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Biomedical subjects

S Hruby

Publications and source records attributed to S Hruby.

At least 19 recordsLinked to original sources
PubMed2001

Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study.

PURPOSE: We evaluated pathological features of prostate cancer detected on repeat prostate biopsy in men with a serum total prostate-specific antigen (PSA) level between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an initial biopsy and compared them to those cancers detected on initial prostate biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of 1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these 820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had clinically localized disease, respectively, and were offered radical prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent radical retropubic prostatectomy. There were statistically significant differences with respect to multifocality (P = 0.009) and cancer location (P < 0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a more apico-dorsal location. In contrast, there were no differences with respect to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P = 0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least 10% of patients with negative prostatic biopsy results will be diagnosed with CaP on repeat biopsy. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy are similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Cancers missed on initial biopsy and subsequently detected on repeat biopsy are located in a more apico-dorsal location. Repeat biopsies should thus be directed to this rather spared area in order to improve cancer detection rates.

Age Factors↗
PubMed2000

Pretreatment prostate-specific antigen as an outcome predictor of targeted transurethral microwave thermotherapy.

OBJECTIVES: To evaluate pretreatment serum prostate-specific antigen (PSA) as an outcome predictor of targeted microwave thermotherapy. METHODS: Seventy-one patients with lower urinary tract symptoms of benign prostatic hyperplasia underwent targeted transurethral microwave thermotherapy using the Targis system. Outcomes 12 months after treatment were evaluated by the International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and quality-of-life (QOL) score. The ability of PSA to predict outcomes was evaluated by linear and logistic regression and receiver operating characteristic curve analysis. RESULTS: Higher pretreatment PSA levels were significantly predictive of an absolute IPSS change of -7.5 or less for patients with moderate baseline symptoms or - 15 or less for those with severe baseline symptoms; an absolute Qmax change of 5 mL/s or greater; an absolute QOL score change of -3 or less; an IPSS at 12 months of 7 or less; a Qmax at 12 months of greater than 12 mL/s; and a QOL score at 12 months of 1 or less. Nevertheless, even without taking pretreatment PSA into account, most patients benefitted substantially from targeted microwave thermotherapy. Thus, 74%, 71%, and 79% of all eligible patients improved 50% or more in IPSS, Qmax, and QOL score, respectively, at 12 months compared with baseline. No significant association between PSA and either prostate or transition zone volume could be demonstrated. CONCLUSIONS: Most patients benefit substantially from targeted microwave thermotherapy. However, higher PSA levels are significantly predictive of more favorable outcomes. This association may reflect patient-to-patient differences in the relative abundance of PSA-producing epithelial cells in the transition zone of the prostate.

Aged↗
PubMed1999

Temporary intraurethral prostatic bridge-catheter compared with neoadjuvant and adjuvant alpha-blockade to improve early results of high-energy transurethral microwave thermotherapy.

