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Biomedical subjects

J D Klein

Publications and source records attributed to J D Klein.

At least 19 recordsLinked to original sources

Renal ENaC subunit, Na-K-2Cl and Na-Cl cotransporter abundances in aged, water-restricted F344 x Brown Norway rats.

Renal sodium reabsorption is a key determinant of final urine concentration. Our aim was to determine whether differences existed between aged and young rats in their response to water restriction with regard to the regulation of abundance of any of the major distal renal sodium transporter proteins. Male Fisher 344 x Brown Norway (F344 x BN) rats of 3-, 10-, 24-, or 31 months of age (3M, 10M, 24M, or 31M) were either water restricted (WR) for 5 days or control (ad libitum water). Major renal sodium transporters and channel subunits were evaluated by immunoblotting and immunohistochemistry. Age did not significantly affect plasma arginine vasopressin or aldosterone levels, but renin activity was only 8% in 31M-WR rats relative to 3M-WR (P<0.05). Extreme aging (31M) led to decreased outer medullary abundance of the bumetanide-sensitive Na-K-2Cl cotransporter and decreased cortical abundance of the beta- and gamma-subunits (70-kDa band) of the epithelial sodium channel (ENaC) (P<0.05). Water restriction significantly (P<0.05) increased the abundance of Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC) across ages. However, these increases were significantly blunted as rats aged. Mean band densities were increased in WR rats (relative to age controls) by 54 and 106% at 3M, but only 25 and 29% at 24M and 0 and 6% at 31M for NKCC2 and NCC, respectively. Aged F344 x BN rats have reduced basal distal tubular renal sodium transporter abundances and blunted upregulation during water restriction, which may contribute to decreased urinary concentrating capacity.

Aging↗

Effect of nitrogen intake on nitrogen recycling and urea transporter abundance in lambs.

Urea recycling in ruminants has been studied extensively in the past, but the mechanisms regulating the amount of urea recycled or excreted remain obscure. To elucidate the role of urea transporters (UT) in N recycling, nine Dorset-Finn ewe lambs (20.8 +/- 0.8 kg) were fed diets containing 15.5, 28.4, and 41.3 g of N/kg of DM for 25 d. Nitrogen balance and urea N kinetics were measured during the last 3 d of the period. Animals were then slaughtered and mucosa samples from the rumen, duodenum, ileum, and cecum, as well as kidney medulla and liver, were collected. Increasing N intake tended to increase N balance quadratically (1.5, 5.1, and 4.4 +/- 0.86 g of N/d, P < 0.09), and linearly increased urinary N excretion (2.4, 10, and 16.5 +/- 0.86 g N/d, P < 0.001) and plasma urea N concentration (4.3, 20.3, and 28.4 +/- 2.62 mg of urea N/dL, P < 0.001), but did not affect fecal N excretion (5.0 +/- 0.5 g of N/d; P < 0.94). Urea N production (2.4, 11.8, and 19.2 +/- 0.83 g of N/d; P < 0.001) and urinary urea N excretion (0.7, 7.0, and 13.4 +/- 0.73 g N/d; P < 0.001) increased linearly with N intake, as well as with the urea N recycled to the gastrointestinal tract (1.8, 4.8, and 5.8 +/- 0.40 g of N/d, P < 0.001). No changes due to N intake were observed for creatinine excretion (518 +/- 82.4 mg/d; P < 0.69) and clearance (46 +/- 10.7 mL/min; P < 0.56), but urea N clearance increased linearly with N intake (14.9, 24.4, and 34.9 +/- 5.9 mL/min; P < 0.04). Urea N reabsorption by the kidney tended to decrease (66.3, 38.5, 29.1 +/- 12.6%; P < 0.06) with increasing N content of the diet. Increasing the level of N intake increased linearly the weight of the liver as a proportion of BW (1.73, 1.88, and 2.22 +/- 0.15%, P < 0.03) but only tended to increase the weight of the kidneys (0.36, 0.37, and 0.50 +/- 0.05%, P < 0.08). Urea transporter B was present in all the tissues analyzed, but UT-A was detected only in kidney medulla, liver, and duodenum. Among animals on the three diets, no differences (P > 0.10) in UT abundance, quantified by densitometry, were found. Ruminal-wall urease activity decreased linearly (P < 0.02) with increasing level of N intake. Urease activity in duodenal, ileal, and cecal mucosa did not differ from zero (P > 0.10) in lambs on the high-protein diet. In the present experiment, urea transporter abundance in the kidney medulla and the gastrointestinal tract did not reflect the increase in urea-N reabsorption by the kidney and transferred into the gut.

