SEARCH · PubMed Health

Results for “Polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,747 records · Page 97Linked to original sources

PubMed1999

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.

An association between the BstUI (Pro/Pro) genotype of the p53 codon 72 polymorphism and lung cancer has been reported previously (X. Jin et al., Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution of p53 codon 72 polymorphism as well as the association of this polymorphism with lung cancer risk and prognosis remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis indicated significant differences in genotype distribution of p53 from other reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United States (P = 0.002), and African-Americans (P = 0.027). In addition, our data suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro showed a significantly increased odds ratio (3.14; confidence interval, 1.48-6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of 2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other genotypes to be diagnosed with lung cancer at the early ages. We further investigated the association of p53 codon 72 polymorphism with prognosis in 133 lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test). Our data suggested that p53 codon 72 polymorphism may play a role in cancer susceptibility and prognosis in specific classes of lung cancer patients in Taiwan.

Adenocarcinoma↗

PubMed1999

[Presinilin 1 gene polymorphism and Alzheimer's disease in Chinese].

OBJECTIVE: To detect the relationship between Presinilin 1(PS1) intronic polymorphism and Alzheimer's disease(AD) in Chinese. METHODS: PS1 intronic polymorphism was genotyped in 58 early-onset AD cases(EOAD), 65 late-onset AD cases (LOAD) and 157 age-matched controls by using PCR methods and RFLP typing. Then the association between PS1 polymorphism and AD was analyzed. RESULTS: (1) In EOAD cases, the frequency of allele 1 increased and the frequencies of allele 2 and genotype 2/2 decreased markedly, but in LOAD cases, no differences were observed. (2) EOAD was significantly associated with allele 1 (RR=2.29), P< 0.05), allele 2 (RR=0.44) and genotype 2/2(RR=0.23, P<0.05) of PS1 polymorphism, while LOAD showed no association with PS1 polymorphism. (3)PS1 polymorphism was associated with AD predominantly in non-ApoE epsilon4, female, early-onset cases. CONCLUSION: PS1 polymorphism was only associated with EOAD in Chinese, and this may be influenced by age of onset and sex.

Aged↗

PubMed2001

A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare.

In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene. No tumour-associated mutations were detected except in 1 melanoma where we found a CC>T* deletion-mutation in the codon 151-152 (exon 5) of the p53 gene. On the basis of our preliminary results, we did extended genotyping of the 500 C>G and 540 C>T polymorphisms in the 3'UTR of the CDKN2A gene in 229 melanoma cases and 235 controls. The T-allele frequency (for 540 C>T polymorphism) in melanomas was significantly higher than in controls (0.14 vs. 0.08; chi(2) = 5.95, p = 0.01; OR = 1.71, 95%CI = 1.11-2.66). The heterozygote frequency for this polymorphism was 0.26 (59/229) in melanomas compared to 0.13 (30/235) in healthy controls (chi(2) = 11.4; p = 0.0007; OR = 2.34, 95% CI = 1.40-3.92). The frequency of the 500 C>G polymorphism in the 3'UTR in the CDKN2A gene was not significantly higher in melanomas compared to healthy controls. The 500 C>G polymorphism, however, was in linkage disequilibrium with approximately 50 kb apart the C>A intronic polymorphism in the CDKN2B gene (determined in 44 melanomas and 90 controls; Fisher exact test, p<0.0001). Finally, the sequence analysis of genomic DNA isolated from T cell lymphocytes of healthy individuals exhibited that the codon reported as last of exon 2 of the CDKN2C gene is rather the first codon of exon 3.

3' Untranslated Regions↗

PubMed2005

Effect of the peroxisome proliferator-activated receptor-gamma C161T polymorphism on lipid profile in Brazilian patients with Type 2 diabetes mellitus.

AIM: The aim of the present study was to examine the effects of the C161T polymorphism of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene in Brazilian subjects with Type 2 diabetes mellitus (T2DM) and controls residing in Sao Paulo City, Brazil. METHODS: Genomic DNA was obtained from 207 patients with T2DM and 170 unrelated normoglycemic individuals (CG). Anthropometric data included: body mass index, waist, hip, waist-to-hip ratio; biochemical parameters: fasting plasma glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, glycated hemoglobin and insulin. Systolic and diastolic blood pressure was also measured. Screening for mutations in the entire coding region of the PPARgamma gene was carried out by PCR, single strand conformational polymorphism analysis (SSCP) and sequencing. C161T polymorphism was analyzed by PCR-RFLP. RESULTS: The C161T polymorphism was the only variant found in exon 6 of the PPARgamma gene. The frequency of the 161T allele in T2DM (0.10) was similar to that found in CG (0.07, p=0.210). Serum triglycerides (p=0.040), VLDL-cholesterol (p=0.040) and Atherogenic Index of Plasma (AIP; p=0.003) were significantly lower in 161T allele carriers than non-carriers in women of the T2DM group. CONCLUSIONS: Our results show that the C161T polymorphism in the PPARgamma gene is not associated with variables related to T2DM or insulin resistance in the Brazilian population. However, a reduction of serum triglycerides and AIP was observed in women with 161T allele of the C161T polymorphism of the PPARgamma gene.