OBJECTIVES: The maximal effect of transurethral microwave thermotherapy (TUMT) for lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) occurs 3 to 6 months after treatment. In the acute period after TUMT, little change in symptoms, quality of life (QOL), and peak urinary flow rate (Qmax) is observed versus baseline. Some men may also develop acute urinary retention secondary to thermally induced edema. Recent reports suggest that early results of TUMT may be improved with concomitant use of either a temporary intraurethral prostatic bridge-catheter (PBC) or neoadjuvant and adjuvant alpha-blocker therapy. This report compares the results of these two adjunctive modalities directly. METHODS: This nonrandomized retrospective comparison of results in 186 patients with LUTS of BPH is based on findings of three recently reported prospective clinical trials. All patients underwent targeted high-energy TUMT. Ninety-one patients received no further treatment (TUMT alone group), 54 an indwelling PBC for up to 1 month (TUMT + PBC group), and 41 neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment (TUMT + tamsulosin group). The International Prostate Symptom Score (IPSS), QOL score, and Qmax were determined at baseline and 2 weeks after TUMT. RESULTS: All three study groups experienced statistically significant improvements in mean IPSS and QOL score at 2 weeks versus baseline (P <0.0005). Nevertheless, the magnitude of improvement was greater in the TUMT + PBC group than the other two groups and greater in the TUMT + tamsulosin group than the TUMT alone group. A high proportion of the TUMT + PBC group (87.8%) attained a 50% or more IPSS improvement, compared with 4.5% of the TUMT alone group and none of the TUMT + tamsulosin group, and a similar pattern of between-group differences was noted with respect to the proportion of patients having 50% or more improvement in QOL score. The TUMT + PBC group was the only group to achieve significant Qmax improvement at 2 weeks compared with baseline. In the TUMT alone group, urinary retention 1 week or longer in duration occurred in 10 (11%) of 91 patients compared with 1 (2.4%) of 41 in the TUMT + tamsulosin group and none in the TUMT + PBC group. Early PBC removal was required in 11% of the TUMT + PBC group as a consequence of urinary retention secondary to clot formation or PBC migration. CONCLUSIONS: Both PBC placement and neoadjuvant and adjuvant alpha-blocker treatment are effective in alleviating symptoms and improving QOL during the acute period after TUMT. PBC usage also resulted in substantial early Qmax improvement. Either of these adjunctive modalities may be appropriate to consider in the treatment of TUMT patients during the early postprocedure recovery period.

Adrenergic alpha-Antagonists↗
PubMed1999

High-energy transurethral microwave thermotherapy in patients with acute urinary retention due to benign prostatic hyperplasia.

OBJECTIVES: To evaluate the efficacy and safety of targeted high-energy transurethral microwave thermotherapy (HE-TUMT) in the treatment of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH). METHODS: In this prospective cohort study, 31 patients with painful AUR due to BPH underwent HE-TUMT. Patient evaluation before treatment and during a 12-week follow-up interval included determination of International Prostate Symptom Score (IPSS), quality of life (QOL) score, peak flow rate (Qmax) by uroflowmetry, and postvoid residual urine. Patients also underwent urodynamic evaluation before treatment and at 16 weeks. RESULTS: By 4 weeks after HE-TUMT, 29 (94%) of 31 patients had regained the ability to void spontaneously. The actuarial median time for restoration of spontaneous voiding was 3.0 weeks (95% confidence interval [CI] 2.2 to 3.8). At 12 weeks, the mean IPSS (9.4; 95% CI 8.3 to 10.5) was 50% below (P <0.0005) that before retention (18.9; 95% CI 18.2 to 19.6). Improvements in the mean QOL score were similar in pattern and relative magnitude to those in the mean IPSS. A 69% increase in mean Qmax (P <0.0005) determined by uroflowmetry was observed by 12 weeks versus 1 week after HE-TUMT. Complications were infrequent. CONCLUSIONS: This study provides preliminary evidence that HE-TUMT may potentially afford a novel and useful option for the patient with AUR who is not a suitable candidate for surgery.

Acute Disease↗
PubMed1999

Total and transition zone prostate volume and age: how do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection?

