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Biomedical subjects

K E White

Publications and source records attributed to K E White.

At least 37 records · Page 2Linked to original sources
PubMed1998

A PDZ domain-containing protein with homology to Diphor-1 maps to human chromosome 1q21.

The novel gene, Diphor-1, was recently cloned from rat kidney and shown to increase phosphate uptake in cells when co-expressed with a Na(+)-Pi cotransporter, indicating that it may play a substantial role in cellular phosphate balance. Previously, the phosphate wasting disorder, autosomal dominant hypophosphatemic rickets (ADHR) was mapped to chromosome 12p13 by linkage analysis. In the present work, PDZK1, a PDZ domain-containing protein highly homologous to rat Diphor-1, was shown to be expressed in human kidney. Based upon its sequence similarity to rat Diphor-1, we considered PDZK1 a feasible candidate gene for ADHR. PDZK1 was found to localize to human chromosome 1q21, thereby ruling it out as a candidate for ADHR.

Animals↗
PubMed1998

NCX1 Na/Ca exchanger inhibition by antisense oligonucleotides in mouse distal convoluted tubule cells.

BACKGROUND: Plasma membrane NCX1 Na+/Ca2+ exchangers mediate cellular Ca2+ efflux. Renal distal convoluted tubule (DCT) cells express transcripts encoding three alternatively spliced NCX1 isoforms: NACA2 (exons B, C, D), NACA3 (exons B and D), and NACA6 (exons A, C, D). We used antisense oligodeoxynucleotides (ODNs) to determine the function of these NACA isoforms on Na+/Ca2+ exchanger activity and expression in DCT cells. METHODS: Sense and antisense ODNs targeting exchanger transcripts were introduced into DCT cells permeabilized with streptolysin O. Na+/Ca2+ exchange activity was assessed by measuring Na+-dependent changes of free intracellular Ca2+ concentration (delta[Ca2+]i), in single cells, when the electrochemical gradient for Na+ was reversed. RESULTS: The change of [Ca2+]i in cells treated with antisense ODNs to a downstream or upstream region common to all NCX1 isoforms was 173 nM (-66%) to the downstream region located in the putative ninth transmembrane domain, and 226 nM (-39%) with ODNs to an upstream region located 5' to the variable portion of the intracellular loop. Antisense ODNs to exon B, present in both NACA2 and NACA3, decreased delta[Ca2+]i by 209 nM (-44%), while antisense ODNs specific for NACA6 (exon A) were without effect. Antisense ODNs specific for exon C, present in NACA2 and NACA6, decreased delta[Ca2+]i by 226 nM (-39%). Northern analysis of mRNA prepared from primary cultures of distal tubule cells revealed exon B- but not exon A-containing transcripts. Immunofluorescence analysis using a polyclonal antibody that recognizes NCX1 confirmed that protein expression was inhibited after treatment with the exon B antisense ODNs. CONCLUSION: These findings show that Na+-dependent cellular Ca2+ efflux in DCT cells is primarily mediated by NACA2 and NACA3.

Animals↗
PubMed1998

A statewide survey of immunization rates in Minnesota school age children: implications for targeted assessment and prevention strategies.

BACKGROUND: A retrospective statewide immunization survey of the 69115 Minnesota children who entered kindergarten in 1992 was conducted. METHODS: Information was collected from school immunization records on date of birth, dates of vaccination for each dose of vaccine, address of residence and race/ethnicity (when available). Immunization rates were assessed retrospectively for each month of a child's life from 2 to 48 months of age. Age-appropriate immunization was defined as receipt of all scheduled vaccines within 30 days of the recommended age. RESULTS: Immunization levels varied by vaccine, age of the child and race/ethnicity. For example at 19 months of age, 73% of students had received measles, mumps, rubella vaccine; however, only 39% had received their fourth dose of diphtheria, tetanus and pertussis vaccine. White, non-Hispanic students consistently had higher vaccination rates than children of other racial/ ethnic groups. For example 45% of white, non-Hispanic students were age-appropriately vaccinated at 16 months of age compared with 25% of Blacks, 30% of American Indians, 30% of white Hispanics and 28% of Asian-Pacific Islanders (Mantel-Haenzel chi square, P < 0.001 for each comparison). Furthermore coverage rates frequently varied significantly by neighborhood, thereby identifying pockets of underimmunization within communities. CONCLUSION: Our data demonstrate that vaccination rates can vary substantially by age, race/ ethnicity and neighborhood. Detailed immunization assessment is necessary so that effective targeted interventions can be developed.

