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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 91 records · Page 5Linked to original sources

Studies of interactions with weak affinities and low-molecular-weight compounds using surface plasmon resonance technology.

Interactions between the immobilized weak-affinity monoclonal IgG antibody 39.5, which is specific for the glucose-alpha 1,4-glucose motif, and various oligosaccharides were studied with surface plasmon resonance technology. The antibody was immobilized at high levels on the surface of the sensor chip and different concentrations of the analytes were injected at 25 and 40 degrees C. The 39.5 antibody exhibited specific binding to maltose, tetraglucose and maltotriose, with dissociation constants Kd in the range from 0.07 mM (25 degrees C) to 1.0 mM (40 degrees C). Association and dissociation rate constants (ka and kd) were rapid and baseline was obtained almost immediately after the end of each antigen injection. This excluded the need for a regeneration step but also made calculation of the kinetic values impossible. Owing to the weak affinity and the small size of the analytes (< 1000 Da), a careful design of control surfaces is demanded to exclude artefactual results.

Animals↗

Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study.

The reason why 10% to 20% of all patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) remains unknown. The aim of this study was to compare the clinical and biochemical presentation in PSC patients with and without hepatobiliary malignancy and to look for risk factors for developing hepatobiliary carcinoma in PSC. All PSC patients (n = 20) with hepatobiliary carcinoma treated at Huddinge Hospital between 1984 and 1995 were age- and sex-matched to 20 PSC patients with end-stage disease without carcinoma. Clinical and biochemical data from four different occasions (time of onset of PSC, 12 and 6 months before and at the time of cancer diagnosis or liver transplantation [Ltx]) were registered. Seventeen patients had CC, 2 had hepatocellular carcinoma (HCC), and 1 had gallbladder carcinoma (GBC). Eighteen of the cancer patients and 19 controls had inflammatory bowel disease (IBD). The number of patients who smoked or were former smokers was significantly higher in the cancer group (P < .0004). The duration of IBD and PSC, extra- and intrahepatic distribution of PSC, surgical and medical treatments did not differ between the two groups. Abdominal pain was the only symptom that was more frequent among cancer patients at the time of cancer diagnosis/Ltx compared with controls. Evaluation of biochemical data did not indicate a more rapid deterioration among cancer patients. The mean value of the tumor marker, CA 19-9, in the cancer group was 700 kU/L; in the control group, it was 46 kU/L (P < .05), although data were only available in 10 cancer patients and 7 controls. Bile duct dysplasia was found in over 60% of patients with PSC and CC in nontumorous liver tissue apart from the tumor. Clinical and biochemical presentation of PSC patients with and without hepatobiliary carcinoma did not differ during the year before cancer diagnosis/Ltx. Smoking seems to be a risk factor for developing hepatobiliary carcinoma in patients with PSC.

Adult↗

The three-dimensional structures of two toxins from snake venom throw light on the anticoagulant and neurotoxic sites of phospholipase A2.

The three-dimensional structures of the class II anticoagulant phospholipase A2 (PLA2) toxin RVV-VD from the venom of Russell's viper, Vipera russelli russelli, and the class I neurotoxic PLA2 Notechis II-5 from the, Australian tiger snake, Notechis scutatus scutatus, were determined to 2.2 A and 3.0 A resolution, respectively. Both enzymes are monomeric and consist of 121 and 119 residues, respectively. A comparison of ten class I/II PLA2 structures showed, among other differences, that the beta-sheet of these enzymes (residues 76-83) is about 90 degrees less twisted in class I than in class II PLA2s. This, along with the insertion of some residues in the region 57-59 in class I enzymes (the elapid loop), could be the main reason for the significant difference in the anticoagulant and (presynaptic) neurotoxic properties between the two classes of PLA2. It seems apparent from sequence and structural comparisons that the toxic site of PLA2 responsible for the strong anticoagulancy of these toxins consists of a negatively charged part, Glu53, together with a positively charged ridge of lysine residues free for intermolecular interactions. These lysines differ between the two classes of PLA2.