OBJECTIVES: To define the role of total prostate (TP) volume, transition zone (TZ) volume, and age as determinants of the utility of prostate-specific antigen (PSA)-based diagnostic parameters for early detection of prostate cancer (PCa) in a prospective multicenter study. METHODS: The study participants were 974 consecutive men with serum total PSA (tPSA) levels of 4 to 10 ng/mL who were referred for early PCa detection or lower urinary tract symptoms. All patients underwent prostate ultrasound examination and sextant biopsy with two additional TZ biopsies. In patients with negative initial biopsies, repeated biopsies were performed at 6 weeks. tPSA, the free/total PSA ratio (f/t PSA), PSA density of the TZ (PSA-TZ), PSA density (PSAD), and PSA velocity (PSAV) were determined and compared across TP volume strata of 30 cm3 or less and greater than 30 cm3, TZ volume strata of 20 cm3 or less and greater than 20 cm3, and various age groups to evaluate the need for volume and/or age-specific reference ranges. RESULTS: PCa was found in 345 (35.4%) of 974 patients and benign prostatic tissue was found in 629 (64.6%) of 947 patients. Across TP volume strata, significantly higher values of tPSA (P <0.01), PSA-TZ, PSAD (P <0.001), and PSAV (P <0.05) and lower values of f/t PSA (P <0.001) were observed in patients with PCa than in those without PCa. Similar results were obtained with respect to TZ volume strata, except in the case of PSAV (P <0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P <0.05) in patients with PCa than in those without PCa for all corresponding age ranges. In patients with PCa, f/t PSA was significantly lower (P <0.001) within the same age ranges. Within each group (PCa or benign), f/t PSA, PSAD, PSA-TZ, and PSAV values were unaffected by age strata. However, PSA parameters dependent on prostate volume (PSAD, PSA-TZ) were statistically lower (P <0.001) in prostates with a higher TP volume (greater than 30 cm3) and TZ volume (greater than 20 cm3); f/t PSA values were unaffected by TP and TZ volumes. CONCLUSIONS: f/t PSA and PSA-TZ were the most powerful parameters to differentiate between benign prostatic tissue and PCa. f/t PSA was the sole parameter unaffected by age and prostate volume. We believe new volume-specific cutpoints, as presented in the current study, should be employed when using PSAD and PSA-TZ for the early detection of PCa.

Adult↗
PubMed1999

Outcome analysis of minimally invasive treatments for benign prostatic hyperplasia.

The armamentarium of minimally invasive treatment modalities for patients with benign prostatic hyperplasia has increased steadily during the past decade. The energy sources used range from microwaves and radiofrequency waves to high-intensity focused ultrasound, with laser vaporization/coagulation/resection and electrosurgical techniques. The large amount of data available allow some conclusions to be drawn concerning the present role of the "gold standard" TURP among the minimally invasive procedures. Although the subjective response after TURP and other minimally invasive procedures is comparable, improvements of flow and urodynamic parameters usually are more pronounced after TURP. Failure rates requiring reintervention (usually TURP) are considerable. Minimally invasive procedures lead to a shift of morbidity from the intraoperative phase, which is reduced (risk of bleeding, TUR syndrome, transfusion) to the postoperative phase. This period is characterized by prolonged urinary retention (ILC, VLAP), significant dysuria (VLAP, TUVP), and nycturia. Recent advances in electrosurgical techniques, such as band TURP loops that facilitate coagulation due to the longer contact time between the electrode and the tissue, have the potential to convert TURP into a less invasive procedure. Finally, high-energy TUMT seems to offer a truly minimally invasive treatment combining efficacy and the need for topical anesthesia only. However, due to a lack of homogeneity of criteria for patient recruitment, parameters of evaluation, and adequate follow-up; accurate guidelines for appropriate patient management have not been established yet.

Catheter Ablation↗
PubMed1999

Combination and multivariate analysis of PSA-based parameters for prostate cancer prediction.

The aim of this study was to evaluate the ability of prostate-specific antigen (PSA)-based parameters including PSA density (PSAD), PSAD of the transition zone (PSA-TZ), percent free PSA, PSA velocity, and their combination to enhance the specificity of PSA for prostate cancer detection in men with serum PSA levels between 4 and 10 ng/mL. We evaluated prospectively 559 consecutive men referred for early detection of prostate cancer who had serum PSA levels between 4 and 10 ng/mL. All men underwent prostatic ultrasonography and sextant biopsy with two additional TZ biopsies. In all cases, if first biopsies were negative an additional set of biopsies was obtained within 6 weeks. The ability of PSAD, PSA-TZ, PSA velocity, percent free PSA, and their combination to improve the detection of prostate cancer was evaluated by univariate and multivariate analysis as well as receiver operating characteristic (ROC) curves. In this prospective study of 559 patients, 217 had prostate cancer and 342 had histologically confirmed benign prostatic hyperplasia. Multivariate analysis and ROC curves showed that PSA-TZ and percent free PSA (f/t PSA) were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve (AUC) for PSA-TZ and percent free PSA were 0.827 and 0.778, respectively (p = .01). Combination of f/t PSA with PSA-TZ (AUC = 88.1%) significantly increased AUC as compared to each of the other parameters alone as well as their combination (p = .02). The next best combinations were PSA-TZ + PSAD, PSA-TZ + PSA, and f/t PSA + PSA. PSA-TZ followed by f/t PSA and PSAD were the most powerful predictors of prostate cancer in referred patients with a serum PSA between 4 and 10 ng/mL. f/t PSA + PSA-TZ was the most effective combination. When volume-independent PSA parameters were taken into consideration, f/t PSA + PSA clearly outperformed the other options.

