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Biomedical subjects

H Hillman

Publications and source records attributed to H Hillman.

At least 19 recordsLinked to original sources
PubMed1994

New considerations about the structure of the membrane of the living animal cell.

The philosophy and assumptions behind the research are summarized. The cell membrane in life is likely to be solid, of unknown thickness and of uncertain biochemistry; the myelin lamellae are artifacts and can not be regarded as sheafs of cell membranes. It is very unlikely that the cell membrane is covered with anatomically distinct receptors or channels. The physiological and biochemical properties attributed to them as structures are quite independent of their anatomy. The ionic channels originally proposed as a result of studies of excitable membranes have now been detected in virtually all membranes in the cell, including endoplasmic reticulum, liposomes and vacuoles. Physiologists believe that channels only open during excitation of nerve and muscle cells, which implies that they are permanently closed in non-excitable cells, although it has been known for more than 50 years that small ions cross the membranes continuously. Explanations are given for the appearance of artifacts.

Animals↗
PubMed1991

Fatty acid levels in the brains of schizophrenics and normal controls.

Essential fatty acids are important constituents of the brain. There is evidence that levels in blood of certain essential fatty acids and their eicosanoid derivatives may be abnormal. We now report that in the frontal cortex of schizophrenic patients there are significant differences from normal in the fatty acid composition of phosphatidylethanolamine. These differences from normal were not found in the cerebellar cortex.

Aged↗
PubMed1991

A new hypothesis for electrical transmission in the mammalian central nervous system.

It has been previously shown that the anatomical synapse does not exist in the living central nervous system, and that receptors are unlikely to be unique molecules sited on particular locations in or on the cell membrane. These conclusions and the rapidity of action of intravenously administered substances necessitated the adumbration of a new electrical hypothesis for the mechanism whereby signals pass from one part of the brain and spinal cord to another. The hypothesis proposed implies some testable predictions.

Animals↗
PubMed1991

A re-examination of the vesicle hypothesis of transmission in relation to its applicability to the mammalian central nervous system.

The methods used to detect transmitters in the central nervous system, and their accuracy, are reviewed. The applicability of each of the seven different criteria used to define a transmitter is then examined, particularly in respect of substances not generally accepted as transmitters, but fulfilling some of these criteria. Twenty-three separate assumptions inherent in the vesicle hypothesis of transmission are identified; some of them are unproved and some unprovable. It is concluded that too many of these assumptions are in the latter two categories, which, from a Popperian viewpoint, render the hypothesis as a whole unwarrantable.

Animals↗
PubMed1989

The effects of transmitters on the affinity of the insoluble fraction of ox brain for Na+ and K+.

The insoluble fraction of ox-brain, which had previously been shown to have a non-linear affinity for Na+ and K+, was prepared. Acetylcholine (1 x 10(-8) mol/l and 1 x 10(-7) mol/l) reduced the affinity of the fraction for Na+ and K+ to zero, while at 1 x 10(-6) mol/l, the affinity for the cations was almost as high as in the absence of the transmitter; the affinities for Na+ and K+ were particularly high, when the supernatant concentrations of these ions exceeded 80-100 mM. Addition of eserine (3 x 10(-5) mol/l) considerably modified the response of the fraction to acetylcholine (1 x 10(-5) mol/l). Atropine (1 x 10(-8) mol/l) in the absence or presence of acetylcholine (1 x 10(-5), or 1 x 10(-4) mol/l) reduced the affinity of the fraction for Na+ and K+ to zero. Epinephrine (3 x 10(-10) mol/l) lowered the affinity for Na+ and K+, while ergotamine itself (1 x 10(-5) mol/l) reduced it to zero. The addition of both epinephrine and ergotamine at the latter concentrations restored the affinity of the fractions for Na+ and K+ to what it had been in the absence of the transmitter or antagonist, previously reported. Norepinephrine (3 x 10(-10) mol/l), or ouabain (1 x 10(-7) mol/l) reduced the affinity of the fraction for Na+ and K+ to zero. Thus, the transmitters and antagonists altered the affinity of the insoluble fraction for Na+ and K+ non-linearity, dependent upon their concentrations, the concentrations of the cations, and the interaction of transmitter and antagonist.

