Chloride channel regulation in the skeletal muscle of normal and myotonic goats

External intercostal muscle biopsies from normal and congenitally myotonic goats were studied in vitro at 30° C using a two-microelectrode square-pulse cable analysis assisted by computer. The resting chloride conductance (G _cl) was estimated from the difference between the mean membrane conductance in chloride-containing and chloride-free bathing media. The protein kinase C (PKC) activator, 4--phorbol-12,13-dibutyrate, (0.1–2.0 M) blocks a maximum of 76% of G _cl in normal goat fibers and induces myotonic hyperexcitability similar to that of congenitally myotonic goat fibers. The G _cl block was partially antagonized by pretreatment with the PKC inhibitor, staurosporine (10 M). The inactive 4-phorbol-12, 13,didecanoate had no effect at 50 M, whereas the active 4- isomer blocked 41% G _cl at 1 M. The nearly absent G _cl of congenitally myotonic goat fibers was not restored by treatment with high concentrations of the PKC inhibitors staurosporine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), or tetrahydropapaveralone (THP). Also, forskolin and cholera toxin, which may increase cyclic adenosine monophosphate (cAMP) levels, or the R(+) clofibric acid enantiomers and taurine, which increase G _cl in normal fibers, were also unable to restore G _cl in myotonic goat fibers. The data suggest that PKC may be a chloride channel regulator in normal goat skeletal muscle fibers, however the molecular defect of congenitally myotonic fibers does not appear to be due to excessive activity of PKC.     

The early diagnosis of impending coagulopathies following surgery and multiple trauma

Summary Blood coagulation problems, either disseminated intravascular coagulation (DIC) or adult respiratory distress syndrome (ARDS) are frequent complications during the recovery of the polytraumatized surgical patient or accident victims. The key to their successful control lies in prompt recognition and aggressive treatment of the disease as soon as it appears. Unfortunately their onset is not usually well defined clinically and success in handling usually depends upon clinical expertise in recognising high risk situations coupled with measurements in the haematological laboratory of changes in plasma coagulation factors.It is suggested in this communication that a relatively simple examination of plasma complement profiles in the high risk, intensive care patient, may not only provide early warning of the onset of a coagulopathy but also distinguish the type. Simple tests are described, based on the assessment of plasma complement C5 levels, which have a high predictive value for the onset of ARDS, a disease with few early clinical manifestations and notably lacking in early changes in haematological parameters.In prospective trials complement tests correctly identified 18 patients who later developed ARDS but were no more effective than haematological tests in the identification of 24 patients who subsequently developed DIC.Abbreviations ARDS adult respiratory distress syndrome - DIC disseminated intravascular clotting     

Die Spulwurmerkrankungen in Darmstadt und Hessen vom Abwasseringenieur gesehen

Ohne ZusammenfassungMit 1 Textabbildung.Im Heft 2 des Gesundheits-Ingenieur 1948 erschien meine Abhandlung Spulwurmplage und Abwasserbeseitigung in Darmstadt. Dem darin behandelten Stoff wurde auch von vielen Hygienikern solches Interesse entgegengebracht, daß ich die Abhandlung in erweiterter Form hier veröffentliche. Die seit der Veröffentlichung im Gesundheits-Ingenieur erzielten Fortschritte sind dabei berücksichtigt.     

Effect of the degree of myocardial hypertrophy associated with an experimental heart defect on the resistance to altitude hypoxia

Summary Experimental coarctation of the abdominal aorta with constriction of its lumen to one-third of the original diameter was created in 18 albino rats. Four months later various degrees of myocardial hypertrophy developed in the animals with a relative weight of the heart ranging from 0.0033 to 0.0069. In elevation in the barochamber, the altitude ceiling of the animals with a relative cardiac weight below 0.0040, did not differ from the normal one. The altitude ceiling proved to be considerably decreased in animals with a relative cardiac weight of over 0.0040. Analysis of ECG recorded during the elevation demonstrated that in the animals with a considerable myocardial hypertrophy reduced resistance to the acute high altitude hypoxia depended on the reduction of the functional resistance of the heart.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 5, pp. 37–40, May, 1963     