Child, Preschool↗
PubMed1997

Molecular dissection of Ca2+ efflux in immortalized proximal tubule cells.

Plasma membrane Ca(2+)-ATPase (PMCA) and the Na+/Ca2+ exchanger participate in regulating cell function by maintaining proper intracellular Ca2+ concentrations ([Ca2+]i). In renal epithelial cells these proteins have been additionally implicated in cellular calcium absorption. The purpose of the present studies was to determine the Ca2+ extrusion mechanisms in cells derived from the proximal tubule. Homology-based RT-PCR was used to amplify PMCA transcripts from RNA isolated from mouse cell lines originating from the S1, S2, and S3 proximal tubule segments. S1, S2, and S3 cells exhibited only PMCA1 and PMCA4 products. PCR product identity was confirmed by sequence analysis. Northern analysis of proximal tubule cell RNAs revealed appropriate transcripts of 7.5 and 5.5 kb for PMCA1 and 8.5 and 7.5 kb for PMCA4, but were negative for PMCA2 and PMCA3. Western analysis with a monoclonal antibody to PMCA showed that all proximal cell lines expressed a reacting plasma membrane protein of 140 kD, the reported PMCA molecular mas. Na+/Ca2+ exchanger (NCX1) mRNA expression, analyzed by RT-PCR, protein expression by Western analysis, and functional exchange activity were uniformly absent from all proximal tubule cell lines. These observations support the idea that immortalized cells derived from the proximal tubule express PMCA1 and PMCA4, which may serve as the primary mechanism of cellular Ca2+ efflux.

Amino Acid Sequence↗
PubMed1997

Molecular and functional identification of beta-adrenergic receptors in distal convoluted tubule cells.

Renal nerve stimulation or circulating catecholamines activate the beta-adrenergic receptors that mediate direct effects on tubular transport. Three subtypes of beta-adrenergic receptors have been characterized: beta 1, beta 2, and beta 3. beta-Adrenergic-receptor effects on Na+ and Ca2+ transport in distal convoluted tubules (DCT) have not been established. The focus of this study was to 1) identify the subtypes of beta-adrenergic receptors in DCT cells and 2) examine functional responses to beta-receptor activation on adenosine 3',5'-cyclic monophosphate (cAMP) formation and Na+ and Ca2+ entry. To determine the subtypes of beta-receptors present, RNA isolated from immortalized mouse DCT cells was reverse transcribed, and the cDNA was amplified using primers designed to reported sequences for beta 1-, beta 2-, and beta 3-receptor subtypes. Products of the appropriate sizes were obtained with beta 1- and beta 2-primers. No product was observed with primers to the beta 3 sequence. Receptor products were confirmed by sequencing and are identical to reported mouse beta 1- and beta 2-receptor sequence. Receptor binding of[3H]dihydroalprenolol was 123 +/- 13 fmol/mg protein, and a 3:1 ratio of beta 1- to beta 2-receptors was observed with DCT cell membranes. Isoproterenol, a beta-receptor agonist, increased cAMP formation 8.5-fold. Pretreatment with the antagonist propranolol abolished agonist-induced cAMP accumulation. Isoproterenol significantly increased 22Na+ uptake to 345 +/- 23 compared with a basal rate of 256 +/- 12 nmol.min-1.mg protein-1 and was blocked with propranolol and beta 1- and beta 2-selective antagonists. Isoproterenol had no effect on 45Ca2+ entry into DCT cells. In summary, DCT cells express three times more beta 1- than beta 2-receptors and express no detectable beta 3-adrenergic receptors. beta-Receptors couple to adenylyl cyclase, and activation of beta-adrenergic receptors increases Na+ but not Ca2+ entry in DCT cells.

Adrenergic beta-Agonists↗
PubMed1996

A national outbreak of Salmonella enteritidis infections from ice cream. The Investigation Team.

