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Biomedical subjects

M Anttila

Publications and source records attributed to M Anttila.

At least 19 recordsLinked to original sources

Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer.

OBJECTIVE: We investigated the expression of matrix metalloproteinase-9 (MMP-9) and its relation to clinicopathologic factors and survival and also to previously analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer. METHODS: The expression of MMP-9 was analyzed immunohistochemically in 292 primary tumors and their 31 metastases. RESULTS: A low proportion of strong MMP-9 expression in cancer cells and high stromal MMP-9 expression correlated with advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9 expression significantly correlated with hyaluronan positivity (p<0.0005), whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10-year disease-related survival (DRS) was found in patients with a high proportion of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05, respectively). However, high stromal expression of MMP-9 indicated short DRS (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or stromal cells were not independent prognostic factors, while in FIGO stage I patients a high percentage of MMP-9 positive cancer cells was associated with long DRS (p=0.008). CONCLUSION: These data suggest that MMP-9 has a dual role in tumor progression, acting against tumor advancement when in tumor epithelium and promoting tumor progression while in the stroma.

Adult↗

Neither hippurate-negative Brachyspira pilosicoli nor Brachyspira pilosicoli type strain caused diarrhoea in early-weaned pigs by experimental infection.

A hippurate-negative biovariant of Brachyspira pilosicoli (B. pilosicolihipp-) is occasionally isolated in diarrhoeic pigs in Finland, often concomitantly with hippurate-positive B. pilosicoli or Lawsonia intracellularis. We studied pathogenicity of B. pilosicolihipp- with special attention paid to avoiding co-infection with other enteric pathogens. Pigs were weaned and moved to barrier facilities at the age of 11 days. At 46 days, 8 pigs were inoculated with B. pilosicolihipp- strain Br1622, 8 pigs were inoculated with B. pilosicoli type strain P43/6/78 and 7 pigs were sham-inoculated. No signs of spirochaetal diarrhoea were detected; only one pig, inoculated with P43/6/78, had soft faeces from day 9 to 10 post inoculation. The pigs were necropsied between days 7 and 23 after inoculation. Live pigs were culture-negative for Brachyspira spp., but B. pilosicolihipp- was reisolated from necropsy samples of two pigs. The lesions on large colons were minor and did not significantly differ between the three trial groups. In silver-stained sections, invasive spirochaetes were detected in colonic mucosae of several pigs in all groups. Fluorescent in situ hybridisation for genus Brachyspira, B. pilosicoli and strain Br1622 was negative. However, in situ detection for members of the genus Leptospira was positive for spirochaete-like bacteria in the colonic epithelium of several pigs in both infected groups as well as in the control group. L. intracellularis, Salmonella spp., Yersinia spp. and intestinal parasites were not detected. The failure of B. pilosicoli strains to cause diarrhoea is discussed with respect to infectivity of the challenge strains, absence of certain intestinal pathogens and feed and management factors.

Animals↗

The effect of antimicrobial growth promoter withdrawal on the health of weaned pigs in Finland.

The use of the antimicrobial growth promoters (AGPs) carbadox and olaquindox has been banned in the European Union (EU) since September 1999. We studied the effects of the withdrawal on the health of weaned piglets on two types of piglet-producing farms (farrowing herds and farrow-to-finish herds) from the different regions of Finland. Farms with no major problems with post-weaning diarrhoea were selected for the study to better evaluate the effect of AGPs alone. Data on production, medication and incidence of diarrhoea were collected from 73 farms during 1 year after the withdrawal. On 29 of these farms, the data collection began 4 months before the withdrawal. The health management of the pigs is considered good in Finland, and special attention has been paid to improve the husbandry practices and management of the farms. Eighty-two percent of the farms in the study were free of both Mycoplasma hyopneumoniae and Sarcoptes scabiei infection. Brachyspira hyodysenteriae infection was not detected in any of the farms. The median number of sows in the herds was 56.0 (IQR=43.0; 72.5) in 2000. The level of antimicrobial use in each herd was classified as low, moderate and high when the percentage of weaned pigs treated for diarrhoea during a 4-month period was 0-5%, 6-19% and > or =20%, respectively. Only on four herds (14%), there was an increase in the level of antibiotic use after the AGP withdrawal, when seasonally corresponding 4-month periods were compared. Fourty-one percent of these 29 farms were categorized as low users of antimicrobials, 38% as moderate users and 21% as high users. The level of antimicrobial use for treatment of diarrhoea after weaning (and the incidence of diarrhoea in weaned piglets) did not increase significantly after the withdrawal of AGPs from weaner feeds according to farmers' evaluations. In this study, the Escherichia coli infection was the most-common cause of diarrhoea in weaned pigs. The age at weaning did not change after the withdrawal of AGPs.

