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Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.

Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL levels, while inducing secretion of forms more similar to those found in women affected by pathological hyperprolactinaemia or in normal women.

Adolescent↗

Efficient targeting of plant disease resistance loci using NBS profiling.

The conserved sequences in the nucleotide-binding sites of the nucleotide-binding site-leucine-rich repeat (NBS-LRR) class of disease resistance (R) genes have been used for PCR-based R-gene isolation and subsequent development of molecular markers. Here we present a PCR-based approach (NBS profiling) that efficiently targets R genes and R-gene analogs (RGAs) and, at the same time, produces polymorphic markers in these genes. In NBS profiling, genomic DNA is digested with a restriction enzyme, and an NBS-specific (degenerate) primer is used in a PCR reaction towards an adapter linked to the resulting DNA fragments. The NBS profiling protocol generates a reproducible polymorphic multilocus marker profile on a sequencing gel that is highly enriched for R genes and RGAs. NBS profiling was successfully used in potato with several restriction enzymes, and several primers targeted to different conserved motifs in the NBS. Across primers and enzymes, the NBS profiles contained 50-90% fragments that were significantly similar to known R-gene and RGA sequences. The protocol was similarly successful in other crops (including tomato, barley, and lettuce) without modifications. NBS profiling can thus be used to produce markers tightly linked to R genes and R-gene clusters for genomic mapping and positional cloning and to mine for new alleles and new sources of disease resistance in available germplasm.

Amino Acid Sequence↗

Harmonized profiloplasty using balanced angular profile analysis.

To evaluate outcomes of aesthetic facial plastic surgery objectively the authors developed a photogrammetric profile analysis method, which they call "balanced angular profile analysis" (BAPA). To develop standards and ways to determine the conformation of various soft tissue segments analytically, 19 mean angular values acquired from the photographs of 71 famous female models (53 Eastern models and 18 Western models) were standardized to provide reference data (recommended aesthetic mean angles [RAMA]), which contain some of the common features and differences between ethnic groups and races. On the basis of the data prepared from angular profile analyses of these photographs, the authors apply their developed method in a practical way to the pre- and postoperative photographs of patients. By using the data provided by BAPA, the clinician can identify delicate profile problems correctly, perform appropriate aesthetic operations, and thus produce better aesthetic results. The authors' harmonized and balanced angular profile analysis can provide surgeons with a way of determining the conformational problems associated with various soft tissue segments of the face. It also offers aesthetic plastic surgeons reference information concerning the creation of an attractive face during the first patient consultation. The authors hope that their straightforward method of profile analysis will provide facial plastic surgeons with a simple tool for profile analysis and surgical planning designed to create an attractive face.

Adult↗

Exploring the associations between preen oil bacterial, chemical and proteomic profiles of passerines.

Preen gland bacteria are thought to be the key producers of preen oil components such as chemosignalling molecules including volatile organic compounds (VOCs) and antimicrobial compounds including peptides and antimicrobial VOCs. However, data on the preen oil bacteriome and chemical composition are limited to a small subset of bird species, and the presence of antimicrobial peptides is largely unexplored. Here, we performed an exploratory study to characterize, for the first time, the preen oil chemical and proteomic profiles and to explore the possible contribution of the bacteriome to the production of preen oil VOCs and antimicrobial peptides (bacteriocins) in eight passerine species, each represented by a single individual. Preen oil bacteriome, chemical and proteomic profiles varied among birds. The bacterial profiles were dominated by the genera Streptococcus, Lactococcus, Corynebacterium and Cutibacterium. The chemical profiles mainly consisted of alcohols, ketones and carboxylic acids. The biological functions primarily associated with the proteomic profiles were proteolysis and response to oxidative stress. Although we were unable to explore a direct association between the bacteriome and chemical profiles, the preen oil contained bacteriocin- and VOC-producing bacterial genera capable of producing detected microbially-derived VOCs (mVOCs), the relative abundance of which varied between birds. Riparian species showed the highest chemical diversity and high abundances of putative preen oil mVOC-producing bacteria, which could suggest habitat-specific adaptations. This exploratory study may significantly contribute to the formulation of hypotheses on the potential role of host ecological factors in the variation of preen oil bacterial, chemical and proteomic profiles in passerines.

