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K Ahmed

Publications and source records attributed to K Ahmed.

At least 91 records · Page 5Linked to original sources
PubMed1995

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.

Adult↗
PubMed1995

Androgenic regulation of protein kinase CK1 in the prostatic cell.

We examined the androgenic regulation of protein kinase CK1 in rat ventral prostate cytosolic and chromatin fractions. On androgen deprivation, CK1 in both the nuclear and cytoplasmic compartments decreases slowly at a similar rate. Stimulation of regrowth in the prostate does not evoke an early differential modulation in the CK1 because it increased in both the cytosol and chromatin only by 24 h after androgenic stimulus. These changes in CK1 relate to its proposed role in cell regulation at mitosis and differ from those in protein kinase CK2 that demonstrates rapid modulations in the nuclear compartment under similar conditions.

Amino Acid Sequence↗
PubMed1994

Growth stimulus-mediated differential translocation of casein kinase 2 to the nuclear matrix. Evidence based on androgen action in the prostate.

Recently, we documented that a significant amount of nuclear casein kinase 2 (CK2) (a ubiquitous multipotential messenger-independent serine/threonine protein kinase) is associated with the nuclear matrix (NM), where it may be involved in the phosphorylation of several intrinsic proteins (Tawfic, S., and Ahmed, K. (1994) J. Biol. Chem. 269, 7489-7493). Both CK2 and NM have been implicated in cell growth and proliferation. To examine whether CK2 in the NM was regulated in relation to a growth stimulus, we employed androgen action in the prostate as a model of growth control. In rats, androgen deprivation leads to a differential loss of CK2 activity and protein from the NM fraction in the prostate. At 24 h after androgen deprivation, the NM-associated CK2 activity as well as immunoreactive protein decline by about 80%. By comparison, total nuclear CK2 activity decreased by only 37%. Androgen administration to the castrated rats evokes a rapid differential increase in CK2 activity in the NM, so that within 1 h following the androgenic stimulus, the CK2 activity increases by 110% in the NM fraction versus 45% in the total nuclei. We propose that the stimulus-mediated differential translocation of CK2 to NM may play a role in the transduction of growth signal.

Androgens↗
PubMed1994

Association of casein kinase 2 with nuclear matrix. Possible role in nuclear matrix protein phosphorylation.

The nuclear matrix is thought to play a fundamental role in the nuclear structure and functions relating to cell proliferation and regulation of gene activity. Phosphorylation of nuclear matrix proteins has been observed, and multiple protein kinases may be involved in this process. Casein kinase 2 is a ubiquitous messenger-independent serine/threonine protein kinase that has been implicated in cellular growth and proliferation. The presence of immunoreactive casein kinase 2 in purified nuclear matrix preparations was demonstrated in rat liver and prostate tissues by employing specific antibodies. The enzyme was active toward the specific decapeptide substrate Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu and exhibited other properties characteristic of casein kinase 2. Phosphorylation of nuclear matrix proteins catalyzed by intrinsic protein kinase activity in intact nuclei was also observed, and the results suggested that this reaction was at least in part catalyzed by casein kinase 2. The profile of nuclear matrix proteins labeled with 32Pi in situ in intact liver cells was similar to that observed in nuclear matrix proteins isolated from nuclei labeled with [gamma-32P]ATP in vitro. Association of casein kinase 2 with the nuclear matrix may be of significance in the post-translational modification of certain proteins in this fraction.

Amino Acid Sequence↗
PubMed1994

Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and cancerous prostate.

In previous work, we had observed that chromatin-associated nonhistone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples [Rayan et al: Cancer Res 45:2277-2282, 1985]. The properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). By employing the specific synthetic substrate for casein kinase 2 (CK-2) for assays in cellular fractions, we have shown that this protein kinase is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. However, sections from prostatic carcinoma samples appeared to show differential staining, depending on the Gleason's grade of the sample. The samples with higher Gleason's grade showed less intense immunostain in the nucleus, compared with samples of lower Gleason's grade. Further, regions of sections in samples with higher Gleason's grade did not show any immunostaining. These differences in the characteristics of CK-2 expression in prostatic carcinoma samples may be potentially significant, but need to be evaluated further for their significance to the pathobiology of prostatic neoplasia.

Amino Acid Sequence↗
PubMed1994

Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate.

