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Biomedical subjects

K Ahmed

Publications and source records attributed to K Ahmed.

At least 55 records · Page 3Linked to original sources

The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells.

We investigated the effects of two mucoregulating drugs, S-carboxymethylcysteine (S-CMC) and N-acetylcysteine (NAC), on the attachment of Moraxella catarrhalis (M. catarrhalis) to pharyngeal epithelial cells. The attachment of M. catarrhalis decreased (33-57%) significantly (P<0.01) in a dose-dependent manner in cells treated with mucoregulating drugs as compared to the control. There was a significant (P<0.01) decrease (35-45%) in the attachment of M. catarrhalis to pharyngeal cells after oral administration of S-CMC. By electron microscopic observation, it was found that there was a fine, granular, electron-dense, ruthenium red-positive layer on the surface of pharyngeal epithelial cells; this layer was absent on cell surfaces treated with mucoregulating drugs. Possibly, this layer contained the portion of M. catarrhalis receptor which is responsible for the attachment of this bacteria to pharyngeal epithelial cells. From the above results, it may be concluded that one of the mechanisms of mucoregulating drugs to decrease the episode of respiratory infections in patients with chronic respiratory diseases is by inhibiting the attachment of bacteria to the upper respiratory tract.

Acetylcysteine↗

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997.

Three hundred sixty-two Streptococcus pneumoniae strains were isolated from children under 5 years of age at Dhaka Shishu (Children) Hospital from 1993 to 1997. The strains were isolated from blood (n = 105), CSF (n = 164), ear swab (n = 61), eye swab (n = 20), and pus (n = 12). Of the 362 isolates, 42 (11.6%) showed intermediate resistance (MIC, <0.1 microgram/ml) and only 4 (1.1%) showed complete resistance (MIC, >2.0 microgram/ml) to penicillin. Penicillin resistance exhibited a strong relationship with serotype 14; 47.8% of the penicillin-resistant strains belonged to this type. A remarkably high (64.1%) resistance to co-trimoxazole was observed, along with a significant increase during the time period studied; there was no relationship to capsular type. By way of contrast, penicillin resistance did not show any significant change during the study period. Resistance to chloramphenicol (2.2%) and erythromycin (1.1%) was rare. The high resistance to co-trimoxazole and its increasing trend demand elucidation of the clinical impact of pneumonia treatment by this antimicrobial and reconsideration of the World Health Organization recommendation for co-trimoxazole administration to children with community-acquired pneumonia at the health care worker level in Bangladesh.

Bangladesh↗

Nuclear matrix and protein kinase CK2 signaling.

The dynamic functional nature of the nuclear matrix dictates that it provide a locus for molecules involved in nuclear transduction of signals, such as those participating in cell growth control. Protein kinases are key elements in a variety of signaling mechanisms and certain of these enzymes have been shown to associate with the NM. Among these, the protein ser/thr kinase CK2 has attracted considerable attention because of its involvement in cell growth. NM appears to be a preferential locus for CK2, as evidenced from its rapid modulation in the NM in response to hormonal and growth factor signals. Differential regulation of CK2 is also noted in the transcriptionally active and inactive nucleosomes. A number of potential substrates for CK2 are localized to the NM. Likewise, distinct substrates for CK2 are noted in the transcriptionally active compared with inactive nucleosomes. The dynamics of phosphorylation of these substrates and that of the association of CK2 activity to these fractions suggests that CK2 may play a role in the functional activities of NM and provide a link between the NM and nucleosomes by serving as a factor in promoting the transition of inactive to active nucleosome.

Animals↗

Day-to-day variability of fasting plasma glucose in newly diagnosed type 2 diabetic subjects.

