Adipose tissue mitochondrial capacity associates with long-term weight loss success.

OBJECTIVES: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities. METHODS: SAT biopsies were obtained from 19 clinically healthy obese subjects (body mass index (BMI) 34.6±2.7 kg m-2) during a weight loss intervention (0, 5 and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg m-2) at baseline. Based on 1-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino-acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography. RESULTS: Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with WL success, and with SAT and VAT glucose uptake. During WL, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 and 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon WL. CONCLUSIONS: Higher mitochondrial capacity in SAT predicts good long-term WL success. WL does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.Data availability:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.

Adipocyte morphology and implications for metabolic derangements in acquired obesity.

BACKGROUND: Adipocyte size and number have been suggested to predict the development of metabolic complications in obesity. However, the genetic and environmental determinants behind this phenomenon remain unclear. METHODS: We studied this question in rare-weight discordant (intra-pair difference (Δ) body mass index (BMI) 3-10 kg m(-2), n=15) and concordant (ΔBMI 0-2 kg m(-)(2), n=5) young adult (22-35 years) monozygotic twin pairs identified from 10 birth cohorts of Finnish twins (n=5 500 pairs). Subcutaneous abdominal adipocyte size from surgical biopsies was measured under a light microscope. Adipocyte number was calculated from cell size and total body fat (D × A). RESULTS: The concordant pairs were remarkably similar for adipocyte size and number (intra-class correlations 0.91-0.92, P<0.01), suggesting a strong genetic control of these measures. In the discordant pairs, the obese co-twins (BMI 30.6 ± 0.9 kg m(-2)) had significantly larger adipocytes (volume 547 ± 59 pl), than the lean co-twins (24.9 ± 0.9 kg m(-)(2); 356 ± 34 pl, P<0.001). In 8/15 pairs, the obese co-twins had less adipocytes than their co-twins. These hypoplastic obese twins had significantly higher liver fat (spectroscopy), homeostatic model assessment-index, C-reactive protein and low-density lipoprotein cholesterol than their lean co-twins. Hyperplastic obesity was observed in the rest (7/15) of the pairs, obese and lean co-twins having similar metabolic measures. In all pairs, Δadipocyte volume correlated positively and Δcell number correlated negatively with Δhomeostatic model assessment-index and Δlow-density lipoprotein, independent of Δbody fat. Transcripts most significantly correlating with Δadipocyte volume were related to a reduced mitochondrial function, membrane modifications, to DNA damage and cell death. CONCLUSIONS: Together, hypertrophy and hypoplasia in acquired obesity are related to metabolic dysfunction, possibly through disturbances in mitochondrial function and increased cell death within the adipose tissue.

Characterising metabolically healthy obesity in weight-discordant monozygotic twins.

AIMS/HYPOTHESIS: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this 'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon. METHODS: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥ 3 kg/m(2)), aged 22.8-35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT. RESULTS: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics. CONCLUSIONS/INTERPRETATION: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.

Murine monoclonal antibodies to PorA of Neisseria meningitidis show reduced protective activity in vivo against B:15:P1.7,16 subtype variants in an infant rat infection model.

The major outer membrane protein PorA of Neisseria meningitidis is the target for bactericidal serosubtyping antibodies and is currently considered as a potential vaccine candidate against group B meningococcal disease. Although the minor antigenic variability of the PorA has been increasingly recognized and described, its implication for vaccine design remains unclear. In this study, the protective activity of murine monoclonal PorA specific antibodies against four isogenic meningococcal P1.7,16 target strains, the prototype P1.7,16a and three loop 4 point mutation variants (designated P1.7,16b to d) constructed from reference strain H44/76 (B:15:P1.7,16a), was evaluated in the infant rat infection model. All monoclonal antibodies had been obtained by immunization of mice with outer membrane protein preparations from meningococcal serosubtype P1.7,16 reference strain H44/76. A challenge dose of 10(5)cfu/pup was given i.p. 1-2 h after the i.p. injection of 1:100 diluted antibodies, and the development of bacteremia was assessed by culturing blood samples taken 6 h after challenge. MN14C11.6, a reference monoclonal antibody for serosubtype P1.7 epitope located in predicted loop 1 (VR1) identical in all the variants, was equally protective against all loop 4 variants. The three P1.16 specific monoclonal antibodies tested (MN5C11G, MN12H2 and 62D12-8) all completely protected animals against the prototype P1.7,16a, variably against the P1.7,16b and P1.7,16c, but not against the P1.7,16d variant. Our findings therefore suggest that certain subtype variants may escape protection in vivo conferred by PorA specific antibodies.

