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Biomedical subjects

G David

Publications and source records attributed to G David.

At least 253 records · Page 14Linked to original sources
PubMed1985

On the mechanism by which phenytoin blocks post-tetanic potentiation at the frog neuromuscular junction.

Post-tetanic potentiation (PTP) was elicited at the frog sartorius and cutaneous pectoris neuromuscular junctions. A 30-sec, 30-Hz tetanus produced a 2- to 3-fold post-tetanic increase in endplate potential (EPP). In surface-recorded responses this PTP decayed in a double exponential way with time constants of 12.7 sec +/- 2.4 (SEM) and 146.8 sec +/- 36.6. In acute experiments 0.2 to 0.8 mM phenytoin (5,5-diphenylhydantoin, DPH) dramatically and reversibly reduced the early component. The late component was also reduced, although to a lesser extent and often not reversibly. DPH reduced PTP even when there was no failure of the EPP during the tetanus. Thus, the DPH effect did not require a complete block of the presynaptic action potential. At longer exposures and higher DPH concentrations EPP failures did develop, and this was associated with a more profound suppression of PTP. PTP was also elicited in tetrodotoxin (TTX)-containing solutions using electronic stimulation of nerve terminals to elicit transmitter release. This PTP had a much shorter duration (about 30 sec) than that seen in normal Ringer's solution and was followed by depression of EPP amplitudes. Thus, sodium entry into nerve terminals enables a mechanism which greatly prolongs PTP. DPH had no effect on PTP in TTX. These results, together with others in the literature, suggest that the reduction of PTP by DPH involves a graded reduction of sodium influx into nerve terminals during high rates of axon stimulation. The development of all-or-none failures of the presynaptic action potential results in even greater suppression of PTP.

Action Potentials↗
PubMed1984

Phenytoin reduces frequency potentiation of synaptic potentials at the frog neuromuscular junction.

The action of the commonly used antiepileptic drug phenytoin on frequency potentials was studied at the frog neuromuscular junction. Whereas the drug, at concentrations of 0.1-0.3 mM, had only a slight effect on EPPs evoked by nerve stimulation at a frequency of 0.5 Hz, it strongly suppressed their potentiation during tetanic nerve stimulation at 30 Hz. The post-tetanic potentiation of the EPPs was also reduced by the drug. These effects occurred without a blockade of invasion of the nerve impulse into the presynaptic terminal during the tetanus, and thus indicate a specific frequency-dependent depressant action of the drug on neurally-evoked transmitter release.

Animals↗
PubMed1984

Improved recovery of post-thaw motility and vitality of human spermatozoa cryopreserved in the presence of dithiothreitol.

Semen was collected in the laboratory from nine healthy donors. The concentrations and the percentages of live and motile spermatozoa in all semen samples were within the normal range. Each sample was diluted with citrate-egg yolk-glycerol medium with and without 5 mM dithiothreitol (DTT). Samples were frozen in liquid nitrogen vapor (-70 degrees C) for 7 min and subsequently stored in liquid nitrogen. The effect of DTT in cryopreservation of sperm was determined by comparing percentage of motile and live spermatozoa between controls and DTT-treated post-thaw samples. Percentage of motile spermatozoa was determined by two techniques, laser Doppler velocimetry (LDV) and light microscopy. The percentage of live spermatozoa was measured by microscopic evaluation after staining with eosin-nigrosin. It was shown that the addition of DTT to the freezing medium significantly improved the recovery of motile and live spermatozoa in the post-thaw samples. The mean motility recovery, as measured by LDV, was 44.9% in the controls as compared to 73.9% in the DTT-treated samples. Similarly the mean recovery of live spermatozoa in the controls and DTT-treated samples was 66.5 and 86.6%, respectively. Based on these results, a new hypothesis implicating lipid peroxidation in cryoinjury is proposed. It is also suggested that the use of DTT in the freezing medium may offer an advantage over the commonly used techniques of human sperm cryopreservation.

Cell Survival↗
PubMed1984

Two monoclonal antibodies to two different epitopes of human growth hormone form a precipitin line when counterdiffused as soluble immune complexes.