Acetylcholine↗
PubMed1989

Uncertainties, artifacts, uncontrolled experiments and incomplete evidence in modern biology.

Major uncertainties of biological measurements in respect of parameters to which they are referred, cytochemical techniques, subcellular fractionation, light microscopy, electron microscopy, examination of cell membranes, dimensions of cells and intracellular movements, are discussed. The assumptions inherent in widely used techniques are noted and their warrant-ability examined. The impact of insufficient control experiments is shown to be considerable. A few important pieces of evidence in current generally accepted theories--mostly from neurobiology--are highlighted. All these problems represent incomplete experiments, from which it is premature to draw conclusions.

Animals↗
PubMed1989

Review of problems of correlations of structure and function in cells.

Many of the correlations in cytology between structure and function compare the metabolism of subcellular fractions with the electron microscopy of the same tissues. Conclusions from subcellular fractionation have generally been derived on the assumption that killing the animal or plant, homogenisation, centrifugation and extraction of the tissues, do not affect the activities of the biochemical structures examined nor their distribution in the subcellular fractions; this assumption has never been tested. There is insufficient literature on the effects of reagents used in histology, immunocytochemistry and electron microscopy, on chemical activities, their distribution, or their visibility in sections. The artifacts of electron microscopy, such as shrinkage and precipitation, are widely recognised but not taken into account sufficiently when structures are examined. No attempts have been made to explain the two dimensional geometry of many 'unit' membranes, nor how a cytoskeleton can cause intracellular movements. Particular examples, such as the alleged location of oxidative phosphorylation along the mitochondrial cristae, the presence of biochemical ribosomal and lysosomal activities without the appearance of ribosomes and lysosomes, and intracellular movements in the believed presence of a cytoskeleton, are given to illustrate the difficulties of widely believed correlations between structure and function in cells.

Animals↗
PubMed1988

Critique of current views on receptors, and a new general theory of receptor location and action in vivo.

The Davson-Danielli model of the cell membrane accounted for nearly all the space within it by suggesting that it was composed of structural proteins and lipids; this would leave virtually no space for the large number of enzymes, carriers, antigens, antibodies, and receptors for hormones, transmitters, drugs and toxins, generally believed to be present within the membranes. The sizes of many of the structural proteins, lipids, enzymes and receptors, have been measured by electron microscopic techniques, and are too large to be located within or next to the Robertson 'unit' membrane or the Singer-Nicolson membrane, without producing bulges; these are never seen by transmission electron microscopy, and rarely by freezing techniques. If they were present but unstained, gaps should appear in the membranes corresponding to the measured dimensions of these macromolecules; such gaps are not seen. It has been assumed that the substances react with receptors located only at the cell membrane, but, in the intact organism, they pass through many cellular phases before having any effect; one hundred and five phases in the passage from the blood to the brain are identified. It is suggested that the receptor is the sum total of all the reactions between the substances added and each of the phase reacting to a differing degree. Experiments which could assess the relative validity of the currently accepted and new ones proposed are listed.

Animals↗
PubMed1985

The anatomical synapse in mammals by light and electron microscopy.

The original descriptions of synapses by light microscopy are examined, and their widths and numbers per neuron soma are compared in light and electron micrographs. Electron micrographs show the synaptic cleft very frequently normal to the plane of section. It is rare to find any connection of the synaptic knobs to any dendrite of another axon, and the granular appearance on the surface of unfixed mammalian neurons can be shown to be due to intracellular particles- probably mitochondria. It is concluded that the anatomical synapse is an artifact. This raises questions about the nature of chemical transmission and the vesicle hypothesis. It may require a reinterpretation of transmission, but does not affect physiological or pharmacological findings about the effects of transmitters.

Animals↗
PubMed1984

Doctor and patient.

Explore the source record for details and available documents.