OBJECTIVE: To determine the day-to-day intraindividual variability of fasting plasma glucose (FPG) in newly diagnosed Caucasian type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 193 newly diagnosed, previously untreated, Caucasian type 2 diabetic subjects (135 men, 58 women) had FPG measured on two consecutive days (FPG1, FPG2). Ethical approval and subjects' full informed consent were obtained. Subjects fasted for 12 h before each study day and rested for at least 30 min before blood was taken. Plasma glucose was analyzed by a glucose oxidase method with intra- and interassay coefficients of variation (CVs) < 2%. Variability of FPG was assessed by comparison of percentage differences (PDs): PD = 100 (FPG2 - FPG1)/FPG1, with averaged FPG (FPGaver = [FPG1 + FPG2]/2). Biological and analytical variability were determined by use of SD2total = SD2biological + SD2analytical, where SD2analytical approximately equal to 2 x (CVglucose measurement)2. Given normally distributed data with zero mean, 95% of daily percentage differences will be expected to fall within a range of +/- 2 SDtotal. RESULTS: Subjects were age 54 +/- 10 years (mean +/- SD) and had BMI of 29.3 +/- 5.3 kg/m2. FPG values for both days were 12.2 +/- 3.4 mmol/l (FPG1) and 12.1 +/- 3.3 mmol/l (FPG2), with a mean paired difference (95% CI) of 0.1 (0.0 to 0.3) mmol/l. The variance of these differences increased with increasing FPGaver. The PDs did not exhibit this effect and were normally distributed (mean -0.6% [-1.7 to 0.4]; SD 7.4% [6.8 to 8.3]), giving a 95% variability (2 SD) of 14.8%. Biological variability (2 SDbiological) was 13.7%. No significant difference in PD was found between men and women (mean difference 1.3% [-1.0 to 3.6]; SDmale 7.4%, SDfemale 7.3%; P = 0.62). CONCLUSIONS: A total of 95% of the FPG values for this group of newly diagnosed type 2 diabetic subjects varied within approximately +/- 15% on a daily basis, with approximately 14% caused by biological variability. As these results are expressed in percentage terms, subjects in the group with higher FPG values are likely to experience larger changes in FPG values measured from day to day. This variability should be considered when using FPG for the diagnosis and/or monitoring of response to treatment in patients with type 2 diabetes.

Adult↗

Attachment of Burkholderia pseudomallei to pharyngeal epithelial cells: a highly pathogenic bacteria with low attachment ability.

Respiratory infections are initiated by the attachment of bacteria to pharyngeal epithelial cells. We studied the attachment of Burkholderia pseudomallei to pharyngeal epithelial cells. After one, two, three, and four washes, there were 22.6+/-8.9, 15.7+/-7.0, 6.8+/-3.1, and 4.6+/-1.1 (mean+/-SD) attached bacteria/cell, respectively. If the bacterial concentration was maintained at 1 X 10(8) colony-forming units (cfu)/ml and three washes were done, at concentrations of 2.5 x 10(4), 5 X 10(4), and 1 x 10(5) cells/ml there were 9.9+/-3.6, 3.3+/-0.8, and 2.5+/-1.1 attached bacteria/cell, respectively. If the cell concentration was kept at 2.5 x 10(4) cells/ml and three washes were done, at bacterial concentrations of 1 x 10(5), 1 X 10(6), 1 X 10(7), 1 x 10(8), and 1 x 10(9) cfu/ml, there were 0.3+/-0.3, 0.6+/-0.6, 1.0+/-0.2, 5.1+/-2.3, and 9.6+/-1.9 attached bacteria/cell, respectively. There were 4.8+/-1.9, 5.5+/-2.5, 5.6+/-1.9, and 6.4+/-2.6 attached bacteria/cell at 0, 30, 120, and 240 min of incubation, respectively. Pharyngeal cells from 10 persons (seven men and three women, mean+/-SD age = 30.7+/-8.1 years, 12 experiments with a single isolate) showed that there were 7.8+/-4.3 attached bacteria/cell. It was found that the efficiency of attachment of this bacteria was very low (7.0+/-3.3 bacteria/cell). Electron microscopy revealed that there were no fimbriae but a thin capsular polysaccharide layer on the surface of B. pseudomallei. Attachment to pharyngeal epithelial cells appeared to be mediated by this structure.

Adult↗

Increased serum levels of interferon-gamma and interleukin-12 during human brucellosis.

Brucellosis is a zoonotic disease that often becomes chronic with a high rate of recurrence. To understand the cytokines induced during this infection we determined the levels of interleukin (IL)-1beta, IL-2, IL-4, IL-8, IL-12, tumor necrosis factor-of (TNF-alpha) and interferon-gamma (IFN-gamma) in serum of patients with brucellosis and compared with those without brucellosis and controls. Control sera were taken from healthy persons residing in an area that was not endemic for brucellosis. The levels of IL-1, IL-2, IL-4, and TNF-alpha were not detectable in all the sera from patients. There was no difference in the level of IL-8 in patients with brucellosis and those without this disease. However, IL-8 was significantly higher in these two groups of patients compared with the controls. Significantly higher levels of IL-12 and IFN-alpha were found in the serum of patients with brucellosis compared with patients without brucellosis and controls. These data indicate that there is induction of Thl type cytokines during human brucellosis.

