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PubMed2006

The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models.

Thermoregulation is an integrated network of neuroendocrine, autonomic and somatosensory responses. Thermoregulatory dysfunction occurs during fluctuations or decline of gonadal hormone levels and results in vasomotor symptoms such as hot flushes and/or night-time sweating. The neurotransmitter serotonin (5-HT), has been reported to play a role in thermoregulation via changes in extracellular 5-HT levels and/or activation of various 5-HT receptors. The purpose of this study was to evaluate the role of the selective 5-HT reuptake inhibitor (SSRI), fluoxetine (FLX), on temperature regulation using ovariectomized (OVX) rodent models of thermoregulation. Single, subcutaneous (s.c.) administration of FLX (3, 10, 30 and 60 mg/kg) dose-dependently reduced core body temperature (CBT). FLX at 3 and 10 mg/kg s.c. showed no statistically significant decrease on tail-skin temperature (TST), whereas at higher doses (30 and 60 mg/kg) a significant decrease in TST was noted in the telemetry model. To mimic chronic SSRI treatment, a 5-HT(1A) antagonist (WAY-100635; 0.3 mg/kg) was administered 20 min prior to FLX (10 mg/kg). This combination showed no significant improvement on temperature dysfunction compared to FLX alone. Similarly, in a morphine-dependent model of temperature dysfunction FLX, was inactive at 10 mg/kg whereas the 30 and 60 mg/kg s.c. dose abated the naloxone-induced increase in TST by 55 and 81%, respectively. In summary, FLX affected CBT at all doses, but alleviated thermoregulatory dysfunction only at higher doses that are non-selective for the 5-HT system.

Animals↗
PubMed1994

Selection for eight-week body weight in two randombred chicken populations under altered water to feed ratios. 1. Selection responses.

A study was conducted to investigate the response to selection for 8-wk BW under selection environments that utilized different dietary salt levels to alter water to feed ratios. The Athens-Canadian (AC) and Athens Randombreds (ARB) served as base populations. A broiler diet consisting of 23% CP and 3,120 kcal of ME/kg was modified to contain .2, .4, and 1.6% dietary salt. Chicks from the AC and ARB populations were divided within full-sib families into three groups, with one group assigned to each of the three dietary salt selection environments. Individual phenotypic selection was conducted within the six lines for high 8-wk BW for six generations with unselected randombred controls included in each generation to measure environmental variation. No differences in 8-wk BW were observed among the three salt selection environments. Lines derived from the ARB population were initially approximately 75 g larger than those derived from the AC population. However, when BW were expressed as percentage deviation from the control in the sixth generation, selection response patterns were similar (AC lines, 28 to 32%; ARB lines, 32 to 36%). These data indicated that selection for 8-wk BW was as effective under high- and low-salt diets as under a normal-salt diet. Realized heritabilities, following correction for environmental variation, ranged from .38 to .46. Failure to correct for environmental variation resulted in large fluctuations in heritabilities across generations. These data provide strong support for inclusion of controls to accurately measure the heritability of BW in selection studies.

Age Factors↗
PubMed1975

Cell cycle specific fluctuations in adenosine 3':5'-cyclic monophosphate and polyamines of Chinese hamster cells.

Chinese hamster V79 cells were synchronized by mitotic selection, which resulted in approximately 95% synchrony. The adenosine 3':5'-cyclic monophosphate level was elevated within 3 hr (G1 phase) and reached a level 2-fold higher than in early G1 within 6 hr (early S phase). An increase in ornithine decarboxylase activity (6-ornithine carboxy-lyase, EC 4.1.1.17), the initial enzyme in the polyamine biosynthetic pathway, was detected within 4 hr and was maximal at 8 hr. Since about 20% of the cells were labeled with [3-H]thymidine at 4 hr, ornithine decarboxylase exhibits cell-cycle specific activity starting in late G1 and continuing through middle S phase. The activity of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxylase, EC 4.1.1.50) increased within 5 hr, i.e., early S phase. It is suggested on the basis of these data and other studies discussed herein that the increase in ornithine decarboxylase activity, which parallels closely the elevation in cyclic AMP, is an example of adenosine 3':5'-cyclic monophosphate-mediated protein synthesis.

Adenosylmethionine Decarboxylase↗
PubMed1995

Fluctuations in visual neglect after stroke?

