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Biomedical subjects

J Hicks

Publications and source records attributed to J Hicks.

At least 19 recordsLinked to original sources

A novel, fully implantable, multichannel biotelemetry system for measurement of blood flow, pressure, ECG, and temperature.

Biotelemetry provides high-quality data in awake, free-ranging animals without the effects of anesthesia and surgery. Although many biological parameters can be measured using biotelemetry, simultaneous telemetric measurements of pressure and flow have not been available. The objective of this study was to evaluate simultaneous measurements of blood flow, pressure, ECG, and temperature in a fully implantable system. This novel system allows the measurement of up to four channels of blood flow, up to three channels of pressure, and a single channel each of ECG and temperature. The system includes a bidirectional radio-frequency link that allows the implant to send data and accept commands to perform various tasks. The system is controlled by a base station decoder/controller that decodes the data stream sent by the implant into analog signals. The system also converts the data into a digital data stream that can be sent via ethernet to a remote computer for storage and/or analysis. The system was chronically implanted in swine and alligators for up to 5 wk. Both bench and in vivo animal tests were performed to evaluate system performance. Results show that this biotelemetry system is capable of long-term accurate monitoring of simultaneous blood flow and pressure. The system allows, within the room, recordings, since the implant transmission range is between 6 and 10 m, and, with a relay, backpack transmission distance of up to 500 m can be achieved. This system will have significant utility in chronic models of cardiovascular physiology and pathology.

Alligators and Crocodiles↗

Deregulated minichromosomal maintenance protein MCM7 contributes to oncogene driven tumorigenesis.

Minichromosomal maintenance protein 7 (MCM7) is an essential component of the replication helicase complex (MCM2-7) required for DNA replication. Although this function is highly conserved among eukaryotes, additional functions for the MCM molecules continue to be described. Minichromosomal maintenance protein 7 is a marker for proliferation and is upregulated in a variety of tumors including neuroblastoma, prostate, cervical and hypopharyngeal carcinomas. To further investigate the general role of MCM7 in tumorigenesis, we generated a mouse model with deregulated MCM7 expression targeted to the basal layer of the epidermis using the keratin 14 (K14) promoter (K14.MCM7). When subjected to a two-stage chemical carcinogenesis protocol (dimethylbenz[alpha]anthracene (DMBA) initiation with 12-ortho-tetradecanoylphorbol-13-acetate promotion), K14.MCM7 mice showed significantly increased incidence and prevalence of tumor development relative to controls. Furthermore, within 40 weeks of treatment over 45% K14.MCM7 mice exhibited tumors that had converted to squamous cell carcinomas versus none in the control group. As predicted from previous skin carcinogenesis studies using DMBA as the initiating agent, Ras mutations where found in more than 90% of tumors isolated from K14.MCM7 mice. Whereas previous studies have shown that MCM7 is useful as a proliferation marker, our data suggest that deregulated MCM7 expression actively contributes to tumor formation, progression and malignant conversion.

9,10-Dimethyl-1,2-benzanthracene↗

RSA-measured inducible micromotion and interface modeling with finite element methods.

Osteolysis is the main cause of aseptic loosening and stem failure. The mechanism that leads to osteolysis is poorly understood; pressure generation caused by reversible stem micromotion may play an important role. We aimed to determine whether dynamically inducible micromotion occurs in vivo at the prosthesis-cement interface and to use these data to develop and confirm a finite element representation of this interface. Dynamically inducible micromotion was measured using radiostereometric analysis in 21 hips implanted with an Exeter stem, at 3 months and 12 months postoperatively, by changing loading from double-leg stance to single-leg stance. Dynamically inducible micromotion occurred at 3 and 12 months; similar micromotion was observed at both time points. At 3 months the head of the stem was displaced posteriorly (0.10 +/- 0.16 mm) and inferiorly (0.08 +/- 0.12 mm) on loading. A Coulomb friction nonbonded representation of the stem-cement interface was used to fit the clinically measured dynamically inducible micromotion. The final finite element model predicted gap opening and closing between the implant and the mantle. This may be a mechanism for generating pressure and distributing wear debris, which are believed to important contributors to failure.

