Search PubMed⌕ Search

Biomedical subjects

W N Khan

Publications and source records attributed to W N Khan.

At least 37 records · Page 2Linked to original sources
PubMed1992

The pregnancy-specific glycoprotein family of the immunoglobulin superfamily: identification of new members and estimation of family size.

The members of the carcinoembryonic antigen (CEA)/pregnancy-specific glycoprotein (PSG) gene family have a characteristic N-terminal domain that is homologous to the immunoglobulin variable region. We have estimated the size of the PSG subfamily by identification of N-domain exons from isolated genomic clones and from total genomic DNA through PCR amplification and DNA sequence determination. The PSG subfamily contains at least 11 different genes. For 7 of these, two DNA sequences differing from each other in 1 to 4 nucleotides were detected. Most likely, they represent different alleles. They are PSG1, PSG2, PSG3, PSG4, PSG5, PSG6, PSG7, PSG8, PSG11, PSG12, and PSG13. Six of the N-domain sequences described here are new. All of the PSGs except PSG1, PSG4, and PSG8 contained the arginine-glycine-aspartic acid sequence at position 93-95 corresponding to the complementarity determining region 3 of immunoglobulin. Parsimony analysis of 24 CEA and PSG sequences using 12 members of the immunoglobulin gene superfamily as outgroups to root the family tree shows that the N-domain of the CEA group genes evolved in one major branch and the PSG group genes in the other.

Amino Acid Sequence↗
PubMed1992

Identification of three new genes and estimation of the size of the carcinoembryonic antigen family.

Using carcinoembryonic antigen (CEA) subgroup-specific degenerate PCR primers, we have identified three new CEA gene family member L/N exons (CGM9, CGM10, and CGM11) and all previously reported L/N exons of the CEA subgroup (CEA, BGP, NCA, CGM1, CGM2, CGM6, CGM7, and CGM8). This suggests that the CEA subgroup contains 11 genes. CGM9, CGM10, and CGM11 seem to be pseudogenes. A deletion of an asparagine in CGM9 results in loss of a glycosylation site, which is conserved throughout the CEA gene family. We have previously suggested the number of genes in the pregnancy-specific glycoprotein (PSG) subgroup to be 11, which together with this study indicates that the CEA gene family contains 22 genes in all. Parsimony analysis of the CEA subgroup interrelationships suggests that CGM7 occupies the most primitive position within the CEA subgroup, being a sister group to the rest. CEA, BGP, NCA, and CGM1 form a fairly well-supported group within the CEA subgroup.

Amino Acid Sequence↗
PubMed1992

Circulating endotoxin and tumor necrosis factor during pediatric cardiac surgery.

OBJECTIVES: To study the hypothesis that endotoxin and tumor necrosis factor-alpha (TNF) are released into the circulation during the perioperative period in children undergoing open-heart surgery, and to assess the possible role of these factors in postoperative morbidity. DESIGN: Prospective study. SETTING: Operating room and ICU of a children's hospital. PATIENTS: Twenty-four consecutive patients undergoing open-heart surgery for repair of congenital heart disease. METHODS: Endotoxin and TNF concentrations were measured in blood samples withdrawn from patients at predetermined time points in the perioperative period. These concentrations were also measured in samples from all fluids and drugs administered to patients. Clinical variables were measured throughout the perioperative period, and the Pediatric Risk of Mortality score was calculated daily. RESULTS: All of the preoperative control samples were negative for endotoxin and TNF. Endotoxin or TNF was detected in the blood of 21 (88%) of 24 patients during or after surgery. Endotoxin (ranging in concentrations from 0.32 to 438 pg/mL) was detected in the blood of 16 (67%) of the 24 patients. The majority of the samples positive for endotoxin were withdrawn during cardiopulmonary bypass and were associated with positive samples from the pump, from cardiotomy suction specimens, and from autotransfused blood. Blood cultures of all patients, except one, were negative for bacterial growth. TNF (ranging in concentrations from 3 to 132 U/mL) was detected in the blood of nine (37%) of the 24 patients. Patients positive for TNF had significantly (p less than .05) lower mean central venous pressures at 20 hrs after surgery and higher mean heart rates postoperatively compared with patients negative for TNF. No differences in other indicators of perioperative morbidity and intraoperative conditions were found, when the groups positive for endotoxin or TNF were compared with the groups negative for endotoxin or TNF, respectively. CONCLUSIONS: Endotoxin and TNF are released into the circulation during and after pediatric open-heart surgery. TNF release may be related to some of the hemodynamic changes observed after open-heart surgery.