Clinical experience suggests that the visual neglect in stroke patients fluctuates over short periods of time. This fluctuation has been variously attributed to fatigue, time of day, previous activities, patient learning and compensation. Such fluctuations have clinical implications for the assessment and rehabilitation of visual neglect but do date no formal study has evaluated the extent of such fluctuation over the course of a day. Twenty-two patients with an acute stroke and 19 patients with convalescent stroke were examined for visual neglect twice on the same day using the Visual Neglect Recovery Index (VNRI), a valid and sensitive measure of the severity of neglect, which could be used to select acute patients for trials of treatment of neglect. The inter-test reliability was extremely high. In contrast to past clinical accounts most patients failed to show significant fluctuation. Although preliminary, this finding suggests that a single assessment of visual neglect, using the VNRI, could help select patients for treatment trials.

Aged↗
PubMed1994

Cyclic changes in the concentrations of peripheral blood immune cells during the normal menstrual cycle.

The optimal availability of immune cells in the peripheral blood streams of women may play a critical role in their response to disease and therapeutic interventions. This study was designed to examine concentrations of circulating white blood cells (WBC) including lymphocyte subsets, during the 24-hr daily and 28-day menstrual cycles. Venous blood (20 ml) from five healthy young women was obtained at 0, 6, 12, and 18 hr on the 6th and 22nd day of the normal menstrual cycle. Cortisol, progesterone (P4), estradiol (E2), total WBC, granulocyte, monocyte, and total lymphocyte levels were measured. Using fluorescent activated cell scanning, levels of T, B, Helper (H), Suppressor (S) and Natural Killer (NK) cells were also determined. Significant differences in the diurnal and Day 6 and 22 means were identified using analysis of variance and the Student's t test. Mean WBC counts differed significantly between individuals and ranged from 3.63 +/- 0.33 to 8.60 +/- 1.00 on Day 6 and 3.75 +/- 0.56 to 9.45 +/- 0.98 on Day 22 (P < 0.05). Fluctuations in the concentrations of peripheral blood immune cells followed a similar pattern for the time points selected. They were lowest in the morning at 6 hr and reached peak concentrations in the evening at 17 hr or at midnight at 24:00 hr. Total WBC and granulocyte levels were consistently highest in the evening at 18 hr while lymphocyte levels either peaked in the evening or at midnight. Between midnight and early morning, levels of WBC, lymphocytes, T, B, H, and S cells all decreased significantly (P < 0.01) and subsequently increased significantly, between 6 hr and noon or noon and 18 hr (P < 0.01). When compared every 12 hr, the levels of WBC, granulocytes, lymphocytes, T, B, H, and S cells showed a significant day time rise between 6 and 18 hr (P < 0.02). NK cells revealed no significant fluctuations for any of the diurnal time point comparisons examined in this study. The WBC means for all subjects on Day 6 was 6.15 +/- 1.96 and on Day 22 was 6.39 +/- 2.14, evidence that the total number of white blood cells was not significantly altered between the 2 days. However when comparing specific time points during the day for the follicular (Day 6) and luteal (Day 22) phases of the menstrual cycle, significant differences were found. Most striking were the monocyte patterns, which revealed a nadir at 12:00 noon on Day 6 and a peak at the same time on Day 22.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1998

Three-dimensional spiral fMRI technique: a comparison with 2D spiral acquisition.

A comparison study was performed of 3D and 2D spiral k-space fMRI techniques using BOLD contrast with a 4.25-min finger-tapping task paradigm. The 3D sequence uses the conventional 2D spiral technique in conjunction with Fourier phase encoding in the slice select direction. Characteristics that were compared included image appearances, signal-to-noise ratio (SNR), fluctuation noise, functional contrast-to-noise ratio (fCNR), detected activation areas, inflow effect, and large vessel involvement. The results showed that, with constant total scan time, the 3D spiral acquisition has higher SNR and fCNR despite its slightly higher fluctuation noise. The capability for thin-slice incoherent averaging is a further advantage of 3D over 2D. With these advantages as well as its intrinsic ability for contiguous slices and image reformatting, the 3D spiral fMRI technique may be superior to its 2D counterpart.

Brain Mapping↗
PubMed1995

Holding on to success: a case study in mental health care reform.