Adult↗

PubMed2000

Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait.

Polymorphism in the human dopamine D4 receptor gene (DRD4) exon III has been associated in some but not all studies of the human personality trait of Novelty Seeking. We searched for polymorphisms in the 5' region of DRD4 and identified six polymorphisms as follows: -1217G Ins/Del, -809G/A, -616C/G, -603T Ins/Del, -602(G)8-9, and -521C/T. Associations between these polymorphisms and personality traits measured by the Temperament and Character Inventory (TCI) were investigated in 86 healthy Japanese volunteers. The -521C/T polymorphism was significantly associated with Novelty Seeking (P = 0.0001). Subjects with the C/C genotype exhibited the highest Novelty Seeking scores and those with the T/T genotype exhibited the lowest. A transient expression method revealed that the T variant of the C-521T polymorphism reduces transcriptional efficiency. The present study suggests a contribution of dopamine D4 receptor availability to individual differences in Novelty Seeking behavior. Molecular Psychiatry (2000) 5, 64-69.

Adolescent↗

PubMed2004

[Study on the polymorphism of interleukin-1 gene and the susceptibility to essential hypertension].

OBJECTIVE: To make investigations on the polymorphism of interleukin-1 (IL-1)gene in Chinese Han population, on its association with essential hypertension, and on the relationship between the genotype of IL-1 and susceptibility to essential hypertension. METHODS: The polymorphisms of IL-1 gene in Han population of Hubei province, including polymorphisms of IL-1alpha (-889C/T), IL-1beta (-511C/T),IL-1beta (+3953C/T), IL-1Ra(+8006T/C) and IL-1Ra (variable number of tandem repeat, VNTR), were analyzed by polymerase chain reaction (PCR) and a combination of PCR-restriction fragment length polymorphism methods in 152 patients with essential hypertension and 168 healthy controls. RESULTS: The polymorphism distributions of IL-1alpha (-889C/T), IL-1beta (+3953C/T), IL-1Ra (+8006T/C) and IL-1Ra (VNTR) showed no differences between the essential hypertension group and control group, but the IL-1beta (-511C/T) exhibited a significant difference between the two groups. CT genotype carriers were at increased risk for essential hypertension (OR=2.54, 95%CI: 1.41-4.58), compared with healthy controls. CONCLUSION: The polymorphism of promotor region -511C/T in IL-1beta gene is probably associated with the susceptibility to essential hypertension.

Aged↗

PubMed2002

Crystallization and transitions of sulfamerazine polymorphs.

A bulk powder of sulfamerazine polymorph II in a narrow distribution of particle size was prepared for the first time. The two known sulfamerazine polymorphs, I and II, were physically characterized by optical microscopy, powder X-ray diffractometry, differential scanning calorimetry, carbon-13 solid-state nuclear magnetic resonance spectroscopy, and measurements of aqueous solubility and density. The thermodynamics and kinetics of the transition between the polymorphs was examined under various pharmaceutically relevant conditions, such as heating, cooling, milling, compaction, and contact with solvents. The two polymorphs were found to be enantiotropes with slow kinetics of interconversion. The thermodynamic transition temperature lies between 51 and 54 degrees C, with polymorph II stable at lower temperatures. Ostwald's Rule of Stages explains the crystallization of the polymorphs from various solvents and may account for the delay in the discovery of polymorph II.

Anti-Infective Agents↗

PubMedDate not supplied

Characterization of polymorphs of a new anti-inflammatory drug.