Child↗
PubMed1991

Biosynthesis of carcinoembryonic antigen (CEA) gene family members expressed in human tumor cell lines: evidence for cleavage of the glycosyl phosphatidyl inositol (GPI) anchor by GPI-PLC and GPI-PLD.

Three Carcinoembryonic Antigen (CEA) gene family members: CEA, Non-specific cross-reactive antigen 50/90 (NCA) and biliary glycoprotein (BGP) were expressed in the colon carcinoma cell lines LS174T and HT29. The CEA, NCA50/90 and four alternatively spliced BGP transcripts (BGP a-d) were identified. The molecular weights of the mature glycoproteins were: CEA, 180kD; NCA50/90, 70-100 kD; BGP, 85, 120 and 140 kD. Pulse chase experiments demonstrated that CEA first appears as a 165 kD high mannose precursor which is trimmed to a 160 kD intermediate and finally transformed into the mature 180 kD glycoprotein. The precursor form of NCA had a molecular weight of 50 kD. CEA and NCA50/90, but not BGP, were linked to the cell membrane via glycosyl phosphatidyl inositol and could be released from the intact tumor cells by glycosyl phosphatidyl inositol-specific phospholipase C. CEA on isolated membranes and in cell lysates, but not on intact cells, was also cleaved by fresh human serum or purified glycosyl phosphatidyl inositol-specific phospholipase D.

Antigens, CD↗
PubMed1990

Carcinoembryonic antigen gene family members in submandibular salivary gland: demonstration of pregnancy-specific glycoproteins by cDNA cloning.

We have recently shown that human submandibular salivary gland and saliva contain a number of glycoproteins belonging to the carcinoembryonic antigen (CEA) gene family. The members of the CEA family can be divided into the CEA subgroup and the pregnancy specific beta 1 glycoprotein (PSG) subgroup. The latter glycoproteins are abundant in placenta and fetal liver. Here we report that PSG's are expressed in normal adult submandibular salivary gland. Thus, cDNA cloning and sequencing gave two clones (SG5 and SG9) which coded for glycoproteins with a domain arrangement of N-A1-A2-B2-C and a third clone (SG8) which coded for a glycoprotein with a domain arrangement of N-A1-B2-C. SG5 is identical to PSG3, and SG9 to PSG1d, while SG8 most probably corresponds to PSG2. The 3' untranslated regions of the different members of the PSG subgroup contain highly homologous segments, suggesting a common evolutionary origin.

Base Sequence↗
PubMed1990

Identification of a new carcinoembryonic antigen (CEA) family member in human fetal liver--cloning and sequence determination of pregnancy-specific glycoprotein 7.

The carcinoembryonic antigen gene family consists of the CEA- and the Pregnancy-Specific Glycoprotein- (PSG) subfamilies. Human fetal liver express several PSGs. Here we report cloning and sequencing of a new PSG subfamily member, PSG7. It is the fifth type of PSG found in fetal liver. PSG7 has the N-A1-A2-B2-C domain arrangement. Unlike other PSGs the N-terminal of PSG7 is unblocked. PSG7 has a cysteine in the C-terminal domain, which may allow dimerization. Variability analysis according to Wu and Kabat reveals that the region in the N-domain corresponding to complementarity determining region 3 of immunoglobulin is different between PSG subfamily members. Many members, including PSG7, contain the RGD sequence in this region. The CD2 region as well as two other short sequences (in N and A1 domains respectively) also show some variability. The function of PSGs is probably linked to the N-domain and the CDR2- and CD3-like regions are most likely responsible for ligand binding.