This article analyzes the changes experienced by a mental health care organization in response to environmental threats and fluctuating expectations. On a general, more theoretical level, the article demonstrates how processes of environmental selection as well as organizational adaptation shape organizational forms. On a concrete, applied level, those administrative practices are articulated that can help ensure that reform efforts are successful. Administrators also must be aware of the inertial forces operating upon stable organizational forms and work to ensure that the organization remains vital and open to change.

Community Mental Health Centers↗
PubMed1988

Apheretic treatment of severe familial hypercholesterolemia: comparison of dextran sulfate cellulose and double membrane filtration methods for low density lipoprotein removal.

The two more widely available techniques for the extracorporeal removal of low density lipoproteins (LDL), dextran sulfate cellulose column and double membrane filtration, were comparatively tested in severe familial hypercholesterolemic patients, both acutely and during a continued 3-month treatment. The selective dextran sulfate procedure removed close to 60% of LDL and 16% of high density lipoproteins (HDL) upon each apheresis, vs. 42% and 32%, respectively, in the case of the semi-selective double membrane filtration. Upon long term biweekly treatments, LDL-cholesterol (LDL-C) decreased, with the selective procedure, from a pre-treatment level of 406.0 +/- 40.7 mg/dl to a value fluctuating between 295.4 +/- 33.8 mg/dl and 116.9 +/- 22.0 mg/dl (highest vs. lowest levels) whereas, in the case of double membrane filtration, LDL-C levels ranged between 334.8 +/- 39.8 mg/dl and 192.3 +/- 49.9 mg/dl. HDL-cholesterol levels were somewhat raised, to a higher extent with dextran sulfate apheresis. The LDL/HDL-cholesterol "atherogenic ratio", decreased from a pre-treatment value of 10.27 +/- 3.04 to values ranging between 3.61 and 6.82 with dextran sulfate and between 6.70 and 7.68 with double membrane plasmapheresis.

Adult↗
PubMed1984

Isolation and characterization of mutator mutants from cultured mouse FM3A cells.

A method to select mutator mutants was developed and 3 mutants were isolated from cultured mouse FM3A cells. Fluctuation analyses revealed that these mutator mutants have increased rates of spontaneous mutation at 3 genetic loci tested (resistance to ouabain, blasticidin S and tunicamycin). None of the 3 mutator mutants showed altered sensitivity to aphidicolin or arabinofuranosylcytosine, and so they differed from the mammalian mutator mutants reported previously. Also, all the mutator mutants had the same sensitivity as wild-type to UV or other DNA-damaging agents. Thus, these mutator mutants do not seem to have any deficiency in the DNA-repair process. To determine whether the mutator activity was due to the intracellular dNTP pool imbalance, 4 dNTPs in these mutator mutants were determined by high-pressure liquid chromatography and compared to that of the wild-type cells. The results show that there is no large dNTP pool imbalance in these mutator mutants. Since the mutator activity is not associated with the dNTP pool imbalance, these mutants may have altered protein(s) directly involved in DNA replication.

Animals↗
PubMed2004

Changes in lipid class and fatty acid composition during development in white seabream (Diplodus sargus) eggs and larvae.

To establish the changes which occur during embryogenesis and early larvae development, eggs, yolk-sac larvae (one day old larvae) and absorbed yolk-sac larvae (three day old larvae) of white sea bream were examined for lipid class and fatty acid composition. The development was characterized by a decrease in all lipid classes with the exception of phosphatidylserine (PS) and fatty free acids (FFA) which increased, and sphingomyelin (SM) which remained unchanged. The changes observed in lipid class content and the decrease in fatty acids in total lipid (TL) reflect the utilization and mobilization of lipids during both embryogenesis and early larvae development. Fluctuations in the relative composition of fatty acids in phosphatidylcholine (PC) during development suggest a selective bulk uptake and catabolism of fatty acids in this lipid class. Unlike PC, catabolism of triacylglycerol (TG) fatty acid appears to be non-selective. During development, the decrease in levels of polyunsaturated fatty acids (PUFA) eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) in total lipid denotes their utilization as energy substrate by Diplodus sargus larvae.

Age Factors↗
PubMed1991

Examination of subconductance levels arising from a single ion channel.