Aged↗
PubMed1991

Magnetic resonance imaging of experimental allergic encephalomyelitis in primates.

The potential use of quantitative MRI to characterize early, as well as late, immune-mediated lesions of multiple sclerosis (MS) has been investigated. Experimental allergic encephalomyelitis (EAE) was induced in 4 male Macaca fascicularis monkeys, and the development of the disease followed using quantitative MRI at 0.15 Tesla. Serial scans were recorded daily, beginning at day 9 after inoculation. Lesions were detected before the onset of clinical signs, due to an elevation in the spin-lattice (T1) and spin-spin (T2) relaxation times. The T1 and T2 values from the lesions were shown to increase over time, indicative of progressive change at a molecular level. The appearance of any new lesions and any changes in existing ones were noted; this allowed dating of the lesions postmortem. Pathological correlation showed the long T1 and T2 values to be associated with the presence of inflammation, demyelination and haemorrhagic necrosis. Microscopically similar lesions had the same MRI characteristics. In addition, these studies showed the oldest lesions to be the most haemorrhagic; this is contrary to the belief that haemorrhage is a secondary event in EAE. The results show that quantitative MRI is sensitive to variable pathology, and has the potential for use in characterizing the pathological progression in MS.

Animals↗
PubMed1991

Myelin basic protein and its free and bound antibodies in cerebrospinal fluid. All three must be determined on each specimen.

Myelin basic protein (BP) in the cerebrospinal fluid (CSF) is an important marker of brain damage, especially of white matter, but low or "normal" values can be misinterpreted if the CSF is not also examined for free and bound antibodies to BP. BP has many epitopes (antigenic determinants) and is very susceptible to fragmentation by proteolytic enzymes that are frequently very active in CSF, especially in patients with neurological diseases. This combination of factors permits BP to be degraded as it is released from myelin and to allow antibodies to those epitopes destroyed by enzymatic action to persist free in the CSF. Other free anti-BP antibodies may simply represent antibody excess. The relatively frequent formation of soluble antigen-antibody complexes with other epitopes on BP permits the existence of anti-BP antibodies bound to BP also in CSF. In addition to these factors that contribute to low values of free BP in CSF, if the analyses are not performed promptly on CSF collected in plastic tubes (polystyrene but preferably polypropylene), the "natural" adhesiveness of BP (immediately to glass, slowly to plastic) can remove it from the CSF, resulting in artifactually low values which can also be misinterpreted as "normal".

Animals↗
PubMed1988

Chronic remitting-relapsing experimental allergic encephalomyelitis induced in monkeys with homologous myelin basic protein.

A chronic remitting-relapsing form of experimental allergic encephalomyelitis (EAE) has been produced in monkeys sensitized to homologous myelin basic protein in Freund's complete adjuvants by the technique of suboptimal treatment after the onset of disease. Not only does the clinical course resemble that of human multiple sclerosis more closely than does the clinical course of acute EAE, but so also does the histological reaction, with more-nearly pure demyelination, rather than the hyperacute hemorrhagic-necrotic lesions that occur so commonly in untreated monkeys with ordinary acute EAE.

Animals↗
PubMed1988

New monoclonal antibodies reactive with defined sequential epitopes in human myelin basic protein.