Customer exposure to gasoline vapors during refueling at service stations.

Gasoline is a volatile complex mixture of hydrocarbon compounds that is easily vaporized during handling under normal conditions. Modern reformulated gasoline also contains oxygenates to enhance octane number and reduce ambient pollution. This study measured the difference in the exposure of customers to gasoline and oxygenate vapors during refueling in service stations with and without vapor recovery systems. Field measurements were carried out at two self-service stations. One was equipped with Stage I and the other with Stage II vapor recovery systems. At Stage I stations there is vapor recovery only during delivery from road tanker, and at Stage II stations additional vapor recovery during refueling. The exposure of 20 customers was measured at both stations by collecting air samples from their breathing zone into charcoal tubes during refueling with 95-octane reformulated gasoline. Each sample represented two consecutive refuelings. The samples were analyzed in the laboratory by gas chromatography using mass-selective detection for vapor components. The Raid vapor pressure of gasoline was 70 kPa and an oxygen content 2 wt%. Oxygenated gasoline contained 7 percent methyl tert-butyl ether (MtBE) and 5 percent methyl tert-amyl ether (MtAE). The geometric mean concentrations of hydrocarbons (C3-C11) in the customers' breathing zone was 85 mg/m3 (range 2.5-531 mg/m3) at the Stage I service station and 18 mg/m3 (range < 0.2-129 mg/m3) at the Stage II service station. The geometric mean of the exposure of customers to MtBE during refueling at the Stage I service station was 15.3 mg/m3 (range 1.8-74 mg/m3), and at the Stage II service station 3.4 mg/m3 (range 0.2-16 mg/m3). The differences in exposure were statistically significant (p < 0.05). The mean refueling times were 57 seconds (range 23-207) at the Stage I and 66 seconds (range 18-120) at the Stage II station. The measurements were done on consecutive days at the various service stations. The temperature ranged from 10 to 17 degrees C, and wind velocity was 2-4 m/s. The climatic conditions were very similar on the measurement days. Based on this study it was found that the Stage II vapor recovery system reduces gasoline emission considerably. The exposure level of customers at the Stage II station during refueling was circa 20-25 percent of the exposure at the Stage I service station when conditions were equal and no other confounding factors such as leaks or spills were present.

Comparison of tanker drivers' occupational exposures before and after the installation of a vapour recovery system.

The purpose of this study was to compare tanker drivers' occupational exposure level before and after the installation of vapour recovery facilities at 14 service stations. Road tanker drivers are exposed when handling volatile petrol liquid in bulk in the distribution chain. The drivers' exposure was studied during the unloading operation as the bulk petrol flowed into underground storage tanks, displacing vapours in the tank space and causing emission to the environment and the drivers' work area. The exposures were measured again when the dual point Stage I vapour recovery systems were installed for recycling vapours. Short-term measurements were carried out in the drivers' breathing zones by drawing polluted air through a charcoal tube during unloading. The samples were analysed in the laboratory by gas chromatography for C3-C11 aliphatic hydrocarbons, tert-butyl methyl ether (MTBE), tert-amyl methyl ether (MTAE), benzene, toluene and xylene. The road tanker loads delivered consisted of oxygenated and reformulated petrol (E95 and E98 brands), which contained on average 13% oxygenates. Before the installation of the vapour recovery system, the geometric mean (GM) concentration of aliphatic hydrocarbons was 65 mg m-3 (range 6-645 mg m-3) in the drivers' breathing zones. After the installation at the same service stations, the corresponding exposure level was 8.3 mg m-3 (range < 1-79 mg m-3). The GM of the MTBE concentrations was 8.6 mg m-3 (range 1-67 mg m-3) without vapour recovery and 1.5 mg m-3 (range < 0.1-10 mg m-3) with vapour recovery. The differences between the aliphatic hydrocarbons and the MTBE exposure levels during the unloading of the road tankers without and with vapour recovery were statistically significant (p < 0.05).

