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Biomedical subjects

M Kaefer

Publications and source records attributed to M Kaefer.

36 records · Page 2Linked to original sources
PubMed1999

Fetal partial urethral obstruction causes renal fibrosis and is associated with proteolytic imbalance.

PURPOSE: We determine whether fetal bladder outlet obstruction induces renal fibrosis, and is associated with an alteration in the regulation of connective tissue degradation and the presence of fibrogenic interstitial cells. MATERIALS AND METHODS: Partial bladder outlet obstruction was surgically induced in 33 fetal sheep at 95 days of gestation. These animals and 24 normal age matched controls were sacrificed at 109, 116 and 135 (term) days of gestation, and the kidneys were rapidly retrieved, drained and weighed. Representative whole kidney samples were snap frozen for assessment of deoxyribonucleic acid, protein and collagen content. Morphometric analysis and alpha-smooth muscle actin immunohistochemistry were performed on histological specimens from formalin fixed kidneys. Tissue extract from fresh kidney specimens were analyzed for metalloproteinase and tissue inhibitor of metalloproteinase activity. Urine samples obtained at the time of sacrifice were analyzed for electrolyte, creatinine and N-acetyl glucosaminidase excretion. RESULTS: All obstructed kidneys were hydronephrotic and larger than age matched controls. Obstructed kidneys at term showed interstitial fibrosis, as measured by increased extracellular matrix volume fraction (45% in male obstructed kidneys versus 2.5% in normal male kidneys, p = 0.0004), increased total collagen content (120 mg./kidney in male obstructed versus 20 mg. in normal male animals, p = 0.016) and collagen/deoxyribonucleic acid content per kidney (2.78 versus 0.53 mg./mg., p = 0.016). Metalloproteinase-1 activity was significantly lower in obstructed kidneys (210 versus 380 U./mg. protein in normal kidneys). Tissue inhibitor of metalloproteinase activity was undetectable in both groups. The presence of an increased population of myofibroblasts often associated with fibrotic processes was seen by alpha-smooth muscle actin staining which was localized to interstitial cells throughout the cortex in obstructed kidneys. CONCLUSIONS: Fetal partial bladder outlet obstruction induces renal interstitial fibrosis as early as 2 weeks after obstruction. A possible mechanism for this process is a shift in proteolytic activity to reduce matrix degradation in obstructed kidneys. These changes might be mediated by the increased number of fibrogenic interstitial cells. The observations suggest several potential approaches to developing an understanding of congenital obstructive uropathy.

Actins↗
PubMed1999

Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome.

PURPOSE: The Beckwith-Wiedemann syndrome is most commonly characterized by macroglossia and abdominal wall defect(s), and it carries a predisposition to embryonal tumors, including Wilms tumor. We report our experience with the character and incidence of renal disease in patients with the Beckwith-Wiedemann syndrome, and discuss the role of radiological followup. MATERIALS AND METHODS: We reviewed the medical records of all patients diagnosed with the Beckwith-Wiedemann syndrome who were treated at our institution between March 1979 and February 1998. Radiological followup consisted of renal ultrasound at approximately 3 to 6-month intervals with the addition of computerized tomography or magnetic resonance imaging (MRI) in patients with an indeterminate lesion(s) or nephrogenic rest(s). RESULTS: A total of 29 patients were identified. Of these cases renal ultrasound showed normal kidneys bilaterally in 19 (70%), simple cysts in 5 (19%), indeterminate lesion(s) in 2 (7%) and nephrocalcinosis in 1 (4%). Nephrogenic rests were followed with MRI in 1 patient, and 1 in whom a 2 cm. mass was revealed by followup MRI underwent partial nephrectomy and chemotherapy for stage I Wilms tumor. CONCLUSIONS: The 3.7% incidence of Wilms tumor in our patients with the Beckwith-Wiedemann syndrome is similar to that in previously published reports. Aggressive follow-up by a sensitive radiological technique is warranted in cases of the Beckwith-Wiedemann syndrome, and associated hemihypertrophy and/or nephromegaly with or without evidence of a Wilms tumor precursor. The detection of suspected malignant disease at an early stage may permit curative nephron sparing surgery.