Animals↗

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women.

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30-40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1], more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

Adipose Tissue↗

Influence of realistic inspiratory flow profiles on fine particle fractions of dry powder aerosol formulations.

PURPOSE: The purpose of the study was to determine how air flow profiles affect fine particle fractions (FPF) (<5 microm) from dry powder aerosol formulations and whether laser diffraction (LD) could be used to measure FPF of aerosols generated by variable flows. MATERIALS AND METHODS: Carrier-based formulations containing 1.5% w/w micronized salbutamol base blended with the 63-90 microm fraction of alpha-lactose monohydrate or sorbitol or maltose were aerosolised from a model glass device using either a constant flow rate or a predetermined flow profile. The FPFs of the same aerosolised particles were first measured by LD and then by a liquid impinger. Volunteer inhalation airflow profiles and 3-phase (acceleration, constant flow rate and deceleration) square wave airflow profiles were generated using the Electronic Lung and an Inhalation Profile Recorder. Similar experiments were conducted for a carrier-free formulation from the Bricanyl Turbohaler. RESULTS: Salbutamol FPFs of all carrier-based formulations were found to increase by increasing the initial flow increase rate (FIR) from 200 to 600 l min(-1) s(-1) although they could be placed in an increasing order of maltose blend < sorbitol blend < lactose blend. A significant linear correlation was found between FPFs measured by LD and by inertial impaction (R (2) = 0.95, p < 0.01, ANOVA). For the Bricanyl Turbohaler, increasing FIR from 120 to 600 l min(-1) s(-1) for a constant peak flow rate (PFR) of 60 l min(-1) increased the mean Terbutaline FPF from 18.2% to 45.5%. For the volunteer inhalation profiles, a higher FIR tended to be associated with higher PFR, leading to a marked increase in drug FPF due to the combined effect of FIR and PFR. CONCLUSION: Drug FPF from either carrier-free or carrier-based formulations is determined by both FIR and PFR. LD is a viable technique to measure the performance of dry powder aerosol formulations at realistic inspiratory flow profiles.

Administration, Inhalation↗

Upper midbrain profile sign and cingulate sulcus sign: MRI findings on sagittal images in idiopathic normal-pressure hydrocephalus, Alzheimer's disease, and progressive supranuclear palsy.

PURPOSE: On magnetic resonance imaging (MRI) sagittal sections, we sometimes encounter abnormal aspects of the superior profile of the midbrain and the cingulate sulcus in patients with dementia. In this preliminary study, we refer to these findings as the "upper midbrain profile sign" and the "cingulate sulcus sign." We prospectively evaluated the usefulness of these signs for the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). MATERIALS AND METHODS: We evaluated the upper midbrain profile sign and the cingulate sulcus sign on MRI sagittal images obtained from 21 people with headaches but no neurological deficit (controls), 10 iNPH patients, 11 AD patients, and 5 PSP patients. The upper midbrain profile sign indicated a concave shape to the superior profile of the midbrain on mid-sagittal images, and the cingulate sulcus sign indicated a narrow, tight aspect of the posterior part of the cingulate sulcus on paramedian-sagittal images. RESULTS: These signs were never seen in any images from the controls. The upper midbrain profile sign was seen in 7 of 10 patients with iNPH, 5 of 11 with AD, and 3 of 5 with PSP. The cingulate sulcus sign was seen in all 10 patients with iNPH but was never seen in any patient with AD or PSP. CONCLUSION: The upper midbrain profile sign could support a diagnosis of PSP but cannot discriminate among iNPH, AD, and PSP. In contrast, the cingulate sulcus sign has a very high sensitivity for iNPH and should facilitate the distinction of iNPH from other dementias. In the clinical setting, it is momentous to evaluate these signs easily by one simple MRI sequence.

