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Biomedical subjects

M Petersen

Publications and source records attributed to M Petersen.

At least 109 records · Page 6Linked to original sources
PubMed1988

In vivo and in vivo/in vitro kinetics of cyclophosphamide-induced sister-chromatid exchanges in mouse bone marrow and spleen cells.

In several acute and chronic exposures to various chemicals in vivo and in vitro, the average sister-chromatid exchange (SCE) frequencies in human, mouse, rat, and rabbit lymphocytes generally decrease with time following treatment. The rate of this decline varies, but little data have been published pertaining to the comparative kinetics of SCEs both in vivo and in vivo/in vitro (exposure of animals to the test compound and culturing of cells) simultaneously in the same tissues. In this study, a single dose of cyclophosphamide (40 mg/kg) was injected for varying periods (6-48 h) and its effects, as assessed by the induction of SCEs, were analyzed under both in vivo and in vivo/in vitro conditions in mouse bone marrow and spleen cells. In vivo, the cyclophosphamide-induced SCEs increased with increasing time up to 12 h, stayed at approximately the same level until 24 h, and then decreased with increase in post-exposure time. However, the SCE levels remained significantly higher than controls at 48 h post-exposure time in both bone marrow and spleen cells. Under in vivo/in vitro conditions, the SCEs in bone marrow decreased with increase in post-exposure time until reaching control values by 48 h post exposure. However, in spleen cells, the decrease in SCE level was gradual, and by 48 h post-exposure time, the cells still had approximately 6 times higher SCEs than the control values. These results suggest that there are pharmacokinetic differences for cyclophosphamide in mouse bone marrow and spleen. Also, there is a differential SCE response to cyclophosphamide under in vivo and in vivo/in vitro conditions.

Animals↗
PubMed1988

Sister-chromatid exchanges induced by triethylenemelamine: in vivo and in vivo/in vitro studies in mouse and Chinese hamster bone marrow and spleen cells.

This study was designed to obtain sister-chromatid exchange (SCE) frequencies in bone marrow and spleen cells of mice and Chinese hamsters under in vivo and in vivo/in vitro systems following treatment of animals with varying doses (15-405 micrograms/kg) of triethylenemelamine (TEM). A dose-related SCE response was found in both species, tissues, and systems analyzed following TEM treatment. In vivo, similar responses were noted for both tissues in both species. However, in vivo/in vitro, the response was lower than in vivo and it varied with the tissue. The spleen cells were more sensitive and gave higher numbers of SCEs than bone marrow of both species at the two highest doses tested (135 and 405 micrograms/kg). These differences may be attributed to cell-culturing effects, type of cells analyzed, species and tissue specificities, and pharmacokinetic properties of the chemical. This study lends support to recently established in vivo/in vitro cell culture methodologies employing mice and Chinese hamsters for comparative cytogenetic analysis.

Animals↗
PubMed1987

Sympathetic skin response in diabetic neuropathy.

The sympathetic skin response (SSR) was studied in 47 diabetic patients selected for the presence of symptoms and clinical signs of peripheral neuropathy and in 24 normal control subjects. The SSR was present in all controls but was absent at the foot in 66% and at the hand in 27.7% of the diabetic patients. Absence of the SSR failed to correlate with other electrophysiologic parameters on routine nerve conduction and electromyographic studies. Although absent SSR was more often found in patients with symptoms of autonomic dysfunction (P less than 0.05), there was no correlation with any specific symptoms of autonomic involvement. The SSR was frequently absent, at least in the foot, in those patients with abnormal cardiac beat-to-beat variability (expiratory: inspiratory, E:I, ratio) and pupil cycle time (PCT). In addition there was a good correlation between the amplitude of the SSR and the value of the E:I ratio (r = 0.81, P less than 0.001). The SSR may be a valuable adjunct in the assessment of autonomic involvement in diabetic neuropathy, but its sensitivity requires further evaluation.

Adult↗
PubMed1987

Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays.

Sister chromatid exchange (SCE) and chromosomal aberration studies have been used to monitor human populations for genotoxic exposure to chemical substances. These monitoring techniques involve collection of blood and/or bone marrow from the exposed subjects and culturing cells for one or two cell cycles with various treatments in culture. The results obtained from such in vivo/in vitro studies may lead to an over- or underestimation of the damage that could occur in vivo. In the present study, which uses a mouse model, the in vivo/in vitro cytogenetic assays (SCEs and chromosomal aberrations) have been compared with similar in vivo systems in bone marrow and spleen cells treated with various doses of cyclophosphamide (CPA). The results indicate a significant difference in CPA-induced cytogenetic endpoints between in vivo and in vivo/in vitro conditions in both organs. However, linear relationships were found between CPA dose and cytogenetic end point analyzed under both conditions. Based on these results it appears that the in vivo/in vitro assay is a useful technique for indicating potential in vivo damage of chemicals.