Expansion of CD14+CD16+Monocytes in Critically Ill Cardiac Surgery Patients

We have asked whether critically ill cardiac valve surgery patients identified by a high APACHE II score exhibit an increase in the number of proin-flammatory CD14⁺ CD16⁺ monocytes. A group of 12 patients was studied over a period of 5 days post cardiac valve surgery for changes in blood monocyte populations. Patients were selected on day 1 post surgery to either be in good clinical condition (APACHE II Score of 14; N = 9) or to be critically ill (APACHE II score of 24; N = 3). The 14 patients had an uneventful course and could leave the ICU after 2–3 days. Among the 24 patients two showed a decrease of the score to 14 within the 5 days of observation and they could leave the ICU thereafter. One 24 patient (patient #2) had a persistently high score and finally died on day 28. Analysis of blood monocytes on day 1 post surgery revealed that the 14 patients had normal values of CD14⁺CD16⁺ monocytes (44 ± 9/l). By contrast the 24 patients had increased values of these cells with 243 ± 106 cells per 1 on day 1. The numbers of CD14⁺CD16⁺ monocytes returned to the control range over the 5 days of observation in 2 of the 24 patients concomitant with the improvement of the APACHE II score. CD14⁺CD16⁺ monocytes remained, however, at a high level in patient #2, the patient with persistently high APACHE II score.     

Altered synthesis of interferon-γ and expression of interferon-γ receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis

Previously we reported disease-specific interaction between interferon- (IFN-) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon- (IFN-) and expression of IFN- receptor (IFN-R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN- concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4⁺ T cells, CD8⁺ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN- or IFN-R mRNA expression by the semiquantitative RT-PCR method.In vitro IFN- synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN- system might be involved in the development of CGN.     

Targeted gene replacement at the endogenousAPRT locus in CHO cells

We demonstrate the feasibility of targeted gene replacement at an endogenous, chromosomal gene locus in cultured mammalian cells, employing a two-step strategy similar to an approach routinely used for genetic manipulation in yeast. Utilizing an APRT⁺ recombinant generated by targeted integration of plasmid sequences (including a functional copy of the gpt gene) at the CHO APRT locus, we have been able to select gpt^– pop-out recombinants that have arisen by intrachromosomal recombination between APRT direct repeats at the targeted integration site. Reciprocal exchanges leading to pop-out of integrated plasmid/gpt gene sequences occur at a rate of 6.3×10^–6 per cell generation. Depending on the site of crossover, such pop-out events result in either replacement or restoration of the original APRT target gene sequence.     

Regulation of ICAM-1 Expression in Mouse Macrophages

In a mouse model of silica (SI) induced lung injury, SI exposure increases expression of intercellular adhesion molecule-1 (ICAM-1) on lung (alveolar/interstitial) macrophages and alveolar type II epithelial cells. To investigate the regulation of SI induced ICAM-1 expression on mouse macrophages, freshly isolated macrophages (alveolar, peritoneal) and macrophage cell lines (MH-S, RAW 264.7) were evaluated for ICAM-1 expression elicited by the particle silica ( quartz; 20 g/ml; 6 g/cm²) or the inflammatory cytokine, TNF (20 ng/ml). TNF significantly increased ICAM-1 expression in all cell types whereas SI elicited an increase in peritoneal macrophages (PM) and the cell line, MH-S. This pattern of increased expression was confirmed by immunocytochemistry. To investigate the regulation of ICAM-1 expression, PM were incubated with SI, TNF or media concomitantly with anti-TNF antibody, the antioxidant, NAC, or the iNOS synthase inhibitor, L-NAME. Both anti-TNF and NAC, but not L-NAME, inhibited elicited (TNF, SI) as well as constitutive (media) ICAM-1 expression. These data demonstrate that both inflammatory cytokines and inorganic particles can increase ICAM-1 expression on mouse macrophages and that this expression is mediated, in part, by TNF and reactive oxygen species.     

Breast cancer in relation to overnutrition

Summary Overnutrition and obesity, mainly due to intake of excess animal fat, have been associated with an increased risk of breast cancer by virtue of: (1) fat serving as a vehicle for fat-soluble environmental carcinogens, (2) fat-derived cocarcinogenic fatty acids and sterols, (3) hypercholesterolemia and increased ovarian and adrenocortical steroid synthesis (estrogens, androgens, cortisol), (4) decreased conversion of estrone to the antiestrogenic 2-hydroxyestrone, (5) increased conversion of androstenedione to the carcinogenic estrone (estradiol), and (6) depression of the immune response. However, the relevance of each of these mechanisms on the risk of breast cancer, remains unclear, despite many epidemiological, endocrinological, and immunological studies in humans and laboratory animals. Thus at present, the cause-effect relationship between overnutrition and breast cancer is not clear, nor is the interplay between nutritional, hormonal, and environmental risk factors of breast cancer understood. It seems that progress regarding overnutrition and risk of breast cancer can be achieved only when the various interrelated factors are evaluated in prospective studies with improved methods.     

