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PubMed1980

[Normal values for the hemoglobin content, hematocrit and the average corpuscular hemoglobin concentration in calves for rearing: fall study, 1976].

Raised calves were analysed for their frequency distributions of haemoglobin, haematocrit, and mean corpuscular haemoglobin concentration, depending on phases of keeping, in two cross-section (n = 146 and 196) and one longitudinal section studies (the latter on three dates, n = 149, 144, and 141). Race, birth weight, age, and live weight of the calves and their fathers as well as lactation age of their mothers were used for reference. All animal groups exhibited at any time of testing significant deviations from Gauss' distribution in all tests undertaken to verify the normality of frequency distributions of the above haematological variables. Those frequency distributions exhibited clearly visible variations, depending on phases of keeping. A concept to meet such conditions is proposed for evaluation of all variables of the red blood count.

Aging↗

PubMed1984

Binaural interactions of single neurons in posterior field of cat auditory cortex.

In the auditory cortex of barbiturate-anesthetized cats, the posterior auditory field (area P) was identified by its tonotopic organization, and single neurons in that field were studied quantitatively with regard to their binaural interactions at their respective best frequencies, using calibrated, sealed stimulating systems. Almost 60% of the neurons studied displayed " summative " binaural interactions in that their responses to binaural, equally intense stimulation of the two ears were stronger than were their responses to monaural stimuli of the same intensity. For these neurons, latent periods were shorter for binaural stimuli than for monaural stimuli. Some field P neurons were sensitive to interaural intensity disparities and manifested that sensitivity in one of two forms. Cells that were excited by stimulation of one ear and inhibited by stimulation of the other typically displayed a sigmoidal relation of spike count to intensive disparity, with spike counts being larger when the disparity favored the contralateral ear. Cells that were unresponsive to monaural stimuli but responded securely to binaural stimuli usually displayed a peaked, nonmonotonic relation of spike count to interaural intensity disparity, with maximal responses being elicited by stimuli with zero or near-zero disparity. Some neurons of low best frequency were sensitive to variations in interaural phase delay. In all cases, this sensitivity was manifested as a cyclical relation of spike count to interaural delay, with the period of the cycle being that of the stimulating tone. The fact that the binaural interactions of field P neurons were similar to those of cells in the primary auditory cortex suggests that the previously described heightened spectral-amplitude selectivity of field P neurons has been achieved without cost to their sensitivity to a variety of parameters of binaural stimulation. The particular sensitivity of cortical neurons to variations in interaural disparities associated with midline or near-midline azimuths might constitute a neural mechanism for the behavioral finding that animals and humans show their greatest acuity in sound localization for stimulus locations in or near the midsagittal plane.

Animals↗

PubMed1997

E-selectin plasma concentration is influenced by glycaemic control in NIDDM patients: possible role of oxidative stress.

Although elevated levels of soluble E-selectin and intercellular cell adhesion molecules-1 (ICAM-1) have been reported in non-insulin-dependent diabetes mellitus (NIDDM), it is not clear by what mechanism this elevation occurs and whether or not it is related to glycaemic control. In this study we analyse: 1) the relation of glycaemic control with the concentrations of E-selectin, vascular cell adhesion molecules-1 (VCAM-1) and ICAM-1 in NIDDM patients: 2) whether metabolic control can affect the oxidative stress (as measured by plasma hydroperoxide concentration and susceptibility of LDL to in vitro oxidation) and hence the adhesion molecule plasma concentrations. Thirty-four (19 males and 15 females) poorly controlled NIDDM patients were studied. All parameters were evaluated at the beginning of the study and after 90 days of dietary and pharmacological treatment. The treatment decreased HbA1c (p < 0.001), E-selectin (p < 0.001), plasma hydroperoxides (p < 0.003) and the susceptibility of LDL to in vitro oxidation (lag phase) (p < 0.0001). Before treatment HbA1c, lag phase and lipid hydroperoxides correlated with E-selectin plasma concentration (r = 0.51, -0.57 and 0.54, respectively, p < 0.01). There was also a correlation between HbA1c and lag phase (p < 0.01) and between HbA1c and lipid hydroperoxides (p < 0.01). In addition, the variations of HbA1c, lag phase and lipid hydroperoxide values correlated with those for E-selectin concentration after 90 days' treatment (r = 0.54, -0.64 and 0.61, respectively, p < 0.01). In multiple linear correlation analysis, however, the partial correlation coefficients of HbA1c (basal and variations) with E-selectin concentration (basal and variations) fell to non-significant values (r = 0.12 and 0.25, respectively) when LDL lag phase and plasma hydroperoxides were kept constant. The results indicate that the improvement of metabolic control in NIDDM patients is associated with a decrease of E-selectin plasma levels; they also suggest that glycaemic control per se is not directly implicated in determining E-selectin plasma concentration; glycaemic control could affect E-selectin concentration through its effect on oxidative stress.