Animal Husbandry↗

Effects of atipamezole--a selective alpha-adrenoceptor antagonist--on cardiac parasympathetic regulation in human subjects.

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.

Adrenergic alpha-2 Receptor Antagonists↗

Pharmacokinetics of deramciclane and N-desmethylderamciclane after single and repeated oral doses in healthy volunteers.

OBJECTIVE: To study the pharmacokinetics and accumulation of deramciclane and its metabolite N-desmethylderamciclane after 60 mg twice daily doses for 4 weeks. METHODS: Sixteen healthy male subjects, age range of 20-29 years, participated in this randomized, double-blind, parallel-group, placebo-controlled study. Ten subjects first received a single 60 mg dose of deramciclane followed by 60 mg deramciclane b.i.d. between days 4 and 31. Six subjects received matching placebo in a similar manner. Pharmacokinetics of deramciclane and N-desmethylderamciclane were determined on days 1, 10, 17, 24 and 31. Plasma prolactin concentrations were measured before drug administration and 4 hours after on the same days. Safety was monitored using repeat laboratory determinations and ECG recordings. RESULTS: The mean (SD) AUC(0-infinity) of deramciclane was 1,251 (385) ng x h/ml after the first dose. The AUC(tau) calculated for the dosing interval was significantly higher at week 1 (p = 0.048) than the AUC(0-infinity) after the first dose but thereafter there was no further accumulation of deramciclane. The mean accumulation indices at weeks 1, 2, 3 and 4 varied between 2.3 and 2.7 with no tendency to increase over time. The mean apparent elimination half-life of deramciclane was 24.9 (3.5) hours after the first dose and 29.3 (9.3) hours after 4-week repeated dosing; this difference was not statistically significant. The accumulation index of N-desmethylderamciclane increased from week 1 to week 2 but remained stable thereafter. The treatment was well tolerated. Plasma prolactin levels were not influenced by deramciclane administration. CONCLUSIONS: Deramciclane administration, 60 mg twice daily for 4 weeks to healthy male volunteers, is well tolerated, and there is no evidence of continuous accumulation of the drug during maintenance treatment. Deramciclane at a dose of 60 mg b.i.d. does not antagonize dopamine receptors to a significant degree.

Adult↗

Canine distemper of vaccine origin in European mink, Mustela lutreola--a case report.

Cases of canine distemper (CD) related to vaccination of exotic carnivores extend over three decades and have been described in at least nine different species. Our report describes a case of acute CD in a European mink, Mustela lutreola, vaccinated with live attenuated CD vaccine licensed for use in fur-farmed mink. The male mink died of an acute grey matter disease with an unusually long incubation period. A female vaccinated at the same time showed no obvious signs of illness. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by subsequent sequencing of the PCR products. The sequenced products of the virus isolated from the mink and of the vaccine batch showed 100% identity. This is the first report in which molecular methods were used to confirm that the disease was caused by the vaccine strain. Based on our findings, it is clearly evident that current CD vaccines cannot be safely used in exotic species.

Animals↗

Selegiline pharmacokinetics are unaffected by the CYP3A4 inhibitor itraconazole.