The infant rat model adapted to evaluate human sera for protective immunity to group B meningococci.

The infant rat infection model previously developed to evaluate protective ability of passively administered murine antibodies to group B meningococcal (MenB) surface antigens was adapted for human sera. Several challenge doses were tested, aiming at sensitive detection of protection with little interassay variability. Doses of 10(5) and 10(6) colony forming units of strain IH5341 (MenB:15:P1.7,16) injected intraperitoneally gave consistently high levels of bacteremia and meningitis developed in 6 h in 50-100% of the pups. A monoclonal antibody mAb735 to the MenB capsule, injected 1-2 h before bacterial challenge, gave full protection at a dose of 2 microg/pup. Sera from adult volunteers immunized with a MenB outer membrane vesicle vaccine reproducibly reduced bacterial counts in the blood and cerebrospinal fluid, whereas a normal human serum, lacking bactericidal and opsonophagocidal activity, was unprotective.

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients.

Hyperinsulinemia has been shown to predict coronary heart disease (CHD) events in both nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene has been linked with abdominal obesity, insulin resistance, and early-onset NIDDM. Therefore, we screened for this polymorphism among 185 unrelated nondiabetic subjects (101 men and 84 women; age, 56+/-1 years [mean +/- SEM]; body mass index [BMI], 27.8+/-0.3 kg/m2) with angiographically confirmed CHD (stenosis > 50% in > or = two coronary arteries), among 119 unrelated patients with NIDDM (90 men and 29 women; age, 62+/-1 years; BMI, 28.7+/-0.4 kg/m2; 95 had CHD by the same criteria and 24 had definite myocardial infarction [MI]), and among 82 healthy men (age, 54+/-1 years; BMI, 26.3+/-0.4 kg/m2) from our previous study. The frequency of the Trp64Arg allele of the beta3-adrenergic receptor gene was similar in nondiabetic patients with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects without CHD (7%). No association was found between cardiovascular risk factors and the codon 64 polymorphism of the beta3-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly related to insulin resistance in nondiabetic and NIDDM subjects with CHD evaluated by the euglycemic clamp technique. These results indicate that the Trp64Arg allele of the beta3-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients.

Working conditions and health in hairdressing salons.

The purpose of the study was to assess the working conditions in hairdressing salons and the influence of work factors on the workers' health. Twenty randomly sampled hairdressing salons in the Helsinki, Finland, metropolitan area were selected for the study. The study was performed during winter 1994-1995; it included a survey of the hairdressing chemicals in use, the measurement of physical and chemical working conditions, and a self-administered questionnaire of the work environment and health of the workers. The air temperature varied between 16-25 degrees C, air velocity 0.02-0.3 m/s, and relative humidity, 18-42 percent. The total dust concentration varied between 66-133 micrograms/m3. The concentration of volatile organic compounds was 84-465 micrograms/m3 and the peaks rose to 25-45 mg/m3. The highest concentration of ammonia detected was 3.5 mg/m3. The long-term concentrations of thioglycolates and persulfates were at their lowest below the detection limit, and at their highest 1.8 micrograms/m3 for thioglycolates and 4.7 micrograms/m3 for persulfates, respectively, and the peaks of persulfates, 30 micrograms/m3. Hairdressing chemicals, awkward work postures, and repetitive movements were the most frequent causes of discomfort and for some had caused a work-related disease. Good general ventilation decreased the health complaints caused by hairdressing chemicals, but caused discomfort as a result of drafts. On average, the physical and chemical working conditions in the hairdressing salons were satisfactory compared with the Finnish criterion for indoor climate. However, the frequent high peak concentrations of chemicals during dyeing, bleaching, permanenting, and aerosol spraying still pose a significant health problem. Although effective general ventilation alleviated the effects of the air pollutants, it could not completely solve the problem. Therefore, local exhaust ventilation is recommended at the mixing places for hairdressing chemicals and wherever they are applied to the hair. According to our results, already increasing the air exchange rate up to 5 to 7 times per hour during the high exposure jobs would improve the situation.

The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.