Adolescent↗
PubMed1998

Heparin-binding EGF-like growth factor in the human prostate: synthesis predominantly by interstitial and vascular smooth muscle cells and action as a carcinoma cell mitogen.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is an activating ligand for the EGF receptor (HER1/ErbB1) and the high-affinity receptor for diphtheria toxin (DT) in its transmembrane form (proHB-EGF). HB-EGF was immunolocalized within human benign and malignant prostatic tissues, using monospecific antibodies directed against the mature protein and against the cytoplasmic domain of proHB-EGF. Prostate carcinoma cells, normal glandular epithelial cells, undifferentiated fibroblasts, and inflammatory cells were not decorated by the anti-HB-EGF antibodies; however, interstitial and vascular smooth muscle cells were highly reactive, indicating that the smooth muscle compartments are the major sites of synthesis and localization of HB-EGF within the prostate. In marked contrast to prostatic epithelium, proHB-EGF was immunolocalized to seminal vesicle epithelium, indicating differential regulation of HB-EGF synthesis within various epithelia of the reproductive tract. HB-EGF was not overexpressed in this series of cancer tissues, in comparison to the benign tissues. In experiments with LNCaP human prostate carcinoma cells, HB-EGF was similar in potency to epidermal growth factor (EGF) in stimulating cell growth. Exogenous HB-EGF and EGF each activated HER1 and HER3 receptor tyrosine kinases and induced tyrosine phosphorylation of cellular proteins to a similar extent. LNCaP cells expressed detectable but low levels of HB-EGF mRNA; however, proHB-EGF was detected at the cell surface indirectly by demonstration of specific sensitivity to DT. HB-EGF is the first HER1 ligand to be identified predominantly as a smooth muscle cell product in the human prostate. Further, the observation that HB-EGF is similar to EGF in mitogenic potency for human prostate carcinoma cells suggests that it may be one of the hypothesized stromal mediators of prostate cancer growth.

Carcinoma↗
PubMed1998

Reservoir calculi: a comparison of reservoirs constructed from stomach and other enteric segments.

PURPOSE: The intestinal augmented bladder has an increased propensity to form urinary calculi. Predisposing risk factors include chronic bacteriuria, urinary stasis and mucus production. Gastric reservoirs have negligible mucus production and the ability to acidify the urine. We determined whether they also have a decreased incidence of stones. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients undergoing augmentation cyptoplasty (215) or creation of a freestanding reservoir (44) between May 1976 and March 1996. Of these cases 83 were augmented with stomach and 179 were constructed from other intestinal segments, (that is ileal, ileocecal, sigmoid and/or a combination of these). Presenting diagnosis, patient age, gender, additional surgical procedures, interval to stone formation and calculous composition were recorded. Patients were excluded from study when there was less than 1 year of followup, as were those with renal or pre-augmentation bladder calculi. RESULTS: Stones formed in 32 of 207 patients (15%) after an average interval of 3.6 years (range 0.5 to 8.6). The majority of stones were composed of struvite (magnesium ammonium phosphate). Reservoirs containing gastric segments were significantly less likely to form calculi than those augmented with other intestinal segments (2 of 70 versus 30 of 137, p <0.0001 Fisher's exact test). Seven additional patients with pre-augmentation bladder stones who subsequently underwent gastrocystoplasty remain stone-free at an average followup of 3.0 years. CONCLUSIONS: Calculous formation is rare in reservoirs that incorporate a gastric segment. In patients with gastric augmentation stones appear only to develop when the patient is on histamine blockade or has a propensity to form stones that only favor an acidic environment, such as uric acid.

Adolescent↗
PubMed1997

Continent urinary diversion: the Children's Hospital experience.