Amino Acid Sequence↗

Nonrandom numerical chromosome abnormalities in basal cell carcinomas.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Adult↗

Epidemiology of pregnancy-induced hypertension and preeclampsia in type 1 (insulin-dependent) diabetic pregnancies in Sweden.

BACKGROUND: The object of this study was to examine if there is an association between pregnancy-induced hypertension (PIH) and/or preeclampsia (PE) and glycemic control assessed by HbA1c in early type 1 diabetic pregnancy, as well as factors such as maternal age, parity, duration of diabetes, presence of diabetes microangiopathy. METHODS: The nationwide collaborative study included 491 type 1 diabetic pregnancies corresponding to about 80%, of the diabetic pregnancies during the study period 1983-1985. A blood sample for determination of HbA1c was obtained in early gestation (median 9 (5-16) weeks). RESULTS: The rate of PIH/PE was 20.6% in the type 1 diabetic pregnancies compared to 5.0% in the background population. The type 1 diabetic pregnancies complicated by PIH/PE were associated with significantly longer duration of diabetes, higher initial HbA1c (8.1% vs 7.4%, p < 0.01), higher rate of nephropathy and retinopathy, while there were no significant differences in maternal age or parity compared to those without PIH/PE. Discriminant analysis revealed that occurrence of nephropathy (p<0.001), retinopathy (p<0.01) and high HbA1c (p<0.01) in early pregnancy were independently and significantly associated with occurrence of PIH/PE. Among the 463 patients without prepregnancy proteinuria 38 (8.2%) had PIH and 53 (11.5%) PE. The group with PE had, compared to the no PIH/PE group, significantly higher HbA1c (8.2% vs 7.4%, p<0.01). HbA1c was not significantly different between the PIH and the no PIH/PE group (7.5% vs 7.4%). Both the PIH and the PE group had significantly higher rate of retinopathy compared to the no PIH/PE group. If early HbA1c was equal to or above control mean by +8 s.d., i.e. > or =10.1% the PI rate was 31.0% compared to 10.2% in those with HbA1c below that value. CONCLUSIONS: We conclude that poor glycemic control in early pregnancy is associated with increased risk of PE in non-proteinuric type 1 diabetic pregnancies.

Adult↗

Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderate-to-severe, chronic heart failure.

AIMS: To evaluate the feasibility of a nurse-monitored, outpatient-care program for elderly patients previously hospitalized with chronic heart failure. METHODS AND RESULTS: Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a randomized study to compare the effect of a nurse-monitored, outpatient-care programme aiming at symptom management, with conventional care. The inclusion criteria were patients classified in New York Heart Association classes III-IV, age 65 years, and eligibility for an outpatient follow-up programme. The total in-hospital population of patients discharged with a heart-failure diagnosis was surveyed. Eighty-nine per cent of all the hospitalized patients (n=1541) were 65 years old. Of these, 69% (n=1058) were treated in the medical wards which were screened. The study criteria were met by 158 patients (15%). No visits to the nurse occurred in 23 cases among the 79 patients randomized to the structured-care group (29%), mainly on account of death or fatigue. The numbers of hospitalizations and hospital days did not differ between the structured-care and the usual-care groups. CONCLUSIONS: Given the selection criteria and the outline of the interventions, the outpatient, nurse-monitored, symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe, chronic heart failure, mainly because of the small proportion of eligible patients and the high drop-out rate. Management of these patients would have to be more adjusted to their home situation.

Aged↗

Metabolic control in children with insulin-dependent diabetes mellitus 5 y after diagnosis. Early detection of patients at risk for poor metabolic control.