Single-channel records often show frequent currents at a main conductance level and occasional currents at subconductance levels. In some instances, the conductances occur at regular levels that are multiples of a minimum conductance. It is well-appreciated that multiple conductance levels may arise either from the co-operative gating of more than one pore or from changes that occur in a single pore. In this paper, we used theoretical models of ion permeation to examine subconductances arising in a single-pore channel. In particular, the work focuses on the following question: how can an ion channel that provides only one aqueous pore through the membrane produce regular subconductances and a main conductance that all have the same selectivity and the same ion binding affinity? The three types of ion permeation models used in this study showed that a single-pore channel can have subconductances because of long-lived conformational states, because of alterations in rapid fluctuations between conformational states, or because of slight alterations in the electrostatic properties in the channel's entrance vestibules. Regular subconductances with the same selectivity and binding affinity can arise in a single pore even if the energy profile changes do not meet the constant peak offset condition. The results show that the appearance of regular subconductance levels in a single-channel recording is not sufficient evidence to conclude that identical pores have co-operative gating, as would arise in a channel that is a multi-pore complex.

Animals↗
PubMed1992

Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours: correlation with steroid receptors.

The frequency of oncogene amplification described in the literature shows a large fluctuation, which could be attributed to the study of relatively small series of tumours, to selection of subgroups of patients, or, especially in retrospective studies, to selection of tumour material from the tumour-bank. To address this question, we have studied amplification of c-myc, HER2/neu and int-2/bcl-1 genes in a series of 1052 collected human breast tumours. The retrospective and prospective subgroups in this collected series of tumours were of equal size. c-myc was amplified in 17.1%, HER2/neu in 18.7% and int-2/bcl-1 in 14.1%, of all breast cancer specimens studied. In the retrospective subgroup the prevalence of amplification was 18.1% for c-myc; 22.6% for HER2/neu and 11.6% for int-2/bcl-1, whereas in the prospective subgroup an incidence of amplification of 16.1%, 15.1% and 16.3% for c-myc, HER2/neu and int-2/bcl-1, respectively was observed. HER2/neu amplification was negatively correlated with oestrogen receptor (ER) and progesterone receptor (PR) status (P less than 0.0001; for both), c-myc amplification was more prevalent in the PR-negative subpopulation (P less than 0.05) and int-2/bcl-1 amplification was positively correlated with ER status (P less than 0.001).

Breast Neoplasms↗
PubMed2000

Fluorescence pharmacokinetics of Lutetium Texaphyrin (PCI-0123, Lu-Tex) in the skin and in healthy and tumoral hamster cheek-pouch mucosa.

We have investigated the pharmacokinetics (PK) of Lutetium Texaphyrin (Lu-Tex), a second-generation photosensitizer, in the Syrian hamster cheek pouch early cancer model. Ten male hamsters, five with chemically induced early squamous cell cancer of the left cheek pouch, received an intracardiac injection of a 10 mg/ml Lu-Tex solution, resulting in a dose of 12 mg Lu-Tex per kg of bodyweight. The PK of the dye have been measured during the 24 h following the injection with an optical-fiber-based spectrofluorometer on the ventral skin, the healthy and the tumoral cheek-pouch mucosa. The Lu-Tex fluorescence is excited at 460 nm and detected around 740 nm. All the measurements yield very similar pharmacokinetic curves. The fluorescence intensity reaches a maximum between two and three hours after the injection and, at its maximum, it is consistently higher (up to 1.5 times) on the tumor than on the healthy mucosa. It remains smaller on the skin than on cheek-pouch mucosa. After 24 h, the Lu-Tex fluorescence is no longer detectable either on the skin, on the lesion or on the healthy mucosa. Moreover, Lu-Tex clearly displays a significant fluorescence selectivity between early carcinoma and healthy mucosa in this model. Furthermore, the inter-animal fluctuations of the fluorescence signal are small (+/-16% on the tumor-bearing mucosa). Eight-minute-long skin-irradiation tests have been performed 24 h after the injection of the Lu-Tex on the ventral skin of 16 additional animals with a solar simulator. No reaction is observed, either macroscopically or microscopically, which further demonstrates, as suggested by the fluorescence measurements, that this photosensitizer is significantly cleared from the skin after 24 h.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

[CTG: microfluctuation].

