Variations in HIV-RNA viral load and CD4 counts of infants and children receiving antiretroviral drug therapy.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
R O'Donnell
Publications and source records attributed to R O'Donnell.
A new paradigm of injury intentionality.
OBJECTIVE: To improve understanding of processes leading to injury and assess more specifically the degree of intentionality. METHODS: A new paradigm was developed that characterizes the act of inflicting injury (self, other, not inflicted) and the motive. Motives are determined for the act of injury and for the outcome. To test this, 986 cases of adolescent injuries in seven hospitals were reviewed. Three investigators independently classified all cases using the new paradigm and three used standard definitions of intent. Inter-rater reliability was measured. RESULTS: Of injuries inflicted by others, 61% were intentional using the standard classification. In the new paradigm 67% were intended acts and 59% involved intentional motive for outcome. Altogether 87% of sports injuries were coded as unintentional acts compared with 96% using standard methods. Using standard classification there was 93% agreement between paired raters, with an average kappa of 0.86. In the new paradigm questions on intentionality of act, outcome, and infliction of act, the agreement was 89%, 91%, 88%, with a kappa of 0.79, 0.80, 0.76, respectively. CONCLUSIONS: This paradigm defines a spectrum of injury intent, enhances understanding of the causal sequence of injury, and has important implications for research and prevention.
Adolescent↗
Communicating bad news: a pediatric department's evaluation of a simulated intervention.
OBJECTIVE: To determine if pediatric residents and emergency department (ED) fellows could improve their ability to counsel and inform standardized patients (SPs) about bad news. METHODOLOGY: A crossover, self-controlled design in which trainees were their own control individuals, and SPs provided feedback after the first interview. The setting was the consultation room in the ED of a large children's hospital. The outcome measures included examining the counseling and informing skills of study participants. RESULTS: Trainees improved their informing skills after being provided feedback in the broad areas of communication and follow-up and in the total number of content areas asked. Their counseling skills improved in two areas: 1) promoting more trust and 2) making parents feel less dependent. Those trainees who scored higher on counseling skills discussed more total and critical content issues with SPs in the study. Trainee feedback revealed a very high rating of the educational process, and the trainees also felt much more confident about their skills after the first and second sessions. CONCLUSIONS: Using SPs to teach residents and ED fellows to give bad news is an effective educational process that provides trainees with interactions that simulate real-life experience
Adult↗
Sonographic detection of uterine and ovarian abnormalities in female survivors of Wilms' tumor treated with radiotherapy.
OBJECTIVE: The purpose of this study was to use sonography to evaluate the size of the ovaries and uterus in survivors of Wilms' tumor who underwent radiotherapy. SUBJECTS AND METHODS: Eighteen survivors of Wilms' tumor had their ovaries and uterus measured on sonography. Their ages at diagnosis and treatment ranged from 14 months to 6 years. Four girls were prepubertal (age, 5-9 years), 11 were postpubertal (age, 11-30 years), and three had primary ovarian failure (age, 15-23 years) at the time of imaging. Findings were compared with those of a control group of 25 prepubertal and 25 postpubertal girls and women. Gonadotropin levels were measured. RESULTS: Three patients who underwent whole abdomen radiotherapy had elevated levels of gonadotropin and primary ovarian failure. Neither ovary was seen in two of the three patients and both ovaries were abnormally small (< or = 1 cm3) in the third patient. The uterus was abnormally small (length, < or = 4 cm) in all three of these patients even though two were being treated with hormone replacement therapy. Ten postpubertal patients who underwent hemiabdomen radiotherapy had normal gonadotropin levels and a normal-sized uterus on sonography; the ovary on the side that received radiotherapy was not seen in three of the 10 patients or was abnormally small (< or = 1.4 cm3) in two of the 10 patients compared with all normal ovaries in the postpubertal control group (p < .0001). One postpubertal patient with bilateral renal bed radiotherapy had normal ovaries and a normal-sized uterus. Significantly more patients in the postpubertal and ovarian failure radiotherapy group (5 [36%] of 14 patients) had one or both ovaries not seen than the control group (none [0%] of 25 patients; p = .0014). The uterus was significantly smaller than normal in three (23%) of the 13 patients in the postpubertal hemiabdomen and ovarian failure radiotherapy group versus none of the 25 patients in the postpubertal control group (p = .0339). CONCLUSION: Postpubertal female survivors of Wilm's tumor who underwent radiotherapy as children may have one or two small or absent ovaries and a small uterus that can be detected by sonography. The response of the uterus to hormone replacement therapy can also be assessed on sonography.