Aged↗

Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS: Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined. RESULTS: Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015). CONCLUSION: Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage.

Adolescent↗

Expression profiling using human tissues in combination with RNA amplification and microarray analysis: assessment of Langerhans cell histiocytosis.

Advances in molecular genetics have led to sequencing of the human genome, and expression data is becoming available for many diverse tissues throughout the body, allowing for exciting hypothesis testing of critical concepts such as development, differentiation, homeostasis, and ultimately, disease pathogenesis. At present, an optimal methodology to assess gene expression is to evaluate single cells, either identified physiologically in living preparations, or by immunocytochemical or histochemical procedures in fixed cells in vitro or in vivo. Unfortunately, the quantity of RNA harvested from a single cell is not sufficient for standard RNA extraction methods. Therefore, exponential polymerase-chain reaction (PCR) based analyses, and linear RNA amplification including amplified antisense (aRNA) RNA amplification and a newly developed terminal continuation (TC) RNA amplification methodology have been used in combination with microdissection procedures such as laser capture microdissection (LCM) to enable the use of microarray platforms within individual populations of cells obtained from a variety of human tissue sources such as biopsy-derived samples {including Langerhans cell histiocytosis (LCH)} as well as postmortem brain samples for high throughput expression profiling and related downstream genetic analyses.

Gene Expression Profiling↗

High-resolution ROMA CGH and FISH analysis of aneuploid and diploid breast tumors.

Combining representational oligonucleotide microarray analysis (ROMA) of tumor DNA with fluorescence in situ hybridization (FISH) of individual tumor cells provides the opportunity to detect and validate a wide range of amplifications, deletions, and rearrangements directly in frozen tumor samples. We have used these combined techniques to examine 101 aneuploid and diploid breast tumors for which long-term follow-up and detailed clinical information were available. We have determined that ROMA provides accurate and sensitive detection of duplications, amplifications, and deletions and yields defined boundaries for these events with a resolution of <50 kbp in most cases. We find that diploid tumors exhibit fewer rearrangements on average than aneuploids, but rearrangements occur at the same locations in both types. Diploid tumors reflect at least three consistent patterns of rearrangement. The reproducibility and frequency of these events, especially in very early stage tumors, provide insight into the earliest chromosomal events in breast cancer. We have also identified correlations between certain sets of rearrangement events and clinically relevant parameters such as long-term survival. These correlations may enable novel prognostic indicators for breast and other cancers as more samples are analyzed.

Aneuploidy↗

The influence of cement viscosity on the early migration of a tapered polished femoral stem.

It is unclear whether it is best to use high-viscosity or low-viscosity cement for fixation of total hip replacement (THR) femoral components. This study examines the influence of cement viscosity on the migration of the Exeter femoral component using roentgen stereophotogrammetric analysis (RSA). Simplex, CMW1 and CMW3 G cements were examined in a total of 46 patients over a 12-month period. The overall pattern of migration for all cohorts was one of subsidence and rotation into valgus. There was no significant difference in any aspect of migration between the groups. In vitro studies demonstrate that low-viscosity cement forms a more stable bone-cement interface. Several groups have examined the in vivo effect of cement viscosity on stem longevity with conflicting results. For a polished, tapered implant that is designed to subside, cement viscosity does not influence the 1-year migration, and it is therefore unlikely to affect long-term outcome.

Aged↗

Restoration-enamel interface with argon laser and visible light polymerization of compomer and composite resin restorations: a polarized light and scanning electron microscopic in vitro study.