OBJECTIVE: Microfluctuation (MF) of fetal heart rate (FHR) is regarded as the most sensitive parameter for diagnosing the condition of the fetus. The MF can only be crudely quantified with the naked eye. Therefore the following questions arise: 1) How can MF be exactly measured numerically? 2) What interrelationships are there between the MF determined electronically, the basal FHR, the oscillation amplitude (OA) of the FHR and the beat-to-beat variability (beat-to-beat var.) 3) What are the effects of hypoxia and acidosis on these index parameters? METHODS: 387 intrapartal FHR tracings were registered directly (F-ECG) with the cardiotocograph (HP instruments) via an RS422 interface and stored on diskette. The data were processed further with a computer program we developed ourselves (MATLAB, the MathWorks Inc., USA). The parameters of the fetal acid-base balance were measured in the blood of the umbilical artery (UA) and umbilical vein (UV) with instruments from Radiometer, Copenhagen (ABL 500, ABL 5) and stored off-line with a selection of clinical data and processed further on a laptop (HP, Omnibook XE 3). The fluctuation of the basal FHR was determined on the basis of the following four parameters: the number of high and low points (extrema) per minute (EXT),the mean beat-to-beat variability per minute and the OA (bpm). In order to correlate the MF of the basal FHR with the parameters of the fetal acid-base balance, only the last 30 CTG minutes ante-partum of each tracing were included. All decelerations and optionally in addition all accelerations were electronically deleted from the FHR curve. RESULTS: Basic statistical values and the distribution of the four index parameters in 5486 minutes of basal FHR were studied: the median of EXT is at 59 and the mean value at 58.9 +/- 13.9 extrema/min. The distribution is normal. The median frequency amounts to 138 bpm, the median OA to 22.2 bpm and the median beat-to-beat variability to 161.7 bpm, respectively. The mean pH value in UA blood was 7.262 +/- 0.064. The acidotic risk (pH, UA < 7.100) reached 1.3 %. There were no pH values below 7.0. With increasing basal FHR, EXT increases highly significantly (r = 0.468, P << 0.0000). EXT decreases highly significantly (r = -0.432, P << 0.0000) with increasing OA. The mean basal frequency shows the best correlation with the base excess in UA blood (r = -0.263, P << 0.0000). Beat-to-beat variability and EXT alone correlate poorly with the actual, pH and BE values (UA). Multiplication of the index parameters leads to an increase of the correlation coefficients when compared with their single values. CONCLUSION: With increasing hypoxia and acidosis the four index parameters do show a complex pattern which is characterized by tachycardia, increase of EXT and opening of the OA. A loss of EXT and a reduction of OA seems to be the result of already severe acidosis (pH, UA < 7.000). Using the four parameters of basal FHR alone, there is no possibility to evaluate fetal jeopardization. Numerical combination (e. g., multiplication) of some index parameters ameliorates their prognostic power and should be used in future online scoring procedures.

Acidosis↗
PubMed2000

The performance of several multiple-sequence alignment programs in relation to secondary-structure features for an rRNA sequence.

The performances of five global multiple-sequence alignment programs (CLUSTAL W, Divide and Conquer, Malign, PileUp, and TreeAlign) were evaluated using part of the animal mitochondrial small subunit (12S) rRNA molecule. Conserved sequence motifs derived from an alignment based on secondary structural information were used to score how well each program aligned a data set of five vertebrate and five invertebrate taxa over a range of parameter values. All of the programs could align the motifs with reasonable accuracy for at least one set of parameter conditions, although if the whole sequence was considered, similarity to the structural alignment was only 25%-34%. Use of small gap costs generally gave more accurate results, although Malign and TreeAlign generated longer alignments when gap costs were low. The programs differed in the consistency of the alignments when gap cost was varied; CLUSTAL W, Divide and Conquer, and TreeAlign were the most accurate and robust, while PileUp performed poorly as gap cost values increased, and the accuracy of Malign fluctuated. Default settings for the programs did not give the best results, and attempting to select similar parameter values in different programs did not always result in more similar alignments. Poor alignment of even well-conserved motifs can occur if these are near sites with insertions or deletions. Since there is no a priori way to determine gap costs and because such costs can vary over the gene, alignment of rRNA sequences, particularly the less well conserved regions, should be treated carefully and aided by secondary structure and conserved motifs. Some motifs are single bases and so are often invisible to alignment programs. Our tests involved the most conserved regions of the 12S rRNA gene, and alignment of less well conserved regions will be more problematical. None of the alignments we examined produced a fully resolved phylogeny for the data set, indicating that this portion of 12S rRNA is insufficient for resolution of distant evolutionary relationships.