Adolescent↗

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Melioidosis is the term given to any infection caused by Burkholderia pseudomallei. This bacteria is one of the important causative agents of life-threatening pulmonary infections in the tropical and subtropical areas. The initiation of respiratory infections is attachment of this bacteria to pharyngeal cells. The precise mechanism of attachment of B. pseudomallei is not known. In this study, we found that asialoganglioside GM1 at concentrations of 25, 12.5, and 5 microg/ml significantly decreased the attachment of B. pseudomallei strain Sp-186 in a dose-dependent manner. On the other hand, asialoganglioside GM2 decreased the attachment of B. pseudomallei, but only at a concentration of 25 microg/ml. At a concentration of 1 mg/ml, glucose, N-acetyl-galactosamine, and galactose caused a significant decrease in attachment. However, at concentrations of 250 microg/ml, no decrease in attachment was observed in B. pseudomallei treated with these carbohydrates. Mannose and fucose at concentrations of 1 mg/ml had no effects on the inhibition of attachment of B. pseudomallei. Four other isolates of B. pseudomallei showed a significant decrease in attachment after treatment with asialoganglioside GM1. We conclude that asialogangliosides GM1 and GM2 are part of the receptor complex for B. pseudomallei on human pharyngeal epithelial cells.

Bacterial Adhesion↗

Role of protein kinase CK2 in phosphorylation nucleosomal proteins in relation to transcriptional activity.

Protein kinase CK2 undergoes rapid translocation to nuclear matrix and nucleosomes on androgenic stimulation of growth in prostatic epithelial cells. Further, CK2 appears to be regulated differentially in the transcriptionally active and inactive nucleosomes. We have investigated the role of CK2 in phosphorylation of nucleosome-associated proteins in the transcriptionally active and inactive nucleosomes that were isolated from ventral prostate subjected to different androgenic status in vivo. Proteins associated with these nucleosomes were phosphorylated via the intrinsic protein kinase activity, using [gamma-32P]ATP in the absence and presence of GTP. Several proteins appear to be potential substrates for CK2 associated with the nucleosomes. Among them are proteins that are differentially associated with the transcriptionally active and inactive nucleosomes. Phosphorylation of several of these proteins is modulated depending not only on their sites of association (i.e., active vs. inactive nucleosomes) but also on the state of transcriptional activity. Differential phosphorylation of specific proteins by CK2 associated with the active and inactive nucleosomes may be pertinent to the process of transcription regulation.

Animals↗

Dynamics of protein kinase CK2 association with nucleosomes in relation to transcriptional activity.

Protein kinase CK2 has been implicated in control of cell growth and proliferation. Since growth stimuli evoke its preferential association with chromatin and nuclear matrix, we examined the dynamics of CK2 in nucleosomes fractionated on the basis of their transcriptional activity in the rat prostate. In this model, androgens induce expression of androgen-dependent genes but inhibit the androgen-repressed genes, whereas absence of androgens has the reverse effect. The level of CK2 was higher in the active than in inactive nucleosomes from normal prostate. Differential alterations in the levels of CK2 activity in the transcriptionally active versus inactive nucleosomes were evoked by androgen deprivation or administration. Comparison of the distribution of CK2 in active and inactive nucleosomes under varying androgenic conditions showed that the relative CK2 activity intrinsic to the transcriptionally active nucleosomes remained fairly stable, concordant with gene activity specific to the androgenic status. However, CK2 associated with inactive nucleosomes declined to a minimal level on androgen deprivation but increased rapidly on androgen administration (reflecting expression of multiple androgen-dependent genes). We suggest a role for CK2 in promoting the conformational transition of inactive nucleosomes to the active form and in the function of transcriptionally active nucleosomes.

Androgens↗

Mechanism of protein kinase CK2 association with nuclear matrix: role of disulfide bond formation.

Nuclear matrix (NM) appears to be an intranuclear locale for significant and dynamic association of the ubiquitous multifunctional messenger-independent serine/threonine protein kinase CK2 that has been implicated in growth control [Tawfic et al. (1996): J Cell Biochem 61:165-171]. We have examined the nature of the association of CK2 with the NM. Nuclei prepared in the presence of a sulfhydryl-blocking reagent such as iodoacetamide demonstrate a reduction in the amount of CK2 associated with the NM to less than 5% of the control. On the other hand, when nuclei are treated with the sulfhydryl crosslinking reagent sodium tetrathionate, NM-associated CK2 increases severalfold. Treatment of nuclei with sodium tetrathionate followed by 2-mercaptoethanol blocks this increase. Nuclei isolated from rat liver and prostate behaved similarly, suggesting an identical mode of association of CK2 with the NM regardless of the organ. These results indicate a role of sulfhydryl interactions such that NM anchoring of CK2 occurs via its beta subunit, which contains several vicinal cysteine residues. Further, various sulfhydryl-blocking reagents inhibited CK2 activity in a concentration-dependent manner, and the inhibitory effect was reversed by agents such as dithiothreitol, implying that cysteine residues in the CK2 play a role in its catalytic activity.