This polarized light (PL) and scanning electron microscopic (SEM) in vitro study investigated the effect of argon laser (AL) and visible light (VL) polymerization on the interfaces between compomer and composite resin restorations and the enamel cavosurfaces. Surface topography by SEM revealed a smooth transition between the restorative materials and adjacent enamel surfaces with no microspaces between the restorations and enamel surfaces. The enamel surfaces showed relatively smooth surface coatings with AL curing compared with exposure of etched prism endings with VL curing. The restoration-enamel interface by PL showed an intimate relationship between the restorative materials and the cavosurface enamel. No differences were found between AL and VL polymerization. With the restoration-enamel interface by SEM, compomers and composite resins were adapted closely to the cavosurface enamel and tags of restorative material protruded into the adjacent cavosurface enamel. Both VL and AL polymerization of compomers and composite resin restorations in vitro produced closely adapted restorations with intimate restoration-enamel interfaces. Such restoration-enamel interfaces may provide a certain degree of resistance against secondary caries formation, and this may be enhanced by the caries protective effect of argon laser irradiation.

Adhesives↗

Rhabdomyosarcoma of the head and neck in children.

OBJECTIVE: The purpose of this study was to determine the rhabdomyosarcoma types involving the head and neck (H&N) region in children and their immunophenotype. DESIGN: Anatomic pathology archives at Texas Children's Hospital were searched for all rhabdomyosarcoma cases over a 20-year period. One-hundred and thirty-seven cases were identified, with 50 being H&N cases. The cases were typed according to the Intergroup Rhabdomyosarcoma Study (IRS) criteria. Immunocytochemistry for myogenic and non-myogenic markers was performed on all H&N cases. Electron micrographs from cases (n=32) where ultrastructural examination had been performed at the time of original diagnosis were reviewed. RESULTS: Children with H&N rhabdomyosarcomas had a mean age of 5.3 years (median 4 years). There was a male predilection (1.7M:1.0F). Primary tumor sites were: face NOS (18%), orbit/periorbital (16%), nasal cavity/nose (14%), lymph nodes (12%), paranasal sinuses (10%), parameningeal (10%), parotid gland (6%), neck (6%), infratemporal fossa/zygoma (2%), buccal mucosa (2%), palate (2%), and larynx (2%). Metastatic disease at diagnosis (33% of all cases) occurred in the bone marrow (11%), cerebrospinal fluid (6%), peritoneal fluid (6%), lung (4%), parietal pleura (2%), pleural fluid (2%) and pericardial fluid (2%). Rhabdomyosarcoma types (IRS criteria) were: embryonal (60%), alveolar (classic and solid subtypes, 28%), botryoid (4%), undifferentiated (4%), spindle cell (2%) and anaplastic (2%). Immunocytochemical findings were: polyclonal desmin (96%); myogenin (96%); muscle-specific actin (74%), smooth muscle actin (12%). Nonmyogenic markers included: vimentin (100%), CD99 (16%), p53 (16%), pancytokeratin (10%), NSE (8%), LCA (6%), CD20 (6%), EMA (2%), and NB-84 (0%, neuroblastoma). Undifferentiated sarcoma expressed only vimentin. By ultrastructural examination, 44% had readily identified z-bands and myofilaments, 37% had infrequent to rare myofilaments and z-bands, and 19% had myotubular intermediate filaments. CONCLUSIONS: Distribution of H&N rhabdomyosarcoma IRS types is similar to that for all primary sites, with the exception that embryonal types are modestly increased while alveolar type is mildly decreased. There are many non-myogenic immunocytochemical markers that cross-react with rhabdomyosarcoma. Differentiation between favorable and unfavorable rhabdomyosarcoma types is important for appropriate therapy, and predicting prognosis and survival.

Adolescent↗

Characteristics and outcome of membranous nephropathy in older patients.

Many patients with idiopathic membranous nephropathy are elderly, but little is known about the natural or treated history of these patients. We have studied a cohort of 155 patients with membranous nephropathy who were recruited and followed-up over a 20 year period. We have compared the clinical features and outcome of the older (>60 years) and younger age groups. There was a higher incidence of an identifiable cause for the nephropathy in older patients. At presentation with idiopathic disease, older patients were more often hypertensive and had worse renal impairment than the younger cohort, but had a similar levels of proteinuria, hypoalbuminemia and hematuria. Thrombotic complications and minor rheumatological complaints were more common in the older patients. Prognosis for life and renal survival was worse in the older onset patients. Treatment was well tolerated in selected older patients and was associated with a better outcome in those selected for treatment.