Blood Glucose↗

PubMed1999

Characterization of Phase I and Phase II hepatic drug metabolism activities in a panel of human liver preparations.

The role of drug metabolism in drug discovery (lead compound selection) and the traditional role of identifying the enzymes involved in biotransformation pathways (reaction phenotyping) have both relied heavily on the availability and use of a human liver bank. The assessment of drug metabolizing enzyme activity and variability in a series of individual human livers is essential when characterizing the enzymes involved in metabolic pathways (i.e. correlation analysis). In this regard, a human liver bank of 21 samples (14 males, six females, and one unknown) was characterized with respect to the activity of several important drug metabolizing enzymes. The total CYP450 content of the livers ranged from 0.06 to 0.46 nmol/mg microsomal protein. The fold variations found in specific enzyme contents were as follows: CYP1A2 (3x), CYP2A6 (21x), CYP2C9 (8x), CYP2C19 (175x), CYP2D6 (18x), CYP2E1 (5x), CYP3A4 (18x), FMO (2.5x), UDPGT (4x), NAT (7x), COMT (5x), ST (5x), TPMT (3x), and GST (2.5x). In general, the fold variation of the Phase II enzymes was lower compared with the Phase I enzymes, with the exceptions of CYP1A2, CYP2E1, and FMO. Similar data were reviewed from other established liver banks and compared with regard to the relative variability observed in drug metabolizing capacities found in this study.

Arylamine N-Acetyltransferase↗

PubMed1974

Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

Journal Article↗

PubMed1992

Rat circadian rhythms entrain to a descending saw-tooth light intensity cycle.

We reexamined whether rat circadian rhythms entrained to the light intensity cycle of a descending saw-tooth (ST-d) form, in which illuminance decreased rectilinearly from 300 lx to 0 lx in 24 h, and abruptly returned to 300 lx (lights-on time). Ambulation, drinking and subcutaneous body temperature were simultaneously monitored in 5 intact, 5 pinealectomized and 5 orchiectomized rats. Additionally, sleep was monitored in the intact rats. In all the rats, entrainment was confirmed during 65 days' exposure to the ST-d cycle. The waveforms of the entrained rhythms were much modified compared with those during LD 12:12. The estimated activity periods of the entrained rhythms straddled the lights-on time of the ST-d cycle. In all the groups of rats, administration of a single ST-d cycle in constant dim red light produced only delay shifts irrespective of its circadian phase, and there was no significant circadian variation in the magnitude of phase shifts. The results indicate that rat circadian rhythms entrain to the ST-d cycle with an unexpected phase position, which cannot be explained by the phase-response curve.

Animals↗

PubMed1997

Methylphenidate: diurnal effects on locomotor and stereotypic behavior in the rat.