OBJECTIVES: The aim of the study was to screen 36 unrelated patients with hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic cases) from a genetically homogeneous area in eastern Finland for variants in the cardiac beta-myosin heavy chain (beta-MHC) and alpha-tropomyosin (alpha-TM) genes. BACKGROUND: Mutations in the beta-MHC and alpha-TM genes have been reported to be responsible for 30% to 40% and less than 5% of familial HCM cases, respectively. However, most genetic studies have included patients from tertiary care centers and are subject to referral bias. METHODS: Exons 3-26 and 40 of the beta-MHC gene and the nine exons of the alpha-TM gene were screened with the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method. Linkage analyses between familial HCM locus and two intragenic polymorphic markers (MYO I and MYO II) of the beta-MHC gene were performed in 16 familial HCM kindreds. RESULTS: A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the beta-MHC gene was found in one proband and two relatives. In addition, a novel Asn696Ser (asparagine converted to serine in codon 696) substitution was found in one HCM patient. No linkage between familial HCM and the beta-MHC gene was observed in 16 familial kindreds. A previously reported Aspl75Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relatives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively. CONCLUSIONS: Our results indicate that the beta-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Aspl75Asn mutation of the a-TM gene is more common than previously reported.

Glucokinase gene islet promoter region variant (G-->A) at nucleotide -30 is not associated with reduced insulin secretion in Finns.

OBJECTIVE: To investigate the effect of the islet promoter region variant (G-->A) at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM. RESEARCH DESIGN AND METHODS: The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests (IVGTTs) were performed in subjects with NGT. The islet promoter region of the GCK gene was amplified with polymerase chain reaction and screened for the variant (-30) using single-strand conformation polymorphism analysis. RESULTS: The islet promoter variant (-30) of the GCK gene was found in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not differ between subjects with and without this variant in any of the three groups. Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant (-30) of the GCK gene. CONCLUSIONS: These results indicate that the variant (-30) of the islet promoter region of the GCK gene does not have a significant effect on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.

Variants of the fatty acid-binding protein 2 gene are not associated with coronary heart disease in nondiabetic subjects and in patients with NIDDM.

OBJECTIVE: To investigate the association of variants of the fatty acid-binding protein (FABP) 2 gene with coronary heart disease (CHD) in nondiabetic subjects and in patients with NIDDM. RESEARCH DESIGN AND METHODS: Cross-sectional study included 135 nondiabetic and 79 NIDDM subjects with stenosis (> 50%) in at least two coronary arteries. A group of 81 healthy nondiabetic men without CHD served as a control population. All exons and intron-exon junctions of the FABP2 gene were amplified with the polymerase chain reaction, and variants were screened with the single-strand conformation polymorphism analysis. RESULTS: The allele frequency of an amino acid polymorphism (alanine-->threonine) in codon 54 of exon 2 of the FABP2 gene was 0.26 in nondiabetic subjects with CHD and 0.27 in NIDDM subjects with CHD. Other variants (GTA 118 GTC, GCGCA-->GCACA in the 3'-noncoding region, and the number of ATT repeats in intron 2) also did not associate with CHD. CONCLUSIONS: The variants of the FABP2 gene are not likely to contribute to the risk of CHD in Finnish nondiabetic and NIDDM subjects.

Exposure of gasoline road-tanker drivers to methyl tert-butyl ether and methyl tert-amyl ether.

