbar segments contained some unusual lesions. There was a reduced number of myelinated axons in the corticospinal tracts as high as the fifth cervical segment. Such retrograde degeneration has been described in human pyramidal tracts only a few times. The results of reported studies of experimental retrograde degeneration have been inconsistent. The course of the fasciculus gracilis, as delineated by gliosis, was atypical, and an unusual glial nodule, possibly neoplastic, was present in the dorsal columns at C8.

Dexamethasone ameliorates cerebral edema, but its effect on normal blood-brain barrier is unknown, as is the site of action. Sixteen normal mice were given dexamethasone, 3 mg/kg intramuscularly or 2 mg/kg intravenously. One to two hours later 10 mg of horseradish peroxidase (HRP) in 0.1 ml of saline was administered intravenously and allowed to circulate for 15 minutes. Brain slices were examined by light and electron microscopy. The number of HRP-permeable arteriolar segments per brain was less in dexamethasone-treated than in control mice (p less than 0.001). In addition, the number of small HRP-filled endothelial vesicles of capillaries and of HRP-permeable and -impermeable arterial segments was less in dexamethasone-treated mice than that for similar vessels in control mice (p less than 0.005, p less than 0.05, and p less than 0.01, respectively). The total number of small vesicles and the number of larger HRP-filled vesicles in arterioles was the same in treated and control mice. Dexamethasone therefore decreased the normal permeability of cerebral blood vessels to HRP. This decrease was accompanied by a decrease in the number of HRP-containing small endothelial vesicles. These data suggest that dexamethasone influences cerebral edema by decreasing the permeability of the cerebral vasculature for macromolecules.

30 Swiss albino mice aged 8 days were injected intraperitoneally with 0.2 ml of a solution of 4% N,N-dimethyl-formamide in 5% dextrose in water containing cholesterol-1,2-(3)H ( approximately 1 mCi/ml). Lung tissue was embedded in an Epon mixture after either acetone and propylene oxide dehydration, partial ethanol and Epon 812 dehydration, or the precipitation of cholesterol by digitonin succeeded by partial dehydration. The distribution of cholesterol-1,2-(3)H in lung parenchyma in 1micro Epon section radioautograms was compared with that in frozen section radioautograms and was found to be independent of the manner of tissue processing. Grain distribution in the tissue was essentially the same whether 16, 63, 93, or 100% radioactivity was retained in the lung. However, grain distribution in the alveolar spaces differed, presumably due to displacement of pulmonary surfactant, which contains cholesterol. Intracellular distribution of cholesterol, in electron microscope radioautograms, was the same with either 51% or 93% retention of radioactivity in the lung. Loss of radioactivity into the various processing solutions was monitored. The various processing techniques have different drawbacks.

The localization of (3)H-labeled cholesterol in nerves undergoing degeneration and regeneration was studied by radioautography at the electron microscope level. Two types of experiments were carried out: (a) Cholesterol-1,2-(3)H was injected intraperitoneally into suckling mice. 5 wk later, Wallerian degeneration was induced in the middle branch of the sciatic nerve, carefully preserving the collateral branches. The animals were then sacrificed at various times after the operation. During degeneration, radioactivity was found over myelin debris and fat droplets. In early stages of regeneration, radioactivity was found in myelin debris and regenerating myelin sheaths. Afterwards, radioactivity was found predominantly over the regenerated myelin sheaths. Radioactivity was also associated with the myelin sheaths of the unaltered fibers, (b) Wallerian degeneration was induced in the middle branch of the sciatic nerves of an adult mouse, preserving the collateral branches. Cholesterol-1,2-(3)H was injected 24 and 48 hr after the operation and the animal was sacrificed 6 wk later. Radioactivity was found in the myelin sheaths of the regenerated and unaltered fibers. The results from these experiments indicate that: (a) exogenous cholesterol incorporated into peripheral nerve during myelination remains within the nerve when it undergoes degeneration. Such cholesterol is kept in the myelin debris as an exchangeable pool from which it is reutilized for the formation of the newly regenerating fibers, especially myelin. (b) exogenous cholesterol incorporated into the nerves at the time that degeneration is beginning is also used in the formation of new myelin sheaths during regeneration, (c) mature myelin maintains its ability to incorporate cholesterol.