Adolescent↗
Unfractionated heparin, time for a change?
BACKGROUND: In Ireland physician transfer to utilisation of Low Molecular Weight Heparin for Venous Thromboembolism has been slow, despite evidence of efficacy and concern about the level of anticoagulation achieved with Unfractionated Heparin. OBJECTIVE: To examine the effectiveness of Unfractionated Heparin administration in a teaching hospital in Ireland. Primary outcomes measured were time to therapeutic APTT and length of hospital stay. METHODS: We identified 50 consecutive eligible patients treated with continuous intravenous unfractionated heparin for Venous Thromboembolism from the period August 1994 to December 1996 at Beaumont Hospital, Dublin, Ireland. Data analysed included length of hospital stay, costing data and anticoagulation parameters (time to therapeutic APTT, percentage of time within therapeutic range, number of diagnostic tests, heparin dosages). RESULTS: A significant number of patients (22%) never achieved therapeutic APTT levels. Of those who did achieve therapeutic APTT levels at some time during their therapy, therapeutic range APTT was maintained only 28% of the time on heparin. 57% of the time results were below therapeutic while 15% of the time results were above therapeutic. Also 26% of the patients were discharged with INR results outside the therapeutic range despite an average length of stay of 13.3 days (over twice the ideal of 6 days). Ineffective anticoagulation influenced hospital length of stay in 60% of cases in our evaluation. Average cost of treatment with Unfractionated Heparin was 5897.86 Pounds versus the projected cost of Low Molecular Weight Heparin at 2562.78 Pounds for 6 days of in-patient therapy or 60.78 Pounds for outpatient therapy (excluding physician visit costs). CONCLUSIONS: Unfractionated Heparin therapy as reviewed in our study is sub-optimal with inadequate anti coagulation and prolonged hospitalisation. Low Molecular Weight heparin, with comparable therapeutic effect documented elsewhere, overall may cost less.
Anticoagulants↗
Malignant lymphoma of the cervix. An unusual presentation and a rare disease.
Malignant lymphomas arising in the uterus are uncommon and are more commonly seen in the cervix than the corpus. Involvement of the cervix as part of a systemic lymphoma is more common than primary lymphoma, but the cervix as the site of presentation is unusual. We report two cases of malignant lymphoma of the cervix. The first patient, a 52-year-old woman, was referred to colposcopy following persistent low grade dyskaryosis on cervical cytology. At colposcopy a Lletz biopsy was performed and a diagnosis of CIN 1 and focal CIN 2 was made. In addition the subepithelial zone revealed a non-Hodgkin's (NHL) B-cell follicular lymphoma. The patient was subsequently staged as NHL Stage 3E. The second patient, a 35-year-old woman, was referred to the gynaecology department with a history of abnormal vaginal bleeding and two abnormal smears. Subsequent cervical biopsy revealed a high grade, large cell, malignant lymphoma, diffuse, B-cell. The patient was staged as Stage IE. Primary lymphoma of the uterine cervix as illustrated in the second case is very unusual. One case had negative cytology and one case had abnormal cells of uncertain origin. This highlights the difficulty of diagnosing cervical lymphoma, a rare but treatable malignancy, on cytology and suggests that cervical biopsy is needed for the confirmation of the diagnosis.
Adult↗
Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase.