We have tested whether soluble immune complexes obtained by mixing human growth hormone (hGH) with one anti-hGH monoclonal antibody (MAb) can form a precipitin line when diffused against another MAb in a polyethylene glycol containing gel. By testing seven anti-hGH MAbs one against the other in this assay, we have found that 10 pairs of MAbs out of the 21 possible combinations formed a line. Apparently, the first MAb formed soluble hGH dimers that were linked by the second MAb into precipitating linear complexes. Since each precipitin line was formed by the cooperative reaction of two MAbs, this sequential reaction of MAbs may be used in methods for the positive selection of MAbs that are suitable for two-site immunoassays.

Antibodies, Monoclonal↗
PubMed1984

Pathology of the cytoskeleton of the human sperm flagellum: axonemal and peri-axonemal anomalies.

A quantitative ultrastructural study was performed on 56 ejaculates showing anomalies of the sperm axonemal complex. The anomalies comprised either the absence of one, or more often several, axonemal structures, or defective elongation of the doublets. Several characteristics relating to the extent and superimposition of the various anomalies could be described and enabled the definition of 6 groups of anomalies. In decreasing order of frequency these were: absence of the doublets and peripheral junctions, absence of the central complex, of the outer dynein arms, of the central junctions, of both dynein arms, and absence of the inner dynein arms and peripheral junctions. Some anomalies caused total immobility, whereas others caused abnormal movement patterns. Abnormalities of the peri-axonemal structures were found in each group. The various light microscopic characteristics of each of the 6 groups represented 6 seminal profiles which should permit their detection during a routine semen analysis. Several specific associations of axonemal and/or peri-axonemal anomalies would suggest some morphogenetic links between them. Relationships between the absence of doublets or the absence of the central complex and disturbances of microtubular polymerization are discussed. Finally, the study has provided new data on the composition of the axoneme.

Dyneins↗
PubMed1984

[The tasks and role of pathology among other medical sciences].

The results of discussion on the current state of pathology in medical science and practical hospital work are presented in this paper which is the author's report on the 2nd symposium of the societies of pathologists in socialist countries. Special attention is drawn to the significance of necropsies in comparing clinical and post-mortem diagnoses, the related numerical materials are provided. The decrease of necropsies of patients dying in hospitals in most countries of the world is noted, and the methods of getting rid of this are indicated both for scientific goals and health service. The increasing necessity of contacts between pathologists and clinicians is pointed out and the ways of realization of this important tool for further development of medicine are traced. The comparative data on the methods of training in pathology in many European countries and USA are presented. The paper is concluded by a review on the state of pathology in the GDR, measures taken by the GDR Ministry of Health and by the Society of GDR pathologists. The confidence is expressed in success of these measures in the process of realization by the GDR government of the X Party Congress and the 5th Plenum of the SUPG Decisions on the development of science and its effectiveness.

Autopsy↗
PubMed1983

Transformed mouse mammary epithelial cells synthesize undersulfated basement membrane proteoglycan.

Proteoglycans deposited in the basal lamina of [14C] glucosamine-labeled normal and [3H]glucosamine-labeled transformed mouse mammary epithelial cells grown on type I-collagen gels, were extracted in 4 M guanidinium chloride and cofractionated over Sepharose CL 4B. The heparan sulfate chains carried by these proteoglycans were isolated by treatment with alkaline borohydride, protease K, chondroitinase ABC, and cetylpyridinium chloride precipitation. Heparan sulfate isolated from transformed cell cultures consistently eluted from DEAE-cellulose at lower salt concentrations and was of smaller apparent Mr when chromatographed over Sepharose CL 6B, than heparan sulfate of normal cell cultures. Experiments using doubly labeled cultures ([3H]glucosamine and [35S]sulfate) demonstrated an approximately 30% reduction in the sulfate/hexosamine ratio in heparan sulfate derived from transformed cultures. Both N- and O-sulfate were decreased. The decreased Mr and decreased sulfation of heparan sulfate upon transformation appear sufficient to explain the altered heparan sulfate/chondroitin sulfate ratios previously observed in these cells. These changes may have implications for the molecular interactions in which these proteoglycans are normally engaged during basal lamina assembly, and cause the poor basal lamina formation displayed by these transformed cells.

Animals↗
PubMed1983

Semen characteristics as a function of age in 833 fertile men.