Three new IgG monoclonal antibodies are described which recognise sequential epitopes of the human myelin basic protein (MBP) molecule in amino acid sequences 36-50, 64-75 and 80-89. Two of the secreting hybridomas were prepared by immunisation of mice with synthetic peptides. This procedure appears to generate antibodies of similar affinities to those made using intact myelin basic protein as the immunogen. It has the advantage that antibodies to preselected regions of the molecule can be made at will and the problem of subsequent epitope localisation is simplified. It is possible with synthetic peptides to generate antibodies of specificities which it would be impossible to achieve by immunisation with intact myelin basic protein. The monoclonal antibodies described here should be useful tools in studies of myelin catabolism in vivo and in vitro. Of particular interest is our Clone 22, making an antibody which reacts equally well with intact human MBP and synthetic peptide sequence 80-89 in liquid phase assays. Antibodies of this rare specificity have been claimed to be able to react with the peptides of myelin basic protein found in the spinal fluid of patients with multiple sclerosis.

Antibodies, Monoclonal↗
PubMed1987

Fluctuations of T- and B-cell subsets in basic protein-induced experimental allergic encephalomyelitis (EAE) in long-tailed macaques.

Experimental allergic encephalomyelitis (EAE) was induced in long-tailed macaques (Macaca fascicularis) by inoculation of autologous myelin basic protein (BP) in complete Freund's adjuvant. Natural killer (NK) cell activity and lymphocyte subsets detected by one- and two-color immunofluorescence were monitored longitudinally in these animals. A decrease in NK cell activity was detected at the onset of clinically defined disease. During the preclinical phase of EAE (5-7 days before the onset of clinical signs) the absolute number of T helper (CD4+) and T suppressor (CD8+) cells in the peripheral blood decreased significantly. Analysis of peripheral blood B cells revealed a selective depletion of IgD+ B cells and a corresponding increase in the number of IgD- B cells prior to and during the onset of clinical signs. Total B-cell numbers were not significantly different between EAE and normal groups. The increased proportion of IgD- B cells in BP-sensitized animals corresponded with the appearance of high titers of circulating anti-BP antibodies. Thus two-color analysis of B-cell subsets may be a sensitive indicator of B-cell activation and of abnormal immune status in EAE. Changes in lymphocyte subsets in macaques with EAE are compared with those in humans with multiple sclerosis.

Animals↗
PubMed1987

In vivo administration of anti-CD4 monoclonal antibody prolongs survival in longtailed macaques with experimental allergic encephalomyelitis.

The in vivo administration of monoclonal antibody (mAb) to the CD4 antigen associated with helper T cells has been successful in prolonging the survival of nonhuman primates with experimental allergic encephalomyelitis (EAE). EAE was induced in 17 outbred longtailed macaques (Macaca fascicularis) by inoculation of homologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). Treatment was begun at the onset of clinical signs. Eleven animals were treated with anti-CD4 mAb Leu3a (eight) or OKT4a (three). Of the six control animals, two received anti-CD8 mAb (Leu2a), and four were treated with saline. Specific T- and B-cell subsets which have been implicated in the development of EAE were monitored throughout the course of the disease by one- and two-color immunofluorescence (IF). The monkey anti-BP antibody and anti-mouse immunoglobulin (IgG) responses were measured by enzyme-linked immunoassay (ELISA) techniques, as were the levels of free-circulating murine IgG. The nature of the infiltrating lymphocytes in the brain was evaluated histologically post mortem. Our results indicate that anti-CD4 mAb can prolong survival and in some cases completely reverse the clinical appearance of the disease; however, relapses did occur. Treatments with Leu3a or OKT4a anti-CD4 mAbs reversed the ongoing depletion of CD4+ and CD8+ cells caused by the development of EAE and appeared to reduce the size and degree of inflammation in brain lesions. These treatments did not induce immunologic tolerance to mouse IgG since all of the anti-CD4-treated animals produced high titers of anti-mouse IgG antibodies. Treatment with Leu2a (anti-CD8) had no effect on the development of EAE. These results suggest that CD4+ cells are important to the pathogenesis of EAE in macaques and that manipulation of this subset with monoclonal antibodies may provide effective treatment of human demyelinating disease.

Animals↗
PubMed1987

Monoclonal antibodies reactive with myelin basic protein.