The present study demonstrates the utility of a diversified analytical approach for the characterization and quantitative analysis for two polymorphs of a new anti-inflammatory agent, (+/-)-7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy-3,4-dihydro -8-propyl- 2H-1-benzopyran-2-carboxylic acid (SC-41930). The existence of two distinct crystal polymorphs of SC-41930 was qualitatively indicated through microscopy and application of thermal methods of analysis. The application of TGA was important for establishing that the two solid forms were, in fact, polymorphs, as opposed to solvated and unsolvated drug substances. The application of IR spectrometry revealed spectral features in the carbonyl stretching region, which were characteristic and unique to the two SC-41930 polymorphs. DRIFT spectrometry was implemented as the sampling method of choice to eliminate the possibility of polymorphic transformations during conventional mulling or KBr pellet sampling procedures. The DRIFT spectrometry procedure permitted development of a quantitative assay for detection of the low-melting polymorph (as an impurity) in high-melting samples. Calibration plots showed acceptable linearity of response from 0 to 25% (w/w) low-melting samples spiked into the high-melting polymorph. The performance characteristics of the method indicated good run-to-run and day-to-day consistency for its intended use.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).

A sponsor of an Abbreviated New Drug Application (ANDA) must have information to show that the proposed generic product and the innovator product are both pharmaceutically equivalent and bioequivalent, and therefore, therapeutically equivalent. Many pharmaceutical solids exist in several crystalline forms and thus exhibit polymorphism. Polymorphism may result in differences in the physico-chemical properties of the active ingredient and variations in these properties may render a generic drug product to be bioinequivalent to the innovator brand. For this reason, in ANDAs, careful attention is paid to the effect of polymorphism in the context of generic drug product equivalency. This review discusses the impact of polymorphism on drug product manufacturability, quality, and performance. Conclusions from this analysis demonstrate that pharmaceutical solid polymorphism has no relevance to the determination of drug substance "sameness" in ANDAs. Three decision trees for solid oral dosage forms or liquid suspensions are provided for evaluating when and how polymorphs of drug substances should be monitored and controlled in ANDA submissions. Case studies from ANDAs are provided which demonstrate the irrelevance of polymorphism to the determination of drug substance "sameness". These case studies also illustrate the conceptual framework from these decision trees and illustrate how their general principles are sufficient to assure both the quality and the therapeutic equivalence of marketed generic drug products.

Biological Availability↗

PubMed2005

Cytotoxic T lymphocyte-associated molecule-4 polymorphisms in Turkish Graves' disease patients and association with probability of remission after antithyroid therapy.

BACKGROUND: One of the candidate genes for susceptibility to Graves' disease (GD) is cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), a negative regulator of T-cell activation. In order to elucidate the relationship of GD with the A/G polymorphism in exon 1 and the C/T polymorphism in the promoter region of the CTLA-4 gene, the frequency of these two polymorphisms was identified in 98 healthy individuals and 77 patients with GD. METHODS: Polymorphisms were analyzed using a PCR-RFLP method. We also examined the relationship between the A/G polymorphism and various clinical and laboratory variables among patients with GD. All patients were treated with an initial dose of propranolol (40-60 mg /day) and PTU (300-400 mg/day). Subjects remained on this treatment for a minimum of 6 months and were followed in our clinic for 1 year after cessation of treatment. RESULTS: The frequency of the GG genotype was significantly higher among patients with GD than among controls of both sexes (P<0.05; odds ratio=3.145, 95% CI=1.212-8.161). There was no difference between patients and controls with regard to the C/T polymorphism. There was no statistical difference in age, sex, cigarette smoking, initial serum thyroid hormone levels, initial goiter size, initial TSH-receptor antibodies, or NOSPECS classification for orbitopathy among the patients with the three different genotypes (GG, AG, and AA). Of the patients with the AA genotype, 17 of 29 (58.6%) were in remission 1 year after PTU withdrawal, while 18 of 33 patients (54.4%) with the AG genotype were in remission 1 year later. However, only 3 of 15 patients (20%) with the GG genotype were in remission 1 year after withdrawal of antithyroid drug therapy (P=0.016 GG/AA, P=0.025 GG/AG). Using 1 year after discontinuation of antithyroid drug therapy as the cut-off point for multivariate logistic regression analysis, we found that the GG genotype, TSH at the end of therapy, and age were independent risk factors for recurrence. CONCLUSION: We conclude that the occurrence of GD is linked to the A/G polymorphism of the CTLA molecule in the Turkish population and is associated with a lower chance of remission after discontinuation of PTU treatment.

Journal Article↗

PubMed2004

Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction.