The dose-response relationship and time course of effect on motor activity after a single dose of methylphenidate given at different times of the light/dark cycle was investigated using a computerized infrared activity analysis system. After 5 to 7 days of acclimation and 2 days of baseline activity recording, rats received a single subcutaneous injection of vehicle (saline) or of 0.6, 2.5, 10 or 40 mg/kg methylphenidate at 08:00, 14:00, 20:00, or 02:00. Recording was then resumed for an additional 36 to 48 hours. The locomotor indices analyzed were horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements. Saline and 0.6 mg/kg did not alter motor activity, but 2.5, 10 and 40 mg/kg significantly increased (P < 0.01) motor activity. The time to the maximum effect and the duration of effect increased with dose. Ten mg/kg had the most robust effect on locomotor activity, while the largest dose, 40 mg/kg, elicited a more focused stereotyped activity that limited the amount of forward ambulation. A single injection of methylphenidate had only transient effects. The locomotor stimulating effects of the lower doses were similar whether given during the light or dark phase, despite the large diurnal variations in baseline activity between the activity phases. The stereotypic effects of the highest dose of methylphenidate, however, varied between the light and dark phase, with a smaller stereotypic effect during the dark phase when compared to administration during the light phase.

Animals↗

PubMed1975

Changes in the intensity and pleasantness of human vaginal odors during the menstrual cycle.

Men and women estimated (by the method of magnitude estimation) the pleasantness and intensity of the odors of vaginal secretions sampled from consecutive phases of 15 ovulatory menstrual cycles of four women. On the average, secretions from preovulatory and ovulatory phases were slightly weaker and less unpleasant in odor than those from menstrual, early luteal, and late luteal phases. However, considerable variation in odor patterns was present across cycles from the same donor, as well as across cycles from different donors. These results indicate that human vaginal odors change slightly in both pleasantness and intensity during the menstrual cycle, but do not support the notion that such odors are particularly attractive to humans in an in vitro test situation.

Animals↗

PubMed2005

Calculation of left ventricle relative pressure distribution in MRI using acceleration data.

Measurements of pressure variations within the cardiac chambers could provide important information for clinical assessments of cardiovascular function. In this work an MRI method for evaluating spatial distributions of intracardiac relative pressure is presented. We first calculated pressure gradients from MR maps of blood acceleration by applying the NS equation. We then used an original algorithm to compute pressure distribution in a region of interest (ROI) by minimizing the pressure gradient curl so that the result in a given pixel is independent of the integration path. The method was assessed in five healthy volunteers by means of MR 2D maps of the blood acceleration in the left ventricle (LV) during ejection and filling phases. The pressure variations calculated from acceleration mapping fit the known physiological variations better than those based on velocity maps acquired in the same volunteers. Furthermore, the optimization algorithm presented here produced the same results as iterative algorithms proposed by other authors, but in much less time and without requiring adjustable parameters or boundary conditions.

Acceleration↗

PubMed1985

DNA and S-phase representation in human growth hormone producing pituitary adenomas.

The DNA contents of 33 pituitary adenomas from patients with acromegaly were analysed with flow-cytofluorometry. Degrees of ploidy and the proliferation rate, expressed as percentage of cells in S-phase, were determined. The aim was to compare these morphological and functional tumour properties with clinical and laboratory parameters to establish a possible relation and to further elucidate the characteristics of these tumours. In 15 tumours (45%) diploid DNA pattern were found, while 18 (55%) showed varying degrees of aneuploidy. The frequency of cells in S-phase showed wide variations and were equally distributed in diploid and aneuploid tumours. Duration of symptoms, age at diagnosis, preoperative growth hormone (GH)- and prolactin (Prl)-levels, tumour size and grade of invasive tumour growth as determined by radiological estimations, did not correlate to ploidy or grade of proliferation. The lack of correlation between DNA pattern and proliferation rate in relation to clinical, laboratory and radiological parameters in tumours causing acromegaly contrasts to the documented relation between the degree of ploidy, cells in proliferation and grade of malignancy reported in tumours of other sites. The 55% aneuploid GH producing tumours indicate a certain malignant transformation. The high frequency of cells in S-phase in several GH secreting tumours completes the malignant morphological and functional cell properties. The benign character of tumours causing acromegaly is therefore in contrast to these findings. The lack of clinical significance of the DNA pattern and the frequency of cells in proliferation in GH producing tumours and the benign character despite malignant cell properties in most of these tumours are difficult to explain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1986

Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies.

