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Biomedical subjects

Q Pan

Publications and source records attributed to Q Pan.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treatment of recurrent otitis media after a previous treatment failure. Which antibiotics work best?

BACKGROUND: Recurrent infection after an episode of otitis media is common in pediatric patients. If a patient experienced primary treatment failure in a preceding episode, physicians often feel pressured to prescribe a broad-spectrum, second-line agent for the next episode rather than a first-line drug. The purpose of our study was to determine whether using a second-line drug resulted in fewer treatment failures in a recurrent otitis episode following an episode of apparent resistance. METHODS: The Practice Partner Research Network database, a national research network of practices that use the same electronic medical record, was reviewed to identify all primary episodes of otitis media over a 2-year period (N = 7807). From this, 1416 pediatric patients with presumed treatment failures were identified. The subset of those with a second otitis media episode more than 90 days after the index episode (N = 343) was selected for study. Of this group, 236 (69%) received first-line antibiotics (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) and the remaining 107 received a broader-spectrum, second-line antibiotic. The primary outcome was the need for an additional antibiotic for otitis media within the next 45 days. RESULTS: Patients receiving first- and second-line antibiotics did not differ in sex or age. However, those receiving second-line antibiotics had a shorter duration between episodes (231 vs 280 days, P = .007). Failure rates for first- and second-line antibiotics in recurrent episodes were not significantly different (13% vs 19%, P = .20). Because the duration between episodes could have affected failure rates, we stratified the time between episodes into short, intermediate, and long duration. Second-line antibiotics were not superior to first-line drugs in any stratum. CONCLUSIONS: For a new otitis media episode in a patient with a previous treatment failure, first-line drugs (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) are just as effective as broader-spectrum, more expensive, second-line antibiotics.

Acute Disease↗
PubMed1998

[Molecular cloning and characterization of novel protein kinase gene DYRK3].

OBJECTIVE: To isolate full length cDNA of a novel protein kinase and to deduce the protein kinase's classification position and functions. METHODS: cDNA libraries gDNA library was screened with a partial cDNA clone which is homologous to human protein kinase DYRK2 as probe. FISH mapping was performed. RESULTS: Two full length cDNAs of a novel protein kinase from human muscle cDNA library and human testis cDNA library were isolated. The full length cDNA from muscle has an open reading frame which is predicted to encode a protein of 588 amino acid residues and the cDNA from testis to encode a protein of 568 amino acid residues. CONCLUSION: Because the sequence from the 27th codon to the 3' end of the cDNA from muscle is identical to that from the 7th codon to the 3' end of the cDNA from testis, they should be different transcripts of the same gene. As the gene is highly homologous to human protein kinase DYRK2, the present authors termed the gene DYRK3. DYRK3 is homologous to many serine/threonine protein kinases such as yeast Yak1, human Clk1, human Mnb, drosophila melanogaster Mnb and Cdk2. DYRK3 should belong to the Clk family in CMGC group of serine/threonine protein kinase. DYRK3 has been mapped to chromosome 1q32 by FISH.

Amino Acid Sequence↗
PubMed1998

Characterization of human gamma 4 switch region polymorphisms suggests a meiotic recombinational hot spot within the Ig locus: influence of S region length on IgG4 production.

Human gamma4 gene RFLPs, revealed after BamHI digestion, show IGHG4 alleles of 9.0 (9.2), 9.4, and 9.6 kb at various frequencies in different ethnic populations. Studies in immunodeficient individuals have previously suggested that the 9.4 BamHI allele is associated with a higher serum level of IgG4 than the 9.0 (9.2) BamHI allele, but it is not clear whether this is associated with the S region itself or other control elements. In addition, a duplication of the 9.4-kb gamma4 allele has recently been observed in a high proportion of normal donors. We therefore undertook a study of the structural basis for the difference in Ab levels in the various gamma4 alleles. We demonstrate that the Sgamma4 alleles differ in length due to deletions and insertions of a varying number of 79-bp Sgamma4 repeat units. Two novel RFLPs, 8.8 and 9.1 kb, were also observed. The alleles are likely to be generated by unequal crossing over, and the breakpoints cluster in Sgamma4 repeat units that contain chi-like motifs, implicating chi-like sequences in the meiotic recombination. Our data support the idea that the 9.4-kb BamHI allele is more productive than the 9.0 (9.2)-kb allele in normal healthy donors, possibly due to the extended switch regions, whereas duplication of the gamma4 gene has no effect on switching and IgG4 serum levels.