Children (n = 38) aged 3-15 y were randomly chosen, at the time of diabetes diagnosis, for conventional management at a hospital ward, or for treatment partly in a training apartment where the family was offered problem-based education and special therapeutic support. HbA1c, blood glucose stability, urinary C-peptide excretions and incidence of hypoglycaemic attacks and diabetes ketoacidosis (DKA) were monitored and some standardized, self-estimated psychological tests were performed during the first 2 y after diagnosis. During the 3 y thereafter, HbA1c, presence of DKA, microalbuminuria, retinopathy and hypertension were monitored. None of the patients demonstrated signs of diabetes microangiopathy or DKA. The overall mean HbA1c level was 7.2% 5 y after diagnosis and 30% of the children had HbA1c values <6.3%. There were no differences in the HbA1c values for the patients treated by the different management regimens. Blood glucose variability (SD) was also similar, with 75% of the values in the range of 3-10 mmol/l. Patients with poor glycaemic control (mean HbA1c >8.3%) year 5 after diagnosis had already the second year after diagnosis significantly higher HbA1c values and blood glucose variability. The fathers of these patients demonstrated a higher degree of maladjustment. On the basis of increasing HbA1c values, high blood glucose variability and psychosocial risk factors such as their fathers' emotional responses, patients at risk for poor metabolic control in the future can be identified within 2 y after diagnosis. Efforts and resources can thus be focused at an early stage on this group.

Adaptation, Psychological↗

Hunger behaviour contributes to early nutritional homeostasis.

OBJECTIVES AND METHODS: Our goal was to describe nutritional homeostasis in healthy exclusively breastfed infants (n = 175) during their first 5 d, by cross-sectional measurements of body weight, blood glucose, plasma insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding-protein-1 (IGFBP-1), free fatty acids (FFA), glycerol, ketone (3-OH-butyric acid) and lactate. We also investigated whether nutrition affected feeding behaviour by timing the interval between feedings. RESULTS: A progressive loss of body weight, as percentage of birthweight, occurred up to 2 d of age, with a maximal decrease of 5.8 +/- 2.1% (mean +/- SD); this was accompanied by inhibition of anabolic hormone and metabolic pathways and an increased mobilization of stored fat and ketogenesis. The interval between feedings decreased between d 1 and 2. Weight gain occurred at 3 d and the following re-feeding phase returned fuel stores to their previous levels and established an anabolic hormonal and metabolic situation. Infants with weight loss exceeding 10% had a further accentuation in their peripheral picture of starvation and a further 7% shortening of the interval between feedings. CONCLUSIONS: breastfeeding on demand is accompanied by a balanced nutritional situation and an increased drive to eat when weight reduction is <6%. However, a weight loss of > or = 10%, probably elicits hunger sensations in response to decreased fuel availability.

Analysis of Variance↗

Lactate compared with pH analysis at fetal scalp blood sampling: a prospective randomised study.

OBJECTIVE: Fetal scalp blood sampling is a widely used method for assessing fetal condition in the event of ominous fetal heart rate patterns. The purpose of this randomised trial was to compare the value of fetal scalp blood lactate and pH management in cases of abnormal intrapartum fetal heart rate tracings. METHODS: Of 341 cases of ominous fetal heart rate patterns, 169 were randomly assigned to pH analysis, and 172 to lactate measurements. Lactate was measured using a lactate card requiring 5 microL of blood and yielding the result within 60 seconds. pH analysis was performed with an ABL 510 acid-base analyser requiring 35 microL of blood and yielding the results within 47 seconds. RESULTS: Unsuccessful fetal blood sampling procedures (no result or an unreliable result) occurred significantly more often in the pH subgroup than in the lactate subgroup (OR 16.1 with 95% CI 5.8-44.7). In the pH subgroup the failure rate was inversely related to the degree of cervical dilatation. Compared with the pH subgroup, the lactate subgroup was characterised by fewer fetal scalp incisions per blood sampling attempt (median 1.0 [interquartile range (IQR) 1-1] vs 2.0 [IQR 1-2]), and significantly less time required for the sampling procedure (median 120 s [IQR 90-147] vs 230 s [IQR 180-300]). The groups did not differ in mode of delivery, neonatal outcome and umbilical artery acid-base balance and lactate levels. CONCLUSION: This trial showed the levels of lactate and pH in fetal scalp blood to be comparable in predicting perinatal outcome, but the procedure to measuring lactate was more successful than that for pH. Owing to its simplicity of performance, lactate analysis is an attractive alternative for intrapartum fetal monitoring.