Aged↗

Dehydroepiandrosterone alters lipid profiles in Zucker rats.

High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.

Adipose Tissue↗

The development of a profile scoring system for early identification and severity assessment of pregnancy-induced hypertension.

Two commonly encountered problems in the management of patients with pregnancy-induced hypertension (PIH) or pregnancy-aggravated hypertension (PAH) are (1) a delay in early recognition of disease, and (2) imprecise assessment of the severity of the disease. Gravid women suffering from PIH may present in a protean manner which can be misleading to the clinician who relies strictly upon classic clinical parameters in the management of the patient. Many hematologic changes associated with PIH have been documented. However, a comprehensive evaluation of these changes, as depicted by simultaneous laboratory testing, has not been reported. The purpose of this study was twofold: (1) to formulate a profile scoring system in which clinical parameters and laboratory tests were utilized in concert, not as a predictor, but as a standardized method of early recognition of PIH, and (2) to evaluate the profile scoring system's accuracy in assessing the severity of the disease. Empirically, a "profile" was developed that included five clinical parameters (rollover test, mean arterial blood pressure, ocular arteriolar vasospasm, hand and facial edema, patellar reflexes) and eight laboratory tests (urine protein, serum urate, urea nitrogen, creatinine, albumin, total proteins, platelet count, and plasma fibrinogen). Values for each parameter and test were categorized into the accepted normal and abnormal ranges for pregnancy. On the basis of the degree of abnormality, weighted numerical scores of increasing magnitude were arbitrarily assigned to the respective value ranges. For a given patient, the sum of the individual parameter and test scores constituted the profile score. The sample population consisted of 108 patients with "at risk" characteristics or clinical manifestations of PIH. From one to six profile scores per patient were obtained between 24 weeks' gestation and the onset of labor. Simultaneously, the clinical status of the patient was evaluated and assigned to one of four categories: (1) no PIH, (2) incipient PIH, (3) mild PIH, and (4) severe PIH. Of the 108 sample patients, 14 did not develop clinical PIH (no PIH), 17 developed mild gestational or intrapartum hypertension only (incipient PIH), 45 manifested mild preeclampsia (mild PIH), and 32 demonstrated severe preeclampsia (severe PIH), four of whom were eclamptic. Profile scores +/- standard error of the mean (SEM) relative to the patient's clinical status were as follows: no PIH = 7.1 +/- 0.5, incipient PIH = 10.7 +/- 0.4; mild PIH = 15.5 +/- 0.4; and severe PIH = 28.3 +/- 0.9. On the basis of our study data, we believe that profile scoring is an effective system for the early identification of PIH. Also, we believe that, when patients with clinically overt PIH are evaluated, this approach enhances our ability to quantitate the severity of the disease objectively.

Blood Pressure↗

Fetal biophysical profile score. VI. Correlation with antepartum umbilical venous fetal pH.

OBJECTIVE: Our objective was to determine the relationship, if any, between the fetal biophysical profile score and antepartum umbilical venous pH. STUDY DESIGN: This was a prospective observational study conducted concurrently in two centers and involving two discrete high-risk groups of fetuses. Fetal biophysical profile scores were compared with umbilical venous pH values measured in blood obtained by immediate cordocentesis. A total of 493 paired observations of biophysical profile score and pH were made; 104 observations were of fetuses with intrauterine growth retardation and 389 observations were of fetuses with alloimmune anemia. RESULTS: In both data sets there was a highly significant linear correlation between biophysical profile score and umbilical venous pH. Poor biophysical profile score performance (a score of 0 of 10) was always associated with a pH < 7.20, whereas the pH was always > 7.20 when the biophysical profile score was 10 of 10. Sequenced sensitivity of short-term biophysical variables in the detection of acidemia was observed. CONCLUSION: The fetal biophysical profile score accurately predicts antepartum umbilical venous pH.