The independent expression of HLA andβ 2-microglobulin on human-mouse hybrids

Direct cytotoxicity and absorption analysis were used to detect HLA antigens on man/mouse somatic cell hybrids. Confirmation of the assignment of the Major Histocompatibility Complex to chromosome 6 was obtained. The same series of hybrids were used to study the interaction between HLA and ₂m on the cell surface. Results obtained from a series of clones indicated that there was complete independence of expression of HLA and ₂m. Human ₂m was found to be unnecessary for the normal serological expression of HLA, suggesting that mouse ₂m could possibly replace human ₂m as a subunit of the HLA molecule. Evidence is presented demonstrating that this is in fact the case. Heteroantisera to human ₂m and alloantiserum to HLA-A2 were used, together with complement, to selectively remove the chromosome coding for ₂m and HLA from a hybrid clone. Manipulation of the karyotype in this way further confirmed the independence of HLA and ₂m on somatic cell hybrids.     

Measurement of β-glucuronidase in effluent of perifused alveolar macrophages challenged with chemically modified chrysotile asbestos

Chrysotile asbestos has been implicated with lung disorders, notably fibrotic lesions and cancer. In vitro, chrysotile fibers are cytotoxic to lung macrophages and stimulate the release of inflammatory mediators. Reports to the effect that chemical modifications of asbestos fibers reduce their cytotoxic and inflammatory potential initiated the present study of three fiber modifications. The cytotoxic and inflammatory effects of magnesium-leached chrysotile, POCL₃-treated chrysotile, and CaO-treated chrysotile were studied in a perifused rat alveolar macrophage culture system, relative to untreated fibers. Natural Canadian chrysotile (UICC B) caused dose-dependent cell mortality and clumping. The release of-glucuronidase (-Glu), a lysosomal enzyme, was also dose dependent. Rhodesian chrysotile (UICC A) caused similar cytotoxic and inflammatory effects. However, magnesium-leached chrysotile was less cytotoxic (39% less) and had a lesser clumping capacity (31% less) than untreated chrysotile. Total secretion of-Glu elicited by magnesium-leached chrysotile was reduced by 43% from the untreated sample, but kinetic monitoring indicates that this reduction in inflammatory potential is only significant during the first 12 h of an 18-h culture period. POCl₃ treatment of chrysotile fibers produced differing effects depending on the length of the fibers under study. Treating fibers with a mean length of 8 m produced a secretion pattern similar to that produced by acid leaching. The total output for the treated sample was 44% lower than with untreated chrysotile; the difference was only significant during the first 12 h of perifusion. Cell mortality and aggregation were not reduced in any important way with POCl₃ treatment of these longer fibers. When ultra-short fibers (mean length=0.8 m) were treated with POCl₃, the total decrease in-Glu output was equal to 41%, and the release of enzyme was significantly lower during the whole 18-h experiment. Cell aggregation was not appreciably affected, but cell mortality was significantly lower than for untreated fibers. CaO treatment did not alter the cytotoxic (cell death and aggregation) or inflammatory (-Glu release) effects of chrysotile asbestos. These results suggest that chemical modifications affecting the integrity of the surface magnesium and/or the polarity of the surface charge of chrysotile can reduce to some extent the cytotoxic and inflammatory properties of this type of asbestos.     

A highly sensitive electroimmunodiffusion method of antigen detection on cellulose acetate films

A highly sensitive electroimmunodiffusion method of detecting antigens on cellulose acetate films is suggested. There are three stages: concentration of the antigen in a discontinuous buffer system on cellulose acetate films; detection of the antigen on the same films by immunodiffusion using a standard test systems; staining the washed films with a protein stain to detect precipitation bands if the reaction takes place in the visible zone, or further treatment by growing precipitates with antiglobulin antibodies or by autoradiography. The method can detect nanogram amounts of -fetoprotein and can be used to discover antigens of different molecular weight and electrophoretic mobility.Laboratory of Immunochemistry and Diagnosis of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR G. V. Vygodchikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 121–124, July, 1977.     