PURPOSE: Continent urinary diversion has become increasingly important for treating childhood urinary tract pathology that cannot be managed by direct reconstructive techniques. We review our 9-year experience with continent diversion. MATERIALS AND METHODS: Since 1986 continent diversions were created in 74 patients 3 to 38 years old (mean age 13.7). The underlying pathological condition was the exstrophy/epispadias complex in 34 patients, neurological disorders in 23, malignancy in 13 and other congenital anomalies in 4. Followup averaged 5.2 years after the last procedure. Nonbladder reservoirs in 39 patients (53%) were fashioned from ileocolic (17), colic (7), gastrocolic (6), sigmoid (3), gastrosigmoid (2), ileosigmoid (2), ileal (1) and gastroileac (1) segments. When possible, the native bladder was incorporated into the reconstructive strategy. A total of 26 patients underwent bladder augmentation with intestine or stomach, including ileal (11), gastric (8), sigmoid (3), gastroileac (2) and ileocolic (2) segments. Nine other patients did not require bladder augmentation. Continence mechanisms were a flap valve (Mitrofanoff principle) in 50 patients, nipple valve in 15 and ileal plication (Indiana pouch) in 9. When the Mitrofanoff principle was used with a native bladder reservoir in 30 cases, outlet resistance was altered by bladder neck division (15), fascial sling placement (6) or Young-Dees-Leadbetter bladder neck reconstruction (2). In the remaining 7 patients the bladder neck remained intact. RESULTS: Excellent continence was obtained. The Mitrofanoff principle initially provided continence in 41 patients (82%). Six of the 9 incontinent patients were dry after a single revision. A total of 13 patients (87%) with nipple valves and 7 (78%) with Indiana pouches were dry, and the remaining 5 were cured after a single revision. Ultimately continence was achieved in 71 of the 74 patients (96%) after a maximum of 2 operations. Of the 48 complications in 29 patients the most common were difficulty in catheterizing (11), stones (11), infection (8) and upper tract deterioration (4). CONCLUSIONS: Many options exist for reconstructing complex anomalies. Choices must be individualized based on patient anatomy. The dry state may be achieved in most cases without resorting to a bag on the abdomen.

Adolescent↗
PubMed1997

Estimating normal bladder capacity in children.

PURPOSE: An accurate estimation of normal bladder capacity can be helpful in evaluating the patient with genitourinary disease and in interpreting urodynamic data. Prior studies have provided initial estimates. We propose 2 new equations that are practical, easy to use and more accurate than those previously published. MATERIALS AND METHODS: We retrospectively reviewed the records of more than 5,000 children undergoing radionuclide cystography at our institution. Radionuclide cystography was conducted by instilling (99m)technetium pertechnetate via gravity drip in awake children. Bladder capacity was believed to be achieved when rate of inflow diminished to a minimal rate, initiation of voiding occurred or significant discomfort was indicated. Patients with vesicoureteral reflux, infravesical obstruction, urinary tract infection, dysfunctional voiding or other lower urinary tract pathology were excluded from the study. Linear and nonlinear regression modeling established the relationship between age and bladder capacity. RESULTS: A total of 2,066 children (598 boys and 1,468 girls) had normal radionuclide cystography and were included in the analysis. Analysis of variance demonstrated that increasing age was strongly predictive of bladder capacity (p <0.0001). Because a nonlinear model was the most accurate formula for all ages (4.5 x age(0.40) = capacity [ounces]), 2 practical linear equations were determined: 2 x age (years) + 2 = capacity (ounces) for children less than 2 years old, and age (years) divided by 2 + 6 = capacity (ounces) for those 2 years old or older. Although girls had larger capacities than boys, the rate of increase was not significantly different between them. CONCLUSIONS: The relationship between normal bladder capacity and age in children follows a nonlinear curve. This nonlinear relationship can be approximated by 2 practical linear formulas that are easy to remember and are derived from a larger population than any prior study. These formulas provided accurate estimations of bladder capacity when prospectively applied to normal patients.

Adolescent↗
PubMed1997

Principles in management of complex pediatric genitourinary plexiform neurofibroma.

Neurofibromatosis is a hamartomatous disorder of neural crest derivation characterized by cutaneous pigmentation and tumor formation in various tissues. Visceral involvement is typically insidious, progressive, and difficult to treat. Plexiform neurofibroma of the urinary tract is rare. Involvement of nearly every genitourinary structure by these lesions has been reported, with the bladder being most commonly involved. In part due to the small number of patients seen at any one institution and the highly variable location and extent of this disease process, a plan for management of individuals with genitourinary neurofibromatosis has not been proposed. In an attempt to define specific goals in treatment of such patients, we reviewed our population of 260 pediatric patients with type 1 neurofibromatosis. We present our series of 5 patients with complex genitourinary lesions and describe specific management principles.

Adolescent↗
PubMed1997

Upsizing of the artificial urinary sphincter cuff to facilitate spontaneous voiding.

