Biomedical subjects

J M Johnson

Publications and source records attributed to J M Johnson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Histological correlation of microcalcifications in breast biopsy specimens.

HYPOTHESIS: Nonpalpable malignant-appearing microcalcifications discovered by mammography geographically target the location of the most important abnormality within the breast. Core needle or open biopsy of these microcalcifications will sample or remove underlying proliferative or invasive disease. DESIGN: A prospective database of 403 consecutive patients undergoing breast biopsy for nonpalpable abnormalities from July 1, 1994, to December 31, 1996, was reviewed to identify biopsies done for indeterminate microcalcifications. Specimens showing atypical hyperplasia, carcinoma in situ, or invasive carcinoma were identified and reviewed by 1 pathologist. The position of microcalcifications larger than 100 microm were recorded in reference to the histological findings. SETTING: A 450-bed referral community teaching hospital in rural Wisconsin. PATIENTS: Indeterminant microcalcifications were identified on mammograms in 167 (41.4%) of 403 patients. Sixty-one (36.5%) of 167 biopsy specimens contained atypical hyperplasia, carcinoma in situ, or invasive carcinoma, and the slides of these 61 initial breast biopsy specimens were reviewed. MAIN OUTCOME MEASURES: Relationship of breast histopathological findings to microcalcifications. RESULTS: In these 61 specimens, 82 areas of atypical hyperplasia, carcinoma in situ, or invasive carcinoma were noted. The microcalcifications correlated with these areas in 43 (52%) of 82 areas on slide review and were present in the most important abnormality in 33 (54%) of 61 biopsy specimens. CONCLUSIONS: Indeterminant microcalcifications identified by mammography may not target the exact location of underlying breast disease. Careful evaluation of the entire biopsy specimen and close follow-up of patients with benign pathologic findings are recommended.

Biopsy↗

PubMed1999

Technical factors in early amniocentesis predict adverse outcome. Results of the Canadian Early (EA) versus Mid-trimester (MA) Amniocentesis Trial.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentered (12) prospective, randomized trial comparing continuous ultrasound-guided early amniocentesis (EA) and mid-trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures 'judged to be difficult' by the operator, and post-procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11. 1 per cent, compared with non-hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first-trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype.

Abortion, Spontaneous↗

PubMed1999

Th2 T cells expressing transgene PDGF-A serve as vectors for gene therapy in autoimmune demyelinating disease.

We hypothesized that T cells can be genetically modified to express growth factor transgene products capable of inducing oligodendrocyte progenitor proliferation. Autoreactive T cells isolated from SWXJ mice immunized with the p139-151 determinant of myelin proteolipid protein (PLP) were transfected with an antigen-inducible transgene for platelet-derived growth factor-A (PDGF), a growth factor important in regulating the development of oligodendrocytes. Isolated antigen-specific T cell clones expressed the PDGF transgene when stimulated with PLP 139-151 peptide and produced biologically active PDGF capable of inducing proliferation of oligodendrocyte progenitor cells. Furthermore, upon adoptive transfer, the PDGF transfected T cells migrated to the CNS and ameliorated ongoing disease. Our data indicate that autoreactive memory Th2 cells can be genetically modified so that upon engagement with self antigen they produce regenerative growth factors capable of mediating tissue repair during autoimmune disease.

Adoptive Transfer↗

PubMed1999

Sacrococcygeal ependymoma: case report and review of the literature.

Ependymomas are uncommon glial cell tumors found within the brain, spinal cord, cauda equina, or filum terminale. Ependymomas originating in the parasacral soft tissues are exceedingly rare. The authors report the case of a 7-year-old boy with a primary ependymoma of the sacrococcygeal area and review the world literature of this tumor at this location.

Child↗

PubMed1999

A lysine-to-arginine change found in natural alleles of the human T-cell lymphotropic/leukemia virus type 1 p12(I) protein greatly influences its stability.