Animals↗
PubMed1987

The influence of capsaicin on membrane currents in dorsal root ganglion neurones of guinea-pig and chicken.

The effect of capsaicin on voltage-dependent membrane currents of isolated dorsal root ganglia (DRG) neurones of guinea-pig and chicken were investigated by the voltage-clamp technique and intracellular perfusion. In both species, administration of capsaicin (3 X 10(-5) M) to the outer surface of the cell membrane reduced the amplitude and accelerated the inactivation of the fast inactivating potassium current. In contrast, 3,4-diaminopyridine (3,4-DAP) reduced the fast potassium current without affecting the inactivation. Combined application of capsaicin and 3,4-DAP was more effective than either drug alone. The slow potassium current was diminished by capsaicin but not affected by 3,4-DAP. Capsaicin (3 X 10(-5) M) applied to the internal surface of the membrane had little effect on the fast outward current but primarily decreased the amplitude of the slow potassium current. Two subpopulations of sodium currents could be demonstrated in guinea-pig neurones according to their tetrodotoxin (TTX) sensitivity. In type I neurones the sodium current was completely blocked by TTX; type II neurones exhibited a TTX-sensitive as well as a TTX-resistant inward current. Capsaicin (3 X 10(-5) M) applied externally reduced the maximal amplitude of both current components. The time course of inactivation was delayed only in the TTX-resistant sodium current. The effect of capsaicin on Na-currents of DRG neurones was similar in guinea-pigs and chicken. In DRG neurones of chicken, only TTX-sensitive currents were observed. In both species the steady-state inactivation of the sodium currents was shifted by capsaicin to more negative potentials.

Animals↗
PubMed1986

Beta-bungarotoxin inhibits a non-inactivating potassium current in guinea pig dorsal root ganglion neurones.

beta-Bungarotoxin (beta-BuTx), at concentrations of 0.45-45 nmol/l, selectively reduced a portion of the noninactivating potassium current (IsK) in dorsal root ganglion neurones of the guinea pig, measured by voltage clamp of internally perfused cells. The average reduction of IsK obtainable with beta-BuTx was 34% and usually not completed within 20 min, but irreversible upon washing for 20 min. The I/V-characteristic of the current blocked by beta-BuTx was almost linear. It is suggested that beta-BuTx selectively blocks a noninactivating subtype of potassium channel.

Animals↗
PubMed1986

A comparison of baseline and cyclophosphamide-induced sister chromatid exchanges in bone marrow and spleen cells of mouse and Chinese hamster.

Baseline sister chromatid exchange (SCE) frequencies were investigated in bone marrow and spleen cells of mice and Chinese hamsters. No significant difference in SCE frequency was noted for bone marrow in both species and for bone marrow and spleen in mice on per cell and per pg DNA basis. However, a significant difference was noted between species in spleen and between cell types in Chinese hamsters. Also, statistically significant differences were noted between species for both cell types when the same data were expressed on per chromosome basis. SCE levels in cultured bone marrow and spleen cells after intraperitoneal administration of the antineoplastic drug cyclophosphamide (10 and 20 mg/kg) differed significantly in mice and Chinese hamsters on per cell, per pg DNA content, and per chromosome basis. The spleen cells were much more sensitive to the effects of cyclophosphamide than bone marrow cells in both species. The replicative indices did not differ significantly between treated and control animals in either bone marrow or spleen cells of both species. Since SCE frequency is a sensitive measure of DNA damage, and bone marrow and lymphocytes are the most widely used cell types in human and animal in vivo assays, the methodologies and results reported here may be useful for comparative mammalian cytogenetic studies.

Animals↗
PubMed1986

Administration of MPTP to the common marmoset does not alter cortical cholinergic function.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4-dihydroxy-phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate-putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4-6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetylcholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Dendrotoxin: a selective blocker of a non-inactivating potassium current in guinea-pig dorsal root ganglion neurones.