OBJECTIVES: Following placement of an artificial urinary sphincter (AUS) in the male child, functional and mechanical alterations can ensue, resulting in an inability to void spontaneously. One possible mechanical etiology in the patient entering puberty is prostatic growth within the fixed mechanical confines of the AUS cuff, resulting in progressive bladder outlet obstruction. Unrecognized infravesical obstruction can, in turn, lead to upper urinary tract deterioration, sepsis, or renal failure. We evaluated the effect of somatic growth and maturation of the male urethra on voiding dynamics in boys with an AUS to specifically determine whether revision of the sphincter cuff (ie, upsizing) is beneficial in restoring the ability to void spontaneously. METHODS: A retrospective review of 124 children with an AUS was performed. Eleven boys were identified whose bladder neck cuffs were later upsized in an attempt to improve bladder emptying. All boys were prepubertal at the time of original cuff placement. The average interval between the initial operation and cuff upsizing was 5 years. RESULTS: Following original sphincter placement, 8 patients emptied to completion spontaneously and 3 patients emptied by intermittent catheterization. All eight of the spontaneous voiders experienced progressive difficulty emptying after they entered puberty and ultimately had to rely on clean intermittent catheterization to empty completely. Follow-up subsequent to cuff exchange averaged more than 5 years (range 1 to 10 years). Despite an average increase of 10 mm in cuff size, all patients continued to depend on intermittent catheterization to empty completely. CONCLUSIONS: Upsizing the bladder cuff in the maturing male who experiences difficulty with bladder emptying does not restore the ability to void spontaneously.

Child↗
PubMed1997

The Mitrofanoff principle in continent urinary reconstruction.

Continent urinary diversion has increasingly become important for treating children and adults with urinary tract pathology that cannot be managed by direct reconstructive techniques. The Mitrofanoff principle, a term that has become synonymous with the flap valve mechanism for promoting the unidirectorial flow of a fluid medium, is a recapitulation of nature's design for the competent ureterovesical junction. Construction of a catheterizable channel using this principle can be performed with a variety of tissues and serves well as a continence mechanism for either the native bladder or intestinal reservoirs. In addition to its utility in managing urinary incontinence, implantation of a catheterizable channel into the cecum can be used to manage fecal incontinence in patients with neurogenic bowel dysfunction.

Adolescent↗
PubMed1997

The sonographic diagnosis of infravesical obstruction in children: evaluation of bladder wall thickness indexed to bladder filling.

PURPOSE: The pathophysiological changes that result from posterior urethral valves depend primarily on the degree and duration of infravesical obstruction. Delayed diagnosis may result in progressive bladder dysfunction, renal parenchymal loss or sepsis. Specific radiographic and clinical criteria predictive of a diagnosis of infravesical obstruction are available in the form of voiding cystourethrography and cystoscopy. However, these modalities share the disadvantage of being invasive in nature. Although noninvasive, sonographic evaluation of bladder thickness has a high degree of variability and it markedly depends on the degree of bladder filling. MATERIALS AND METHODS: Bladder wall thickness and bladder diameter were assessed in 15 children with posterior urethral valves, and 10 age and sex matched children with no bladder dysfunction. Ultrasound was performed before intervention (that is catheter placement or valve ablation). RESULTS: A positive predictive value of 93% was achieved between the 2 groups when bladder wall thickness was indexed to inner wall diameter in the anteroposterior or transverse dimension. Mean bladder wall thickness divided by mean inner bladder diameter plus or minus standard deviation was 0.402 +/- 0.25 in the obstructed population and 0.094 +/- 0.025 in controls (p = 0.0004). CONCLUSIONS: The bladder thickness index is a sensitive sonographic predictor of infravesical obstruction. Application of this index as a noninvasive screening tool for the patient with persistent voiding dysfunction may prove beneficial for identifying infravesical pathology.

Child↗
PubMed1997

Increased renal echogenicity: a sonographic sign for differentiating between obstructive and nonobstructive etiologies of in utero bladder distension.