Complex structures of a naturally occurring variant of human class pi glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures reveal that the xenobiotic substrate-binding site (H-site) is located at a position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network connects the five water molecules and the side chains of R13 and N204. V104 is positioned such that the introduction of a methyl group (the result of the V104I mutation) disturbs the H-site water structure and alters the substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2 A) with the sulfur atom of the product. There is a short hydrogen bond (2.5 A) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an electrophilic participant in the addition of glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is found in the cavity between beta2 and alphaI. The location and properties of this HEPES-binding site fit a possible non-substrate-binding site that is involved in noncompetitive inhibition of the enzyme.
Animals↗
Regulation of chitin synthase activity in the dimorphic fungus Benjaminiella poitrasii by external osmotic pressure.
The effects of changes in external osmotic pressure on chitin synthase activity of a dimorphic fungus, Benjaminiella poitrasii, have been investigated. Mycelial and yeast cells incubated in medium of low osmolality (distilled water, 0 mOsm) for 10 min had 2-3-fold higher specific activities of native chitin synthase in mixed membrane preparations than cells that had been subjected to a high osmolality medium (1.2 M sorbitol in distilled water, 1612 mOsm). Cells suspended in media of different osmolalities for 10 min were also affected in the extent of germ tube formation. Germ tube formation was highest in cells incubated in low osmolality medium. The addition of protein phosphatase inhibitors (cyclosporin A, 1.2 micrograms/ml; cantharidin, 20 microM) abolished the effect of hypo-osmotic stress on chitin synthase activation of yeast mixed membrane preparations. The presence of protein kinase inhibitors (genistein, 40 micrograms/ml; H-7, 100 microM) and a Ca2+ channel blocker (verapamil, 50 microM) reduced chitin synthase activity to 50-60% of that observed in cells under hypo-osmotic shock. These inhibitors also inhibited germ tube formation. This suggests that chitin synthase activity and yeast hyphal morphogenesis are both subject to regulation by osmotic pressure, phosphorylation and calcium.
Calcium Channel Blockers↗
Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties [corrected; erratum to be published].
We report the isolation and characterization of a cDNA encoding a novel member of the GABA receptor gene family, epsilon. This polypeptide is 506 amino acids in length and exhibits its greatest amino acid sequence identity with the GABAA receptor gamma3 subunit (47%), although this degree of homology is not sufficient for it to be classified as a fourth gamma subunit. The epsilon subunit coassembles with GABAA receptor alpha and beta subunits in Xenopus laevis oocytes and transfected mammalian cells to form functional GABA-gated channels. alpha1beta1epsilon GABAA receptors, like alpha1beta1gamma2s receptors, are modulated by pentobarbital and the steroid 5alpha-pregnan-3alpha-ol-20-one but, unlike alpha1beta1gamma2s receptors, are insensitive to flunitrazepam. Additionally, alpha1beta1epsilon receptors exhibit rapid desensitization kinetics, as compared with alpha1beta1 or alpha1beta1gamma2s. Northern analysis demonstrates widespread expression of a large epsilon subunit transcript in a variety of non-neuronal tissues and expression of a smaller transcript in brain and spinal cord. Sequence analysis demonstrated that the large transcript contained an unspliced intron, whereas the small transcript represents the mature mRNA, suggesting regulation of expression of the epsilon subunit via neuronally restricted RNA splicing. In situ hybridization and immunocytochemistry reveal a pattern of expression in the brain restricted primarily to the hypothalamus, suggesting a role in neuroendocrine regulation, and also to subfields of the hippocampus, suggesting a role in the modulation of long term potentiation and memory.
Amino Acid Sequence↗
Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-ox y-7,8,9,10-tetrahydrobenzo(a)pyrene.