Organic oxygenates, namely, methyl tert-butyl ether (MTBE) and methyl tert-amyl ether (MTAE), are added to gasoline to reduce carbon monoxide in exhausts and to enhance the octane number. The aim of this study was to investigate road-tanker drivers' exposure to oxygenate vapors during road-tanker loading and unloading as well as to evaluate the measurements of these ethers and their metabolites in the urine as a means of assessing the uptake of the ethers. A total of 11 drivers in different parts of Finland were trained to monitor their exposure with personal samplers, to report their working conditions, and to collect their whole-day urine samples. Charcoal tubes of the air samples were analyzed for MTBE, MTAE, benzene, toluene, and aliphatic hydrocarbons. For biological monitoring purposes the two main oxygenates, tertiary ethers MTBE and MTAE, as well as their main metabolites, tertiary alcohols tert-butanol (TBA) and tert-amyl alcohol (TAA), were determined in urine specimens. On average the drivers were exposed to vapors for short periods (21 +/- 14 min) three times during a work shift. The mean concentrations of MTBE and MTAE (mean +/- SD) were 8.1 +/- 8.4 and 0.3 +/- 0.4 mg/m3. The total MTBE uptake during the shift was calculated to be an average of 106 +/- 65 mumol. The mean concentrations of MTBE, TBA, MTAE and TAA detected in the first urine after the work shift were 113 +/- 76, 461 +/- 337, 16 +/- 21, and 40 +/- 38 nmol/l, and those found the next morning, 16 h later, were 18 +/- 12, 322 +/- 213, 9 +/- 10, and 20 +/- 27 nmol/l. The good relationship (r = 0.84) found between MTBE exposure and postshift excretion suggests that urinary MTBE can be used for biological monitoring of exposure, but at the present low level of exposure the corresponding metabolite TBA is not equally reliable. The determination of MTAE and its metabolite TAA in urine is sensitive enough to detect the low degree of exposure to MTAE, but in this study the data were too scarce to allow calculation of the correlations due to very low levels of MTAE exposure.

Subclass distribution of IgA antibodies in saliva and serum after immunization with Haemophilus influenzae type b conjugate vaccines.

IgA subclass distribution of antibodies against capsular polysaccharide (PS) of Haemophilus influenzae type b (Hib) was studied in saliva and serum samples of children vaccinated with two (n = 58) or three doses (n = 53) of Hib vaccine. One month after the second dose of Hib conjugate vaccine, at 7 months old, 40% of the children had IgA1 and 41% had IgA2 anti-Hib PS antibodies in saliva. One month after the third dose, at 15-25 months old, IgA1 was the predominating subclass; 72% of the children had IgA1, 26% had IgA2 anti-Hib PS in saliva. The mean concentration of IgA1 anti-Hib PS, expressed as optical density (OD) values, was significantly higher after three doses (OD 80.7) than after two doses (OD 18.9). The mean concentration of IgA2 did not change significantly after the third dose (OD 23.8 after two doses, OD 18.1 after three doses). In serum, IgA1 anti-Hib PS predominated both after two (17% had IgA1, none had IgA2) and three doses (72% had IgA1, 4% had IgA2) of Hib vaccine. In conclusion, both IgA1 and IgA2 anti-Hib PS were found in saliva of immunized children after two doses of Hib conjugate vaccine, whereas the third vaccine dose induced a shift towards IgA1 anti-Hib PS dominance in saliva.

Detection of polar and macrocyclic trichothecene mycotoxins from indoor environments.

A method is described for the qualitative and semi-quantitative simultaneous determination of both non-macrocyclic and macrocyclic trichothecene biotoxins from samples derived from indoor environments. The method includes extraction, sample pre-treatment and reversed-phase HPLC separation followed by tandem mass spectrometric identification and quantification using electrospray ionization on a quadrupole ion trap mass analyser. Aqueous methanol was used in the initial extraction and solvent partitioning and solid-phase extraction in the purification of samples. The HPLC separation was run on-line with electrospray ionization MS-MS detection. The detection limits and recoveries of the procedure varied from 1 to 1000 pg and from 31 to 92%, respectively. As the method includes few and not very labour intensive sample treatment steps, it should allow for a high throughput of samples with good prospects of automation.

Mechanism of antibody-mediated reduction of nasopharyngeal colonization by Haemophilus influenzae type b studied in an infant rat model.

The mechanism of antibody-mediated reduction of Haemophilus influenzae type b (Hib) carriage was studied in the infant rat colonization model. Monoclonal Hib polysaccharide (PS) antibody (MAb) given intranasally or intraperitoneally and human secretory anti-Hib PS IgA given intranasally inhibited colonization by Hib during the entire follow-up period (2-48 h after challenge) but did not affect colonization by Hi, a noncapsulated variant of Hib. F(ab')2 fragments, prepared from the MAb or from human serum anti-Hib IgG reduced Hib colonization as efficiently as the uncleaved molecules. Complement depletion by cobra venom treatment had no effect on the antibody-mediated reduction of Hib colonization. These results indicate that Fc-mediated activities of immunoglobulins are not essential in the reduction of Hib colonization. Instead, antibodies to Hib most likely reduce colonization by a direct effect on growth of the bacteria or their adherence to the nasopharyngeal mucosa.