The HTLV-1 singly spliced open reading frame I protein, p12(I), is highly unstable and appears to be necessary for persistent infection in rabbits. Here we demonstrate that p12(I) forms dimers through two putative leucine zipper domains and that its stability is augmented by specific proteasome inhibitors. p12(I) is ubiquitylated, and mutations of its unique carboxy-terminus lysine residue to an arginine greatly enhance its stability. Interestingly, analysis of 53 independent HTLV-1 strains revealed that the natural p12(I) alleles found in ex vivo samples of tropical spastic paraparesis-HTLV-1-associated myelopathy patients contain a Lys at position 88 in some cases, whereas arginine is consistently found at position 88 in HTLV-1 strains from all adult T-cell leukemia-lymphoma (ATLL) cases and healthy carriers studied. This apparent segregation of different alleles in tropical spastic paraparesis-HTLV-associated myelopathy and ATLL or healthy carriers may be relevant in vivo, since p12(I) binds the interleukin-2 receptor beta and gammac chains, raising the possibility that the two natural alleles might affect differently the regulation of these molecules.

Adult↗

PubMed1999

Altered reflex control of cutaneous circulation by female sex steroids is independent of prostaglandins.

We tested the hypothesis that the shift in the cutaneous vasodilator response to hyperthermia seen with elevated female reproductive hormones is a prostaglandin-dependent resetting of thermoregulation to higher internal temperatures, similar to that seen in the febrile response to bacterial infection. Using water-perfused suits to control body temperature, we conducted heat stress experiments in resting women under conditions of low and high progesterone and estrogen and repeated these experiments after an acute dose of ibuprofen (800 mg). In six women the hormones were exogenous (oral contraceptives); three women had regular menstrual cycles and were tested in the early follicular and midluteal phases. Resting oral temperature (Tor) was significantly elevated with high hormone status (P < 0.05); this was not affected by ibuprofen treatment (P > 0.2). The Tor threshold for cutaneous vasodilation was significantly increased by high hormone status (+0.27 +/- 0.07 degrees C, P < 0. 02); the shift was not affected by ibuprofen treatment (with ibuprofen: +0.29 +/- 0.08 degrees C, P > 0.2 vs. control experiments). The Tor threshold for sweating was similarly increased by high hormone status (+0.22 +/- 0.05 degrees C, P < 0.05); this shift was not influenced by ibuprofen (with ibuprofen: +0.35 +/- 0. 05, P > 0.1 vs. control experiments). Thus the shift in thermoregulatory control of skin blood flow and sweating mediated by female reproductive steroids is not sensitive to ibuprofen; it therefore appears that this shift is independent of prostaglandins.

Adult↗

PubMed1999

Reflex control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones.

To determine whether cardiovascular influences of exogenous female steroid hormones include effects on reflex thermoregulatory control of the adrenergic cutaneous vasoconstrictor system, we conducted ramp decreases in skin temperature (T(sk)) in eight women in both high- and low (placebo)-progesterone/estrogen phases of oral contraceptive use. With the use of water-perfused suits, T(sk) was held at 36 degrees C for 10 min (to minimize initial vasoconstrictor activity) and was then decreased in a ramp, approximately 0.2 degrees C/min for 12-15 min. Subjects rested supine for 30-40 min before each experiment, and the protocol was terminated before the onset of shivering. Skin blood flow was monitored by laser-Doppler flowmetry and arterial pressure by finger photoplethysmography. In all experiments, cutaneous vasoconstriction began immediately with the onset of cooling, and cutaneous vascular conductance (CVC) decreased progressively with decreasing T(sk). Regression analysis of the relationship of CVC to T(sk) showed no difference in slope between phases (low-hormone phase: 17.67 +/- 5.57; high-hormone phase: 17.40 +/- 8.00 %baseline/ degrees C; P > 0.05). Additional studies involving local blockade confirmed this response as being solely due to the adrenergic vasoconstrictor system. Waking oral temperature (T(or)) was significantly higher on high-hormone vs. low-hormone days (36.60 +/- 0.11 vs. 36.37 +/- 0.09 degrees C, respectively; P < 0.02). Integrative analysis of CVC in terms of simultaneous values for T(sk) and T(or) showed that the cutaneous vasoconstrictor response was shifted in the high-hormone phase such that a higher T(or) was maintained throughout cooling (P < 0.05). Thus reflex thermoregulatory control of the cutaneous vasoconstrictor system is shifted to higher internal temperatures by exogenous female reproductive hormones.