PURPOSE: The combination of in utero bladder distension and bilateral hydroureteronephrosis in male fetuses may result from a number of pathological processes. The prenatal and postnatal treatment of patients with an enlarged bladder is dictated by the specific etiology leading to these changes. We propose specific ultrasonographic criteria for differentiating between obstructive and nonobstructive etiologies in these fetuses. MATERIALS AND METHODS: We reviewed the medical records and prenatal imaging studies of 18 cases of marked in utero bladder distension in which a diagnosis of posterior urethral valves, the megacystis-megaureter association or the prune-belly syndrome was confirmed postnatally. Amniotic fluid volume and renal echogenicity were assessed before knowledge of the specific diagnosis. Oligohydramnios was graded as mild, moderate or severe. Increased renal echogenicity was defined as greater echogenicity of the renal cortex and/or medulla than of adjacent liver tissue. Postnatal imaging, clinical course and outcome were also reviewed. RESULTS: The study included 15 cases with adequate followup, including 8 in which a diagnosis of posterior urethral valves was confirmed postnatally. Nonobstructive etiologies included the megacystis-megaureter association in 6 cases and the prune-belly syndrome in 1. Seven of the 8 patients with posterior urethral valves had moderate to severe oligohydramnios, whereas all but 1 with a nonobstructive etiology had normal amniotic fluid. Seven of the 8 cases with posterior urethral valves had a marked bilateral increase in renal echogenicity, while none of the nonobstructive cases had this finding. CONCLUSIONS: Increased renal echogenicity and oligohydramnios in the setting of bladder distension are highly predictive (87%) of an obstructive etiology. This finding is important in the prenatal counseling and treatment of boys with bilateral hydronephrosis and marked bladder dilatation.

Diagnosis, Differential↗
PubMed1997

Pressure at residual volume: a useful adjunct to standard fill cystometry.

PURPOSE: Determining the role of the bladder in incontinence and/or upper urinary tract deterioration involves the cystometrographic evaluation of detrusor compliance. Management decisions based on information provided by standard fill water cystometry assume that data reflect the physiological state of the patient but this is not always true. We report the use of pressure at residual volume as a physiological measurement to aid in the interpretation of data obtained during standard fill urodynamics. MATERIALS AND METHODS: All patients presenting to our urodynamic suite for standard cystometry between June 1994 and December 1995 underwent measurement of bladder pressure at insertion of the urodynamic catheter. Residual volume and pressure measured before draining this urine, that is pressure at residual volume, were recorded. The bladder was then filled at a rate equal to or less than 10% per minute of known or predicted capacity. When a volume equal to the residual volume had been instilled, filling pressure was recorded and the remainder of the standard urodynamic evaluation was completed. Uncooperative patients as well as those with an active infection or residual volume less than 10 ml. were excluded from further analysis. RESULTS: In 152 children pressure at residual volume was compared to filling pressure and the difference was analyzed. Filling pressure was higher than pressure at residual volume in the majority of cases. In 59 children there was a positive change (filling pressure greater than pressure at residual volume) of 5 cm. water or greater and in 13 there was a negative change (pressure at residual volume greater than filling pressure) of 5 cm. water or less. When only cases in which pressure at residual volume was greater than 5 cm. water were analyzed, 46 and 33% had a difference between filling pressure and pressure at residual volume of 5 cm. water or greater and 10 cm. water or greater, respectively. CONCLUSIONS: Pressure at residual volume is physiological, simple to determine and may provide additional information regarding storage characteristics of the bladder. In the context of the clinical history differences between pressure at residual volume and filling pressure may help to interpret standard fill cystometry data.

Adolescent↗
PubMed1996

Characterization of type I 5 alpha-reductase activity in DU145 human prostatic adenocarcinoma cells.