OBJECTIVE: To characterise the effects of itraconazole, a potent inhibitor of CYP3A4, on the pharmacokinetics of selegiline in healthy volunteers. METHODS: In this randomised, placebo-controlled crossover study with two phases, 12 healthy volunteers took either 200 mg itraconazole or matched placebo once daily for 4 days. On day 4, a single 10-mg oral dose of selegiline hydrochloride was administered. Serum concentrations of selegiline and its primary metabolites desmethylselegiline and l-methamphetamine were determined up to 32 h. A caffeine test was performed on day 3 of both phases, by measuring the plasma paraxanthine/caffeine concentration ratio 6 h after caffeine intake, to examine the role of CYP1A2 in selegiline pharmacokinetics. In addition, the effects of itraconazole on the metabolism of selegiline in vitro were characterised by using human liver microsomes. RESULTS: Itraconazole had no significant effects on the pharmacokinetic variables of selegiline, desmethylselegiline or l-methamphetamine, with the exception that the AUC of desmethylselegiline was increased by about 10% (P < 0.05). There was a significant correlation between the AUC(desmethylselegiline)/AUC(selegiline) ratio and the paraxanthine/caffeine ratio (r = 0.41; P < 0.05), suggesting involvement of CYP1A2 in the formation of desmethylselegiline. In experiments with human liver microsomes, itraconazole had no inhibitory effect on the formation of either desmethylselegiline or l-methamphetamine from selegiline. CONCLUSIONS: The pharmacokinetics of selegiline in healthy volunteers were unaffected by the potent CYP3A4 inhibitor itraconazole. In addition, itraconazole showed no inhibitory effect on the biotransformation of selegiline to desmethylselegiline and l-methamphetamine by human liver microsomes. These findings suggest that selegiline is not susceptible to interaction with CYP3A4 inhibitors.

Adult↗

CYP2C19 polymorphism is not important for the in vivo metabolism of selegiline.

OBJECTIVES: To address the relevance of cytochrome P-450 (CYP) 2C19 polymorphism for the pharmacokinetics and dynamics of selegiline and its two known primary metabolites, desmethylselegiline and l-methamphetamine. METHODS: Six extensive (mephenytoin S/R ratio < 0.3; EM) and six poor (mephenytoin S/R ratio > 0.8; PM) hydroxylators of S-mephenytoin ingested a single 10-mg oral dose of selegiline hydrochloride. Serum concentrations of selegiline, desmethylselegiline and l-methamphetamine were measured by gas chromatography--mass spectrometry for up to 48 h. In addition, the platelet monoamine oxidase type B (MAO-B) activity was measured for 14 days to describe possible differences in the pharmacodynamics of selegiline and its metabolites between EM and PM. RESULTS: The CYP2C19 phenotype had no significant effects on the pharmacokinetic variables of selegiline. PM of S-mephenytoin had 68% higher mean AUC of desmethylselegiline (P = 0.0017) than EM, but no significant differences were observed in other pharmacokinetic parameters of desmethylselegiline. Contrary to desmethylselegiline, the serum l-methamphetamine concentrations were slightly lower in PM, but no statistically significant differences were observed in l-methamphetamine pharmacokinetics between the two CYP2C19 phenotypes. Accordingly, the magnitude of MAO-B inhibition showed no significant differences between the study groups. CONCLUSIONS: CYP2C19 polymorphism does not seem to be crucial for the metabolism or clinical effects of selegiline.

Adult↗

Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model.

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.

Animals↗

Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2).

Immune responses induced by intramuscular DNA immunization with Chlamydia pneumoniae genes coding for the major outer membrane protein (MOMP), cysteine-rich outer membrane protein 2 (Omp2) or the heat shock protein 60 (Hsp60) were studied. BALB/c mice were vaccinated intramuscularly three times at 3-week intervals and challenged intranasally 2 weeks after the last injection. Immunization with pmomp or phsp60 showed 1.2-1.5 log reduction in the mean lung bacterial counts after the challenge. Specific antibodies were detected only in sera of the mice immunized with pomp2 and phsp60. Although immunization with pomp2 resulted in a strong serum antibody response against Omp2 protein, it failed to protect the mice. Immunization with any of the three vaccines did not reduce the severity of histologically assessed pneumonia, but resulted in significantly higher lymphoid reaction in the lung indicating immunological memory.

Animals↗

Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables.