Adult↗

PubMed1999

Influence of female reproductive hormones on local thermal control of skin blood flow.

Progesterone and estrogen modify thermoregulatory control such that, when both steroids are elevated, body temperature increases and the reflex thermoregulatory control of cutaneous vasodilation is shifted to higher internal temperatures. We hypothesized that the influence of these hormones would also include effects on local thermal control of skin blood flow. Experiments were conducted in women in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive use. Skin blood flow was measured by laser-Doppler flowmetry, and local temperature (T(loc)) was controlled over 12 cm(2) around the sites of blood flow measurement. T(loc) was held at 32 degrees C for 10-15 min and was then decreased at one site from 32 to 20 degrees C in a ramp over 20 min. Next, T(loc) was increased from 32 to 42 degrees C in a ramp over 15 min at a separate site. Finally, T(loc) at both sites was held at 42 degrees C for 30 min to elicit maximum vasodilation; data for cutaneous vascular conductance (CVC) are expressed relative to that maximum. Whole body skin temperature (T(sk)) was held at 34 degrees C throughout each study to minimize reflex effects from differences in T(sk) between experiments. Baseline CVC did not differ between phases [8.18 +/- 1.38 (LH) vs. 8. 41 +/- 1.31% of maximum (HH); P > 0.05]. The vasodilator response to local warming was augmented in HH (P < 0.05, ANOVA). For example, at T(loc) of 40-42 degrees C, CVC averaged 76.41 +/- 3.08% of maximum in HH and 67.71 +/- 4.43% of maximum in LH (P < 0.01 LH vs. HH). The vasoconstrictor response to local cooling was unaffected by phase (P > 0.05). These findings indicate that modifications in cutaneous vascular control by female steroid hormones include enhancement of the vasodilator response to local warming and are consistent with reports of the influence of estrogen to enhance nitric oxide-dependent vasodilator responses.

Adult↗

PubMed1999

An oligonucleotide-ligation assay for the differentiation between Cyclospora and Eimeria spp. polymerase chain reaction amplification products.

An oligonucleotide-ligation assay (OLA) was developed and compared to a restriction fragment length polymorphism (RFLP) test for distinguishing between 294-bp polymerase chain reaction (PCR) amplification products of the 18S rRNA gene from Cyclospora and Eimeria spp. The PCR/OLA correctly distinguished between three Cyclospora, three E. tenella, and one E. mitis strains and the ratio of positive to negative spectrophotometric absorbance (A490) values for each strain ranged from 4.086 to 15.280 (median 9.5). PCR/OLA provides a rapid, reliable, spectrophotometric alternative to PCR/RFLP.

Animals↗

PubMed1998

Image-guided or needle-localized open biopsy of mammographic malignant-appearing microcalcifications?