Base Sequence↗
PubMed1998

Antisense oligonucleotides targeted against protein kinase Cbeta and CbetaII block 1,25-(OH)2D3-induced differentiation.

It is now recognized that protein kinase C (PKC) plays a critical role in 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) promotion of HL-60 cell differentiation. In this study, the effects of phosphorothioate antisense oligonucleotides directed against PKCalpha, PKCbeta, PKCbetaI, and PKCbetaII on HL-60 promyelocyte cell differentiation and proliferation were examined. Cellular differentiation was determined by nonspecific esterase activity, nitro blue tetrazolium reduction, and CD14 surface antigen expression. Differentiation promoted by 1,25-(OH)2D3 (20 nM for 48 h) was inhibited similarly in cells treated with PKCbeta antisense (30 microM) 24 h prior to or at the same time as hormone treatment (86 +/- 9% inhibition; n = 4 versus 82 +/- 8% inhibition; n = 4 (mean +/- S.E.), respectively). In contrast, cells treated with PKCbeta antisense 24 h after 1, 25-(OH)2D3 were unaffected and fully differentiated. PKCalpha antisense did not block 1,25-(OH)2D3 promotion of HL-60 cell differentiation. Next, the ability of PKCbetaI- and PKCbetaII-specific antisense oligonucleotides to block 1,25-(OH)2D3 promotion of cell differentiation was examined. PKCbetaII antisense (30 microM) completely blocked CD14 expression induced by 1, 25-(OH)2D3, whereas PKCbetaI antisense had little effect. Interestingly, PKCbetaII antisense blocked differentiation by 87 +/- 7% (n = 2, mean +/- S.D.) but had no effect on 1,25-(OH)2D3 inhibition of cellular proliferation. These results indicate that the effects of 1,25-(OH)2D3 on HL-60 cell differentiation and proliferation can be dissociated by blocking PKCbetaII expression.

Calcitriol↗
PubMed1998

Identification of Bacteroides fragilisby a modified immuno polymerase chain reaction (mIPCR), using a specific monoclonal antibody.

Bacteroides fragilis is the anaerobic species most commonly isolated from human clinical specimens, and is resistant to many antimicrobial agents. A monoclonal antibody, mAb4H8 (IgG3), reacting with a specific epitope in the lipopolysaccharide (LPS) isolated from most of the B. fragilis strains, was produced and employed with modified Immuno Polymerase Chain Reaction (mIPCR) for identification of B. fragilis with a detection limit of 10(4) cfu/mL bacterial suspension. A number of bacterial strains were examined, including B. fragilis, Bacteroides spp. other than B. fragilis and other genera. All the B. fragilis strains with the immunodominant (beta1,6-linked D-galactosyl chain) epitope were positive. None of the other strains showed the positive reaction. The results indicate that mIPCR assay with mAb4H8 has a high specificity and high sensitivity.

Journal Article↗
PubMed1998

Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.

Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate. More than 50% of the cases of profound early-onset deafness are caused by genetic factors. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss. Mutations in the gene encoding connexin 26 (GJB2) cause both autosomal recessive and dominant forms of hearing impairment. To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene (GJB3) encoding human gap junction protein beta-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.

Adult↗
PubMed1997

Promotion of HL-60 cell differentiation by 1,25-dihydroxyvitamin D3 regulation of protein kinase C levels and activity.

The hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] promotes differentiation of a number of cell types including HL-60 promyelocytic leukemia cells. It is now established that protein kinase Cbeta (PKCbeta) plays a critical role in HL-60 cell maturation to a monocyte/macrophage phenotype. In the present study, we investigated the importance of PKCbeta levels and activation in 1,25-(OH)2D3-mediated differentiation of HL-60 cells. Cell differentiation promoted by 1,25-(OH)2D3 at 48 hr was 39 +/- 3% (mean +/- SEM) nitroblue tetrazolium (NBT) positive and at 72 hr it was 35 +/- 2% NBT positive and 70% CD14 positive. Thus, promotion of cell differentiation by 20 nM 1,25-(OH)2D3 treatment was maximal at 48-72 hr. When PKCbeta levels and cell differentiation were assayed at 72 hr, treatment with 20 nM 1,25-(OH)2D3 for the initial 6 hr increased PKCbeta levels by 175% but had little effect on cell differentiation (7 +/- 2% NBT positive; 11% CD14 positive). The effect of ionomycin, a calcium ionophore, on PKCbeta levels and cell differentiation also was examined. Alone, 5 microM ionomycin promoted few cells (3% CD14 positive) to differentiate. In contrast, cells treated with 5 microM ionomycin for 66 hr after a 6-hr pretreatment with 20 nM 1,25-(OH)2D3 resulted in 34 +/- 5% NBT positive cells and 73% CD14 positive cells. Quantitatively, this induction of differentiation was identical to that observed in cultures continuously treated with 1,25-(OH)2D3 (35 +/- 2% NBT positive; 70% CD14 positive). Therefore, ionomycin seemed to replace the requirement for the continuous presence of 1,25-(OH)2D3. Chelerythrine chloride (3 microM), a specific PKC inhibitor, blocked differentiation promoted by 1,25-(OH)2D3 alone (82 +/- 2% inhibition) or in sequence with ionomycin (86 +/- 3% inhibition). Taken together, our data show that the capacity of 1,25-(OH)2D3 to both increase PKCbeta levels and activate PKC is utilized to promote HL-60 cell differentiation. These data further suggest that 1,25-(OH)2D3 has a genomic action to increase PKCbeta levels and also a nongenomic action requiring its continuous presence to promote HL-60 cell differentiation.