BACKGROUND: In September 1994, the Minnesota Department of Health detected an increase in the number of reports of Salmonella enteritidis infections. After a case-control study implicated a nationally distributed brand of ice cream (Schwan's) in the outbreak, the product was recalled and further epidemiologic and microbiologic investigations were conducted. METHODS: We defined an outbreak-associated case of S. enteritidis infection as one in which S. enteritidis was cultured from a person who became ill in September or October 1994. We established national surveillance and surveyed customers of the implicated manufacturer. The steps involved in the manufacture of ice cream associated with cases of S. enteritidis infection were compared with those of products not known to be associated with infection matched for the date of manufacture. Cultures for bacteria were obtained from ice cream samples, the ice cream plant, and tanker trailers that had transported the ice cream base (premix) to the plant. RESULTS: We estimate that S. enteritidis gastroenteritis developed in 224,000 persons in the United States after they ate Schwan's ice cream. The attack rate for consumers was 6.6 percent. Ice cream associated with infection contained a higher percentage of premix that had been transported by tanker that had carried nonpasteurized eggs immediately before (P = 0.02). S. enteritidis was isolated from 8 of 226 ice cream products (3 percent), but not from environmental samples obtained from the ice cream plant (n = 157) or tanker trailers (n = 204). CONCLUSIONS: This nationwide outbreak of salmonellosis was most likely the result of contamination of pasteurized ice cream premix during transport in tanker trailers that had previously carried nonpasteurized liquid eggs containing S. enteritidis. To prevent further outbreaks, food products not destined for repasteurization should be transported in dedicated containers.

Adolescent↗
PubMed1996

Na+/Ca2+ exchange in rat osteoblast-like UMR 106 cells.

Ca2+ efflux from osteoblasts is thought to be mediated by Na+/Ca2+ exchange and by a plasma membrane Ca(2+)-ATPase. The presence of plasma membrane Na+/Ca2+ exchange was determined in rat UMR 106 osteosarcoma cells by functional and molecular studies. Na+/Ca2+ exchange activity was tested by measuring changes of [Ca2+]i in single cells. After Na+ loading the cells and removing extracellular Na+, the direction of exchange was reversed and [Ca2+]i increased by 100%. Multiple isoforms of the NCX1 gene product, encoding plasma membrane Na+/Ca2+ exchangers, were cloned from UMR 106 cells and a sample of primary human osteoblasts using homology-based RT-PCR. Isoforms NACA3, NACA7, and NACA10 were found in UMR 106 cells, whereas human osteoblasts expressed NACA3 and NACA7. Transcripts for NCX2 and the Na+/Ca2+, K+ exchanger were not detected. Northern analysis of UMR 106 cells with a probe to the NCX1 gene product revealed the presence of a transcript of 7 kb, the size of the exchanger message. Western analysis of UMR 106 cell membrane preparations with a polyclonal antibody specific for the NCX1 exchanger showed the presence of reacting proteins consistent with the reported masses of the exchanger at 125 and 85 kD. These results demonstrate Na(+)-dependent Ca2+ efflux from UMR 106 cells and the presence of several NACA isoforms in UMR 106 and primary human osteoblasts.

Aged↗
PubMed1996

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome.

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group. PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti. RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar. CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Adolescent↗
PubMed1996

Structural and functional analysis of Na+/Ca2+ exchange in distal convoluted tubule cells.