The conversion of testosterone (T) to dihydrotestosterone (DHT) has been demonstrated to be catalysed by at least two isoforms of human steroid 5 alpha-reductase, designated types I and II. Type II 5 alpha-reductase expression predominates in human accessory sex tissues, localized to the fibromuscular stromal compartment. The type I isoform predominates in skin, prostatic epithelia and, to a lesser extent, in prostatic fibromuscular stroma. The significance of the type I isoform to prostatic cellular growth and function remains undefined. In cultured DU145 cells, we evaluated the metabolism of [14C]-T and demonstrated the time-dependent formation of [14C]-DHT. Oxidative metabolism (conversion of [14C]-T to [14C]-androstenedione) and the formation of conjugated androgen metabolites occurred at a relatively low rate in the DU145 cells. Using human type I 5 alpha-reductase cDNA, Northern blot analysis of DU145 cell mRNA revealed high levels of type I isoform expression. Analogous probing of the DU145 cells with a human 5 alpha-reductase II cDNA failed to reveal expression of the type II isoform. The expression of functional type I activity has been confirmed pharmacologically using isoform-selective 5 alpha-reductase inhibitors. Reductive metabolism of [3H]-T in the DU145 cells was inhibited in a concentration-dependent manner by LY306089, a potent non-steroidal type I-selective inhibitor (IC50 = 10.0 nM). SKF105657, a steroidal type II-specific inhibitor was distinctly less active at inhibiting [3H]-DHT formation. LY306089 was a non-competitive inhibitor of type I 5 alpha-reductase in DU145 cellular homogenates with an apparent Ki value of 4.0 nM. These studies have identified and pharmacologically defined type I 5 alpha-reductase activity in an androgen-insensitive prostatic cancer cell line and provide the basis for additional investigations into the significance of type I 5 alpha-reductase to human prostatic pathophysiology.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

An alternative surgical technique for the management of afferent limb structure in Kock pouch continent urinary diversion.

Stenosis of the afferent limb has recently been recognized as a rare cause of upper urinary tract obstruction in patients with a Kock pouch continent urinary diversion. Usually, it can be managed by endoscopic balloon dilation but occasionally open surgical reconstruction is required. We describe an alternative simpler surgical technique that was used in a patient who presented with anuria due to afferent limb stenosis 13 years after the construction of a Kock pouch continent urinary diversion.

Adult↗
PubMed1995

Posterior urethral valves, pressure pop-offs and bladder function.

The pop-off mechanisms that sometimes occur with posterior urethral valves have well recognized implications for renal function, such that 1 or both kidneys can be protected from the deleterious effects of elevated bladder pressures. What has not been defined is the significance, if any, of pressure pop-offs to the developing bladder and ultimate bladder function. To answer this question we reviewed the records of 63 boys with posterior urethral valves. Eight boys who were not yet toilet trained had unevaluable bladder outcomes. Of the 55 remaining boys there was 1 or more pressure pop-off in 39 (71%), including massive (grade 5) reflux, massive reflux associated with ipsilateral renal dysplasia, a patent urachus, large diverticula and urinomas. Bladder outcomes were judged as favorable or unfavorable on the basis of urodynamic parameters and/or patient clinical status. A statistically significant positive correlation was found between the presence of a pop-off and a favorable outcome. Favorable characteristics were found in 34 of 39 bladders (87%) with pressure pop-offs. In contrast, only 9 of 16 bladders (55%) without pressure vents had favorable outcomes. In addition, 5 of the remaining 7 boys without pressure vents have required augmentation cystoplasty. A direct correlation between absolute number of pop-offs and favorable bladder outcome was also noted, further emphasizing this relationship. The presence of a pressure pop-off is a favorable prognostic sign for ultimate bladder function in boys with posterior urethral valves.

Adolescent↗
PubMed1988

Soluble and bound acid protease activity of myelin from bovine cerebral white matter and spinal cord.

Isolated myelin of bovine spinal cord was found to degrade exogenous myelin basic protein (MBP) at pH 4.4. Electrophoretic peptide patterns were consistent with limited proteolysis of MBP. Some of the proteolytic activity was soluble at increased ionic strength, some remained bound, withstanding extraction at 37 degrees C for up to 12 hr. While being measurable with exogenous MBP, bound protease degraded neither bound MBP nor any other major intrinsic myelin protein. Both soluble and bound protease activity was completely inhibited by pepstatin A. The patterns of limited proteolysis of MBP they produced were identical. Myelin of cerebral white matter also exhibited soluble and bound acid protease activity which was likewise inhibited by pepstatin A. Protease activity of spinal cord and cerebral myelin is therefore suggested to be due to a cathepsin D-like endopeptidase, present in a loosely and tightly bound form. Both forms increased by 50 to 80% in activity when myelin was isolated from mixtures of white and cortical gray matter. While increased soluble activity of myelin is consistent with binding of cathepsin D of lysosomal origin during the isolation of myelin the tightly bound form might point to a principal mechanism through which exogenous proteins may become attached to the myelin sheath in vivo.

Animals↗