Adrenal Cortex Hormones↗

Glomerulonephritis induced by recombinant collagen IV alpha 3 chain noncollagen domain 1 is not associated with glomerular basement membrane antibody: a potential T cell-mediated mechanism.

Glomerulonephritis is believed to result commonly from Ab-mediated glomerular injury. However, Ab-associated mechanisms alone cannot explain many cases of human glomerulonephritis. We developed a rat model of human anti-glomerular basement membrane (GBM) disease to investigate T cell and Ab response, and their associations with the disease. A single immunization of highly denatured recombinant mouse collagen IV alpha3 chain noncollagen domain 1 (rCol4alpha3NC1) induced severe glomerulonephritis in 100% of Wistar Kyoto rats, 33% of which died of this disease around day 35 postimmunization. The renal pathology demonstrated widespread glomerular damage and a mononuclear cell infiltration within the interstitial tissue. T cells from immunized rats responded not only to rCol4alpha3NC1, but also to isolated rat GBM. Sera Abs to rCol4alpha3NC1 were detectable in 100% of the rats, but only 20% of the rats had low levels of Ab to isolated rat GBM by Western blot, and none by immunofluorescence. Furthermore, IgG/M binding to or C3 deposition on endogenous GBM in immunized rats were not detected in most of the experimental rats, and showed no statistical correlation with disease severity. Additionally, no electronic dense deposition in the glomeruli was detected in all rats. Those data revealed a disassociation between the disease and anti-GBM Ab. T cell-mediated mechanisms, which are currently under our investigation, may be responsible for the glomerular disease.

Animals↗

RcoA has pleiotropic effects on Aspergillus nidulans cellular development.

Aspergillus nidulans rcoA encodes a member of the WD repeat family of proteins. The RcoA protein shares sequence similarity with other members of this protein family, including the Saccharomyces cerevisiae Tup1p and Neurospora crassa RCO1. Tup1p is involved in negative regulation of an array of functions including carbon catabolite repression. RCO1 functions in regulating pleiotropic developmental processes, but not carbon catabolite repression. In A. nidulans, deletion of rcoA (DeltarcoA), a recessive mutation, resulted in gross defects in vegetative growth, asexual spore production and sterigmatocystin (ST) biosynthesis. Expression of the asexual and ST pathway-specific regulatory genes, brlA and aflR, respectively, but not the signal transduction genes (i.e. flbA, fluG or fadA) regulating brlA and aflR expression was delayed (brlA) or eliminated (aflR) in a DeltarcoA strain. Overexpression of aflR in a DeltarcoA strain could not rescue normal expression of downstream targets of AflR. CreA-dependent carbon catabolite repression of starch and ethanol utilization was only weakly affected in a DeltarcoA strain. The strong role of RcoA in development, vegetative growth and ST production, compared with a relatively weak role in carbon catabolite repression, is similar to the role of RCO1 in N. crassa.