Analysis of Variance↗

Relationship between the fetal biophysical profile score, umbilical artery Doppler velocimetry, and fetal blood acid-base status determined by cordocentesis.

OBJECTIVE: Fetal hypoxia-acidosis is part of the terminal pathway leading to intrauterine fetal death. A central premise of antepartum surveillance is that identification and timely delivery of the hypoxic or acidotic fetus will prevent intrauterine death and decrease long-term neurologic damage. The optimal method to identify fetal hypoxia-acidosis has not been determined. We attempted to compare the performance of the biophysical profile score and umbilical artery Doppler velocimetry in the identification of fetal acidemia, hypoxemia, and hypercarbia as determined by pH and gas analysis of fetal blood obtained by cordocentesis. STUDY DESIGN: Fetal biophysical profile and umbilical artery Doppler velocimetry studies were performed before cordocentesis in 24 patients (26 to 40 weeks). Umbilical vein pH and blood gas values were determined in all cases. The pulsatility index of the umbilical artery was obtained with pulsed Doppler equipment. Receiver-operator characteristic curve analysis and stepwise multiple logistic regression were performed to examine the relationship between biophysical profile score, umbilical artery Doppler velocimetry, and acid-base status. RESULTS: The prevalence of fetal acidemia (pH 2 SD below the mean for gestational age) was 41.7% (10/24). There was a significant relationship between the change in umbilical artery pulsatility index and fetal acidemia (chi 2 = 26.6, p < 0.001) and hypercarbia (chi 2 = 22.9, p < 0.001), but not hypoxemia (chi 2 = 1.0, p > 0.1), and between the biophysical profile score and fetal acidemia (chi 2 = 11.1, p < 0.001) and hypercarbia (chi 2 = 9.0, p < 0.005), but not hypoxemia (chi 2 = 2.3, p > 0.1). Stepwise multiple logistic regression demonstrated that umbilical artery Doppler velocimetry was a better explanatory variable for acidemia and hypercarbia than the biophysical profile score. CONCLUSION: A strong relationship between the degree of fetal acidemia and hypercarbia and the results of umbilical artery Doppler velocimetry and biophysical profile was found. However, umbilical artery Doppler velocimetry was a better explanatory variable for these outcome than the biophysical profile score.

Acid-Base Equilibrium↗

Perceptions of facial profile and their influence on the decision to undergo orthognathic surgery.

Eighty patients, who had previously been evaluated by an oral surgeon and an orthodontist as requiring orthognathic surgery, completed questionnaires rating their perceptions of their own profiles. Half of the patients had decided to undergo surgical correction of their jaw deformities, while the other half had decided against surgical treatment. In addition, booklets containing pretreatment photographs of all 80 patients were mailed to 37 oral surgeons, 46 orthodontists, and 43 lay persons. These three groups of evaluators rated the patients' profiles, using the same rating scales that the patients had used. Cephalometrically, the two patient groups were statistically the same in all skeletal and soft-tissue measures except for ANB (mean difference = 1.8 degrees) and soft-tissue AN-pogonion (mean difference = 2.4 degrees). Differences in these dimensions were considered in subsequent data analyses. Results of this study support the following conclusions: In spite of the fact that surgical treatment may be recommended by dental specialists and indicated by cephalometric measurements, self-perceptions of profile are more important in the patient's decision to elect surgical correction; the perception by others that the profiles of patients deciding against surgery are closer to ideal may have some influence on their decision against surgical correction of their jaw deformities; oral surgeons and orthodontists evaluate facial profiles similarly, but surgeons are more likely to recommend surgical correction; lay persons are more likely to rate an individual's profile as being normal than are dental specialists in orthodontics and oral surgery; in contrast, individuals perceive their own profiles differently than orthodontists, oral surgeons, and lay persons, particularly with respect to the mandibular and dentoalveolar dimensions.

Adolescent↗

The separate profile structures of the functional calcium pump protein and the phospholipid bilayer within isolated sarcoplasmic reticulum membranes determined by X-ray and neutron diffraction.