Animals↗

Isolation of pathogenic bacteria from induced sputum from hospitalized children with pneumonia in Bangladesh.

A prospective study was carried out on 157 patients admitted to a paediatric hospital in Dhaka, Bangladesh to determine the bacteria present in the induced sputum of paediatric patients with X-ray proven pneumonia. Their ages ranged from 21 days to 11 years; 65 per cent of them were male and 35 per cent were female. The most affected age group was between 6 months and 2 years old. Respiratory secretions produced by induced cough were taken by swab from the oropharynx for culture and smear. The predominant bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis and Gram-negative bacilli. Serotyping of H. influenzae revealed that 76 per cent were non-typable and 18 per cent were of type b; 23.5 per cent of isolates of H. influenzae were beta-lactamase producing. MIC90 of penicillin against S. pneumoniae and H. influenzae were 0.025 and 3.13 micrograms/ml respectively. Ampicillin, penicillin G (benzylpenicillin), amoxycillin, and gentamicin were administered for the treatment of these patients. All cases were apparently improved, on the basis of clinical evaluation, and discharged from the hospital.

Age Distribution↗

Attachment of nontypable Haemophilus influenzae to human pharyngeal epithelial cells mediated by a ganglioside receptor.

Nontypable Haemophilus influenzae (NTHI) is one of the major pathogens of human respiratory infections and has the ability to attach to pharyngeal epithelial cells. We characterized the epithelial cell receptor to which NTHI bind. Neuraminidase pretreatment of pharyngeal epithelial cells resulted in a significant decrease in NTHI attachment, suggesting sialic acid as an important component of the receptor. The attachment was not decreased in NTHI pretreated with 1,000 microg/ml of fucose, N-acetyl-neuraminic acid, N-acetyl-glucosamine, N-acetyl-galactosamine, acetyl-salicylic acid and colominic acid. Only treatment with gangliosides D1a, D1b and D2 at a concentration of 12.5 microg/ml significantly decreased the attachment. On the other hand, treatment with gangliosides M1, M2, M3, D3, T1b and asialoganglioside M1 did not decrease the attachment of NTHI. Only ganglioside D2 inhibited the attachment significantly at a concentration of 12.5 ng/ml. Other isolates of NTHI showed a decrease in attachment after treatment with ganglioside D2. Treatment of cells with anti-human GD2 monoclonal antibody also decreased the attachment of NTHI in a dose-dependent manner. This study indicates that sialic acid glycoconjugate, GD2, is one of the receptors of NTHI on human pharyngeal epithelial cells.

Antibodies, Monoclonal↗

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent.

UNLABELLED: Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice. METHODS: We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated. RESULTS: The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively. CONCLUSION: FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.

Amino Acids↗

Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma.

PURPOSE: A number of peptidases which can metabolize certain bioactive peptides and growth factors have been identified in seminal plasma. Our goal in this study was to determine molecular properties and the tissue source(s) for one of these peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma. MATERIALS AND METHODS: We measured the activities of DPP IV with the dipeptide glycylprolyl-p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of men who were vasectomized or with different sperm concentrations, and in prostatic and seminal vesicle secretions of men undergoing prostatic surgery. RESULTS: DPP IV in seminal plasma of vasectomized men was a membrane associated dimer comprised of subunits of approximately 110 kDa. Its activity did not differ in seminal plasmas of vasectomized, azoospermic, oligozoospermic and normozoospermic men indicating no correlation with the concentration of sperm originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity were present in prostatic secretion, but absent from that of the seminal vesicles. These data indicate that the prostate gland is the primary source of DPP IV activity in seminal plasma. There was little variation in its activities in repeat seminal plasma samples from the same individual, and there was no change in its activity with age to 50 years. CONCLUSIONS: DPP IV in seminal plasma was derived from the prostate gland and it may be useful as a bioindicator of prostate function and/or disease with age in men.

Dipeptidyl Peptidase 4↗

Association of protein kinase CK2 with nuclear matrix: influence of method of preparation of nuclear matrix.

