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Biomedical subjects

K Cao

Publications and source records attributed to K Cao.

At least 19 recordsLinked to original sources

[Intestinal microbiota alterations after digestive tract reconstruction surgery and their impacts on host physiology].

The gut microbiota, acknowledged as the human body's 'second genome', plays a pivotal role in maintaining health. Digestive tract reconstruction surgery profoundly alters the anatomical structure and physiological environment of the gastrointestinal tract, thereby inducing significant shifts in the intestinal microbiota. These microbial changes subsequently influence host physiological functions through metabolic, immune, neuroendocrine, and other pathways. For instance, Roux-en-Y gastric bypass surgery enriches short-chain fatty acid(SCFA)-producing Bacteroides, improving systemic insulin sensitivity. Conversely, pancreaticoduodenectomy leads to a marked enrichment of potential pathobionts such as Klebsiella and Clostridium, which may elevate the risk of infections and tumor recurrence. This review comprehensively summarizes the characteristic changes in the gut microbiota following various digestive tract reconstruction procedures and discusses their multifaceted impacts on host physiology, aiming to provide insights for future experimental research and clinical practice.

Humans↗

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population.

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.

Black or African American↗

Strategies for evaluating B*18 allelic diversity by sequence-based typing applied to studies of a population from Singapore and African-Americans.

Strategies to resolve B*18 alleles which carry a deletion in intron 1 close to the 5' end of exon 2 relative to other HLA-B alleles or a null allele mutation in exon 1 and to resolve ambiguities among allele combinations including B*18 are described. B*18 allele frequencies from volunteer donors recruited for two hematopoietic stem cell registries show the presence of two alleles, B*180101 and B*1802, in a population from Singapore and only B*180101 in African-Americans.

Black or African American↗

Twenty-three novel HLA-B alleles identified during intermediate-resolution testing.

Twenty-three novel human leukocyte antigen-B alleles are described: B*070204, *0738, *0742, *0821, *130202, *1312, *1575, *1598, *1599, *270507, *2728, *350104, *3558, *3811, *3931, *3932, *4045, *4107, *420501, *4812, *510106, *5520, and *5616. Thirteen of the variants are single-nucleotide substitutions from their most homologous allele, eight resulting in amino acid changes (B*0742, *1312, *1598, *1599, *3558, *3931, *4107, and *5616) and five with silent substitutions (B*070204, *130202, *270507, *350104, and *510106). Three alleles (B*0738, *4812, and *5520) differ by five nucleotide changes, altering four amino acids. The remaining seven alleles differ from their most similar alleles by two to three nucleotides, altering from one to two amino acids.

Alleles↗

Searching for HLA-DRB1*1206 in volunteer marrow donors in four US population groups.

The frequencies of DRB1*12 alleles were determined in four US population groups by DNA sequencing. Only DRB1*120101 (or DRB1*1206 or *1210) and DRB1*120201 alleles were identified, the latter primarily in the Asian American population. Additional testing of a subset of samples to detect the presence of DRB1*1206 found all of the alleles to be DRB1*120101 (or DRB1*1210). Retesting of six samples previously typed as DRB1*1206 found only DRB1*120101 (or DRB1*1210).

Black or African American↗

Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.