Patient Advocacy↗
PubMed1983

Reduction in mortality from upper gastrointestinal haemorrhage.

A study of 2377 cases of haemorrhage from the upper gastrointestinal tract shows a significant fall in mortality rate--from 15.5% in the period of retrospective study from 1961 to 1970 to 7% in the prospective study from 1972 to 1982. The fall in mortality rate from non-variceal bleeding was from 12.8% to 5%. In the second five years of the prospective study, the total mortality rate was 5.8%, with 4.5% for non-variceal haemorrhage. This improvement occurred despite a significant rise in the proportion of patients of 60 years of age and over, and was particularly evident in patients with bleeding chronic gastric ulcers. There was also a significant reduction in mortality in the 60 years and over age group in the latter five years of the prospective study. The data suggest that there were three aspects of management which were important in the reduction of mortality. These were early fibreoptic endoscopic diagnosis, improved resuscitation and postoperative care, and early control of bleeding from oesophageal varices by balloon tamponade and surgery in selected cases. These complicated procedural aspects of management are best applied in a special unit for the treatment of patients with haemorrhage from the upper gastrointestinal tract. It is concluded that there has been significant progress in the treatment of this problem during the last decade.

Age Factors↗
PubMed1983

Dying and death, with special reference to brain death. A bibliography.

A bibliography of dying and death has been made, with special reference to the brain. It does not claim to be comprehensive. Short references have been omitted unless they contained new information not published elsewhere. When books or papers have been written in other languages, their titles have been translated, and their original languages indicated. It has not always been possible to find the complete page references to these.

Animals↗
PubMed1982

Preparation of an insoluble fraction of ox brain and its affinity for Na+ and K+.

A water insoluble fraction was prepared from ox cerebrum by homogenization in water, dialysis against water, washing with water and drying in air at 293 degrees K. The fraction represented 15.5 +/- 3% (n = 8) of the weight of the fresh brain; it contained means of 81% (n = 6) of the lipid, found in freshly dried ox brain samples, and 46% (n = 5) (biuret method) or 51% (n = 3) (6) of the protein, respectively. The Na+ and K+ concentrations were measured by atomic emission flame photometry, firstly, in prepared media, and then after 4 ml of the same media had been mixed with 1 g of the insoluble fraction at 310 degrees K for 20 min; the concentration in the fraction was calculated from that found in the medium. The concentration in the medium (mM) after incubation was compared with that calculated to be in the fraction, (mumol/g). When the insoluble fraction was mixed with Krebs Ringer saline containing bicarbonate and glucose, modified so that the ratios of NaCl and KCl varied-(although together they always added up to 150 mM)-there was a mean of 2.6 times as much Na+ or K+ in the fraction (mumol/g) as in the media (mM) when the latter contained up to 80 mM Na+ or K+. When the concentration of the cations in the media exceeded this value, the concentration of Na+ in the fraction rose considerably, while the concentration of K+ fell to zero. When only Ca2+ or only Mg2+ was omitted from the Krebs-Ringer bicarbonate glucose saline, the fraction did not take up Na+ or K+ from the medium at any concentration. On electron microscopy the fraction was granular and amorphous and contained myelin figures. The fraction did not take up any significant volume of oxygen measured manometrically either in the modified Krebs-Ringer solutions or in a mitochondrial substrate.

Animals↗
PubMed1980

Artefacts in electron microscopy and the consequences for biological and medical research.

It has been previously shown that the endoplasmic reticulum, the Golgi apparatus, the lysosomes, the nuclear pores, and the cristae of the mitochondria could not exist in living cells. Therefore, study of them in all life sciences, or any apparent correlation between their 'structure' and 'function' should be abandoned. The consequences to biological and medical research of such conclusions are considered. Semantic and logical analyses of experiments should always be done, and all the assumptions inherent in them should be identified and tested. Research should be more directed to studies on whole living animals, rather than to metal deposits, precipitation patterns, homogenates, or tissue fixed or subjected to other powerful physical and chemical agents known to change them drastically.

Animals↗