Nucleolin is an abundant nucleolar phosphoprotein which has been implicated as a factor in various stages of ribosome synthesis, including transcription. Since androgens exert a profound effect on the rRNA synthesis in the target organ prostate, we have examined the nature of androgenic regulation of the amount and phosphorylation of nucleolin in this tissue. Phosphorylation of prostatic nucleolin is catalyzed in part by heparin-sensitive casein kinase 2 (CK-2) and by another (heparin-insensitive) protein kinase. Both the amount and phosphorylation of prostatic nucleolin are profoundly sensitive to androgens. Rapid reduction in the level and phosphorylation of nucleolin occurs following androgen deprivation, which corresponds to the ensuing cessation of prostatic growth leading to involution. Further, the loss of nucleolin phosphorylation and its degradation appear to be concordant. Administration of a single injection of 5 alpha-dihydrotestosterone to castrated animals causes an early increase in the amount and phosphorylation of nucleolin, starting in the prereplicative phase in the prostatic cell nucleus. These data suggest that early androgenic regulation of nucleolin expression and phosphorylation may play a role in nucleolar control mechanisms relevant to prostatic cell growth.

Androgens↗
PubMed1994

The role of ultrasound in the management of peritonsillar abscess.

A distinction between a peritonsillar abscess and peritonsillitis is useful clinically, as the former requires surgical drainage while the latter merely requires treatment with antibiotics. To evaluate the diagnostic implications of performing ultrasonography of the tonsils in patients with clinically diagnosed peritonsillar abscess, 27 patients underwent ultrasound examination before needle aspiration of the abscess was performed. Ultrasound was able to detect peritonsillar abscess in 91 per cent of the cases (sensitivity rate), with a false negative rate of nine per cent and a false positive rate of 20 per cent. The specificity of the test was 80 per cent, and was able to differentiate abscess from peritonsillitis in 88.9 per cent. On the basis of these results we conclude that ultrasonography of the tonsils in patients thought to have peritonsillar abscess is a useful adjunct, enhancing diagnostic accuracy and reducing unnecessary surgical drainage.

Adult↗
PubMed1994

Expression of fimbriae and host response in Branhamella catarrhalis respiratory infections.

Sputum during the acute exacerbation of chronic respiratory diseases were observed under the electron microscope, to determine the in vivo expression of surface structures of Branhamella catarrhalis (B. catarrhalis), the polymorphonuclear neutrophil (PMN) response to B. catarrhalis infections, and the composition of sputum. It was found that during infection fimbriae are expressed in B. catarrhalis. However, there were sparsely to densely fimbriated bacteria in each sputum sample. The length of the fimbriae were from 50 to 76 nm. In the sparsely fimbriated B. catarrhalis, external to the cell wall, a thin, granular, electron-dense layer was observed. Due to the presence of fimbriae, this layer was not seen in densely fimbriated B. catarrhalis. Blebs were also found in B. catarrhalis. PMNs were found to phagocytose both B. catarrhalis and debris. Evidence was found that debris were formed mainly by the destruction of PMNs. Bacteria as well as debris were phagocytosed by PMNs.

Adult↗
PubMed1994

Significance of the casein kinase system in cell growth and proliferation with emphasis on studies of the androgenic regulation of the prostate.

Protein phosphorylation is a significant mechanism in many cellular functions, including genomic regulation and control of cell proliferation. Thus, investigations of protein kinases (PKs) in appropriate experimental models are of intense current interest. Employing androgenic regulation of the rat ventral prostate (RVP) as an experimental model, we have investigated certain nuclear PK reactions with the aim of defining their role in androgen-mediated genomic regulation in the prostate and their implications for human prostate pathobiology. The author's laboratory identified androgen-sensitive PKs in the prostatic cell nucleus that might be involved in regulation of the gland. These PKs are analogous to casein kinase 1 (CK-1) and casein kinase 2 (CK-2), which are important multipotential enzymes in growth regulation and cell proliferation. Because CK-2 demonstrated a greater androgen sensitivity, we investigated the mechanism of its regulation at the level of transcription in the RVP, finding that androgens exert a substantial tissue-specific effect on its expression. However, regulation of CK-2 gene transcription does not appear to be an early event in androgen action, an observation that did not accord with our previous documentation of an early androgenic modulation of nuclear CKs in the prostate. Studies to uncover alternative mechanisms of regulation of CK-2 yielded a potentially important observation that androgenic regulation involves changes in the association of the enzyme with subnuclear compartments as an early event in its growth control function. Additionally, chromatin preparations from human benign prostatic hyperplasia (BPH) demonstrate a large enhancement in intrinsic CK-2 activity compared with normal tissue. An increase also is observed in specimens of prostatic carcinoma, although the change is less substantial than that in BPH. There appears to be a correlation between the localization of CK-2 in sections of prostatic carcinoma and the Gleason grade, a measure of the degree of differentiation. Further investigations of the cellular as well as the molecular mechanisms of CK-2 regulation in the prostate as an experimental model of the response to influences on growth may yield new insight into the function of this PK.