The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia. Distributions of genotypes at all loci and in all populations fit Hardy-Weinberg equilibrium expectations. There was not a single allele predominant at any of the loci in these populations, with the exception of A*3002 [allele frequency (AF) = 0.233] in Zambians and Cw*1601 (AF = 0.283) in Malians. This distribution was consistent with balancing selection for all class I loci in all populations, which was evidenced by the homozygosity F statistic that was less than that expected under neutrality. Only in the A locus in Zambians and the C locus in Malians, the AF distribution was very close to neutrality expectations. There were six instances in which there were significant deviations of allele distributions from neutrality in the direction of balancing selection. All allelic lineages from each of the class I loci were found in all the African populations. Several alleles of these loci have intermediate frequencies (AF = 0.020-0.150) and seem to appear only in the African populations. Most of these alleles are widely distributed in the African continent and their origin may predate the separation of linguistic groups. In contrast to native American and other populations, the African populations do not seem to show extensive allelic diversification within lineages, with the exception of the groups of alleles A*02, A*30, B*57, and B*58. The alleles of human leukocyte antigen (HLA)-B are in strong linkage disequilibrium (LD) with alleles of the C locus, and the sets of B/C haplotypes are found in several populations. The associations between A alleles with C-blocks are weaker, and only a few A/B/C haplotypes (A*0201-B*4501-Cw*1601; A*2301-B*1503-Cw*0202; A*7401-B* 1503-Cw*0202; A*2902-B*4201-Cw*1701; A*3001-B*4201-Cw*1701; and A*3601-B*5301-Cw*0401) are found in multiple populations with intermediate frequencies [haplotype frequency (HF) = 0.010-0.100]. The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci. Comparison of the genetic distances measured by the distribution of alleles at the HLA class I loci in the sub-Saharan populations included in this and other studies indicate that the Luo population from western Kenya has the closest distance with virtually all sub-Saharan population so far studied for HLA-A, a finding consistent with the putative origin of modern humans in East Africa. In all African populations, the genetic distances between each other are greater than those observed between European populations. The remarkable current allelic and haplotypic diversity in the HLA system as well as their variable distribution in different sub-Saharan populations is probably the result of evolutionary forces and environments that have acted on each individual population or in their ancestors. In this regard, the genetic diversity of the HLA system in African populations poses practical challenges for the design of T-cell vaccines and for the transplantation medical community to find HLA-matched unrelated donors for patients in need of an allogeneic transplant.

Africa South of the Sahara↗

Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression.

The immunologic and virologic factors that impact on the rate of disease progression after acute infection with human immunodeficiency virus (HIV) type 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was studied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Although altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL responses. In addition to a rapid decline in CD3+CD4+ cells, elevated percentages of CD8+CD45RA+ and CD8+CD57+ cells and diminished CD8+CD45R0+ and CD8+CD28+ cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. Cloned viral envelopes were found to have unusually broad patterns of coreceptor usage for cell-cell fusion, although infectivity studies yielded no evidence of infection via these alternative receptors. The infectivity studies demonstrated that these isolates and their envelopes maintained an R5 phenotype throughout the course of disease. The absence of demonstrable anti-HIV CTL reactivities, coupled with a protracted course of seroconversion, highlights the importance of robust HIV-specific immune responses in the control of disease progression.

Acute Disease↗

Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies.

Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environmental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions including 1q21, 3q21, 4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of these overlap with loci implicated in other autoimmune/inflammatory diseases. Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucleotide arrays comprising approximately 12 000 known genes to initiate a more comprehensive analysis of the transcriptional changes that occur in involved and uninvolved skin of 15 psoriatic patients versus six normal controls. Expression levels of the transcripts detected on the arrays were first used to determine the relationship of samples to each other using hierarchical clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were differentially expressed in involved psoriatic skin versus normal skin. These differences were independent of the gender, age, skin site and HLA class I status of the patient. Ten of the 177 genes were also differentially expressed in uninvolved skin, and several mapped to regions previously shown to harbor psoriasis susceptibility loci.

Autoimmune Diseases↗

HLA diversity, differentiation, and haplotype evolution in Mesoamerican Natives.

Genetic variation of the Human Leukocyte Antigen region (HLA) in three Amerindian populations from the Southern Mexican state of Oaxaca, the Zapotec, Mixtec and the Mixe is examined. Individuals were typed using PCR-SSOP for four class II loci (DRB1, DQA1, DQB1, DPB1) and three class I loci (HLA-A, -B, and -C). Based on known HLA distributions, European admixture ranged from 1% to 10%. Individuals with European alleles were excluded from subsequent analysis. New alleles were revealed at each of the class I loci. In general, genotype frequencies were in Hardy-Weinberg equilibrium, although some deviations were detected. Allele frequency distributions at the DRB1, DQA1, DQB1 and HLA-A loci in all populations were more even than expected under neutrality, supporting a model of balancing selection at these loci. A history of directional selection for DPB1 in all three populations was indicated, as homozygosity values were significantly above expected values. Allele frequency distributions at HLA-B and HLA-C did not differ significantly from neutrality expectations. The data also provide evidence from linkage disequilibrium that strong haplotypic associations are present across the entire HLA region in each of the populations. Significant overall linkage disequilibrium exists between all pairs of loci typed in these populations, except those which include the DPB1 locus. These associations exist despite the fact that the recombination fraction between HLA-A, in the class I region, and DQB1, in the class II region, may exceed 0.02. One explanation is that selective pressures are maintaining the relationships between particular alleles at these loci in these populations. These relationships are maintained in general across the entire HLA region in the Oaxacan Amerindians, with the exception of DPB1.