Tumor specimens from 78 epithelial ovarian cancer patients were examined for loss of heterozygosity (LOH) at 11 microsatellite markers at chromosomes 3p14.2, 6q27, 8p12, 11p15.5, 11q23.1-q24, 16q24.3, and 17p13.1, to evaluate the involvement, possible clustering, and prognostic significance of these lesions in the progression of the disease. The LOH analysis was performed on polymerase chain reaction (PCR)-amplified DNA from sections of paraffin-embedded tumor and normal tissue pairs. In addition to primary tumors, specimens of metastatic tissues were studied from 19 patients. In the combined results from primary and metastatic tumors, LOH frequencies varied between 31% (6q27) and 69% (17p13.1). Only LOH at chromosomal regions 3p14.2 (D3S1300), 11p15.5 (D11S1318), 11q23.3-q24 (D11S1340 and D11S912), 16q24.3 (D16S476 and D16S3028), and 17p13.1 (D17S938) was associated with an adverse disease course. Our results indicate that LOH at 17p13.1 occurs independently from the other chromosomal sites studied, and is an early event in ovarian tumorigenesis. The LOH at 16q24.3, 11q23.3/q24, and 11p15.5 seems to occur later. The LOH at 11p15.5 and 11q23.3 was associated with reduced cancer-specific survival time; therefore, the studied markers could be located close to genes with influence on patient survival. Of the studied chromosomal regions, the most important tumor suppressor genes involved in the evolution of ovarian cancer appear to be located on chromosomes 11, 16, and 17. The genetic heterogeneity observed in primary and metastatic specimens demonstrates that there are multiple pathways involved in the progression of ovarian cancer.

Chromosome Deletion↗

Evaluation of toremifene for reversal of multidrug resistance in renal cell cancer patients treated with vinblastine.

PURPOSE: Expression of P-glycoprotein (Pgp), which confers the multidrug resistance (MDR) phenotype, is thought to contribute to the insensitivity of renal cell cancer (RCC) to chemotherapy. The development of Pgp inhibitors for clinical application has been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration. Toremifene is able to reverse MDR and sensitise RCC to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in particular the acute phase protein alpha1-acid glycoprotein (AAG), which may limit tissue availability. In this phase I-II study we assessed the tolerability of short courses of high dose toremifene in combination with vinblastine and evaluated the key determinants of MDR reversal in vivo. METHODS: Twenty-seven patients with metastatic RCC received escalating doses of oral toremifene for 3 days every 2 weeks in combination with vinblastine 6 mg/m2 i.v. on day 3 of each cycle. The serum concentration of toremifene, its metabolites and AAG were measured and the effect of patients' serum on inhibition of Pgp in vitro was determined. RESULTS: Twenty-six patients were evaluable for response. Eight patients (31%) had stable disease and 18 patients (69%) progressive disease. The mean serum concentration of toremifene at 780 mg daily for 3 days was 7.82 microM [standard deviation (SD) 2.48, range 2.50 to 14.70], which exceeds that known to reverse MDR in vitro. The serum concentration of the major metabolite of toremifene, N-demethyltoremifene, which also reverses MDR, was 5.13 microM (SD 1.78, range 1.80 to 9.00). In 60% of patients the pre-treatment AAG concentration was above that known to block the effects of toremifene in vitro. However, addition of serum from patients on toremifene to MCF-7 adr cells in vitro inhibited Pgp-mediated efflux of rhodamine 123. CONCLUSIONS: We have shown that short course, high-dose toremifene in combination with vinblastine is generally well tolerated and that the concentration of toremifene required to reverse MDR in vitro is achievable in vivo.

Administration, Oral↗

Out-patient management does not impair outcome of pregnancy in women with type 1 diabetes.

In recent years, out-patient protocols have mainly displaced historical obstetric management of diabetic pregnancy. The impact of the change from centralized in-patient to decentralized out-patient treatment on glycaemic control and its effects on the outcome of newborns in diabetic pregnancies was therefore studied using the population-based data on 296 pregnancies in 224 women with type 1 diabetes over 10 years (1986-1995) in the two northernmost provinces of Finland. The area comprises one tertiary level and four other central hospitals. The change of policy was effected in 1990 and to determine the impact of this change, the study period was divided in two (period 1, 1986-1990, n = 135; period 2, 1991-1995, n = 161). At the first antenatal contact (mean 9.9 weeks of gestation) 73% of women had unsatisfactory glycaemic control, but it improved rapidly with pregnancy and was significantly better (P < 0.05) in the second study period. The incidence of congenital malformations was somewhat greater (NS) in period 2 but perinatal mortality did not change. Out-patient management does not impair outcome in type 1 diabetic pregnancy.