BACKGROUND: The evaluation and initial management of abnormalities detected on screening mammography have evolved substantially over the last decade. This study was designed to evaluate the most appropriate initial diagnostic biopsy technique for patients presenting with malignant-appearing microcalcifications on screening or diagnostic mammography. STUDY DESIGN: An institutional review of a prospective database was performed to compare initial image-guided breast biopsy (IGBB) and needle-localized open biopsy (NLOB) in patients presenting with malignant-appearing microcalcifications. Patients with atypical hyperplasia (AH) or carcinoma in situ (CIS) were identified and reviewed separately. Measures of outcomes included the total number of procedures, time from initial biopsy to definitive treatment, charges, and percentages of patients who required both procedures. RESULTS: A total of 17,121 patients underwent mammography from July 1994 to December 1996 at Gundersen Lutheran Medical Center. Indeterminate microcalcifications were found in 167 patients and were the reason for IGBB in 112 and NLOB in 55 patients. Histologic results included 81 patients (48%) with benign lesions, 25 (15%) with invasive cancers, and 61 (37%) having a proliferative finding including AH or CIS. Ductal CIS was present in 42 (72%) of the 61 proliferative lesions. Comparisons were made between the groups of patients with CIS or AH who underwent initial NLOB (n = 25) versus those having initial IGBB that was followed by a secondary NLOB (n = 25). The median elapsed time to definitive therapy was 20 days (range 0 to 336 days) for initial IGBB followed by NLOB and 7 days (range 0 to 79 days) for an initial NLOB performed for suspicious microcalcifications (p = 0.0367). The total number of procedures performed on each patient and total costs were also less for patients having an initial NLOB. CONCLUSIONS: The time to definitive local therapy, the number of procedures, and overall charges were less for patients with AH or CIS having initial NLOB as opposed to initial IGBB. Careful initial evaluation of microcalcifications may identify some patients for whom an initial NLOB remains the most appropriate procedure. Such patients desiring breast-conserving therapy may benefit in terms of time to definitive treatment, total number of procedures performed, and cost if a careful NLOB is the initial procedure performed as a formal lumpectomy.

Adult↗

PubMed1998

Physical training and the control of skin blood flow.

The process of physical training places frequent significant demands for increased blood flow to cardiac and skeletal muscle tissues and sets into action adaptive responses to better enable the circulatory system to meet those demands. These adaptive changes and the associated mechanisms are dealt with elegantly in other portions of this symposium. The repeated bouts of dynamic exercise with training also expose the temperature regulatory system to increased body temperatures and attendant demands for increased heat loss. These frequent demands for increased heat loss lead to adaptations in the control of the cutaneous circulation. There are consistent results among the limited number of studies conducted to test this question directly. The primary result is that skin blood flow in the trained state is higher at a given level of internal temperature than in the sedentary or less trained state. This result is seen in both cross-sectional and longitudinal comparisons, in older and younger subjects, in responses to heat at rest and during exercise, and in the changes with detraining as well as those attending training. In some studies this adjustment is made by a shift in the threshold internal temperature at which skin blood flow begins to rise, whereas in others it is accomplished by an increase in the sensitivity of the skin blood flow-internal temperature relationship. Reasons for this variation are not clear. The cutaneous circulation is controlled by vasoconstrictor and separate vasodilator nerves, but it is not clear how much of the training effect is manifest through one or the other neural system. However, indirect data suggest that vasoconstrictor activity is generally reduced and that active vasodilator activity is initiated at lower internal temperatures. It is also not clear to what extent the mechanism for the training effect is through the acclimatization process, as opposed to the influence of training, itself. In any case, the adjustments in control of the cutaneous circulation with physical training increase the capacity of the circulation to transport and eliminate heat as that training process increases the capacity of the active tissues to produce that heat.

Adaptation, Physiological↗

PubMed1998

Muscle metaboreceptor modulation of cutaneous active vasodilation.

PURPOSE: Isometric handgrip exercise in hyperthermia has been shown to reduce cutaneous vascular conductance (CVC) by inhibiting the cutaneous active vasodilator system. METHODS: To identify whether this response was initiated by muscle metaboreceptors, in seven subjects two 3-min bouts of isometric handgrip exercise in hyperthermia were performed, followed by 2 min of postexercise ischemia (PEI). An index of forearm skin blood flow (laser-Doppler flowmetry) was measured on the contralateral arm at an unblocked site and at a site at which adrenergic vasoconstrictor function was blocked via bretylium iontophoresis to reveal active cutaneous vasodilator function unambiguously. Sweat rate was measured via capacitance hygrometry, CVC was indexed from the ratio of skin blood flow to mean arterial pressure and was expressed as a percentage of maximal CVC at that site. In normothermia, neither isometric exercise nor PEI affected CVC (P > 0.05). RESULTS: The first bout of isometric handgrip exercise in hyperthermia reduced CVC at control sites and this reduction persisted through PEI (pre-exercise: 59.8 +/- 5.4, exercise: 49.8 +/- 4.9, PEI: 49.7 +/- 5.3% of maximum; both P < 0.05), whereas there were no significant changes in CVC at the bretylium treated sites. The succeeding bout of isometric exercise in hyperthermia significantly reduced CVC at both untreated (pre-exercise: 59.0 +/- 4.8, exercise: 47.3 +/- 4.0, PEI: 50.1 +/- 4.1% of maximum; both P < 0.05) and bretylium treated sites (pre-exercise: 61.4 +/- 7.3, exercise: 50.6 +/- 5.1, PEI: 53.9 +/- 6.0% of maximum, both P < 0.05). At both sites, CVC during PEI was lower than during the pre-exercise period (P < 0.05). Sweat rate rose significantly during both bouts of isometric exercise and remained elevated during PEI. CONCLUSIONS: These data suggest that the reduction in CVC during isometric exercise in hyperthermia, including the inhibition of the active vasodilator system, is primarily mediated by muscle metaboreceptors, whereas central command or muscle mechanoreceptors have less influence.