The PVSG study is unique in that it is prospective and composed of 432 patients randomized to three treatment arms. This study also provides the opportunity for serial studies of numerous sequential biopsies. Large numbers of cases with sequential biopsies covering the entire long course are essential to appreciate the full spectrum of tissue changes in this disease. The PVSG was initiated in 1967 and in mid-1985 approximately one third of the patients are alive and on protocol. For these reasons, the results must still be considered preliminary. Pretreatment biopsies from patients randomized in the PVSG have been analyzed for total cellularity, megakaryocyte concentration, and reticulin content. Considerable variation in these elements was found in these biopsies. Sequential posttreatment biopsies from these patients have also been studied and correlated with the clinical course of the disease. None of the morphologic parameters analyzed was shown to be of prognostic significance. Early in the course of PV the marrow reticulin content is almost always normal. The length of the developmental stage is unknown and the precise timing of the clinical onset may be difficult. Therefore, the 11% of patients that showed a significant increase in reticulin on initial evaluation may have had PV longer than was indicated clinically. If large numbers of sequential biopsies are studied, an increase in reticulin content can frequently be demonstrated during the active phase of the disease and before the onset of the spent phase. Currently 39 patients (9%) have developed the spent phase, or PPMM. PPMM occurred in about the same incidence in the patients treated with myelosuppressive therapy as by phlebotomy alone, the spent phase occurring in 16 patients treated by phlebotomy alone, 11 with chlorambucil, and 12 with 32P. The course of the reticulin fibrosis is slowly progressive. There is some evidence for regression in a few patients in the erythrocytotic phase, but sampling variation cannot be completely ruled out. At this time in the study, AL has developed in 37 patients (8.6%). The incidence of AL is quite low in the phlebotomy group (three cases). Presumably this represents the natural incidence in PV unmodified by therapeutic agents. The frequency is approximately equal and quite high in the chlorambucil and 32P groups. There are 19 cases in the chlorambucil-treated group and 15 in the 32P-treated group. The leukemias that developed in the PV patients occurred either de novo or following PPMM.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed2003

Long-term variations in dissolved trace elements in the Sagami River and its tributaries (upstream area), Japan.

We investigated long-term variations in dissolved chemical species in water sampled from the Sagami River and its tributaries, Japan. The samples were taken monthly from May 1993 to April 2000 at 28 sampling sites in the Sagami River system. In this paper, we concentrate on 17 sites in the upper catchment. Twenty-four major to trace elements (Li, Mg, Al, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, As, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, W, Tl, Pb, U) were determined by using conventional Q-pole ICP-MS with direct nebulizalion. Water flux was measured from 1995. The data for most species were subjected to fast Fourier transformation (FFT) to extract dominant periodicities, their magnitudes, and their phases. Clear seasonal variations were observed for Al, V, As, Rb and Cs at some sampling points, especially in the tributaries. The seasonal variations may be due to either anthropogenic causes, such as irrigation or wastewater discharge, or natural causes, such as water temperature, pH, redox condition, water flux, or activity of microorganisms. We found no correlation with pH. Water temperature may not be a main controlling factor, although the seasonal variability would be correlated with it. Hydrologic factors may have only minor effects. We suggest that most of the seasonal variation might be correlated with the irrigation of rice paddies. It was difficult to identify all the causes of the seasonal variability. To investigate interannual trends, we used centered 12-month moving averages to eliminate seasonal variations. The water quality of the uppermost streams was generally constant, being controlled by springs on Mt. Fuji. However, in 1993 and 1998, V, As, Rb, Cs and U were depleted briefly, possibly by dilution by overflow from Lakes Kawaguchi and Yamanaka. Hydrologic factors may be more important for interannual variability than seasonal variability. Some heavy trace elements (Zn, Ni, Cd and Sb) showed very irregular variations with high concentration peaks. These elements were discharged from either factories or abandoned mine tailings.