OBJECTIVES: The goal of this study was to describe the mapping and ablation of polymorphic ventricular tachycardia (VT) after myocardial infarction (MI). BACKGROUND: The initiating mechanisms of polymorphic VT after MI have not been reported. METHODS: Five patients (four males; age 61 +/- 7 years) with recurrent episodes of polymorphic VT after anterior MI (left ventricular ejection fraction 32 +/- 7%) despite revascularization and antiarrhythmic drugs were studied. All patients demonstrated frequent ventricular premature beats (PBs) initiating polymorphic VT. Pace mapping and activation mapping were used to identify the earliest site of PB activity. The presence of a Purkinje potential preceding PB defined its origin from the Purkinje network. Electroanatomic voltage mapping was performed to delineate the extent of MI. RESULTS: The PBs were observed in all cases to arise from the Purkinje arborization in the MI border zone. These PBs were right bundle-branch block in all five patients, with morphologic variations in the limb leads in four; one also had a left bundle-branch block morphology. The coupling interval of the PB to the preceding QRS complex demonstrated significant variations (320 to 600 ms). During PB, the Purkinje potential at the same site preceded the QRS complex by 20 to 160 ms and was associated with different morphologies. Repetitive Purkinje activity was documented during polymorphic VT. Splitting of Purkinje activity and Purkinje to muscle conduction block were also observed. Ablation at these sites eliminated all PBs. At 16 +/- 5 months follow-up using defibrillator memory interrogation, no patient has had recurrence of arrhythmia. CONCLUSIONS: The Purkinje arborization along the border-zone of scar has an important role in the mechanism of polymorphic VT in patients after MI. Ablation of the local Purkinje network allows suppression of polymorphic VT.

Aged↗

PubMed2004

Infrared studies of the polymorphic states of the fenamates.

Infrared spectroscopy has been used to characterize the polymorphic purity as well as to study the thermal conversion of three of the more common fenamates between their different crystalline forms via measuring changes in the NH stretch region that occur between 3300 and 3350 wavenumbers. Shifts in band frequency for mefenamic acid result from differences in internal hydrogen bonding between the NH group and either the carbonyl or hydroxyl groups of the acid moiety. Due to out-of-plane rotations about the central N-C(ring2) bond additional polymorphic states have been suggested for flufenamic and tolfenamic acids. Rates of conversion are given for flufenamic, mefenamic, and tolfenamic acids at temperatures between 85 and 160 degrees C depending on the polymorphic transition for a particular analyte. Subsequently, these rates are used to calculate the activation energy for the observed polymorphic transition. Values of 71.6, 49.0, and 50.8 kcal/mol are obtained respectively for (1) the polymorph I to II transition of mefenamic acid, (2) the polymorph I to II transition of tolfenamic acid, and (3) the polymorph III to I transition of flufenamic acid.

Spectrophotometry, Infrared↗

PubMed2004

Chromosomal inversion polymorphisms and adaptation.

Chromosomal inversion polymorphisms continue to be identified from an increasing number of populations of insects, plants, bacteria and humans. In the fruit fly Drosophila, chromosomal polymorphisms were used in classic studies of natural selection. Recent molecular genetic studies suggest that inversion polymorphisms are dynamical systems. These studies also indicate patterns of disequilibrium and variation that are consistent with co-adapted gene complexes. Although these complexes have yet to be identified, recent studies have identified traits, such as body size, that are linked to inversion polymorphisms. Selection acting on these polymorphisms is strong because latitudinal clines in inversion frequency become re-established rapidly after a new continent is colonized. A combined molecular and phenotypic approach is helping to identify the role of inversion polymorphisms in adaptive divergence, but the genes responsible for associations between traits and inversion polymorphisms remain to be identified.

Journal Article↗

PubMed2000

Solid-state study of polymorphic drugs: carbamazepine.

Polymorphs of a compound have solid crystalline phases with different internal crystal lattices; in pharmaceuticals, differences due to polymorphism and pseudopolymorphism can affect bioavailability and effective clinical use. The aim of this work was to obtain the different polymorphic modifications of the anticonvulsant drug, carbamazepine, and to characterise them by means of typical structure-sensitive analytical techniques, such as FT-IR spectroscopy, XRPD and DSC. Further investigations were also performed by Hot Stage FT-IR thermomicroscopy, which permitted the visible and spectroscopic characterisation of the polymorphic forms during heating. Our results confirm the existence of three different polymorphic forms for anhydrous carbamazepine: Form III, the commercial one, Form I, obtained by heating Form III and Form II, crystallised from ethanolic solution. Substantial differences were detected among the polymorphs with regard to solid-state properties. Moreover, Hot Stage FT-IR thermomicroscopy proved its analytical potential to characterise the drug's polymorphism.

Anticonvulsants↗

PubMed2002

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry.