Amino Acid Sequence↗

The impact of ultrasound examinations on the management of children with suspected appendicitis: a 3-year analysis.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the usefulness of ultrasonography in the routine management of children with suspected appendicitis in a children's hospital. METHODS: Data from surgical, radiologic, and pathologic databases were cross referenced retrospectively to allow for review of all children undergoing appendectomy and all children undergoing an ultrasound scan to rule out appendicitis in the 3-year period August 1, 1996 to July 31, 1999. RESULTS: Pathology reports were available for 1,007 of 1,032 patients undergoing appendectomy. Eighty-four percent had acute appendicitis (26% of these were perforated). Fifty-eight percent of all children undergoing appendectomy had at least 1 preoperative ultrasound scan. Eighty-six percent of those having ultrasound scans had acute appendicitis compared with 82% of those who did not have an ultrasound scan (P <.05 chi(2) Test). During the same period, 2,056 ultrasound examinations were performed by staff radiologists who were available 24 hours a day to rule out appendicitis. Ultrasonography in this setting had a sensitivity of 89%, specificity of 95%, positive predictive value of 86%, and a negative predictive value of 96% (true-positives, n = 496; false-positive, n = 81; true-negative, n = 1,417; false-negative, n = 62). An alternate ultrasound diagnosis was offered in 157 children. CONCLUSIONS: Ultrasound scan improves diagnostic accuracy in children with suspected appendicitis. The high negative predictive value of ultrasound scan, especially when used repeatedly, may reduce the need for admission to hospital for clinical observation to rule out appendicitis.

Adolescent↗

Compartmentalized bone regeneration of cranial defects with biodegradable barriers: an animal model.

In bony defects of the cranium, bone healing may be complicated by prolapse of surrounding tissue into the defect. This tissue acts as an impediment to prevent the migration of osteogenic cells, leading to impaired bone formation. It has been previously shown that a membrane placed over the bony defect inhibits the connective tissue cells from entering the wound and theoretically improves bone formation. The use of a proven resorbable material, Lactosorb, is used in this animal model and has shown a significant increase in autogenous bony formation. The majority of previous work was accomplished with nonresorbable material that resulted in foreign body formation. This paper is unique because resorbable material in the animal model is relatively inexpensive and easy to use and has allowed successful autogenous bony regeneration.

Absorbable Implants↗

Patterns of genetic architecture for life-history traits and molecular markers in a subdivided species.

Understanding the utility and limitations of molecular markers for predicting the evolutionary potential of natural populations is important for both evolutionary and conservation genetics. To address this issue, the distribution of genetic variation for quantitative traits and molecular markers is estimated within and among 14 permanent lake populations of Daphnia pulicaria representing two regional groups from Oregon. Estimates of population subdivision for molecular and quantitative traits are concordant, with QST generally exceeding GST. There is no evidence that microsatellites loci are less informative about subdivision for quantitative traits than are allozyme loci. Character-specific comparison of QST and GST support divergent selection pressures among populations for the majority of life-history traits in both coast and mountain regions. The level of within-population variation for molecular markers is uninformative as to the genetic variation maintained for quantitative traits. In D. pulicaria, regional differences in the frequency of sex may contribute to variation in the maintenance of expressed within-population quantitative-genetic variation without substantially impacting diversity at the genic level. These data are compared to an identical dataset for 17 populations of the temporary-pond species, D. pulex.

Animals↗

Emergency department right upper quadrant ultrasound is associated with a reduced time to diagnosis and treatment of ruptured ectopic pregnancies.

OBJECTIVE: To determine whether the time to diagnosis and treatment of patients with ruptured ectopic pregnancy is significantly less for patients who had emergency department (ED) right upper quadrant (RUQ) ultrasound (US) compared with those who had US in the radiology department. METHODS: The authors conducted a retrospective review of eligible patients presenting to an urban ED between January 1990 and December 1998. Patients were included in the study if they were seen in the ED, had a discharge diagnosis of ruptured ectopic pregnancy, were brought immediately to the operating room after a definitive diagnosis of ectopic pregnancy rupture was made, and had more than 400 mL of intraperitoneal blood found at the time of surgery. The ED, hospital, radiology, and operative records were reviewed to determine presenting vital signs, intraperitoneal blood loss, time to diagnosis, time to treatment, and type of US performed. RESULTS: There were 37 patients enrolled; 16 received ED RUQ US (group I) and 21 had a formal US in radiology (group II). The ages, pulses, systolic blood pressures, and volumes of hemoperitoneum were similar between the two groups. The average time to diagnosis from ED arrival was 58 minutes for group I (SD = 57; 95% CI = 28 to 87) and 197 minutes for group II (SD = 82; 95% CI = 162 to 232) (p < or = 0.0001). The average time to operative treatment was 111 minutes (group I) (SD = 86; 95% CI = 69 to 153) and 322 minutes (group II) (SD = 107; 95% CI = 270 to 364) (p < or = 0.0001), respectively. CONCLUSIONS: Patients with ruptured ectopic pregnancy, who were selected to have RUQ US performed in the ED by emergency physicians, had an average decrease in time to diagnosis of two and a quarter hours, and an average decrease in time to treatment of three and a half hours, compared with those having a formal pelvic US in the radiology department. Further prospective investigation is needed to determine whether ED RUQ US can safely expedite care of patients with suspected ectopic pregnancy.