Nuclear matrix (NM) plays a role of fundamental structural and functional significance as the site of replication, transcription, and RNA processing and transport, acting as an anchor or attachment site for a variety of enzymes and other proteins involved in these activities. We have previously documented that protein kinase CK2 translocates from the cytosol to the nucleus, where it associates preferentially with chromatin and NM, in response to certain growth stimuli. Considering that characteristics of the isolated NM can depend on the procedural employed for its isolation, we compared three standard methods for NM preparation to confirm the association of intrinsic CK2 with this structure. Our data suggest that the method used for isolating the NM can qualitatively influence the measurable NM-associated CK2. However, all three methods employed yielded qualitatively similar results with respect to the stimulus-mediated modulation of NM-associated CK2, thus further supporting the notion that NM is an important site for physiologically relevant functions of CK2. In addition, core filaments and cytoskeleton that were isolated by two of the preparative methods had a small but significant level of associated CK2 activity.

Animals↗

Nuclear matrix proteins as malignant markers in squamous cell carcinoma of the head and neck.

OBJECTIVE: To test the hypothesis that transformation of normal upper aerodigestive mucosa to squamous cell carcinoma of the head and neck (SCCHN) is associated with specific changes in nuclear matrix (NM) proteins. DESIGN: Retrospective, nonrandomized investigation using a cellular fractionation sequence followed by 2-dimensional gel electrophoresis analysis of NM proteins. SUBJECTS: Nuclear matrix proteins were extracted from a cohort of 12 pathologic SCCHN specimens and 5 normal specimens of oropharyngeal mucosa. RESULTS: All SCCHN specimens examined expressed 11 NM proteins that were not detected in normal mucosa. Conversely, at least 4 NM proteins that were expressed by all specimens of normal mucosa were absent from all SCCHN tumors. Seven NM proteins were common to carcinomas and normal specimens. Spindle cell histological variants of squamous cell carcinoma had distinct NM patterns. CONCLUSIONS: Malignant transformation of normal upper aerodigestive mucosa to SCCHN is associated with specific changes in NM composition. These data suggest that different NM proteins might serve as specific tumor markers.

Antigens, Nuclear↗

The increasing burden of disease in Bangladeshi children due to Haemophilus influenzae type b meningitis.

A laboratory-based study of diagnosed bacterial meningitis in the national paediatric hospital identified 852 cases of meningitis in the 8-year period 1987-1994. There were 587 culture-positive cases, of which Haemophilus influenzae (47%) and Streptococcus pneumoniae (32%) accounted for 80%. H. influenzae showed a remarkable increase of 700% during the study period. Most of the H. influenzae cases (90%) occurred in the 1st 2 years of life. Analysis of culture-negative specimens by antigen detection in the last 2 years also revealed the predominance of H. influenzae (71.4%) and S. pneumoniae (22.4%). Typing of H. influenzae isolates during this time showed that 98% of the strains were type b. This retrospective hospital-based study indicated a pronounced increase in the incidence of H. influenzae meningitis and strongly supports the need for large-scale Hib vaccination for young children. However, such nationwide intervention will probably need to be based on a prospective on a prospective and population-based surveillance of H. influenzae infections.

Age Distribution↗

Moraxella (Branhamella) catarrhalis adherence to human bronchial and oropharyngeal cells: the role of adherence in lower respiratory tract infections.

To study the role of Moraxella (subgenus Branhamella) catarrhalis (B. catarrhalis) adherence to airway cells in lower respiratory tract infections, the in vitro attachments of B. catarrhalis to upper airway (oropharyngeal) and lower airway (bronchial) epithelial cells were compared. The adherence of 4 strains (1 nonfimbriated and 3 fimbriated) of B. catarrhalis to respiratory tract epithelial cells collected from 11 patients with chronic pulmonary disease (CPD) and 11 healthy individuals was evaluated. Both the fimbriated and nonfimbriated strains showed increased attachment to oropharyngeal cells in the CPD patients (mean +/- SEM; 25.0 +/- 3.2/cell; P < 0.01) when compared to the control subjects (12.1 +/- 1.1/cell). On the average, the attachment to bronchial cells was 6.1 to 13.6 times greater per surface area (bacteria/micron2) than the attachment to oropharyngeal cells. The fimbriated strains tended to adhere in higher numbers to bronchial cells (19.0 +/- 1.8/cell) than the nonfimbriated strain (8.7 +/- 1.2/cell), although there was no difference between the CPD and control groups. In conclusion, the attachment of B. catarrhalis to oropharyngeal cells may be an enhancing factor for colonization in the upper respiratory tract in patients with CPD, and elevated adherence of the bacteria to bronchial cells may suggest pathogenic importance when mucociliary function is impaired.

Adult↗