Female↗

Cadmium may be a risk factor for osteoporosis.

OBJECTIVES: The primary study aim was to examine the possible role of cadmium as a risk factor for osteoporosis by determining the bone mineral density (BMD) in workers previously exposed to cadmium. A second objective was to validate the BMD data obtained with a movable instrument. METHODS: 43 workers who were exposed to cadmium for < or = 5 years before 1978 were studied. Cadmium in blood (B-Cd) and urine (U-Cd) were used as dose estimates. The BMD was assessed in the forearm, the spine, and the hip (neck and trochanter) with a dual energy x ray absorptiometry (DXA) instrument. Age and sex matched reference populations were used to compute Z scores, commonly used to assess osteoporosis. RESULTS: The mean forearm Z score was -0.60 (95% confidence interval (95% CI) -1.08 to -0.12) in the group exposed to cadmium. The mean Z score for the spine was -0.47 (95% CI -0.92 to -0.03), for the hip neck -0.40 (95% CI -0.75 to -0.05), and for the hip trochanter -0.22 (95% CI -0.52 to -0.07). The decrease in forearm BMD was correlated with age (p = 0.002) and B-Cd (p = 0.040). No such correlations were found for the other sites. Workers with tubular proteinuria had a lower forearm BMD (p = 0.029) and a lower Z score (p = 0.072) than workers without tubular proteinuria. CONCLUSIONS: There was a suggested dose-effect relation between cadmium dose and bone mineral density. Furthermore, there was a dose-response relation between cadmium dose and osteoporosis. Cadmium may be a risk factor for the development of osteoporosis at lower doses than previously anticipated.

Absorptiometry, Photon↗

Serum leptin levels in young females with insulin-dependent diabetes and the relationship to hyperandrogenicity and microalbuminuria.

To investigate the relationship between leptin levels and IDDM with and without microalbuminuria, fasting serum levels of leptin, insulin, insulin-like growth factor-1 (IGF-1), sex hormone-binding globulin (SHBG), testosterone (SHBG) ratio, blood pressure and body mass index (BMI) were measured in 18 normo- and 11 microalbuminuric females with >5 years of IDDM, and 24 healthy controls in late puberty. Leptin levels were higher in micro- than normoalbuminuric IDDM patients, and lower in healthy controls than in both IDDM groups (p < 0.05, respectively). In multiple regression analysis, presence of IDDM and BMI independently contributed to increased leptin values (R2 = 0.34, p < 0.001). Including IDDM females only, solely low IGF-1 and high testosterone/SHBG were associated with leptin (R2 = 0.39, p = 0.009). Albumin excretion rate (AER) was correlated to leptin (r = 0.48, p = 0.01). With AER as the dependent variable only serum leptin and diastolic blood pressure added to the regression (R2 = 0.59, p < 0.001). In conclusion, serum leptin, independently of BMI, is: (1) increased in IDDM females of late puberty; (2) associated with low IGF-1 and hyperandrogenemia, and (3) related to increased albumin excretion rate in IDDM females.

3-Hydroxybutyric Acid↗

Vasoconstriction during acute hypervolemic hemodilution in hypertensive patients is not prevented by calcium blockade.

The reduction of blood viscosity by moderate acute hypervolemic hemodilution in untreated hypertensives can be associated with a secondary vasoconstriction. The aim of this study was to examine whether a vasodilating therapy prevents this hemodynamic reaction. Twelve hypertensive patients (WHO stage II) were treated with the vasoselective calcium channel blocker isradipine in a placebo-controlled, double-blind, crossover study. Acute hypervolemic hemodilution was performed twice: at the end of the placebo period and after two months of treatment. Hemodilution was achieved by the intravenous infusion of 1000 mL saline over a 10- to 15-minute period. Arterial blood pressure, heart rate, cardiac output (dye dilution), renal blood flow, glomerular filtration, natriuresis, hematocrit, whole blood, and plasma viscosity were assessed before and after infusion. Flow resistance and vascular hindrance in the central and renal circulation were calculated. Acute hemodilution associated with a significant reduction of blood (P<0.01) and plasma (P<0.01) viscosity did not influence the mean arterial pressure and cardiac output. Consequently, the total flow resistance remained unchanged. However, as a result of hemodilution, the calculated vascular hindrance index in the systemic circulation increased, indicating a vasoconstrictive reaction, both with placebo (from 5.22 to 6.07 U x mPa(-1) x s(-1), P < 0.05) and during chronic treatment with calcium blockade (from 3.75 to 4.22 U x mPa(-1) x s(-1), P<0.02). Vasoconstriction was not observed in the renal circulation, either during the placebo or active treatments. The results of this study indicate that the systemic vasoconstriction evoked by the acute moderate hypervolemic hemodilution in hypertensive patients was not prevented by a calcium channel blockade.