New monoclonal antibodies (MAbs) to myelin basic protein (BP) reveal epitopes to be in sequences 22-34, 75-82, 83-96, 118-131 and 125-131. Comparison of these results with those previously reported suggest that almost every sequence of about 10 amino acid residues may be sufficiently antigenic to make a single MAb but that certain regions are immunodominant, strong enough to make practically the same MAb repeatedly. One of these new MAbs (clone 3) has especially interesting reactivity, sharply limited to residues 75-82 in bovine and porcine BP: Lys-Ala-Gln-His-Gly-Arg-Pro. Whales presumably have the same sequence, since their BPs are fully reactive with clone 3 MAb, but all other species of BP, with known sequences of BP, have at least two changes in this sequence. Deletion of Lys75 (as in a tryptic peptide of porcine BP) reduces reactivity with the MAb about 10-fold, whereas substitution of Ala76 by Ser (as in all other species of BP) and either deletion of Gln77 (as in human, monkey and rabbit BP) or His78 (as in the guinea pig and rat BP) or substitution of Pro82 by Thr (as in human, monkey, rat and mouse BP) eliminates reactivity. We speculate that woodchuck and prairie dog BPs in this region closely resemble chicken BP, which has about 2% of the original reactivity. However, squirrel BP is unique, probably having only one of the changes in this region of BP, since it possesses 10-20 times the reactivity of chicken BP but still only 20-50% of the original reactivity with clone 3 MAb, a degree of reactivity not seen with any other species of BP.

Amino Acid Sequence↗
PubMed1986

Region-specific immunoassays for human myelin basic protein.

Three monoclonal antibodies reactive with human myelin basic protein have been used to develop immunoradiometric assays for this protein. Clone 1, a mouse IgG2a, is reactive with an epitope in the region 129-138. Clone 2, a mouse IgG1, is reactive with the region 119-131. Clone 12, a rat IgG, is reactive with the region 86-96. Competition experiments show that the reactions of Clone 1 and Clone 2 are mutually exclusive, probably because of steric effects. In contrast, when either Clone 1 or Clone 2 react they cause minimal interference with the subsequent binding of Clone 12. Less than 1 ng/ml of myelin basic protein can be detected in each of the two immunoradiometric assays developed. Clone 12 can also be used on its own in a competitive immunoassay to detect around 2 ng/ml. Using an extraction technique before the assay, serum or plasma can also be investigated. Assays for defined regions of myelin basic protein should prove valuable in identifying the products of myelin catabolism in patients with demyelinating disease.

Amino Acid Sequence↗
PubMed1986

Evidence for specific polypeptide chain folding in myelin basic protein from reactions between fragments of the protein and monoclonal antibodies.

The specificities of two monoclonal IgM antibodies (18.25 and 21.14.2) evoked in mice with guinea pig myelin basic protein were examined and interpreted in terms of a specific folding of the protein's polypeptide chain. Studies with guinea pig and rabbit myelin basic protein fragments showed that a region encompassing the central Phe-Phe (87-88) sequence is obligatory, but not sufficient, for reactivity with antibody 18.25. Appreciable reactivity was observed for rabbit peptides 22-95 and 45-151, and lower, but significant, reactivity was shown by peptide 32-95. Only very weak reactivity was seen with peptide 44-95. No reactivity was observed with peptide 1-95 after its lysine residues were acetylated, acetamidinated, or guanidinated. These results have been interpreted in terms of a polypeptide chain folding that creates an epitope within sequence Val-Val-His-Phe-Phe-Lys-Asn-Ile-Val (84-92). The specific conformation of this epitope, which includes probably the Lys-89 and possibly the Asn-90 and Val-92 side chains, could be formed by the association of sequence 84-92 with either sequence Ile-Leu-Asp-Ser-Ile-Gly-Arg-Phe-Phe (37-45) or with sequence Val-Leu-Ser-Arg-Phe (108-112) to form beta-sheet structures essentially identical with those that appear to be present in the intact BP [Martenson R.E.J. Neurochem. 46, 1612-1622 (1986)]. The second monoclonal antibody, no. 21.14.2, reacts only with guinea pig myelin basic protein and fragments containing the species-restricted sequence Arg-Ala-Asp-Tyr-Lys-Ser-Lys (129-135).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