Amino Acid Sequence↗
PubMed1990

Treatment of Pseudomonas meningitis with ceftazidime with or without concurrent therapy.

In ongoing studies in Europe and the United States, 10 pediatric patients with bacterial meningitis caused by Pseudomonas species were treated with ceftazidime. Pseudomonas aeruginosa was isolated from the CSF of 7 patients and other Pseudomonas species from the remaining 3. Eight of the 10 patients had received previous antimicrobial treatment which included aminoglycosides in 6, along with ticarcillin and ureidopenicillins in 3. Ceftazidime was administered 10 to 42 days in dosages ranging from 109 to 300 mg/kg/day. Seven of the 10 patients received ceftazidime only for 10 to 42 days. The other 3 patients received amikacin in 2 and gentamicin and tobramycin in the other. Seven patients were cured clinically and 3 died; 9 were cured bacteriologically and one who was presumed cured on the basis of clinical response subsequently died. Sterilization of the cerebrospinal fluid occurred at 48 hours to 12 days. Ceftazidime appears useful in treating bacterial meningitis caused by Pseudomonas species.

Adolescent↗
PubMed1989

Carcinoembryonic antigen gene family: molecular cloning of cDNA for a PS beta G/FL-NCA glycoprotein with a novel domain arrangement.

Human fetal liver contains a family of carcinoembryonic antigen related glycoproteins called the pregnancy specific beta 1 glycoprotein/fetal liver non specific cross-reactive antigen (PS beta G/FL-NCA) glycoprotein family. The sequence for the major FL-NCA species has been reported [Khan et al., Proc. Natl. Acad. Sci. USA 1989, 86 in press]. Two additional CEA-related fetal liver glycoproteins FL-NCA-2 and 3 were cloned, sequenced and expressed. FL-NCA-3 is a new gene family member. It has a unique domain arrangement (N-A2-B2-T) and contains a hydrophobic tail. FL-NCA-3 has a molecular weight of approximately 54 kD and is released from the transfected cells. Like three other members of the family, FL-NCA-3 contains the Arg-Gly-Asp sequence in a position in the N-domain corresponding to complementarity determining region 3 of immunoglobulin. FL-NCA-2 is identical in structure to PS beta G-D previously found in placenta. The PS beta G/FL-NCA glycoprotein family may be involved in processes related to cell adhesion and cell differentiation.

Amino Acid Sequence↗
PubMed1989

Molecular cloning and expression of cDNA for a carcinoembryonic antigen-related fetal liver glycoprotein.

Carcinoembryonic antigen (CEA) is considered to be an embryonic antigen that is reexpressed in carcinomas. However, at the molecular level little is known about fetal forms of CEA. We have studied fetal liver, which was originally considered to contain CEA. A first-trimester cDNA library from fetal liver was screened with CEA-specific probes, and a dominant cDNA clone was identified and sequenced. This 1.7-kilobase cDNA codes for a complete protein of 426 amino acids, of which 34 constitute a leader peptide. Structurally, it can be divided into four immunoglobulin-like domains homologous to CEA (N-A1-A2-B2) and a hydrophobic tail (12 residues). The A and B domains each contain two cysteines; the N domain has none. The protein has seven potential sites for asparagine-linked glycosylation. It is a form of pregnancy-specific beta 1-glycoprotein (PS beta G) but differs from other PS beta G species at the C terminus. The N and A1 domains show 45% and 51% amino acid sequence identity with the corresponding domains of the three CEA family members whose sequences have been determined. Expression studies showed that the cDNA codes for a 72-kDa glycoprotein that reacts immunologically with antisera to CEA, biliary glycoprotein I, and PS beta G. The 72-kDa glycoprotein was released from the transfected cells. At least six mRNA species were identified in human tissues by using this cDNA as a probe. Genomic DNA analysis with an N-domain-specific probe indicated that the number of genes is relatively small.

Amino Acid Sequence↗
PubMed1989

Aztreonam in the treatment of gram-negative meningitis and other gram-negative infections.