The detailed profile structure of the isolated sarcoplasmic reticulum membrane was studied utilizing a combination of X-ray and neutron diffraction. The water and lipid profile structures within the sarcoplasmic reticulum membrane were determined at 28 A resolution directly by neutron diffraction and selective deuteration of the water and lipid components. The previously determined electron density profile structure of the sarcoplasmic reticulum membrane at 12 A resolution was subjected to model refinement analysis constrained by the neutron diffraction results, thereby providing unique higher resolution calculated lipid and protein profile structures. It was found that the lipid bilayer profile structure of the isolated sarcoplasmic reticulum membrane is asymmetric, primarily the result of more lipid residing in the inner versus the outer monolayer of the sarcoplasmic reticulum lipid bilayer. The asymmetry in the lipid composition was necessarily coincident with a complimentary asymmetry in the protein mass distribution between the two monolayers in order to preserve the overall cross-sectional area of lipid and protein throughout the lipid bilayer region of the sarcoplasmic reticulum membrane profile structure. Approximately 50% of the mass of the total protein was found to be localized externally to the sarcoplasmic reticulum membrane lipid bilayer protruding from the outer lipid monolayer into the extravesicular medium. The structural features of the protein protrusion appear to be rather variable depending upon the environment of the sarcoplasmic reticulum membrane. This highly asymmetric structural organization of the sarcoplasmic reticulum membrane profile is consistent with its primary function of unidirectional calcium transport.

Animals↗

Coagulation profile as a predictor for post-tonsillectomy and adenoidectomy (T + A) hemorrhage.

The risk of hemorrhage after tonsillectomy and adenoidectomy (T + A) was studied in 1061 children. Twenty-seven (2.5%) had at least one abnormality on a preoperative coagulation profile consisting of a prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT) and platelet count (PC). Of these 27 who had an initially abnormal test (PTT or bleeding times only), 8 had diagnosed coagulopathies by hematology evaluation (Group A), and 17 had repeat tests which returned to normal (Group B). Two borderline tests (PTT) were not repeated (Group C). Sixty-four patients (6.0%) bled after T + A. Six of these (9.3%) had an initially abnormal coagulation profile--one in Group A (12.5%), four in Group B (23.5%) and 1 in Group C (50%). This is in contrast to the bleed rate of 5.7% for the 1034 children with normal coagulation profiles. Although it is not surprising that 6 (22.2%) children with an initially abnormal coagulation profile bled, of note is that 4 of them had an initially abnormal coagulation profile which upon repeat testing returned to normal. However, none of these four bleeders required active intervention for control. Coagulopathies were newly diagnosed in 7 (0.57% of total group; 25.9% of 27 with abnormal laboratory values). One additional child had a known intrinsic platelet dysfunction prior to surgery. Only one child was newly identified by a positive family history for abnormal bleeding. These results suggest that new hematologic disorders were diagnosed infrequently. An initially abnormal coagulation profile may identify those more likely to bleed after surgery (22.6% vs. 5.5%). A coagulation profile which includes a PTT and BT may be a valuable screening tool for children undergoing T + A.

Adenoidectomy↗

Assessment of spatial and temporal velocity profiles distal of normally functioning Björk-Shiley prosthesis by the Doppler method.

By Doppler echocardiography, the performance of heart valve prostheses is assessed with the aid of maximal transprosthetic velocities, which, however, may not be representative for the full spatial velocity profile in the vicinity of mechanical valve substitutes due to flow separation by the open occluder. The purpose of this study was to determine characteristics of velocity profiles downstream of a normally functioning Björk-Shiley prosthesis. In a pulsatile flow apparatus, different flow rates of 6.3 and 8.4 l/min were delivered. Using a spatially and temporally resolving ultrasonic Doppler method, velocity profiles 20 and 30 mm distal from the prosthesis were registered and displayed in a three-dimensional grid. The spatial velocity profile was found to deviate substantially from a flat profile at these transducer positions at the two flow conditions. Distal to the minor orifice, velocities measured only 70 and 80% of those downstream of the major orifice. In between, a region of relatively slow moving flow was present. The shape of the profiles remained essentially unchanged during acceleration and deceleration of flow. Thus, spatially resolved velocity profiles downstream of mechanical prostheses can be registered by an ultrasonic Doppler device. These findings may be useful for the detection of beginning malfunction both in the experimental and the clinical setting.