The relationship between age and semen characteristics has been studied; any effect due to the influence of the length of abstinence preceding ejaculation was eliminated. There is an improvement in semen characteristics up to 25 years of age, followed by a leveling off and a subsequent decrease. This variation is not significant as far as the sperm count, semen volume, and the total number of spermatozoa are concerned. The variation, although small, is highly significant for the morphologic characteristics and prefreeze and postthaw motility. The values for the older subjects were significantly lower for postthaw motility in the group 36 to 40 years of age, in the group 41 to 45 years of age for morphologic normality, and in the group 46 to 50 years of age for prefreeze motility. The lower values in the group 21 to 25 years of age are particularly noticeable with regard to morphologic characteristics. The same curve is encountered in the variation with age of each abnormal form, but the most marked variation is found in the increased percentage of coiled tails, which first appears in the group 36 to 40 years of age.

Adult↗
PubMed1983

Ultrastructural morphometry of the human sperm flagellum with a stereological analysis of the lengths of the dense fibres.

The dimensions of the various regions of the flagellum and the length of each of the dense fibres has been determined by transmission electron microscopy of a large number of spermatozoa from ten men. The overall mean length of the flagellum was 60.5 micron, and its diameter diminished from 0.88 micron in the midpiece to 0.17 micron at the terminal filament. The midpiece and terminal filament as measured in longitudinal sections had variable lengths among spermatozoa (3.4 +/- 0.5 (S.D.) micron and 3.1 +/- 1.0 micron respectively). Stereological analysis was used to estimate the length of the principal piece (53 micron) and the dense fibres. These latter fibres were of unequal length and extended along 60% of the length of the principal piece. They fell into 3 groups with respect to their lengths: (i) fibres 3 and 8 were short (6 micron); (ii) fibres 4, 2 and 7 were of medium length (17, 18 and 21 micron respectively); and (iii) the longest fibres were 5, 6, 9 (31, 32 and 31 micron respectively) and fibre 1 which was a little longer (35 micron). Although there was variation in the length of the various fibres among spermatozoa, the order of their termination was relatively constant. The relationship between these quantitative data regarding the structural characteristics of the dense fibres and the shape of the flagellar wave is discussed.

Cytoskeleton↗
PubMed1983

Motility of human sperm without outer dynein arms.

Motility of human sperm lacking outer dynein arms has been studied before and after selection of the motile fraction of spermatozoa by migration in a saline solution. The flagellar wave forms appeared normal in both the seminal plasma and saline but the rate of forward progression, the head velocity and the beat frequency were approximately half of those observed with normal sperm. However the spermatozoa were capable of moving forward and of migrating out of the seminal plasma.

Adenosine Triphosphatases↗
PubMed1983

[Ciliary disorders of the bronchi in children].

The present study relates to 39 children, 24 boys and 15 girls, aged 1 to 17 (mean age, 6 1/2 years) suffering from chronic airflow obstruction without muco-viscidosis. The search for a ciliary anomaly was motivated either by the coexistence of situs inversus (group I: 12 cases) or by the negative or scanty aetiological history (group II: 27 cases). The investigation of the cilia consists of a study of ciliary motility and an ultrastructural study of biopsy specimens using the electron microscope. Groups I and II were similar as regards severity of disease, assessed by the incidence of bronchiectasis and chronic hypoxia at rest; a higher incidence of neonatal respiratory distress was noted in group I (7 cases against 4 in group II). Ciliary immotility was particularly noted in group I (7 cases) and one case of weak motility in group II. The major ultrastructural anomalies of the axonemal complex were seen as well in both groups I and II; it was noted that all the structures may be totally or partially missing with the exception of the peripheral microtubules. The discussion centred on three points: 1. In the first analysis, the discordance between the existance of major ultrastructural anomalies of the axonemal complex, a priori incompatible with the conservation of ciliary motility on light microscopy; the link seems to lie in the percentage of cilia affected, the existence of ciliary dyskinesia and finally the disorientation of the basal corpuscles. 2. The immunologic abnormalities sometimes associated with a syndrome of ciliary immotility: that is the anomalies of leucokyte migration under the control of microtubular structures in the peri-centriolar region. 3. The practical consequences. Current treatment rests on daily respiratory physiotherapy and antibiotics adapted for cases of superinfection; also there are drugs stimulating ciliary activity perhaps by the effect on their residual motility; some substances carrying ATP and ATP-ase may re-establish ciliary motility anulled by the absence of dynein arms; also the observations of major ultrastructural abnormalities ought to lead to better genetic counselling than at present, where the mode or modes of transmission are uncertain.