Comparison of five different vaccination schedules with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine.

OBJECTIVE: To compare seroresponses to five different vaccination schedules for Haemophilus influenzae type b (Hib)-tetanus toxoid conjugate (PRP-T) vaccine in infants. DESIGN: Four different two-dose schedules were compared, with doses given at 1 and 3 months, 2 and 4 months, 2 and 6 months, or 4 and 6 months of age. One group received three doses at 2, 4, and 6 months of age. The PRP-T vaccine was given in the same syringe with diphtheria-tetanus-pertussis (DTP) vaccine; inactivated polio vaccine (IPV) was given in a separate syringe. Anti-Hib polysaccharide antibodies were measured by radioimmunoassay in sera taken before each immunization, 1 month after the second dose, at 7 and at 12 to 24 months of age. SUBJECTS: A total of 196 healthy infants were enrolled between November 1990 and November 1992. RESULTS: After one dose of PRP-T there were no significant differences in geometric mean antibody concentrations (0.09 to 0.13 microgram/ml) or in fold responses among the schedules. The response to the second dose was significantly higher than the response to the first dose given at the same age. The geometric mean antibody concentration was lower in the group vaccinated at 1 and 3 months than in the groups vaccinated at 2 and 4 months, 2 and 6 months, or 4 and 6 months. The three-dose schedule resulted in a significantly higher final antibody concentration than the best two-dose schedule (p <0.001). In most children (64% to 93%), the antibody concentration remained at least 0.15 microgram/ml up to the age of 12 to 24 months. CONCLUSIONS: The Hib conjugate vaccine, PRP-T, administered concomitantly with DTP vaccine and IPV, was immunogenic with schedules starting at 1 to 4 months of age. Two injections of PRP-T vaccine were immunogenic enough to maintain protection up to 12 to 18 months of age.

Exposure of tanker drivers to gasoline and some of its components.

The purpose of this study was to measure the exposure of road tanker drivers at work to gasoline and some of its components. The occupational hygiene measurements were made in two depots (one in northern Finland and the other in southern Finland) and in 11 service stations of a Finnish oil company during the loading and delivery of road tankers. Of the 21 measurements made, four were taken during top submerged loading of the road tankers and six during bottom loading at the depot. Eleven measurements were made during delivery at service stations. The duration of measurements varied from 10 to 44 min. The exposure of road tanker drivers to C3-C11 hydrocarbons of gasoline was under 300 mg m-3 during bottom loading measurements and during top loading exceeded 300 mg m-3 two measurements (50%). During delivery at service stations the exposure to C3-C11 hydrocarbons of gasoline exceeded 300 mg m-3 in four measurement (36%). The exposure of road tanker drivers during delivery depended mainly on the distance between working area and the emission point of discharging vapours from the tank, vents and wind direction. The mean exposures of road tanker drivers to benzene during loading and delivery were 1.1-18 mg m-3 in various situations. The mean exposures to n-hexane, to toluene and to xylene were 0.7-6.0, 1.4-11 and 0.8-4 mg m-3, respectively. The exposures to methyl-tert-butyl ether were between 13 and 91 mg m-3. All measurements were made during the summer. However, the temperature varied between 4 and 22 degrees C.

Immunologic priming by one dose of Haemophilus influenzae type b conjugate vaccine in infancy.

Immunogenicity of one dose of Haemophilus influenzae type b (Hib) conjugate vaccine in infancy and its ability to induce immunologic memory was studied in infants immunized at 4 and 14 months with either PRP-OMP (Hib polysaccharide conjugated with Neisseria meningitidis group B outer membrane protein complex) or PRP-T (Hib polysaccharide-tetanus toxoid conjugate) and compared with three doses of the same vaccines at 4, 6, and 14 months. Each group received diphtheriatetanus-pertusis vaccine at 3, 4, and 5 months of age. At 7 months of age, both vaccines were immunogenic after one dose, even though higher antibody concentrations were achieved after two doses. A booster dose given at 14 months resulted in a high antibody concentration and a strongly IgG-dominated isotype distribution, speaking for a secondary-type response in all groups, including those who had received only one dose in infancy. Subsequent persistence of antibodies suggestive of full protection for up to 36 months was similar in all groups.