Adult↗

ER-YAG laser pretreatment effect on in vitro secondary caries formation around composite restorations.

PURPOSE: This in vitro study determined if Er-YAG laser used in instead of acid-etching influenced artificial secondary caries formation in enamel and root surfaces. MATERIALS AND METHODS: Class V cavities were prepared in buccal and lingual surfaces of 10 extracted caries-free molars, with cervical margins in the root surface and occlusal margins in enamel. The specimens were randomly assigned to 2 groups: Group 1: Enamel and dentin etched with 35% phosphoric acid gel (Scotchbond 15s, rinse 10s; n=5 teeth with 2 cavities per specimen, 10 occlusal and 10 root surface margins at caries risk). Group 2: Enamel and dentin surfaces conditioned using a pulsed Er-YAG laser (KAVO) with 2.94 microm wavelength, 250 micros pulse duration, 300 mJ for enamel and 250 mJ for root surface pulse energy, 2 Hz repetition rate, and water cooling (n=5 teeth with 2 cavities per specimen, 10 occlusal and 10 root surface margins at caries risk). The cavity preparations were restored with a wet-bonding technique (Scotchbond 1 adhesive system) and a hybrid resin, light-cured composite (Z100, A3 shade), according to the manufacturer's instructions. Acid-resistant varnish was applied leaving the restoration and a 1 mm rim of adjacent surface enamel and root surface exposed. The specimens were thermocycled (5-50 degrees C, 500 cycles, dwell time 30s). Following artificial caries formation (2.2 mM calcium, 2.2 mM phosphate, 50 mM acetic acid, 5.0 mg/L fluoride, pH 4.25, 10 days), longitudinal sections (3/tooth, 30 occlusal and cervical caries risk sites per group) were taken for polarized light microscopic examination (water imbibition). Primary surface lesion depth and wall lesion frequency was determined and compared between groups (Student's t-test). RESULTS: Er-YAG laser irradiation resulted in a 56% reduction in primary enamel surface lesion depth (116 microm mean depth) when compared with the acid-etched group (263 microm mean depth), and a 39% decrease in root surface lesion depth (194 microm mean depth) compared with that (316 microm mean depth) for acid-etching pretreatment (P< 0.05). Wall lesion frequency was similar (P>0.05) between treatment groups.

Acetates↗

Multiple transcripts of MUC3: evidence for two genes, MUC3A and MUC3B.

The MUC3 gene encodes a transmembrane mucin-type glycoprotein. A number of consistent single nucleotide changes were observed in different MUC3 cDNAs from a single individual, suggesting the presence of at least three different transcripts per individual. This transcript heterogeneity is due both to the existence of a second copy of the MUC3 gene and to allelic changes. Sequencing of the second MUC3 shows that it has the same C-terminal domain and intron/exon structure as the previously described MUC3. The tandem repeat domain has the same amino acid consensus sequence but shows more substitutions. The unique exonic sequences range from 94 to 100% identity at the nucleotide level and correspondingly few amino acid changes have been identified. The introns show around 95% identity. We propose to name this second gene MUC3B, MUC3A being reserved for the first MUC3 gene. MUC3B, like MUC3A, is expressed in intestine and Caco-2 cells.

Alleles↗