Calcitriol↗
PubMed1997

Allotype-associated variation in the human gamma3 switch region as a basis for differences in IgG3 production.

High and low serum concentrations of IgG3 are associated with the human G3 m(b) and G3 m(g) allotypes, respectively. We previously hypothesized that a low frequency of switching is the most likely defect in (g) allotype-positive individuals, and therefore analyzed the structure, recombination breakpoints, and binding of nuclear proteins to the switch (S)gamma3 regions of these two allotypes. There are no allotype-associated differences in the length and basic structure of the Sgamma3, since both contain eighteen 79-bp repeats. However, we found a number of allotype-associated nucleotide changes. As in the mouse system, there is a preferential switching to the B site, or switch nuclear protein/nuclear factor-kappaB motif, with a clustering of switch breakpoints at the most 5' residue of the B site. The B site sequence used most frequently in switching was found to be mutated at this nucleotide in the (g) allotype-associated Sgamma3. This change was shown by electrophoretic mobility shift assay to alter the binding of the switch nuclear protein/nuclear factor-kappaB protein to the B site. Taken together, these data suggest that polymorphism within Sgamma3 may contribute to allotype-associated differences in IgG3 switching, and that specific sequences within the Sgamma3 79-bp repeats could be mechanistically important for switch recombination.

Animals↗
PubMed1997

Dental disease in the Chinese Yin-Shang period with respect to relationships between citizens and slaves.

Seventy-one skulls from the Yin-Shang period tombs of Anyang, China, were examined for the incidence of observable dental diseases, including dental caries, alveolar bone resorption (an index of periodontal disease), ante-mortem tooth loss and tooth attrition. Because the remains were excavated from tombs with funerary items, the burials are believed to be of Anyang citizens. Our study indicates carious tooth frequency in the Yin-Shang period was rather low (2.9-4.0%). Periodontal disease frequency was 18.3-26.9%, and ante-mortem tooth loss frequency was 2.0-7.5%. To determine the relative prevalence of overall dental health in the Yin-Shang populations, observations from the 42 male crania were compared to those from 183 male crania of slaves from "sacrificial pits" from the Yin-Shang period (Inoue et al. [1992] J. Anthropol. Soc. Nippon 100:1-29). Results from this comparison indicate no apparent difference between social classes in younger age groups. However, in the older ages the rates of the ante-mortem tooth loss, periodontal disease and tooth attrition were significantly higher in the citizen sample. The findings would suggest dietary development in the Yin-Shang period was not dissimilar enough between social classes to induce clear differences in dental diseases at least at younger ages. Conversely, it appears there must have been significant differences between social classes diets in the earlier phase of the Yin-Shang period to produce the differences in dental disease present in the older samples.

Age Factors↗
PubMed1997

Diet and discrepancy between tooth and jaw size in the Yin-Shang period of China.