Renal distal convoluted tubules (DCT) are a major site of hormone-regulated, active calcium absorption. Calcium exit across basolateral plasma membranes is thought to be mediated by Na+/Ca2+ exchange and a Ca(2+)-ATPase. In this report the presence and function of Na+/Ca2+ exchangers in DCT cells were assessed. cDNAs encoding a conserved region and the variable regions of three alternatively spliced isoforms of the Na+/Ca2+ exchanger, NACA2, NACA3, and NACA6, were isolated in a ratio of 7:12:1 using homology-based reverse transcription-polymerase chain reaction (RT-PCR) with RNA from an immortalized mouse DCT cell line. Northern blots probed with a 32P-labeled PCR product from a conserved region of the exchanger were positive for a single transcript of 7 kb in primary cultures of distal tubule cells (cortical ascending limb + DCT cells), consistent with the reported size of the exchanger in other tissues. Na+/Ca2+ exchange was assessed by measuring sodium-dependent changes of intracellular calcium ([Ca2+]i), in single cells. In the presence of an outward Na+ gradient, [Ca2+]i increased by 240%. Collapsing the Na+ gradient with monensin inhibited the rise of [Ca2+]i. Removal of extracellular Ca2+ or the addition of an Na+ ionophore inhibited the rise of [Ca2+]i. The intracellular Na+ concentration decreased upon removal of extracellular Na+ in parallel with the rise of [Ca2+]i. Western analysis performed on membranes prepared from DCT cells or primary cultures of distal tubule cells with a polyclonal antibody revealed bands at approximately 125 and 85 kDa, consistent with reported sizes for exchanger protein. These findings show that Na+/Ca2+ exchanger transcripts, protein, and activity are present in DCT cells and that Na(+)-dependent Ca2+ efflux may be mediated by NACA2, NACA3, and NACA6.

Amino Acid Sequence↗
PubMed1995

Estimating immunization coverage from school-based childhood immunization records.

To determine the accuracy of school-based childhood immunization records and to describe the effects of their use on estimates of community-wide immunization coverage, we verified the immunizations to 72 months of age for children born in 1986 to residents in Dallas County, TX, and in Minnesota. Verified immunizations were compared with those documented in the school record. Major transcription errors accounted for fewer than 1% of discrepancies between school and provider records. For 99 subjects with 987 verified immunizations in Minnesota, age-appropriate immunization coverage estimated from the school records was within two percent of actual coverage. For 86 subjects with 981 verified immunizations in Dallas County, age-appropriate immunization coverage from the school records underestimated actual coverage by as much as 21%. The primary factor explaining the underestimate in Dallas was incomplete school immunization records for 33 (38%) subjects and 126 (13%) immunizations. Selective recording of immunizations related to the minimum state requirements in Texas contributed to incomplete school records in Dallas County. Verification of the completeness of records selected to estimate immunization coverage is essential if the estimates are used to monitor trends or to make public policy decisions.

Child↗
PubMed1994

Physician attitudes and practices regarding universal infant vaccination against hepatitis B infection in Minnesota: implications for public health policy.

Physician attitudes and practices regarding universal infant vaccination against hepatitis B virus infection in Minnesota were assessed approximately 1 year after publication of the Immunization Practices Advisory Committee recommendations. Four-hundred eighteen Minnesota family physicians and pediatricians were sent self-administered questionnaires, with follow-up by telephone. Among physicians who provide care to infants, 67 (29%) of 234 family physicians and 29 (50%) of 58 pediatricians routinely offered hepatitis B vaccine to all infants (overall 33%) (P = 0.002). The recommendations of the Immunization Practices Advisory Committee, the American Academy of Pediatrics and the American Academy of Family Physicians had the greatest positive influence on physicians' opinions regarding routine hepatitis B vaccination. The factors with the greatest negative influence on their opinions were the low prevalence of hepatitis B virus infection in Minnesota and the addition of three injections to the current childhood immunization schedule. Universal infant hepatitis B vaccination remains controversial among Minnesota family physicians and pediatricians. We believe, given the variability in hepatitis B virus incidence and prevalence in the United States and the relatively low risk of most infants, that a single national policy based solely on universal infant immunization may be difficult to implement.

Adult↗
PubMed1994

Sellar emptiness on routine magnetic resonance imaging.

Magnetic resonance imaging (MRI) has provided a clear view of the sella turcica and the pituitary gland, even on "routine" procedures that invariably include the sagittal T1-weighted sequence. A pituitary gland that does not fully occupy the sella is a common observation, even in normal individuals. Terms such as "empty sella" and "partially empty sella" have become more commonly used, occasionally giving rise to some confusion regarding their clinical significance. In a prospective study of 50 "near-normal" patients, based exclusively on the midsagittal T1-weighted image, we have found a statistically significant increase in sellar emptiness with age, a phenomenon that is more prominent in women. The finding of an empty or partially empty sella on routine MRI of the brain is therefore usually of no clinical significance.