Adult↗

PubMed1998

The epitope spreading cascade during progression of experimental autoimmune encephalomyelitis and multiple sclerosis.

We have made the following observations regarding self-recognition during the development and progression of murine experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS): 1) chronic progression of EAE is accompanied by a sequential, predictable cascade of neo-autoreactivity, commonly referred to as epitope spreading, presumably caused by endogenous self-priming during autoimmune-mediated tissue damage; 2) there is an invariant relationship between the progression of EAE and the emergence of epitope spreading; 3) progression of EAE can be inhibited by the induction of antigen-specific tolerance to spreading determinants after onset of initial neurologic symptoms; 4) CD4+ Th 1 cells responding to spreading determinants are autonomously encephalitogenic; 5) epitope spreading occurs during the development of MS and in some cases involves HLA-DP class II-restricted self-recognition; and 6) progression of both EAE and MS is accompanied by the decline of primary T-cell autoreactivity associated with disease onset and by the concurrent emergence of the epitope spreading cascade. Our studies directly challenge the traditional view that EAE and MS are initiated and maintained by autoreactivity directed against a single predominant myelin protein or determinant. Our results indicate that progression of EAE and MS involves a shifting of T-cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during disease progression.

Animals↗

PubMed1998

Nitric oxide and cutaneous active vasodilation during heat stress in humans.

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions, L-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38-38.5 degreesC, internal temperature rose from 36.66 +/- 0.10 to 37.34 +/- 0.06 degreesC (P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 +/- 2 to 44 +/- 5% of maximum, but only rose from 13 +/- 2 to 30 +/- 5% of maximum at L-NAME-treated sites (P < 0.05 between sites) during heat stress. L-NAME had no effect on sweat rate (P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.

Adult↗

PubMed1998

A survey of hantavirus antibody in small-mammal populations in selected United States National Parks.

Hantavirus activity in 39 National Parks in the eastern and central United States was surveyed by testing 1,815 small mammals of 38 species for antibody reactive to Sin Nombre virus. Antibody-positive rodents were found throughout the area sampled, and in most biotic communities. Antibody was detected in 7% of 647 deer mice (Peromyscus maniculatus), 2% of 590 white-footed mice (P. leucopus), 17% of 12 rice rats (Oryzomys palustris), 3% of 31 cotton rats (Sigmodon hispidus), and 33% of 18 western harvest mice (Reithrodontomys megalotis). Antibody was also found in three of six species of voles, and in one of 33 chipmunks (Tamias minimus). Prevalence among Peromyscus was highest in the northeast. Although few cases of hantavirus pulmonary syndrome have been identified from the eastern and central regions, widespread infection in reservoir populations indicates that potential exists for human infection throughout much of the United States.

Animals↗

PubMed1998

Template preparation for PCR and RFLP of amplification products for the detection and identification of Cyclospora sp. and Eimeria spp. Oocysts directly from raspberries.