Ninety patients (41 males, 49 females) with a diagnosis of meningitis, urinary tract infection (UTI), gastroenteritis or other miscellaneous gram-negative infections were enrolled. Their ages ranged from 7 days to 10 years, with a mean age of 4 months. 58 (63%) patients had an etiology confirmed by either positive culture (52; 89%) or latex agglutination (6; 10%). 41 of these patients had meningitis diagnosed by positive CSE culture (38) or by positive CSF latex agglutination (3); 27/41 patients also had positive blood cultures. Aztreonam MIC100 for 27 isolates of Haemophilus influenzae, all ampicillin-sensitive, was 0.19 micrograms/ml; 4 Salmonella sp., 1 Neisseria meningitidis and 1 Serratia marcescens isolates were inhibited by 0.19 micrograms/ml, and the MIC100 for 2 Klebsiella pneumoniae, 1 Proteus vulgaris and 2 Pseudomonas aeruginosa isolates were 0.045 and 0.19, 0.022 and 12.5 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aztreonam↗
PubMed1988

Spectinomycin disk zone diameter as a predictor of outcome in clinical treatment of gonorrhea.

The MICs for 41 Neisseria gonorrhoeae strains from patients receiving spectinomycin treatment were determined by the agar dilution method and compared with the zones of inhibition produced by disks containing 100 micrograms of spectinomycin. Our data demonstrated a good correlation between the two methods. Moreover, a zone of inhibition of less than or equal to 15 mm was a good predictor of clinical treatment failures with spectinomycin.

Drug Resistance, Microbial↗
PubMed1987

Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae.

Because of the high prevalence of penicillinase-producing Neisseria gonorrhoeae in the Republic of Korea, spectinomycin has been used there in the primary treatment of gonococcal infections in U.S. military personnel since 1981, but there have been increasingly frequent reports of treatment failures with spectinomycin. We conducted a clinical study to determine the efficacy of spectinomycin treatment in 124 U.S. servicemen in the Republic of Korea who had urethral gonococcal infections. Ninety-seven patients were treated with spectinomycin alone and evaluated in a follow-up visit. In eight patients (8.2 percent), this treatment was unsuccessful. Antibiotic-sensitivity testing on isolates from seven of the patients with treatment failure demonstrated that six isolates were highly resistant to spectinomycin (minimal inhibitory concentration, greater than or equal to 100 micrograms per milliliter). None of the spectinomycin-resistant strains had become resistant to penicillin, either through the production of penicillinase or through a chromosomal mutation. Although the mechanism of spectinomycin resistance appears to be a chromosomal mutation, these isolates were generally sensitive to other antibiotics. The prevalence of resistance to spectinomycin resulted in the substitution of ceftriaxone for the primary treatment of gonorrhea acquired by U.S. military personnel in the Republic of Korea. We believe that the rapid emergence of spectinomycin resistance in this population mandates a cautious approach to widescale use of the drug and indicates a need to broaden current surveillance programs.

Adolescent↗
PubMed1987

Penetration of sulbactam and ampicillin into cerebrospinal fluid of infants and young children with meningitis.

Infusions of 50 mg of sulbactam per kg per day and 400 mg of ampicillin per kg per day in divided doses to infants and children with bacterial meningitis produced levels in cerebrospinal fluid approximately one-third those in serum. Concentrations in cerebrospinal fluid of 5.5 micrograms of sulbactam per ml and 16.0 micrograms of ampicillin per ml declined within a few days of therapy to 1.9 microgram of sulbactam per ml and 5.2 micrograms of ampicillin per ml.

Adolescent↗
PubMed1985

Ceftazidime in the treatment of meningitis in infants and children over one month of age.