Tooth to denture base discrepancy (the discrepancy) is the difference between the dental arch length and the sum of crown diameters of teeth in the jaw, a concept which was originally developed in orthodontics. Since the cause-effect relationship between a soft diet and the discrepancy has been demonstrated, the size of the discrepancy should indicate the amount of load on the masticatory system from chewing foods in jaws from archaeological periods. The dietary condition of 71 citizens compared to that of 186 slaves from the Yin-Shang period of China was reconstructed through a study of the discrepancy. The prevalence of the discrepancy in the Yin-Shang period was around 15%, almost the same as it was during the later Jomon to Yayoi (3000-2000 BP) periods, when rice agriculture was introduced into Japan, and also the same as for present-day pastoralists around Lake Turkana, Kenya. Although the frequency of the discrepancy was slightly higher in male citizens, there were no significant differences in the frequencies between male citizens and female citizens or slaves. The differences in diet may not have been fundamental since the Yin-Shang period would be at the very beginning of the age in which differences of diet according social class began to appear, with implications for the load on the masticatory system. At that time agriculture may not been sufficiently intensified in variety or quantity to have produced a differentiation of the diet between social classes.

Adult↗
PubMed1997

Structural analysis of human gamma 3 intervening regions and switch regions: implication for the low frequency of switching in IgG3-deficient patients.

High and low serum concentrations of IgG3 are associated with the human G3m(b) and G3m(g) allotypes, respectively. In the present study, we analyzed the structure of the S gamma 3 and I gamma 3, the switch frequency, switch breakpoints and the levels and initiation sites of I gamma 3 transcripts both in normal blood donors expressing (b) or (g) allotypes as well as IgG3-deficient (D) patients. A low switch frequency to gamma 3 was found in the (g) allotype IgG3D patients which may be caused in part by the allotype-associated mutations in the S gamma 3 region and in part by additional individual mutations observed in the A (SNAP) and B (SNIP/ NF-kappa B) sites in the S gamma 3 repeat region. A higher I gamma 3 germ-line (GL) transcriptional rate was seen in cells from the IgG3D patient, suggesting that low levels of GL I gamma 3 transcripts are not a major contributing factor to the defect. However, individual mutations in the I gamma 3 region and differential splicing of GL I gamma 3 transcripts were found which may affect the switching process.

Base Sequence↗
PubMed1997

Biphasic waveforms for ventricular defibrillation: optimization of total pulse and second phase durations.

Waveform parameters may affect the efficacy of ventricular defibrillation. Certain biphasic pulse waveforms are more effective for ventricular defibrillation than monophasic waveforms, but the optimal biphasic waveform parameters have not been identified. The purpose of this study was to investigate the effects of total pulse duration and the duration of the second (negative) phase on voltage and energy defibrillation requirements using biphasic waveforms. Defibrillation efficacy was evaluated in an isolated rabbit heart model using the Langendorff technique. The biphasic waveform was a truncated exponential with the initial voltage of the second phase equal to 50% of the final voltage of the first phase. An up/down protocol was used to determine the 50% probability-of-success levels (E50) for delivered energy and initial voltage. First, using pulse waveforms with equal positive and negative phase durations, test waveforms with total durations of 4 ms (2 ms positive + 2 ms negative), 6 ms (3 + 3 ms), and 16 ms (8 + 8 ms) were compared to the control waveform of 8 ms (4 + 4 ms) in 30 experiments. Defibrillation voltage requirements with 4 ms (174 +/- 56 V) were higher (P = 0.001) compared to 8 ms (127 +/- 49 V). Defibrillation voltage requirements for the 6-ms and 16-ms waveforms were similar to the 8-ms control waveform. Delivered energies tended to be higher with the 4-ms waveform. A second series of 40 experiments were performed to compare monophasic (4 + 0 ms) and three asymmetric biphasic waveforms (4 + 2 ms, 4 + 8 ms, and 4 + 16 ms) to the symmetric control waveform (4 + 4 ms). The monophasic (2.15 +/- 1.21 J) and the 4 + 16 ms waveform (1.86 +/- 1.09 J) required higher energies (P < or = 0.05) than the control waveform (1.24 +/- 0.41 J and 0.87 +/- 0.7 J, respectively). The monophasic waveform also resulted in greater voltage requirements (223 +/- 64 V) compared to the control waveform (160 +/- 26 V) (P = 0.02). Energy and voltage requirements were similar for the 4 + 2 ms and 4 + 8 ms waveforms compared to the control. Defibrillation requirements with biphasic waveforms were affected by total and second phase duration. For waveforms with equal phase durations, total durations between 6-16 ms resulted in the lowest values for defibrillation. For waveforms with variable second (negative) phase durations, durations ranging from 50%-200% of the first phase did not affect defibrillation efficacy.

Animals↗
PubMed1997

The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure.