Antihypertensive Agents↗

Mortality from asthma and cancer among sulfite mill workers.

OBJECTIVES: The aims of the present case-referent study were to investigate whether sulfite workers show increased mortality from asthma, chronic obstructive pulmonary disease or certain malignancies of interest in relation to sulfite mill work. The main exposure from the pulping processes is from sulfur dioxide, wood dust and terpenes. METHODS: The subjects of the study were all the men who died between 1960 and 1989 and who were aged 40 to 75 years at death (N = 780) in the parishes surrounding 3 sulfite mills. The men who died from asthma (N = 13), COPD (N = 20), lung cancer (N = 33), stomach cancer (N = 35), or brain tumor (N = 10) formed the case group. All the subjects, except the cases in question, were used as referents. As a proxy variable of exposure, job titles from the registers of deaths and burials were used, and 24% of the subjects were classified as exposed. RESULTS: There was an increased mortality from asthma [odds ratio(OR) 2.8, 90% confidence interval (90% CI) 1.1-6.8] and brain tumors (OR 3.3, 90% CI 1.2-8.9) among the sulfite workers. The mortality due to lung cancer was not significantly increased (OR 1.4, 90% CI 0.7-2.6), and there was a reduced mortality from stomach cancer (OR 0.4, 90% CI 0.2-0.9). CONCLUSIONS: The increased asthma mortality may be due to accidental exposure to irritating gases, such as sulfur dioxide. The increased risk for brain tumors has no obvious explanation.

Adult↗

Neonatal morbidities in gestational diabetes mellitus.

The currently accepted definition of gestational diabetes mellitus (GDM) is rather broad. One might expect that fetal and neonatal complications that may occur in GDM pregnancy would be similar to those in pregestational diabetic pregnancy. Comparative evaluation of reported data on morbidity in GDM are often hampered by confounding variables (maternal age, parity, obesity) as well as the influence of factors such as ethnic origin, diagnostic criteria, and intervention during pregnancy. Recent observations indicate that GDM may be associated with increased incidence of fetal malformation and perinatal mortality. Such poor outcome is likely confined to a subset of GDM patients in whom diabetes was present but unrecognized before pregnancy. The most frequent and significant morbidity is fetal macrosomia, which in turn is associated with increased risk of birth injuries and asphyxia. In a nationwide study in Sweden (1991-1993) of a large series (n = 3.322) of treated GDM pregnancies, perinatal mortality rate was not increased; but the rate of preeclampsia was doubled, and the rate of emergency cesarean section was 1.6 times higher than in the background population. The rates of fetal macrosomia (> or = 4,500 g), asphyxia, and transient tachypnea were two to three times higher than normal Erb's palsy was 0.7 and 5% in vaginally delivered infants weighing < 4,500 and > or = 4,500 g, respectively. There is a clear need to define the various levels of glucose intolerance in the mother that may have an adverse effect on the offspring. Of equal importance is to standardize and systematize the criteria used to assess the significance of any such impact.

Diabetes, Gestational↗

Superantigen-targeted therapy: phase I escalating repeat dose trial of the fusion protein PNU-214565 in patients with advanced gastrointestinal malignancies.