Journal Article↗

PubMed1990

The ferritin family of iron storage proteins.

The ferritins are a family of proteins produced in a variety of amounts and types depending on the state of development of an animal, or the state of differentiation of a particular cell type, or the environment. Iron storage is the main function of the ferritins when iron is needed for intracellular use (housekeeping) for iron proteins such as ribonucleotide reductase, cytochromes, oxidases, nitrogenases, or photosynthetic reaction centers or for extracellular use by other cells (specialized). Under abnormal conditions, such as the breach of transferrin-receptor-controlled incorporation of iron, ferritin can also serve to detoxify excess intracellular iron. The structure of ferritin is very complex, consisting of a protein coat of 24 polypeptide subunits, approximately 20 kDa, which surrounds an inorganic phase of hydrous ferric oxide. The polypeptide subunits, bundles of four alpha helices, display remarkable conservation of sequence among plants and animals, which is probably related to the necessity of forming the hollow sphere pierced by 14 channels through which iron may pass. In spite of the conserved regions of sequence, there are multiple genes for ferritin polypeptide subunits within an organism; at the moment three distinct subunit types, H H'(or M), and L, have been identified which are expressed in a cell-specific fashion. How many different subunit types exist, the influence on function, and the number of genes required to encode them are currently being actively investigated. Not only does the protein coat of ferritin display variations, the inorganic phase of ferritin can vary as well. For instance, differences can occur in the number of Fe atoms (up to 4500), as well as in the phosphorus content and in the degree of hydration and order. Such observations have depended on the use of a variety of physical techniques such as X-ray diffraction, EXAFS, and Mössbauer spectroscopy. The same approaches, as well as EPR spectroscopy, have been used to monitor the path taken by Fe as it passes from mononuclear Fe(II) outside the protein coat to polynuclear Fe(III) inside the protein coat. Both mononuclear Fe(II) and Fe(III) have been observed, as well as dimeric Fe(II)-O-Fe(III), and Fe(III)-oxo bridged clusters attached to the protein. A possible protein site for the Fe(III) cluster is a groove on the inner surface of the dimeric interface, suggested by the structure and from the affect of natural cross-links between subunit pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2001

Unusual effects of separation conditions on chiral separations.

Unusual effects in liquid chromatographic separations of enantiomers on chiral stationary phases are reviewed with emphasis on polysaccharide phases. On protein phases and Pirkle phases reversal of the elution order between enantiomers due to variation of temperature and mobile phase composition has been reported. Most of the nonanticipated observations have dealt with the widely used polysaccharide phases. Reversed retention order and other stereoselective effects have been observed by variation of temperature, organic modifier and water content in nonpolar organic mobile phases.

Chromatography, Liquid↗

PubMed2000

Gene families encoding phase- and size-variable surface lipoproteins of Mycoplasma hyorhinis.

A prototype family of seven genes encoding the variable surface lipoproteins (Vlps) of Mycoplasma hyorhinis is characterized in the pathogenic SK76 strain, using long-range PCR to amplify and analyze the single chromosomal region containing expressed genes vlpA to -G, each of which is subject to phase and size variation. Smaller families of vlp genes in subclones of SK76 or in another strain of M. hyorhinis, GDL, can be attributed to deletions of specific vlp genes from the prototype array described here. Two genes, vlpA and the newly revealed vlpG, contain repeat motifs in their 3' coding regions that differ from the short tandem repeats in other vlp genes yet retain structural features common to all vlp gene products. SK76 and GDL vlp gene families are similarly organized and show sequence similarity between corresponding individual vlp genes. In light of the extensive potential for diversity within the vlp gene system, such conservation provides a provisional basis to hypothesize that vlp genes may exist in specific arrays that endow selected functions while retaining common structural features required during phase-variable expression of this set of gene products.