The voltage clamp technique was used to study the effects of dendrotoxin (DTX) on outward potassium currents in internally perfused dorsal root ganglion neurones of guinea-pig. Sodium currents were eliminated by tetrodotoxin (TTX, 2 mumol/l), calcium currents and calcium-activated potassium conductances were abolished by intracellular perfusion of cells with KF. Depolarizing voltage shifts from a holding potential of -90 mV yielded a fast transient outward current (IfK) and a delayed non-inactivating outward current (IsK). These currents could be separated by shifting the membrane potential to -50 mV, where IfK was almost completely inactivated. DTX, at concentrations of 0.14-1.4 nmol/l selectively reduced a portion of the non-inactivating potassium current, leaving the transient outward current unaffected. Once manifested, the action of DTX could not be reversed by washing. The I-V characteristic of the current blocked by DTX is almost linear and quite different from the one of the 'DTX-resistant' portion of IsK, which shows a non-linear I-V curve. Tetraethylammonium (TEA, 30 mmol/l) strongly reduced IfK and IsK. However, subsequent application of DTX was still able to further reduce IsK. 3,4-diaminopyridine (3,4-DAP, 500 mumol/l) unselectively reduced IfK and a portion of IsK. The remainder of the latter could not further be reduced by DTX, suggesting a similar action of the two blockers on non-inactivating potassium currents. From the results presented, it is suggested that dendrotoxin selectively blocks a non-inactivating subtype of potassium channel.

4-Aminopyridine↗
PubMed1986

Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates.

We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists between metabolic detoxication and resistance to infection in normal mice was altered during a short-term preexposure to CD or DE.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Medical and industrial hygiene characterization of the cotton waste utilization industry.

We studied 260 workers in the cotton waste utilization industry and 310 "blue-collar" control workers from nondusty industries in the same geographic area of the United States by respiratory symptom questionnaire and by pre- and postshift spirometry. We excluded 75 cotton workers and 75 control workers from statistical analysis because of prior hazardous occupational exposures. Plant-wide, 8-hour time-weighted average exposures ranged from 0.28 mg/m3 to 7.80 mg/m3. The overall prevalence of symptoms compatible with byssinosis was 5.9% in cotton workers and 4.7% in the controls. Cotton workers with less than 2 years of employment had a significantly greater prevalence of bronchitis than their control counterparts. The cotton workers with 2 years or more of employment had significantly greater prevalences of bronchitis, shift decrement in forced expiratory volume in 1 second (FEV1) of greater than or equal to 10%, and FEV1/FEV1-predicted less than 80%, than their control counterparts. Regression analysis showed that for matched cotton and control workers, the percentage decrement in FEV1 over the shift was significantly greater for cotton workers; and that in all cotton workers, longevity in industry had a negative effect on the before-shift forced vital capacity (FVC). This study suggests that there are both acute and chronic effects of cotton exposure in the cotton waste utilization industry.

Adult↗
PubMed1985

Spirometry reference values for nonexposed blue-collar workers.

Epidemiologic research into occupationally related lung disease often requires the comparison of a study population with an external reference group. To establish such a reference group, carefully selected blue-collar workers who had no obvious adverse occupational pulmonary exposure performed simple spirometry, were administered a standard questionnaire, and had standard chest roentgenograms taken. Prediction equations were established for six pulmonary function indices, and a method is given for using these equations to compare a study group with this external nonexposed group. Asymptomatic nonsmokers with negative roentgenograms were extracted from the overall group, and comparison with published data for other such normal groups indicated that the present group is similar to most of them, indicating that there are no serious biases in the present group.

Adult↗
PubMed1984

Prevalence of chest symptoms in nonexposed blue-collar workers.

Epidemiological investigations of lung disease induced by occupational exposures often require prevalence estimates for various respiratory symptoms in subjects without the exposure in question. A standard respiratory questionnaire was administered to carefully selected, nonexposed blue-collar workers (n = 1,372), and linear logistic prediction equations were developed for nine symptoms. For each smoking status, equations were fit employing race, sex, age, height, weight, and education as independent variables. These results can be used as descriptive statistics, as prediction equations from an external control group, and as a guide for selecting risk factors for adjustment of symptom prevalences in other population studies.

Adult↗
PubMed1984

Low-dose chronic inhalation of diesel exhaust and/or coal dust by rats: effect of age and exposure on lung and liver cytochrome P-450.

Rats were exposed by inhalation to low levels of diesel exhaust and/or coal dust, seven hours/day, five days/week for 24 months. Cytochrome P-450-associated benzo[a]pyrene hydroxylase and 7-ethoxycoumarin deethylase activities were assayed in lung and liver microsomes after 3, 6, and 24 months. When data were analysed across all time intervals and adjusted for age, lower benzo[a]pyrene hydroxylase activity was observed in lung microsomes from rats exposed to diesel exhaust plus coal dust than in those exposed to coal dust alone. Data are discussed in terms of interaction between diesel exhaust and coal dust and effect of infectious agents.

7-Alkoxycoumarin O-Dealkylase↗