Alleles↗

Sequence-based typing of HLA class I alleles in Alaskan Yupik Eskimo.

In comparison to South America, native North Americans tend to be less diverse in their repertoire of HLA class I alleles. Based upon this observation, we hypothesized that the Yupik Eskimo would exhibit a limited number of previously identified class I HLA alleles. To test this hypothesis, sequence-based typing was performed at the HLA-A, -B and -C loci for 99 Central Yupik individuals from southwestern Alaska. Two new class I alleles, A*2423 and Cw*0806, were identified. While A*2423 was observed in only one sample, Cw*0806 was present in 26 of the 99 individuals and all of the Cw*0806 samples contained B*4801. Allele Cw*0806 differs from Cw*0803 by a single nucleotide substitution such that Cw*0803 may be the progenitor of Cw*0806. Allele Cw*0803 was originally characterized as unique to South America, but detection of Cw*0803 in the Yupik indicates that Cw*0803 was a founding allele of the Americas. The presence of new alleles and previously unrecognized founding alleles in the Yupik population show that natives of North America are more diverse than previously envisioned.

Alaska↗

Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations.

The HLA system is the most polymorphic of all human genetic systems. The frequency of HLA class I alleles and their linkage disequilibrium patterns differ significantly among human populations as shown in studies using serologic methods. Many DNA-defined alleles with identical serotypes may have variable frequencies in different populations. We typed HLA-A, B, and C loci at the allele level by PCR-based methods in 1,296 unrelated subjects from five major outbred groups living in the U.S.A (African, AFAM; Caucasians, CAU; Asian, ORI; Hispanic, HIS, and North American Natives, NAI). We detected 46, 100 and 32 HLA-A, B, and C alleles, respectively. ORI and HIS presented more alleles at each of these loci. There was lack of correlation between the levels of heterozygosity and the number of alleles detected in each population. In AFAM, heterozygosity (>90%) is maximized at all class I loci. HLA-A had the lowest heterozygosity in all populations but CAU. Tight LD was observed between HLA-B and C alleles. AFAM had weaker or nonexistent associations between alleles of HLA-A and B than other populations. Analysis of the genetic distances between these and other populations showed a close relationship between specific US populations and a population from their original continents. ORI exhibited the largest genetic distance with all the other U.S. groups and were closer to NAI. Evidence of admixture with CAU was observed for AFAM and HIS. HIS also had significant frequencies of AFAM and Mexican Indian alleles. Differences in both LD and heterozygosity levels suggest distinct evolutionary histories of the HLA loci in the geographical regions from where the U.S. populations originated.

Alleles↗

Transcatheter closure of secundum atrial septal defect with a new self-expanding nitinol double disk device (Amplatzer device): experience in Nanjing.

PURPOSE: Various devices have been developed for the transcatheter closure of secundum atrial septal defect (ASD II) to avoid the morbidity, discomfort, and thoracotomy scar associated with surgical closure. The purpose of this study was to evaluate the safety and efficacy of the Amplatzer septal occluder for transcatheter closure of ASD II. PATIENTS AND METHODS: Only patients who were clinically diagnosed with ASD II were selected. The anatomy of ASD had to meet certain echocardiographic criteria. Under the guidance of echocardiography and fluoroscopy, the implantation of the device was accomplished as recommended by the manufacturer. RESULTS: Thirty patients (median age 18.4 years) with an ASD II underwent transcatheter closure. Procedure time ranged from 30-200 minutes and fluoroscopy time from 10-50 minutes. The diameter of the ASD measured by echocardiography ranged from 13-25 mm, while both the stretched diameters of the ASDs and the sizes of the devices ranged from 18-34 mm. The successful placement rate was 100%. The residual shunt rate was 100% immediately after device implantation and 10% after 24 hours. After 3 months, 3.3% of the patients had a (trivial) residual shunt. The device did not affect the surrounding structures of ASD. No embolization of the device occurred. CONCLUSION: The Amplatzer device designed for the closure of ASD II can be implanted easily and also is retrievable. Due to a low ratio of residual shunt and few complications, this device is a good choice for transcatheter closure of ASD II. Long-term follow-up will be required for widespread clinical use.