Antibody-directed, superantigen-induced cytotoxicity has been shown to have potent in vitro and in vivo antitumor effects in preclinical models. In the present study, PNU-214565, a recombinant fusion protein consisting of the Fab of the monoclonal antibody C242 and staphylococcal enterotoxin A (SEA), was used in an escalating repeat dose Phase I clinical trial in patients with advanced gastrointestinal malignancies. A prior single-dose Phase I clinical trial had demonstrated safety at doses of 1.5 ng/kg with toxicities of fever and hypotension that were not dose related. Twenty-seven patients (age range, 36-75 years; median, 62; 14 males and 13 females; 23 colorectal and 4 pancreatic) were treated in the present study with one cycle of four consecutive daily 3-h infusions of PNU-214565 at doses of 0.15 ng/kg (n = 3); 0.5 ng/kg (n = 3), 1.5 ng/kg (n = 4), 2.75 ng/kg (n = 12), and 3.5 ng/kg (n = 5). All patients had a good performance status [Eastern Cooperative Oncology Group: PS = 0 (n = 15), PS = 1 (n = 12)]. As in the single-dose trial, fever and hypotension were the most common toxicities. Dose-limiting toxicity (DLT), consisting of transient hypotension responsive to dopamine, was experienced by one patient treated at the 2.75 ng/kg dose level. One patient with pancreatic cancer metastatic to the liver experienced a partial response of hepatic metastases with stable pancreatic head abnormalities by computed tomography scan. Further dose escalation was suspended when two patients treated in a companion repeat dose Phase I study experienced DLT at the 4 ng/kg dose level. Multiparameter analyses on all patients treated in the two companion single-dose and two-repeated-dose Phase I trials revealed that the levels of patients' pretreatment anti-SEA antibodies protected against toxicity at a given drug dose. By jointly considering weight and the baseline anti-SEA concentration in a patient, it is possible to assign a PNU-214565 dose that will induce systemic cytokine release (a surrogate test to assess for the presence of uncomplexed drug and its ability to induce systemic cellular activation) without DLT. This pharmacodynamically based dosing scheme will be tested in future repeated-dose clinical trials and will define maximally tolerated doses of this powerful new immunotherapy approach.

Adult↗

Male reproductive pattern in a glass producing area.

The objective of the study was to evaluate the reproductive pattern among male crystal glassworkers in comparison to other males in a restricted area in the south-east part of Sweden. The parish register information was gathered for all men with job titles registered, decreased at the age above 20 years during 1950-1982. The comparison of reproductive patterns was made between groups of glassworkers, farmers and workers of other occupations. As an indicator of fertility, birth rates and time to first child-birth were calculated. Male sex ratios (number of boys/all child-births) were calculated as a measure of reproductive disturbances. The total birth rates as well as the birth rates for sons were slightly decreased among glassworkers when compared to the group of non-farmers/non-glassworkers and significantly decreased when compared to farmers. The total birth rate of the non-farmer/non-glassworker group was also significantly decreased compared to farmers. No differences in sex ratios among children born or in time to first child-birth were seen between the three groups. Among the glassworkers, the reduction in birth rates was most pronounced among engravers/grinders both in comparison to farmers and others. The results indicate that paternal exposure in crystal glassworks might somewhat negatively affect the male reproduction at least in a historical perspective. The mechanisms behind this cannot be concluded from this study.

Adult↗

Alanine insertion scanning mutagenesis of lactose permease transmembrane helices.

A priori, single residue insertions into transmembrane helices are expected to be highly disruptive to protein structure and function. We have carried out a systematic analysis of the phenotypes associated with Ala insertions into transmembrane helices in lactose permease, a multispanning Escherichia coli inner membrane protein. Insertion of alanine into the center of 7 transmembrane helices was found to abolish stable integration of lactose permease into the membrane or uphill lactose transport. A more detailed Ala insertion scan was made of transmembrane helix III. The results pin-point a central region of approximately 2 helical turns that is crucial for lactose permease stability and/or activity. A Trp scan in this region identified 2 residues essential for lactose permease stability. From these results, it appears that transmembrane helices have differential sensitivities to single residue insertions and that such mutations may be useful for identifying structurally and/or functionally important helix segments.

Alanine↗