Blood Flow Velocity↗

Antimitochondrial antibody profiles determined at early stages of primary biliary cirrhosis differentiate between a benign and a progressive course of the disease. A retrospective analysis of 76 patients over 6-18 years.

Seventy-six patients with clinically and histologically defined primary biliary cirrhosis, who were in stage I/II at the time of first diagnosis and could be followed for 6-18 years (mean 10 years), were analysed with respect to their clinical course. Forty-four of the 76 patients remained in stage I/II during the observation period (group 1), while 32 progressed to late stages (group 2). Sera of these patients were retested for anti-M2, anti-M4, anti-M8 and anti-M9 antibodies by ELISA and the complement fixation test (CFT). Four different AMA-profiles A-D could be differentiated in these patients: profile A, only anti-M9 positive by ELISA; B, anti-M9 and/or anti-M2 positive by ELISA; C, anti-M2, anti-M4 and/or anti-M8 positive by ELISA; and D, anti-M2, anti-M4 and/or anti-M8 positive by ELISA and CFT. When the natural courses of patients and the four different AMA-profiles were compared retrospectively it became evident that 97% of group 2 patients already had the AMA-profile C/D at entry into the study. Of the patients in group 1 70% had the AMA-profile A/B. Increases in bilirubin levels during the course of the disease were observed preferentially in patients of group 2 (profile C/D). We conclude that the determination of AMA-profiles in PBC patients is a sensitive approach for the early prediction of the outcome of the disease.

Adult↗

Profiling of endogenous brain peptides and small proteins: methodology, computer-assisted analysis, and application to aging and lesion models.

Significant advances in the technology for the isolation of peptides and small proteins have permitted their identification as biologic markers and enhanced the study of the posttranslational life of proteins. The protocol described here examined large numbers of tissue-derived peptides and small proteins, extracted in low pH and boiled so that proteolysis was interrupted. These were then fractionated batchwise using size exclusion and ion-exchange chromatography. Profiles of species in the peptide pools were then generated on reverse-phase high-performance liquid chromatography (HPLC). The HPLC profiles were evaluated with chromatographic analysis software to identify and quantify peptide peaks and with data compilation programs to sort this information into spreadsheets for comparison of profiles among groups. Using rodent brain, the effects of postmortem delay or age were examined. Postmortem delay produced limited alterations to the profiles, but the effect of age was more pronounced. Many changes were apparent until 12 months, after which the profiles became more constant. Additional peptide profiling of the hippocampus demonstrated changes in peptide content as a function of perforant pathway ablation. The major strengths of HPLC-mediated peptide profiling are that it lends itself to automation and can be used to detect changes in peptides and small proteins among experimental groups or subjects without any prior assumptions concerning which ones might be altered.

Aged↗

Validation of hourly pain intensity profiles with chronic pain patients.

This study examines how empirically derived pain intensity profiles relate to psychological adjustment in chronic pain patients. Hourly pain intensity ratings over the course of a day of 189 chronic pain patients were categorized into 6 groups using a hierarchical regression analysis technique. The profiles reflected linear, curvilinear, multilinear or "no profile" effects. Judges' ratings of pain intensity profiles were found to be less reliable than ratings based on empirical analysis. The majority of patients showed linear profiles while 26% of the patients showed no consistent relationship between hourly pain intensity and time of day. Patients who showed no consistent trend in their pain ratings reported having significantly higher ratings of emotional distress. They tended to have conflicts at home and showed more pain behavior than patients who had a distinct pain profile. Support is given for the potential clinical utility of pain rating profiles.

Adolescent↗