Androgens↗
PubMed1994

Mechanism of intracellular regulation of protein kinase CK2: role of stimulus-mediated subnuclear association.

In our studies of protein kinase CK2, or casein kinase 2, we have focused on its regulation in relation to altered genomic activity in response to androgen action (through the function of the androgen receptor) in the male accessory sex gland, the prostate. We have documented that androgens exert a profound effect on CK2 in the prostate. Investigation of androgenic regulation of the molecular expression of prostatic CK2 suggested that CK2 gene transcription, although substantial in the prereplicative phase of cell proliferation, is not an early event in androgen action. The lack of rapid transcriptional regulation of CK2 by androgens suggested an alternative mechanism for our original observations on the early regulation of CK2-mediated reactions. A rigorous analysis of the CK2 in different compartments of the prostatic cell has suggested its differential regulation. For example, androgen withdrawal results in a rapid loss of CK2 protein and activity in the prostatic cell nucleus, whereas the activity and protein in the cytosol undergoes a slow decline over several days. A single dose of 5 alpha-dihydrotestosterone (5 alpha-DHT) given to 6-d castrated animals results in an increase in nuclear enzymatic activity as well as immunoreactive CK2 protein within 1 h, while a concomitant decrease is apparent in the cytosolic fraction. Within the nucleus, there appears to be a differential androgenic regulation of CK2 such that the enzyme associated with chromatin and nuclear matrix (NM) demonstrates a substantially greater androgen sensitivity than the enzyme in the nucleoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome.

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative. Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV. The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered. Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related "stealth" virus that is able to establish a clinically persistent human infection.

Adult↗
PubMed1993

Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate.

Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcellular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5 alpha-dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate.

Amino Acid Sequence↗
PubMed1993

Neutrophil response to Pseudomonas aeruginosa in respiratory infection.

Sputum from patients with acute exacerbation of respiratory infection by Pseudomonas aeruginosa was observed under the electron microscope. External to the cell wall of P. aeruginosa a granular, electron-dense material was observed which is suggestive of capsule. It is supposed that stabilization of capsule occurred by the host antibody, which was produced due to chronic infection by P. aeruginosa. Mucoid type of microcolonies were observed with a fibrous matrix of exopolysaccharide. Other types of microcolonies were surrounded by granular substances or fine fibers. Neutrophil was found to be partially surrounding the microcolony in an attempt to defense. Debris was formed mainly by the destruction of the neutrophil. Most neutrophils were found full of phagocytosed debris; in contrast only a few neutrophils were found to have phagocytosed P. aeruginosa. This study concludes that instead of phagocytosing bacteria, neutrophil phagocytosed debris and bacteria were not completely eradicated. Therefore, this might be one of the factors in the pathogenesis of respiratory infection and persistent colonization by P. aeruginosa.

Aged↗
PubMed1993

Neutrophil response to nontypable Haemophilus influenzae in respiratory infections.

Sputa from patients with respiratory infections by nontypable Haemophilus influenzae (H. influenzae) were investigated by electron microscopy. The cell wall of H. influenzae appeared wavy and nonwavy. In the cell wall the peptidoglycan layer was ill-defined. These patients had adequate IgG response in the serum against H. influenzae. However neither capsule nor fimbriae were found. Different stages of phagocytosis and destruction of the bacteria by polymorphonuclear neutrophils (PMN) were observed. PMNs were also found to phagocytose the debris. Evidences were found that the debris is formed mainly by the destruction of polymorphonuclear neutrophil. Extracellular lysosomes were also observed, which may have a role in destruction of both bacteria and host tissue. It was concluded that nontypable H. influenzae are nonfimbriated and noncapsulated during infection. Debris are the end product of PMN destruction, and phagocytosis of debris by PMNs has a role in the pathogenesis of chronic respiratory diseases.

Adult↗
PubMed1993

Day-case adenoidectomy--is it safe?

A controlled prospective study was performed on 429 consecutive children undergoing adenoidectomy, of which 263 were day-cases. Adenoidectomy was done alone, or in combination with other minor procedures. There was only one reactionary haemorrhage in each group, and these were early and easily recognized by the recovery staff. No other significant complication was seen. Adenoidectomy in children as a day-case procedure is safe and cost-effective.

Adenoidectomy↗