Animals↗

Youth and tobacco.

Youth around the world take up smoking and use tobacco products at high rates. Young people may not grasp the long-term consequences of tobacco use, although tobacco consumption and exposure has been shown to have significant negative health effects. Youth use a variety of tobacco products that are smoked, chewed, or sniffed, including machine-manufactured cigarettes, cigars, bidis, kreteks, sticks, and snuff. Prevention efforts have focused on countering those aspects that are believed to contribute to smoking uptake, such as tobacco industry advertising and promotion, and access to tobacco. There are many aspects of tobacco promotion through the media that have been more difficult to control, however, such as product placement within popular cinema movies. Once a youth has taken up tobacco, he or she is more likely than an adult to become addicted and should be offered treatment for tobacco cessation. Although there is not yet sufficient evidence to prove efficacy, the same treatments are suggested for youth as are recommended for adults, including nicotine replacement products. Given the severity of the tobacco epidemic worldwide and the devastating health effects on an individual and population basis, there are currently many efforts to curtail the tobacco problem, including the World Health Organization (WHO) sponsored Framework Convention on Tobacco Control. It is through comprehensive and collaborative efforts such as this that the global hazard of tobacco is most likely to be overcome.

Adolescent↗

Improving adolescent health outcomes.

Adolescent morbidity and mortality are more often due to preventable causes and to risky behavioral choices than to "natural" causes, such as cardiovascular disease or cancer. The leading causes of death among adolescents in Western, industrialized nations are unintentional injuries, especially motor vehicle crashes, homicide, and suicide. The physical and cognitive development of adolescents also results in increased risky behavioral choices, and to high rates of sexually transmitted diseases, substance use and misuse, and inadequate nutrition. These lifestyle choices also have repercussions that last into adulthood. Brief counseling interventions by physicians or other clinicians have been shown to be effective in modifying health risk behaviors in adolescents. Adolescents also have indicated both a belief that physicians should counsel them on risk behaviors and a willingness to discuss risk behaviors if asked about them in a confidential manner. In this paper, we review the leading causes of adolescent morbidity and mortality in the United States and Western Europe, including injuries, violence, depression and suicide, substance use, sexual activity, and nutrition, physical activity, and eating disorders. In addition, we describe the effectiveness of physician counseling for reduction or prevention of specific risk behaviors and the importance of providing comprehensive, confidential care. Additionally, we describe the results of a recent study of implementation of Adolescent Preventive Service Guidelines in community and migrant health centers that increased risky behavior screening and counseling for adolescent patients seen for routine/well care visits.

Adolescent↗

The care of HIV-infected adults in rural areas of the United States.

OBJECTIVE: This study describes the population of HIV-infected adults receiving care in rural areas of the United States and compares HIV care received in rural and urban areas. METHODS: Interviews were conducted with a nationally representative sample of 367 HIV-infected adults receiving health care in rural areas and 2806 HIV-infected adults receiving health care in urban areas of the contiguous United States. RESULTS: We estimate that 4800 HIV-infected persons received medical care in rural areas during the first half of 1996. Patients in rural HIV care were more likely than patients in urban HIV care to receive care from providers seeing few (<10) HIV-infected patients (38% vs. 3%; p <.001). Rural care patients were less likely than urban care patients to have taken highly active antiretroviral agents (57% vs. 73%; p <.001) or Pneumocystis carinii pneumonia prophylactic medication when indicated (60% vs. 75%; p =.006). CONCLUSIONS: Few American adults received HIV care in rural areas of the United States. Our findings suggest ongoing disparities between urban and rural areas in access to high-quality HIV care.

Adult↗

UT-A urea transporter protein in heart: increased abundance during uremia, hypertension, and heart failure.

Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic rats, the abundance of the 56-kDa protein increased 1.9-fold compared with pair-fed, sham-operated rats, whereas the 51- and 39-kDa proteins were unchanged. We also detected UT-A2 mRNA in hearts from control and uremic rats. Because uremia is accompanied by hypertension, the effects of hypertension per se were studied in uninephrectomized deoxycorticosterone acetate salt-treated rats, where the abundance of the 56-kDa protein increased 2-fold versus controls, and in angiotensin II-infused rats, where the abundance of the 56 kDa protein increased 1.8-fold versus controls. The 51- and 39-kDa proteins were unchanged in both hypertensive models. In human left ventricle myocardium, UT-A proteins were detected at 97, 56, and 51 kDa. In failing left ventricle (taken at transplant, New York Heart Association class IV), the abundance of the 56-kDa protein increased 1.4-fold, and the 51-kDa protein increased 4.3-fold versus nonfailing left ventricle (donor hearts). We conclude that (1) multiple UT-A proteins are detected in rat and human heart; (2) the 56-kDa protein is upregulated in rat heart in uremia or models of hypertension; and (3) the rat results can be extended to human heart, where 56- and 51-kDa proteins are increased during heart failure.

Adult↗

Delivery of smoking prevention and cessation services to adolescents.

OBJECTIVES: To describe the delivery of smoking prevention and cessation screening and counseling practices to adolescents and to examine the effect of physician specialty, sex, practice characteristics, and familiarity with preventive care guidelines on the delivery of smoking cessation counseling services. METHODS: Cross-sectional self-reported survey of pediatricians and family physicians in 3 New York metropolitan statistical areas who had seen 1 or more adolescents for well care within the past 6 months. RESULTS: Of 564 eligible physicians, 371 (66%) responded. Physicians reported asking most adolescents about smoking (91%) but were less likely to ask about peer smoking use (41%) or smokeless tobacco use (32%). Similarly, they reported assessing motivation to quit for 81% of smokers, but less often helped set quit dates (34%) or scheduled follow-up visits (28%). Family physicians were more likely to provide more effective smoking cessation interactions than pediatricians (mean smoking counseling performance score, 61 vs. 53; P<.001). Family physicians were also more likely to be familiar with National Cancer Institute guidelines than pediatricians (48% vs. 27%; P<.001). Female physicians reported having spent more time with their last adolescent patient (mean, 26 vs 21 minutes; P<.001) and more often spent time alone with adolescent patients (85% vs. 76% of visits; P<.001) than did male physicians. In multivariate modeling, specialty, familiarity with National Cancer Institute guidelines, time spent, and confidentiality factors were associated with better smoking counseling performance. CONCLUSION: Familiarity with smoking cessation guidelines and physician's specialty and practice style with adolescents are associated with better delivery of tobacco cessation counseling to adolescents.

Adolescent↗

Performance of a predictive model for streptococcal pharyngitis in children.

CONTEXT: Group A beta-hemolytic streptococcus (GABHS) pharyngitis is a common childhood illness. The clinical diagnosis is difficult to determine and laboratory tests have limitations; hence, the condition is generally overdiagnosed and overtreated. Several clinical pediatric-specific predictive models have been published but none have been prospectively studied. OBJECTIVE: To test the performance of a previously published predictive model for GABHS pharyngitis in children in different clinical settings and during different seasons. DESIGN: Prospective cohort study. SETTINGS: Pediatric emergency department and 2 pediatric outpatient clinics. PATIENTS: Children aged between 1 and 18 years with pharyngitis on initial examination at study sites between April 1, 1999, and March 31, 2000. INTERVENTIONS: Recording of clinical features during initial evaluation using a standardized form and recovery of GABHS from patients' throats using reference standard methods. MAIN OUTCOME MEASURES: Posttest probability for GABHS positive throat culture associated with the model's positive predictors (moderate to severe tonsillar swelling, cervical lymphadenopathy [moderate to severe tenderness and enlargement of cervical lymph nodes], scarletiniform rash, and the absence of coryza) and the models' negative predictors (absence of the above signs and the presence of coryza). RESULTS: Of 587 patients analyzed, 218 (37%) had a positive throat culture for GABHS. Forty-nine percent were boys. Mean +/- SD age was 6.7 +/- 3.9 years. There was no difference between the subsets within the sample. The posttest probability values for a positive throat culture associated with positive and negative predictors of the model were 79% and 12%, respectively. CONCLUSIONS: A pediatric predictive model for GABHS pharyngitis performed better than physicians' subjective estimates for a positive throat culture and was comparable with a rapid antigen detection test. The model performed consistently well in different populations and across seasons. It can be useful if reliable microbiological testing and/or follow-up are not attainable.