Ceftazidime, a new beta-lactamase-resistant cephalosporin, was compared with a combination of ampicillin and chloramphenicol for the treatment of meningitis in 100 infants and children aged one month to 15 years. In this open, randomized trial conducted in the Dominican Republic, 61 patients received 50 mg/kg of ceftazidime intravenously every eight hours; 39 received ampicillin plus chloramphenicol in conventional dosages. Seventy-eight of the patients had discernible isolates in samples from cerebrospinal fluid, six had a positive diagnostic Directogen result, and the remainder either had miscellaneous pathogens evident in samples of cerebrospinal fluid, bacteriologic growth in cultures of blood samples only, or no bacteriologic growth in cultures of either cerebrospinal fluid or blood. Among patients with discernible etiologic agents in samples of cerebrospinal fluid, 11 of 57 (19 percent) ceftazidime-treated patients died, and five of 27 (19 percent) patients treated with the combination died. Mortality by pathogen was as follows for patients who received ceftazidime or ampicillin plus chloramphenicol, respectively: Hemophilus influenzae, two of 27 (7 percent) and one of 15 (6 percent); Streptococcus pneumoniae, six of 12 (50 percent) and two of five (40 percent); Neisseria meningitidis, none of 11 (0 percent) and one of six (17 percent); and Salmonella, neither of two (0 percent) and one of one (100 percent). Overall mortality in the ceftazidime group was 20 percent versus 21 percent in the combination group. No significant toxicities were noted in the patients treated with ceftazidime.

Adolescent↗
PubMed1985

Erythromycin-sulfisoxazole vs amoxicillin in the treatment of acute otitis media in children. A double-blind, multiple-dose comparative study.

A fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl (erythromycin-sulfa) was compared with amoxicillin for the treatment of acute otitis media (AOM) in children. Of 145 patients studied, 76 boys and 69 girls were compliant and were evaluated for drug efficacy (72 amoxicillin, 73 erythromycin-sulfa). Based on otoscopic and tympanometric results, cure rates at ten to 14 days for AOM due to all organisms were 83% (63/72) for amoxicillin and 89% (65/73) for erythromycin-sulfa; for Haemophilus species (including mixed infections), they were 84% for amoxicillin (26/31) and 83% for erythromycin-sulfa (20/14). Cure rates for ampicillin-resistant Haemophilus were 1/1 for amoxicillin and 7/8 (88%) for erythromycin-sulfa; one patient (12%) had persistent AOM at day 10. Of the patients with AOM due to Streptococcus pneumoniae, 82% (29/35) in the amoxicillin-treated group and 98% (39/40) in the erythromycin-sulfa-treated group were cured. Patients with S pneumoniae as the initial infecting organism who were treated with amoxicillin had significantly more clinical recurrences then their erythromycin-sulfa-treated counterparts, 66% (8/12) vs 33% (3/9). There was no difference between treatment groups in recurrence rates for patients with Haemophilus as the initial infecting organism. On the treatment day indicated, the following number of patients had middle ear effusion: by days 10 to 14, 38% (27/72) amoxicillin-treated patients and 48% (35/73) erythromycin-sulfa-treated patients; by day 28, 10% (7/71) amoxicillin-treated patients and 16% (11/70) erythromycin-sulfa-treated patients. There were no significant differences in adverse reactions. The erythromycin-sulfa combination is safe and effective treatment for AOM, including ampicillin-resistant Haemophilus.

Acute Disease↗
PubMed1982

Evaluation of cefaclor in acute otitis media caused by ampicillin-resistant H. influenzae.

Cefaclor was used to treat 13 children with acute otitis media caused by ampicillin-resistant strains of Hemophilus influenzae. The children were re-examined on days 4, 10, and 28. Pharmacologic compliance was assessed by means of a bioinhibition assay on a urine specimen obtained on days 4, 7, and 10. Nine of the 13 children had evidence by tympanogram of residual otitis media with effusion (secretory otitis media). Of these, three were noted to have a bulging, yellow or grey eardrum, which suggested an ongoing acute process. A second middle ear culture was obtained from two of the 3 children, but no pathogens were recovered. Two others had recurrence of otitis shortly after cessation of therapy. Cefaclor is an acceptable antibiotic for the treatment of ampicillin-resistant acute otitis media; but, after cefaclor therapy, some children continued to have a bulging eardrum and sterile pus in the middle ear or had recurrences of otitis soon after cessation of therapy.

Acute Disease↗