Amino Acid Sequence↗

PubMed1979

The evaluation of uterine activity: a comparative analysis.

In this study a comparison is made between the most widely accepted method of expressing uterine activity, Montevideo units, and an automated on-line method expressed as uterine activity units. Although the actual numerical expression differs, the percentage of variation when the two values are compared is small at various phases of labor. The variation between the methods for uterine activity required to progress from 4 to 6 cm cervical dilatation and from 6 to 10 cm cervical dilatation is less than 5%. Both methods closely agree on the actual expression of uterine activity or uterine work.

Amniotic Fluid↗

PubMed1985

Acute phase response in infectious disease.

In considering the pathology associated with infectious diseases, the most common host response to such infection is inflammation. The mechanism(s) whereby inflammation is initiated and the cell types involved will dictate the kinds of acute phase plasma changes that can be seen associated with the infection. Bacteria seem to initiate the classical type of inflammatory response and plasma protein changes similar to those seen in experimental inflammation induced by chemical means. Viruses, on the other hand, in the absence of cytopathology do not appear to induce the same kind of inflammatory changes and avoid the induction of the acute phase protein response since they may not initiate activation of monocytes and/or macrophages. Those viruses that do cause macrophage activation would be expected to have acute phase protein changes associated with that activation. Parasites, however, appear to initiate the acute phase plasma response only when their migration leads to tissue destruction and local inflammation such as caused by parasitemia with Trypanosoma cruzi in the mouse or with migration of Nippostrongylus brasiliensis in the rodent. Human parasitic diseases require much more investigation in order to clarify the role played by acute phase proteins in the subsequent establishment of the host-parasite relationship. We postulate that the macrophage or monocyte on interaction with the infectious pathogen becomes activated and secretes a number of factors, including interleukin 1 and hepatocyte-stimulating factor, which have a marked effect on the total acute phase reaction. In addition to an effect on phagocytic and immune systems, the mediators cause hepatocytes to markedly increase the secretion of plasma acute phase proteins. Some of these proteins return to the site of inflammation and interact with the infectious pathogen and/or cells and proteins of the host, thereby affecting the final outcome of inflammation. We also propose that the initial interaction of an organism such as a parasite and the mammalian host involves early recognition by the macrophage, thereby initiating both the humoral and cellular acute phase reactions and subsequently affects the immune response against the parasite. Variations in the acute phase reaction may help to explain differences in susceptibility to infectious organisms and the presence or lack of host killing mechanisms for the parasite.

Acute-Phase Proteins↗

PubMed1984

[Modulated parasystole. An arrhythmia waiting for diagnostic criteria. Deductive analysis of a case].

We report a case of ventricular parasystole in which the long interectopic intervals are always less than a multiple of the short interectopic intervals. Assuming a regular ectopic discharge, the above said phenomenon could theoretically be due to relative prolongation of the short interectopic intervals caused by delayed ectopic-ventricular conduction of the second consecutive conducted impulse (a Wenckebach-like phenomenon). Nevertheless, this hypothesis may be ruled out in this case by the analysis of a long tracing. The unusual relationship between the interectopic intervals may be explained assuming the modulation of the parasystolic activity by sinus beats. Experimental work has shown that despite the protection (or entrance) block, the sinus or dominant rhythm may affect the automaticity of a parasystolic focus by means of electrotonic influence. It has been pointed out that sinus impulses falling in the first part of the ectopic cycle delay the next ectopic discharge, while relatively late sinus beats (falling in the last 30-40% of the ectopic cycle) are able to anticipate the delivery of the parasystolic impulse. The phenomenon of modulation is marked by a characteristic biphasic phase-response curve. In the reported case a phase-response curve has been obtained, which explains the parasystolic cycle variations according to the phase of the cycle in which the sinus beats fall. The obtained curve is quite similar to those observed experimentally, therefore the diagnosis of modulated parasystole appears to be very likely.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