This paper details the development of a method using parallel-beam X-ray powder diffractometry as a novel means of determining polymorphic composition in intact compacts. Two polymorphic systems, chlorpropamide and glycine, were selected. The polymorphic components were weighed, mixed, and compressed using a Carver press with 3/8-in. concave tooling. The compacts were then analyzed using parallel-beam X-ray powder diffractometry in transmission geometry. The data were processed using the profile-fitting module in the Shimadzu XRD-6000 software V 4.1 (for NT 4.0/98). The integrated intensity ratio of a selected peak for each crystal form was used for quantitation of each polymorph. Excellent linear correlation was observed for both polymorphic systems. The convex shape of the compact surface had no effect on the XRD patterns. Since parallel-beam X-ray diffractometry is not sensitive to the shape of the sample surface, it provides a simple method for quantifying polymorphs in intact compacts. Further work to extend this to formulated tablets is ongoing. The relatively larger variation in one of the peaks in the chlorpropamide study was found to be consistent with the computational analysis of the slip behavior of the stable polymorph. This method provides the first reported non-invasive X-ray diffraction pattern quantitation of crystal forms in intact compacts.

Chemistry, Pharmaceutical↗

PubMed1997

Polymorphous low-grade adenocarcinoma: glial fibrillary acidic protein staining in the differential diagnosis with cellular mixed tumors.

Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland carcinoma arising primarily within the oral cavity. Most of these tumors are readily diagnosed; occasionally, however, they may be confused histologically with cellular mixed tumors. The difficulty stems from the bland cytologic nature of cellular mixed tumors and their organizational diversity, together with the irregular pushing growth at their interface with adjacent soft tissues, on histologic examination. Because of this diagnostic problem, we evaluated the use of glial fibrillary acidic protein localization in the differential diagnosis of polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma) and twelve cellular mixed tumors were selected and stained for glial fibrillary acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin system and examined independently by each investigator. In addition, five tumors with limited material (three cellular mixed tumors and two polymorphous low-grade adenocarcinoma) from the consultation service of one author were evaluated using the same techniques. Two polymorphous low-grade adenocarcinoma stained positive in very focal areas and only in the epithelial component; staining did not occur in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed glial fibrillary acidic protein. Only one tumor did not express glial fibrillary acidic protein. In mixed tumors with only focal staining, the most helpful differential diagnostic feature was positive staining of the mesenchyme-like cells adjacent to epithelial nests. We did not find this latter staining pattern in any of the polymorphous low-grade adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Aurophilic interactions in cationic gold complexes with two isocyanide ligands. Polymorphic yellow and colorless forms of [(cyclohexyl isocyanide)2AuI](PF6) with distinct luminescence.

Crystallographic studies of yellow and colorless forms of [(C(6)H(11)NC)(2)Au(I)](PF(6)) show that they are polymorphs with differing, but close, contacts between the gold atoms which form extended chains. In the colorless polymorph the gold cations form linear chains with a short Au...Au contact (3.1822(3) A) indicative of an aurophilic attraction. The structure of the yellow polymorph is more complicated with four independent cations forming kinked, slightly helical chains with very short Au...Au contacts of 2.9803(6), 2.9790(6), 2.9651(6), and 2.9643(6) A. However, in the related compound, [(CH(3)NC)(2)Au(I)](PF(6)), each cation is surrounded by six hexafluorophosphate ions and there is no close Au...Au contact despite the fact that the isocyanide ligand has less steric bulk. The crystalline colorless and yellow polymorphs are both luminescent at 298 K, lambda(max): 424 nm (colorless) or 480 nm (yellow). Colorless solutions of the two polymorphs have identical absorption spectra and are nonluminescent at room temperature. Freezing solutions of [(C(6)H(11)NC)(2)Au(I)](PF(6)) produces intense luminescence which varies depending upon the solvent involved. Each polymorph melts to give a colorless but luminescent liquid which reverts to the yellow polymorph upon cooling.

Journal Article↗

PubMed2005

Experimental and computational growth morphology of two polymorphs of a yellow isoxazolone dye.

We report on the crystal structures and the experimentally found and the computationally predicted growth morphologies of two polymorphs of a yellow isoxazolone dye. The stable polymorph I has a blocklike habit, and the metastable polymorph II grows as fine needles, nucleating only by heterogeneous or contact nucleation. The habits of both polymorphs depend on the supersaturation during growth. The experimental observations are compared with predictions of the attachment energy model and kinetic Monte Carlo lattice simulations in which the growth is modeled as an "atomistic process", governed by surface energetics. These Monte Carlo simulations correctly predict the shape and the dependence on supersaturation of the crystal morphology for both polymorphs: for polymorph I, a strong dependence on supersaturation is found from the simulations. For polymorph II, the order of morphological importance is reproduced correctly, as well as the needlelike morphology.

Journal Article↗