Adult↗

Factors predicting peri- and neonatal outcome in diabetic pregnancy.

A population-based birth cohort including 296 consecutive type 1 diabetic births in a geographically defined catchment area was used to evaluate factors predicting poor perinatal and neonatal outcome. Though perinatal mortality has decreased (17.1/1000 births at 28 or more weeks of gestation), the neonatal morbidity rate still remains high despite improved maternal metabolic control and developed antepartum surveillance. Poor glycemic control during the first weeks of pregnancy was the most important risk factor (relative risk (RR) 2.91; 95% confidence interval (CI) 1.29-6.55) predicting adverse neonatal events such as long (>10 days) stay in the neonatal unit, malformation or perinatal death. The risk was further increased in cases of severe diabetes (White class F-R; RR 2.75; 95% CI 1.59-4.76) and primiparity (RR 1.64; 95% CI 1.02-2.65). By evaluating these risk factors at the first antenatal visit, a subgroup with a particular need of counselling and intensive feto-maternal monitoring can be identified.

Adult↗

Selegiline metabolism and cytochrome P450 enzymes: in vitro study in human liver microsomes.

Although being a drug therapeutically used for a long time, the enzymatic metabolism of selegiline has not been adequately studied. In the current work we have studied the cytochrome P450 (CYP)-catalyzed oxidative metabolism of selegiline to desmethylselegiline and 1-methamphetamine and the effects of selegiline, desmethylselegiline and 1-methamphetamine on hepatic CYP enzymes in human liver microsomes in vitro. The apparent Km values for desmethylselegiline and 1-methamphetamine formation were on an average 149 microM and 293 microM, and the apparent Vmax values, 243 pmol/min./mg and 1351 pmol/min./mg, respectively. Furafylline and ketoconazole, the known reference inhibitors for CYP1A2 and CYP3A4, respectively, inhibited the formation of desmethylselegiline with Ki value of 1.7 microM and 15 microM. Ketoconazole inhibited also the formation of 1-methamphetamine with Ki of 18 microM. Fluvoxamine, an inhibitor of CYP1A2, CYP2C19 and CYP3A4, inhibited the formation of desmethylselegiline and 1-methamphetamine with Ki values of 9 and 25 microM, respectively. On the basis of these results we suggest that CYP1A2 and CYP3A4 contribute to the formation of desmethylselegiline and that CYP3A4 participates in the formation of 1-methamphetamine. In studies with CYP-specific model activities, both selegiline and desmethylselegiline inhibited the CYP2C19-mediated S-mephenytoin 4'-hydroxylation with average IC50 values of 21 microM and 26 microM, respectively. The Ki for selegiline was determined to be around 7 microM. Selegiline inhibited CYP1A2-mediated ethoxyresorufin O-deethylation with a Ki value of 76 microM. Inhibitory potencies of selegiline, desmethylselegiline and 1-methamphetamine towards other CYP-model activities were much lower. On this basis, selegiline and desmethylselegiline were shown to have a relatively high affinity for CYP2C19, but no evidence about selegiline metabolism by CYP2C19 was obtained.

Amphetamines↗

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs.

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).

Analgesia↗

Acquired immunity to Chlamydia pneumoniae is dependent on gamma interferon in two mouse strains that initially differ in this respect after primary challenge.

The role of gamma interferon (IFN-gamma) in a Chlamydia pneumoniae mouse model was studied by in vivo neutralization in two inbred mouse strains. During primary C. pneumoniae infection, neutralization of IFN-gamma increased both the numbers of bacteria and the pneumonia score in the lungs of C57BL/6 mice but not BALB/c mice. During reinfection, the bacterial counts in the lungs were increased by IFN-gamma neutralization in both mouse strains. Thus, the effect of IFN-gamma neutralization was dependent on the genetic background in primary infection. However, IFN-gamma appeared to be equally important in both mouse strains during reinfection.

Animals↗