Raspberries were epidemiologically associated with cyclosporiasis outbreaks during 1996 and 1997. The 18S rRNA genes of Cyclospora cayetanensis and several species of a closely related genus, Eimeria, were sequenced and primers for a nested PCR developed in a previous study. The ability to distinguish amplified products of Cyclospora sp. from those of Eimeria spp. is important for testing food and environmental samples. Therefore, an RFLP analysis of amplified products was used to differentiate Cyclospora cayetanensis from Eimeria spp. PCR inhibitors and the low levels of Cyclospora oocysts present in raspberries make template preparation for PCR challenging. Several approaches for PCR template preparation from raspberry samples were evaluated. Template preparation methods using various washing and concentration steps, oocyst disruption protocols, resin matrix treatment, DNA precipitation, and/or the addition of nonfat dried milk solution to a PCR using modified primers were evaluated first with oocysts of Eimeria tenella then refined with oocysts of C. cayetanensis. Approximately 10 E. tenella oocysts per PCR or approximately 19 C. cayetanensis oocysts per PCR were detected with the optimized template preparation method. The addition of 20 microliters of raspberry wash sediment extract and nonfat dried milk solution did not inhibit the amplification of DNA from as few as 10 E. tenella and 25 C. cayetanensis oocysts in a 100-microliter PCR. The nucleotide sequences of C. cayetanensis and the Eimeria spp. are 94 to 96% similar in the amplified region, but the amplification products from the two genera were distinguished using an RFLP analysis with the restriction enzyme MnlI.

Animals↗

PubMed1998

The incidence of Listeria spp., Salmonella spp., and Clostridium botulinum in smoked fish and shellfish.

The frequency of occurrence of Listeria spp., Salmonella spp., and Clostridium botulinum is samples of smoked finfish and smoked shellfish was analyzed over a 5-year period. Listeria monocytogenes were isolated from 14% of 1,080 samples. For those samples where the smoke process was known, the incidence of L. monocytogenes was higher in cold-smoked than hot-smoked products (51 of 240 cold-smoked compared to 19 of 215 hot-smoked products). Listeria species other than L. monocytogenes were also detected (in 7.2% of cold-smoked and 3.8% of hot-smoked products). The time and temperature smoke processing guidelines are reviewed for a few state authorities. L. monocytogenes was isolated from 15.2% of the 559 samples of foreign origin. There were four countries for which more than 70 samples were analyzed: Canada, Norway, the Philippines, and the United Kingdom. The occurrence of L. monocytogenes in samples from these four countries was 14.3%, 23.7%, 0%, and 16.1%, respectively. The 521 samples originating in the United States were processed by 194 plants. Thirty-seven plants in 13 states produced contaminated product. Salmonella species were isolated from 5 (3.2%) of 156 samples tested for this organism. All positive samples were of foreign origin (4 from the Philippines and 1 from the United Kingdom). No C. botulinum spores were detected in any of the 201 vacuum-packed samples tested for this organism.

Animals↗

PubMed1997

Stabilization of myelin mRNAs as measured in a brain slice system.

The stabilization and destabilization of myelin mRNA is increasingly recognized as a major control point in regulating myelin gene expression. A brain slice system was developed and characterized to study mRNA stability in actively myelinating oligodendrocytes. The mRNA half-life of a major CNS myelin protein, proteolipid protein (PLP), was measured to be 5 hr. The half-life of another CNS myelin protein mRNA, myelin basic protein (MBP), was measured to be greater than 12 hr. A long half-life for MBP mRNA is consistent with MBP mRNA being stable long enough to be translocated to the myelin internode where it is then translated. Using semi-quantitative reverse transcriptase-PCR, it was determined that there was no differential stabilization between the two major PLP mRNA isoforms, PLP and DM20. It was also determined that protein synthesis was required for the specific stabilization of PLP/DM20 mRNAs. Inasmuch as PLP is a major structural protein of the CNS myelin, the PLP/DM20 mRNAs have relatively short half-lives. However, the PLP/DM20 mRNAs half-lives may be increased by the action of trans-acting factors that are themselves very labile.

Animals↗