In this study, we demonstrate that the active site architecture of the human glutathione (GSH) S-transferase Pi (GSTP1-1) accounts for its enantioselectivity in the GSH conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo(a) pyrene (anti-BPDE), the ultimate carcinogen of benzo(a)pyrene. Furthermore, we report that the two polymorphic forms of human GSTP1-1, differing in their primary structure by a single amino acid in position 104, have disparate activity toward (+)-anti-BPDE, which can also be rationalized in terms of their active site structures. When concentration of (+)-anti-BPDE, which among four BPDE isomers is the most potent carcinogen, was varied and GSH concentration was kept constant at 2 mM (saturating concentration), both forms of hGSTP1-1 [hGSTP1-1(V104) and hGSTP1-1(I104)] obeyed Michaelis-Menten kinetics. The V(max) of GSH conjugation of (+)-anti-BPDE was approximately 3.4-fold higher for hGSTP1-1(V104) than for hGSTP1-1(I104). Adherence to Michaelis-Menten kinetics was also observed for both isoforms when (-)-anti-BPDE, which is a weak carcinogen, was used as the variable substrate. However, (-)-anti-BPDE was a relatively poor substrate for both isoforms as compared with (+)-anti-BPDE. Moreover, there were no significant differences between hGSTP1-1(V104) and hGSTP1-1(I104) in either V(max) or K(m) for (-)-anti-BPDE. The mechanism of differences in kinetic properties and enantioselectivity of hGSTP1-1 variants toward anti-BPDE was investigated by modeling of the two proteins with conjugation product molecules in their active sites. Molecular modeling studies revealed that the differences in catalytic properties of hGSTP1-1 variants as well as the enantioselectivity of hGSTP1-1 in the GSH conjugation of anti-BPDE can be rationalized in terms of the architecture of their active sites. Our results suggest that the population polymorphism of hGSTP1-1 variants with disparate enzyme activities may, at least in part, account for the differential susceptibility of individuals to carcinogens such as anti-BPDE and possibly other similar carcinogens.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Stabilization of asthma mortality.
BACKGROUND: Rates of death from asthma in the United States have increased since 1978. OBJECTIVE: To identify and evaluate recent trends in asthma mortality. METHODS: Analysis of data from the National Center for Health Statistics identifying asthma (ICD 493) as the underlying cause of death in the 50 United States and the District of Columbia with rates of death from asthma by age, race, and sex and age-adjusted rates of death by race. The Bureau of the Census provided population data by age, race, and sex that permitted calculation of rates of death at 5 through 34 years of age. The Departments of Health of Australia, Canada, Great Britain, and New Zealand provided numbers of deaths from asthma and population data from which we have calculated rates of death. RESULTS: Rates of death from asthma in the United States increased from .8 per 100,000 general population in 1977 and 1978 to 2.0 in 1989 and have been 1.9 or 2.0 since then until an increase to 2.1 in 1994. A significant difference in regression over groups indicates a difference in average rates between 1979 through 1987 compared with 1988 through 1994. Rates of death from asthma have been much higher for white females than white males with an increasing disparity. Rates of death from asthma at 5 through 34 years of age have been much greater in blacks than whites with no significant change in rates across time from 1980 through 1994. Age-adjusted rates for blacks over all ages increased from 1.5 in 1977 and 1978 to 3.5 in 1988 with rates no higher than that until an increase to 3.7 in 1994. Age-adjusted rates for whites increased from .5 in 1977 to 1.2 by 1989 with none higher than that since then through 1994. Comparison of slopes indicates a significantly greater increase for blacks than whites (F = 68.296, P < .0001). Equality of slopes tests indicate significantly greater age-adjusted rates of increase for each race separately for 1979 through 1987 compared with 1988 through 1994. CONCLUSION: Since 1988 rates of death from asthma in the United States for most ages have stabilized at rates more than 50% higher than those of 1979, but there has been only a suggestion of stabilization of rates at 5 through 34 years of age, ages at which certification of death as due to asthma is most accurate. Rates of death have been much higher for blacks than whites, and among whites rates have increased more for females than males. These differences might be due to difference in prevalence or severity of differences in accuracy of diagnosis. Improvements in management would reduce asthma mortality.