Adolescent↗

Teratogen update: Lyme disease.

We reviewed the world literature concerning the reproductive effects of Lyme disease (LD). Borrelia burgdorferi, which is the etiology of LD, is a spirochete and, as such, may share the potential for causing fetal infection, which may occur in the setting of maternal spirochetemia. Information concerning the effects of gestational LD derives from case reports and series, epidemiologic studies, and experimental animal models. Although provocative, these studies fail to define a characteristic teratogenic effect. However, skin and cardiac involvement have predominated in some reports. Pregnancy wastage has been suggested primarily by animal studies. Gestational LD appears to be associated with a low risk of adverse pregnancy outcome, particularly with appropriated antibiotic therapy. Suggestions for management of clinical situations are presented.

Animals↗

In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates.

The in vitro activities of meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin against 130 clinical isolates of group C and G streptococci, including vancomycin-tolerant isolates, were evaluated. Meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin MICs at which 90% of the isolates were inhibited were 0.06, 2.0, 0.25, 0.5, and < or = 0.016 microg/ml, respectively. Meropenem, linezolid, quinupristin-dalfopristin, and penicillin were active against group C and G streptococci, including vancomycin-resistant strains.

Acetamides↗

Localization of the urea transporter UT-B protein in human and rat erythrocytes and tissues.

A new polyclonal antibody to the human erythrocyte urea transporter UT-B detects a broad band between 45 and 65 kDa in human erythrocytes and between 37 and 51 kDa in rat erythrocytes. In human erythrocytes, the UT-B protein is the Kidd (Jk) antigen, and Jk(a+b+) erythrocytes express the 45- to 65-kDa band. However, in Jk null erythrocytes [Jk(a-b-)], only a faint band at 55 kDa is detected. In kidney medulla, a broad band between 41 and 54 kDa, as well as a larger band at 98 kDa, is detected. Human and rat kidney show UT-B staining in nonfenestrated endothelial cells in descending vasa recta. UT-B protein and mRNA are detected in rat brain, colon, heart, liver, lung, and testis. When kidney medulla or liver proteins are analyzed with the use of a native gel, only a single protein band is detected. UT-B protein is detected in cultured bovine endothelial cells. We conclude that UT-B protein is expressed in more rat tissues than previously reported, as well as in erythrocytes.

Amino Acid Sequence↗

Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism.

The Na-K-2Cl cotransporter NKCC1 is an important volume-regulatory transporter that is regulated by cell volume and intracellular Cl(-). This regulation appears to be mediated by phosphorylation of NKCC1, although there is evidence for additional, cytoskeletal regulation via myosin light chain (MLC) kinase. NKCC1 is also activated by growth factors and may contribute to cell hypertrophy, but the mechanism is unknown. In aortic endothelial cells, NKCC1 (measured as bumetanide-sensitive (86)Rb(+) influx) was rapidly stimulated by serum, lysophosphatidic acid, and fibroblast growth factor, with the greatest stimulation by serum. Serum increased bumetanide-sensitive influx significantly more than bumetanide-sensitive efflux (131% vs. 44%), indicating asymmetric stimulation of NKCC1, and produced a 17% increase in cell volume and a 25% increase in Cl(-) content over 15 min. Stimulation by serum and hypertonic shrinkage were additive, and serum did not increase phosphorylation of NKCC1 or MLC, and did not decrease cellular Cl(-) content. When cellular Cl(-) was replaced with methanesulfonate, influx via NKCC1 increased and was no longer stimulated by serum, whereas stimulation by hypertonic shrinkage still occurred. Based on these results, we propose a novel mechanism whereby serum activates NKCC1 by reducing its sensitivity to inhibition by intracellular Cl(-). This resetting of the Cl(-) set point of the transporter enables the cotransporter to produce a hypertrophic volume increase.