Adolescent↗
PubMed1982

[Autopreservation of semen prior to sterilizing treatment].

Among 511 subjects candidate to autopreservation of semen prior to sterilizing treatment, satisfactory preservation was possible in 40% of patients with Hodgkin's disease and 15% of patients with carcinoma of the testis. This difference in percentage is related to differences in alterations of semen before any treatment. The semen of 9% of the patients was used for insemination; 95% wished that preservation be continued. Spontaneous recovery is possible, notably in carcinoma of the testis. Despite the risk of psychological problems, autopreservation should be recommended in cases with moderate initial alterations of the semen.

Hodgkin Disease↗
PubMed1982

Defective basal lamina formation by transformed mammary epithelial cells: a reduced effect of collagen on basal lamina (heparan sulfate-rich) proteoglycan degradation.

Invasive, spontaneously transformed mammary epithelial cells derived from the normal NMuMG cell line have lost the ability of their parental cells to respond in vitro to the presence of a collagen substratum by forming a continuous glycosaminoglycan (GAG)-rich basal lamina. On collagen, the cells synthesize 35S-GAG at the same rates, but the transformed cells accumulate less 35S-GAG than the normal cells because a larger fraction of their newly synthesized 35S-GAG is rapidly degraded. Chromatography of the 35SO4-containing materials from cultures on collagen indicates that the reduced accumulation of 35S-GAG by the transformed cells reflects less of a heparan sulfate-rich proteoglycan fraction which has been found in the basal lamina. On plastic substrata, however, the normal and transformed cells have near identical rates of 35S-GAG synthesis and degradation and they accumulate similar low amounts of the basal lamina proteoglycan fraction, which is rapidly degraded. Thus, transformation appears to impair the ability of the cells to reduce basal lamina proteoglycan degradation in response to collagen. This impairment may prevent the neoplastic cells from forming a complete basal lamina and, therefore, allow local invasion.

Animals↗
PubMed1981

Type I collagen reduces the degradation of basal lamina proteoglycan by mammary epithelial cells.

When mouse mammary epithelial cells are cultured on a plastic substratum, no basal lamina forms. When cultured on a type I collagen gel, the rate of glycosaminoglycan (GAG) synthesis is unchanged, but the rate of GAG degradation is markedly reduced and a GAG-rich, basal lamina-like structure accumulates. This effect of collagen was investigated by comparing the culture distribution, nature, and metabolic stability of the 35S-GAG-containing molecules produced by cells on plastic and collagen. During 48 h of labeling with 35SO4, cultures on collagen accumulate 1.4-fold more 35S-GAG per microgram of DNA. In these cultures, most of the extracellular 35S-GAG is immobilized with the lamina and collagen gel, whereas in cultures on plastic all extracellular 35S-GAG is soluble. On both substrata, the cells produce several heparan sulfate-rich 35S-proteoglycan fractions that are distinct by Sepharose CL-4B chromatography. The culture types contain similar amounts of each fraction, except that collagen cultures contain nearly four times more of a fraction that is found largely bound to the lamina and collagen gel. During a chase this proteoglycan fraction is stable in cultures on collagen, but is extensively degraded in cultures on plastic. Thus, collagen-induced formation of a basal lamina correlates with reduced degradation and enhanced accumulation of a specific heparan sulfate-rich proteoglycan fraction. Immobilization and stabilization of basal laminar proteoglycan(s) by interstitial collagen may be a physiological mechanism of basal lamina maintenance and assembly.

Animals↗
PubMed1981

Study of a group of 484 fertile men. Part I: distribution of semen characteristics.

The semen characteristics studied were the sperm count, semen volume, morphology and pre-freeze and post-thaw motility. Two categories of fertile men were investigated: semen donor candidates for artificial insemination and pre-vasectomy subjects. Since mean values for each variable in the two series were similar, they could be considered as a single group of 484 fertile men. Only those subjects whose ejaculates were obtained after an abstinence of 5 days or less were retained. The distribution, mean and percentiles were determined for each variable. The 10th and 90th percentiles for sperm count, percentage of motile forms and percentage of normal cells were respectively 25 and 180 million per ml, 60% and 80% and 50% ad 75%. The three variables, sperm count, semen volume and total number of spermatozoa which were dependent on abstinence were analysed in the same manner for 3 days of abstinence. The group studied seemed to be as representative and as well defined as possible.

Adult↗