Adolescent↗
Evaluation of awakening and recovery characteristics following anaesthesia with nitrous oxide and halothane fentanyl or both for brief outpatient procedures in infants.
This study compared recovery characteristics and postoperative ventilatory function when halothane, fentanyl or combination of halothane and fentanyl in addition to N2O were used for intraoperative anaesthesia in term infants undergoing hernia repair as outpatients. Sixty-six full term ASA PS I infants ages 1-12 months were studied. All received inhalation induction with N2O, O2 and halothane, followed by intravenous atropine and atracurium, tracheal intubation, and controlled ventilation. For anaesthesia maintenance, patients were randomized into one of three groups. Group I received 70% N2O, 30% O2 and halothane. Group II received 70% N2O, 30% O2, halothane and 2 micrograms.kg-1 fentanyl. Group III received 70% N2O, 30% O2 and 10 micrograms.kg-1 fentanyl. Awakening times were similar in all three groups, however, Group I patients had significantly shorter recovery and discharge times than those of Group II and III. None of the patients experienced postoperative apnoea or periodic breathing. One patient in Group III experienced two brief episodes of bradycardia not associated with apnoea or arterial desaturation (SpO2 > 90% for greater than 30 s). Decreased SpO2 occurred less frequently in Group I (5.9%) compared to Group II (22.7%) and Group III (19.0%) patients, however, the group differences were not significant. Transcutaneous CO2 (TcCO2) values were not statistically different among the three groups. Pain scores were initially lower in Groups II and III, but at 120 min the differences were not significant. Postoperative apnoea was not observed in this study. SpO2 < 90% and TcCO2 > 9 kPa (70 mmHg) was more common in infants receiving 2 and 10 micrograms.kg-1 fentanyl than in infants receiving halothane and nitrous oxide anaesthesia. Infants < 3 months old did not have a higher incidence of SpO2 < 90% or significantly higher TcCO2 values when compared to infants > 3 months old. Fentanyl in doses used in this study did not prolong awakening time but did prolong recovery and discharge times in outpatient infants.
Ambulatory Surgical Procedures↗
Porphyria cutanea tarda and hematologic malignancy--a report of 4 cases.
Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.
Aged↗
Obstetrical brachial plexus palsy (OBPP) outcome with conservative management.
Resurgence of neurosurgical intervention of obstetrical brachial plexus palsy prompted our review of 186 patients evaluated between 1981 and 1993, correlating clinical examination, electrodiagnosis, and functional outcome with conservative management. Eighty-eight percent had upper brachial plexus palsies, and 63% were mild. Forty-two infants required no long-term follow-up because they rated 1 or 2 on initial physical examination. Comparing first and last follow-up clinical findings of the remaining 149 patients, there was high agreement (correlation r= 0.81; P < 0.001). Pearson correlation of initial physical exam with electrodiagnosis at three intervals was relatively stable (r= 0.87, 0.88, 0.69). One hundred eight (72%) of the patients remained in their original severity groups. Thirty-three of 41 patients with discrepant follow-up scores improved by at least one category. Eight patients deteriorated. The natural pathophysiology and recovery of OBPP is presented.
Brachial Plexus↗
Surfactant content in children with inflammatory lung disease.