Adult↗
PubMed1993

Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination.

OBJECTIVE: To determine the incidence of invasive Haemophilus influenzae type b disease in children living in Minnesota and Dallas County, Texas, before and since introduction of plain polysaccharide vaccine in 1985, and conjugate vaccine in 1988. Initially, use of these vaccines was limited to infants 18 months of age and older. DESIGN: Identification of culture-proven cases of H influenzae type b disease was through systems of active, laboratory-based surveillance. The mean incidence of disease (cases observed/100,000 child-years) for 1983 and 1984 served as a baseline for comparison with subsequent years through 1991. PARTICIPANTS: Children less than 5 years of age in Minnesota and Dallas County, Texas. Overall, there were 2557 confirmed age-eligible cases of invasive H influenzae type b disease from 1983 through 1991. RESULTS: Between the 1983-1984 baseline and 1991, the incidence of H influenzae type b disease decreased 85% in Minnesota and 92% in Dallas. Notably, declines in incidence were observed in children in the age group being vaccinated as well as in infants younger than 18 months of age prior to introduction of vaccination. CONCLUSION: In two widely separated areas of the United States, a profound decrease in the incidence of H influenzae type b disease has occurred. The data suggest that vaccination may be protecting against disease, as well as decreasing the spread of infection to unvaccinated infants.

Bacterial Capsules↗
PubMed1993

Role of egg consumption in sporadic Salmonella enteritidis and Salmonella typhimurium infections in Minnesota.

The incidence of Salmonella enteritidis infections has increased in the eastern United States, and consumption of undercooked eggs has been associated with outbreaks of S. enteritidis. In Minnesota, the incidence of S. enteritidis infections doubled from 1980 to 1990; however, no egg-associated outbreaks were identified. A case-control study was conducted to examine potential exposures for S. enteritidis and Salmonella typhimurium infections in Minnesota adults. Sporadic cases of S. enteritidis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.9-14.2; P = .003) and S. typhimurium infection (OR, 2.4; CI, 1.1-5.5; P = .03) were more likely to have consumed undercooked eggs or egg-containing foods during the 3 days before onset of illness compared to a similar reference period for controls. In addition, the extent to which eggs were cooked was directly associated with illness (chi 2 test for trend, P < .001). These findings demonstrate that eggs are important vehicles for S. enteritidis and S. typhimurium, even in the absence of recognized outbreaks.

Adolescent↗
PubMed1992

A multistate outbreak of Salmonella javiana and Salmonella oranienburg infections due to consumption of contaminated cheese.

OBJECTIVE: To determine the source of an outbreak of Salmonella javiana and Salmonella oranienburg infections. DESIGN: Laboratory-based statewide surveillance for Salmonella infections and two separate case-control studies. SETTING: Community- and industry-based studies conducted from May through October 1989. PARTICIPANTS: Thirty-one culture-confirmed outbreak-associated cases of S javiana infection and 60 community controls matched for telephone prefix, gender, and age in case-control study I; 50 cases, 100 community controls, and 64 family member controls in case-control study II. RESULTS: One hundred thirty-six culture-confirmed cases of S javiana infection and 11 cases of S oranienburg infection were associated with the outbreak in Minnesota. Outbreak-associated cases were also identified in Wisconsin (15 cases), and in Michigan and New York (one case each). Cases were more likely than controls to have consumed mozzarella cheese manufactured at a single cheese plant (plant X) or cheese that had been shredded at processing plants that also shredded cheese manufactured at plant X (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.7 to 23.2; P < .01). The outbreak-associated strains of both serovars were isolated from two unopened 16-oz (0.45-kg) blocks of mozzarella cheese produced at plant X. The most probable numbers of Salmonella organisms in these samples were 0.36/100 g and 4.3/100 g. CONCLUSIONS: The potential for bacterial pathogen contamination of cheese during manufacture and processing has important epidemiologic implications, particularly because cheese consumption has recently increased in the United States. Low-level contamination of a nationally distributed food product can cause geographically dispersed foodborne outbreaks that may be difficult to detect.

Adolescent↗