Adolescent↗

On-line sample preparation for high throughput reversed-phase LC/MS analysis of combinatorial chemistry libraries.

An on-line sample preparation method utilizing a time-programmed autosampler is described for high throughput liquid chromatography/mass spectrometry (LC/MS). This approach is particularly helpful for the LC/MS analysis of samples which require solvents incompatible with HPLC in the sample preparation process. The on-line sample preparation approach minimizes a bottleneck in throughput and improves sample recovery under some circumstances.

Chromatography, High Pressure Liquid↗

Apolipoprotein E polymorphism in the early onset of coronary heart disease.

OBJECTIVE: To assess the relationship between apolipoprotein E (apoE) polymorphism and the early onset of coronary heart disease (CHD) and the effect of apoE on lipids and lipoproteins in healthy Chinese subjects. METHODS: Sixty-eight patients with CHD younger than 55 years (CHD1), 136 patients with CHD older than 65 years (CHD2), and 136 healthy subjects were enrolled, and their plasma levels of triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were determined. The apoE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: apoE 3/4 genotype and E4 allele frequency in the CHD1 group were higher than those in the CHD2 group and healthy subjects, while no differences were found between CHD2 and healthy subjects. Meanwhile, the plasma levels of TC and low density lipoprotein cholesterol (LDL-C) were higher in the CHD2 group than in both CHD1 group and healthy subjects. Each apoE isoprotein has variable TC and LDL-C levels that is E2 (E2/2 + E2/3) < E3(E3/3) < E4(E4/4 + E3/4). CONCLUSION: apoE is one of the genetic factors that affect TC and LDL-C levels, and apoE 4 has a very close relation to CHD, suggesting that apoE 4 is an independent genetic factor of the early onset of CHD.

Adult↗

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. RESULTS: All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). CONCLUSION: Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.

Adolescent↗

Treatment of aplastic anemia by the kidney-tonifying and mediating method.

In this series of 65 cases of aplastic anemia, 26 cases were treated by the kidney-tonifying and mediating method, 19 cases by western drugs, and the remaining 20 cases only by tonifying the kidney as controls. The results showed that the kidney-tonifying and mediating method was significantly superior in the total effective rate to the method of western drugs and that of tonifying the kidney alone (P < 0.01), and it was also superior in the improvement of symptoms, myelogram, and peripheral blood count to the other two methods.

Adolescent↗

[The intraoperative application of neural response telemetry with the nucleus CI24M cochlear implant].

OBJECTIVE: To test device integrity and objective auditory reaction for cochlear implant patients intraoperatively. METHODS: Our protocol for intraoperative testing of the implant device includes device electrode impedance test and neural response telemetry (NRT), which measures the electrically evoked auditory nerve compound action potentials (ECAP). RESULTS: We completed electrode integrity tests and NRT intraoperatively on 40 patients with the Nucleus CI24M cochlear implant. We have measured normal implant function on all 40 patients and obtained ECAP results from 39 patients. Out of 33 patients with normal inner ear, typical ECAPs were recorded in 195 electrodes in all 198 testing electrodes(98.5%). In 7 patients with inner ear Mondini dysphasia, affirmative ECAP waveforms were recorded in 26 electrodes in all 42 testing electrodes. The basal electrode ECAP threshold was higher than that of the epical one. CONCLUSIONS: The intraoperative measurements of device function and NRT are quite simple, quick and with high accuracy. Inner ear malformation is an important factor that may affect NRT results.

Action Potentials↗