Animals↗

97- and 117-kDa forms of collecting duct urea transporter UT-A1 are due to different states of glycosylation.

UT-A1 is an extremely hydrophobic 929-amino acid integral membrane protein, expressed in the renal inner medullary collecting duct, with a central role in the urinary concentrating mechanism. Previous immunoblotting studies in rats have revealed that UT-A1 is present in kidney in 97- and 117-kDa monomeric forms and that the relative abundance of the two forms is altered by vasopressin treatment and other treatments that altered urinary inner medullary urea concentration. The present studies were carried out using protein chemistry techniques to determine the origin of the two forms. Peptide-directed polyclonal antibodies targeted to five sites along the polypeptide sequence from the NH2 to the COOH terminus labeled both forms, thus failing to demonstrate a significant deletion in the primary amino acid chain. The 97- and 117-kDa monomeric forms were both reduced to 88 kDa by deglycosylation with N-glycosidase F, indicating that a single polypeptide chain is glycosylated to two different extents. Studies using nonionic detergents for membrane solubilization or using homobifunctional cross-linkers demonstrated that UT-A1 exists as a 206-kDa protein complex in native kidney membranes. The mobility of this complex was also increased by deglycosylation. Both the 97- and 117-kDa proteins, as well as the 206-kDa complex, were immunoprecipitated with UT-A1 antibodies. We conclude that UT-A1 is a glycoprotein and that the two monomeric forms (97 and 117 kDa) in inner medullary collecting duct are the consequence of different states of glycosylation.

Animals↗

Improving adolescent preventive care in community health centers.

OBJECTIVE: To evaluate implementation of the Guidelines for Adolescent Preventive Services (GAPS) in Community and Migrant Health Centers (CMHCs). DESIGN: Before and after comparison of health center policy, clinician and adolescent self-report, and chart reviews in 5 CMHCs. PARTICIPANTS: Eighty-one preintervention and 80 one-year postintervention providers and 318 preintervention and 331 postintervention 14- to 19- year-old adolescent patients being seen for well visits at 5 CMHCs. INTERVENTION: Health center staff were trained to implement GAPS and were provided resource materials, patient questionnaires, and clinician manuals. MAIN OUTCOME MEASURES: Delivery of and receipt of preventive services and perceived access to care. RESULTS: CMHC systems changes were related to stronger leadership commitment to adolescent care. Providers reported high levels of preventive services delivery before and after guideline implementation. After guideline implementation, adolescents reported increases in having discussed prevention content with providers in 19 of 31 content areas, including increased discussion of physical or sexual abuse (10% before to 22% after), sexual orientation (13% to 27%), fighting (6% to 21%), peer relations (37% to 52%), suicide (7% to 22%), eating disorders (11% to 28%), weapons (5% to 22%), depression (16% to 34%), smokeless tobacco (10% to 29%), and immunizations (19% to 48%). Adolescents were also more likely to report knowing where to get reproductive or mental health services and were more likely to have received health education materials. Implementation also increased documentation of recommended screening and counseling in 51 of 79 specific content areas assessed in chart reviews. CONCLUSION: Implementing GAPS increased the receipt of preventive services at these health centers. Adolescents received more comprehensive screening and counseling, more health education materials, and had greater access to care after implementation. GAPS implementation may help improve the quality of care for adolescents.

Adolescent↗

Condom use by adolescents.

The use of condoms as part of the prevention of unintended pregnancies and sexually transmitted diseases (STDs) in adolescents is evaluated in this policy statement. Sexual activity and pregnancies decreased slightly among adolescents in the 1990s, reversing trends that were present in the 1970s and 1980s, while condom use among adolescents increased significantly. These trends likely reflect initial success of primary and secondary prevention messages aimed at adolescents. Rates of acquisition of STDs and human immunodeficiency virus (HIV) among adolescents remain unacceptably high, highlighting the need for continued prevention efforts and reflecting the fact that improved condom use can decrease, but never eliminate, the risk of acquisition of STDs and HIV as well as unintended pregnancies. While many condom education and availability programs have been shown to have modest effects on condom use, there is no evidence that these programs contribute to increased sexual activity among adolescents. These trends highlight the progress that has been made and the large amount that still needs to be accomplished.

Adolescent↗