Leptin is an adipocyte-derived hormone that interacts with a putative receptor(s) in the hypothalamus to regulate body weight. The relationship of leptin to metabolic abnormalities associated with obesity together with hormonal and substrate regulation of leptin have not been extensively studied. Therefore, 116 subjects (62 men and 54 women) with a wide range of body weight [body mass index (BMI), 17-54 kg/m2] were characterized on a metabolic ward with regard to body composition, glucose intolerance, insulin sensitivity, energy expenditure, substrate utilization, and blood pressure. Eighty-five of the subjects had normal glucose tolerance (50 men and 35 women), and 31 had noninsulin-dependent diabetes mellitus (12 men and 19 women). In both men and women, fasting leptin levels were highly correlated with BMI (r = 0.87 and r = 0.88, respectively) and percent body fat (r = 0.82 and r = 0.88, respectively; all P < 0.0001). However, men exhibited lower leptin levels at any given measure of obesity. Compared with those in men, leptin levels rose 3.4-fold more rapidly as a function of BMI in women [leptin = 1.815 (BMI)-31.103 in women; leptin = 0.534 (BMI)-8.437 in men] and 3.2 times more rapidly as a function of body fat [leptin = 1.293 (% body fat)-24.817 in women; leptin = 0.402 (% body fat)-3.087 in men]. Hyperleptinemia was associated with insulin resistance (r = -0.57; P < 0.0001) and high waist to hip ratio (r = 0.75; P < 0.0001) only in men. On the other hand, during the hyperinsulinemic euglycemic clamp studies, hyperinsulinemia acutely increased leptin concentrations (20%) only in women. There was no correlation noted between fasting leptin levels and either resting energy expenditure or insulin-induced thermogenesis in men or women (P = NS). In stepwise and multiple regression models with leptin as the dependent variable, noninsulin-dependent diabetes mellitus did not enter the equations at a statistically significant level. The data indicate that there are important gender-based differences in the regulation and action of leptin in humans. Serum leptin levels increase with progressive obesity in both men and women. However, for any given measure of obesity, leptin levels are higher in women than in men, consistent with a state of relative leptin resistance. These findings have important implications regarding differences in body composition in men and women. The observation that serum leptin is not related to energy expenditure rates suggests that leptin regulates body fat predominantly by altering eating behavior rather than calorigenesis.

Adipose Tissue↗
PubMed1997

Isolation and characterization of a new chromosome 8q24.1 band-specific microsatellite polymorphism.

A clone, containing a 24-dinucleotide (CA)-repeat sequence, was isolated from chromosome 8q24.1 band-specific pUC19 library. It was localized to target chromosome using human-rodent hybrid cell panel. Eleven alleles were estimated from 56 unrelated individuals and the heterozygosity reaches 0.835. Linkage analysis of 11 Chinese pedigrees showed significant evidence for linkage of this new marker to three dinucleotide repeat markers at 8q23-24.1 region, with the most likely position of the marker between D8S85 and D8S199.

Alleles↗
PubMed1997

[Primary study on Fas-mediated apoptosis in the liver tissue of patients with chronic hepatitis B].

Apoptosis may be the cause of cell death that activate gene due to certain factors. It has been suggested that apoptosis is mediated through Fas antigen. To evaluate the role of the Fas antigen and apoptosis in chronic hepatitis B (CHB), we observed the Fas expression and nuclear DNA fragement in CHB hepatic tissue using immunohistochemistry and TUNEL method respectively. The results showed that the Fas antigen expressing cells located mainly in inflammation infiltrating area but less in non-inflammation infiltrating area; the positive cells were found particularly among infiltrating lymphocytes at the advancing edges of "piecemeal necrosis" near the portal regions. The expression of Fas was detected mainly in the cytoplasm of hepatocytes. 46 samples from 56 CHB patients were Fas positive, the posive rate reached 82%. The Linear Correlation and Regression analysis suggested that there was a direct correlation between nuclear DNA fragement and Fas expression. These findings suggest that the apoptosis mediated through Fas antigen may play an important role in pathogenesis of CHB.

Adolescent↗
PubMed1997

[Isolation of band-specific (CA)n microsatellites from human chromosome 8q24.1].

Fourty eight recombinant plasmids containing CA repeats were isolated from human chromosome 8q24.1 band-specific pUC19 library. Among them, inserted DNA fragments from 12 plasmids were sequenced, and one new highly polymorphic (CA)n microsatellite was obtained (coding: D8S7F). It contained 11 alleles. The estimated heterozygosity reached 0.84 and 0.83 among Chinese Han Nationality people and American Anglo-Saxons respectively. It was assigned to chromosome 8 by using a human-rodent hybrid cell panel.

Base Sequence↗