Algorithms↗
PubMed1990

Biliary sludge: a critical update.

Biliary sludge has been for many years a poorly defined entity, usually with low amplitude, nonshadowing echoes within the most dependent part of the gallbladder, which shift under the influence of postural changes. From a sonographic point of view, the detection of sludge implies the coexistence of small-sized, solid components and of a gel-like embedding material. The chemical nature of biliary sludge has recently been recognized to be predominantly composed of a coaggregate of cholesterol monohydrate crystals and liquid crystalline droplets, and in some cases, such as obstructive jaundice or symptomatic liver diseases, by bilirubin granules, all embedded in a gel matrix of mucous glycoproteins. From a pathogenic point of view, biliary sludge is often associated with biliary stasis, or with conditions characterized by impaired gallbladder contraction, such as prolonged total parenteral nutrition, fasting, and pregnancy. Other causes include mucus hypersecretion, which may favor cholesterol nucleation and crystal growth, and bile infection. Sludge may be an intermediate step in the formation of different types of stones. From an epidemiological point of view, sludge is quite rare in the asymptomatic, free-living population, but may be common in selected series of symptomatic patients. From a clinical point of view, sludge often has a fluctuating course, including frequent disappearances and reappearances, suggesting that the early stages of gallstone formation are reversible.

Bile↗
PubMed1984

Xenopus oocyte resting potential, muscarinic responses and the role of calcium and guanosine 3',5'-cyclic monophosphate.

Resting potential (r.p.) and muscarinic response mechanisms were studied in Xenopus laevis oocytes using the voltage-clamp technique. Insertion of micro-electrodes into the oocyte produced a 'shunt' membrane conductance which partially sealed after a few minutes. The oocyte resting potential (measured with a single intracellular electrode) ranged from -40 to -60 mV. Ouabain and low K+ solution depolarized both follicles and denuded oocytes. The electrogenic Na+-K+ pump was more active in the latter. In the presence of ouabain, the r.p. agreed with the constant field theory. alpha (PNa+/PK+) was 0.12 in follicles and 0.24 in denuded oocytes. beta (PCl-/PK+) was 0.4 in both. At [Na+]o lower than 70 mM, the r.p. deviated considerably from the constant field predictions. The relatively large value of alpha indicated the major role of Na+ in oocyte r.p. determination. The oocyte muscarinic response was separated into four distinct components: the fast depolarizing Cl- current, 'D1'; the slow depolarizing Cl- current, 'D2'; the slow hyperpolarizing K+ current, 'H'; and the large membrane Cl- current fluctuation, 'F'. The H response reversal potential showed a Nernst relationship to [K+] and was selectively blocked by intracellular injection of tetraethylammonium (TEA). The D1 and D2 reversal potential showed a Nernst relationship to [Cl-]. In Ca2+-deficient, EGTA-containing medium, D2 and F were abolished and D1 and H were reduced. Verapamil inhibited all responses. Increasing [Ca2+]o caused a significant increase in D1, D2 and F response amplitudes. Intracellular injection of 0.6-10 pmol guanosine 3',5'-cyclic monophosphate, induced a large outward K+ current, similar to the muscarinic H response.

Acetylcholine↗
PubMed1976

Multiple-aminoglycoside-resistant mutants of Bacillus subtilis deficient in accumulation of kanamycin.

Three classes of spontaneous multiple-aminoglycoside-resistant (mar) mutants of Bacillus subtilis were isolated by plating on a low (1.2 mug/ml) concentration of kanamycin sulfate and were found to be resistant also to low concentrations of paromomycin, neomycin and gentamicin. The three classes could be distinguished one from another by their degree of cytochrome deficiency, respiration deficiency, and susceptibility to kanamycin lethality. A fluctuation test showed that the mutations were spontaneous and not induced by the conditions of selection. Representative strains from two classes of mutants (mar-2 and mar-3) accumulated aminoglycoside very poorly in comparison with the parent strain, whereas a strain of the third class (mar-1) inactivated aminoglycoside present in the growth medium. The mar-3 strain studied (aroD163) had previously been shown to be a menaquinone auxotroph (Farrand and Taber, 1973) and to be deficient in amino acid uptake (Bisschop et al., 1975). Such mutants, which are resistant to low concentrations of aminoglycosides, may be of use in elucidating the biochemical and genetic bases of certain bacterial transport systems.

Aminoglycosides↗