OBJECTIVE: To determine surfactant profiles of tracheal secretions in mechanically ventilated children with respiratory failure secondary to bacterial pneumonia, viral pneumonitis, adult respiratory distress syndrome (ARDS), and cardiopulmonary bypass. DESIGN: Prospective, cohort study. SETTING: Tertiary, multidisciplinary, pediatric intensive care unit. PATIENTS: One hundred twenty pediatric patients with respiratory failure requiring mechanical ventilation. INTERVENTIONS: Routine tracheal aspirates were collected from children with bacterial pneumonia, viral pneumonitis, ARDS, postcardiopulmonary bypass, and a postsurgical control group. Samples were obtained on days 1, 2, 3, after every week of intubation and on the day of extubation. MEASUREMENTS AND MAIN RESULTS: The tracheal aspirates were analyzed by high-performance liquid chromatography for lecithin/sphingomyelin rations and by enzyme-linked immunosorbent assay for surfactant proteins A and B. Lung compliance and the oxygenation index were measured on each day of sample collection. On day 1, patients with bacterial pneumonia, viral pneumonitis, and ARDS had decreased lecithin/sphingomyelin ration (p < .001), and those patients with bacterial pneumonia and viral pneumonitis had decreased surfactant protein A/protein concentration (p < .001). The lecithin/sphingomyelin ratios and surfactant protein A/protein concentration were significantly different among the groups (p < .001), with the bacterial pneumonia and viral pneumonitis groups having higher lecithin/sphingomyelin ratios and increased surfactant protein concentrations before extubation. Pulmonary compliance was lower and the oxygenation index was higher than controls (p < .001) in patients with bacterial pneumonia, viral pneumonitis, and ARDS. Pulmonary compliance was correlated weakly with lecithin/sphingomyelin ratio (r2 = .11, p < .001) and surfactant protein A/protein concentration (r2 = .03, p < .05). Surfactant protein B was similar in the diagnostic groups. Surfactant content in tracheal secretions from cardiopulmonary bypass patients was equivalent to controls. CONCLUSION: Abnormal tracheal aspirate surfactant phospholipids and surfactant protein A were noted in children with bacterial pneumonia, viral pneumonitis, and ARDS, but not in children on cardiopulmonary bypass.
Cardiopulmonary Bypass↗
Epileptic seizure as a sign of cerebrospinal fluid shunt malfunction.
Epilepsy was evident in 308 of 817 (38%) children with shunted hydrocephalus. The first seizure occurred after shunting in 181 of 817 (22%), a median of 1.6 years after the original shunt procedure. The incidence of seizures was not statistically different in the parietooccipital, parietotemporal, or frontal region. Over a 15-year period, 16 of 544 (2.9%) visits to the emergency room for seizures culminated in shunt revision, and 16 of 1,831 (0.9%) shunt revisions were associated with a seizure. Although seizures in shunted patients are not uncommon, a seizure is seldom an indication of shunt malfunction.
Brain↗
A comparison of two column agglutination technologies for routine antibody screening using the indirect antiglobulin technique.
Two commercial column agglutination technologies were compared for routine antibody screening using the indirect antiglobulin technique with 1000 heparinised blood samples from a general hospital. The I.D. microtyping system (Diamed) utilises a Sephadex gel, and the Biovue system (Ortho Diagnostics) consists of a column containing minute glass beads. Both systems have antihuman globulin incorporated into them resulting in agglutinates being trapped and allowing free red cells to pass through to the base. The purpose of this study was to compare the two technologies with the minimum amount of variables possible. The spin tube antiglobulin technique was not included in this study as this technology has not been used in this laboratory since January 1991. The systems compared well, despite different serological problems.
Blood Grouping and Crossmatching↗
Characterization of recombinant human interleukin 4 receptor from CHO cells: role of N-linked oligosaccharides.
Interleukin 4 (IL-4) mediates its biological activities through interaction with its receptor on the cell surface. A recombinant extracellular domain of the alpha subunit of human interleukin 4 receptor was expressed in CHO cells and purified to homogeneity by a combination of ion exchange and immunoaffinity chromatography. Analysis of the purified protein by MALDI MS provided an average mass of 38,241 Da while microsequencing identified the site of the signal sequence processing to be Ser23-Gly24. The receptor was highly glycosylated, containing N-linked complex oligosaccharides with bi-, tri-, and tetraantennary structures. Five of the six potential glycosylation sites could be assigned to Asn residues 53, 98, 128, 134 and 176. N-deglycosylation increased aggregation and reduced solubility of the receptor but did not affect its IL-4 binding activity. These observations provide preliminary insights into the role of N-linked oligosaccharides in IL-4 receptor biosynthesis and function at the cell surface.
Amino Acid Sequence↗