Isolierung von Amoeben des Typs „Hartmannella-Acanthamoeba“ und „Naegleria“ aus Kaltblütern

Zusammenfassung Aus einer großen Anzahl von Kaltblütern, insbesondere Reptilien, wurde eine Reihe von Amoebenstämmen isoliert, die auf Grund von Größe und Kernstruktur dem Typus Hartmannella-Acanthamoeba und Naegleria zuzuordnen sind. Häufig traten diese Amoeben bei Reptilien zusammen mit typischen Entamoeben auf. In den Fällen, in denen nur Hartmannella gefunden wurden, lag aber bei der Mehrzahl der Tiere ebenfalls eine charakteristische Amoebiasis vor, so daß anzunehmen ist, daß auch diese Amoeben pathogene Eigenschaften gegenüber dem Reptilgewebe besitzen. Besonders zu erwähnen ist, daß auch das Gehirn besiedelt werden kann. Kotuntersuchungen lieferten aber auch den Beweis, daß klinisch gesunde Tiere diese Amoeben beherbergen können, ein Befund, der für die Epidemiologie von Bedeutung sein kann. Inwieweit diese Amoeben eine Pathogenität dem Warmblüter gegenüber besitzen, ist noch ungeklärt.

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Isolation of amoebae of the type Hartmannella-Acanthamoeba and Naegleria from cold-blooded vertebrates

Summary Many strains of the complex Hartmannella-Acanthamoeba and Naegleria amebae could be isolated from cold-blooded vertebrates, especially reptiles. The morphology of the nucleus and the size of these amebae separate them distinctly from the classical genus Entamoeba. In many cases the Hartmannella were associated with typical amebae of the genus Entamoeba, but we could see such infections also were the Hartmannella-types, were not mixed with other amebae. In spite of that we found the characteristic amebic alterations of the tissue. It is to conclude that these amebae have a pathogenic capability against the reptile tissue. In six cases the brain was also infected. A number of strains were isolated from feces only and no clinical symptoms could be observed. These observations may be important for the epidemiology at least in such cases were amphibians and reptiles have contact to unchlorinated swimming pools or in which these animals are kept as pets. — Pathogenicity against warm-blooded vertebrates is not tested as yet.

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Nach brieflicher Auskunft von Prof. Dr. W. Balamuth (Univ. of California, Berkely) handelt es sich bei dem an ihn gesandten Stamm 2 um eine Naegleria-Art.

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Durchgeführt mit Mitteln der Deutschen Forschungsgemeinschaft.     

Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase

The immunomodulatory effects of morphine are well established; however, suprisingly little is known about the immunomodulatory properties of the major metabolites of morphine. The present study tests the hypothesis that expression of inducible nitric oxide synthase (iNOS) is modulated by the administration of the morphine metabolite, morphine-6-glucuronide. The initial study using rats shows that morphine-6-glucuronide administration (0, 1.0, 3.163, 10 mg/kg s.c.) results in a pronounced reduction in lipopolysaccharide (LPS)-induced expression of iNOS (inducible nitricoxide synthease) in spleen, lung, and liver tissue as measured by western blotting. Morphine-6-glucuronide also produces a reduction in the level of plasma nitrite/nitrate, the more stable end-product of nitric oxide degradation. In a subsequent study, administration of the opioid receptor antagonist, naltrexone (0.1 mg/kg) prior to the injection of morphine-6-glucuronide (10 mg/kg) blocks the morphine-6-glucuronide induced reduction of iNOS expression and plasma nitrite/nitrite levels indicating that the effect is mediated via the opioid-receptor. This study provides the first evidence that morphine-6-glucuronide alters the expression of iNOS.     

Use of B-IV zonal rotor centrifugation as a simple tool for the separation of adeno-associated X7 virus (AAV X7) from helper adenoviruses

Summary The use of zonal rotor centrifugation in the separation of AAV X₇ virus from its helper adenovirus is reported. AAV X₇ virus was perfectly separated from its helper adenovirus. Adeno-associated X₇ virus was found to separate in par tides with an S rate of 72–82 S, and a density in CsCl of 1.30–1.32, and virions with a sedimentation coefficient of 135–147 Svedbergs, with a density of 1.37–1.38.     

Proliferation and metastases formation of larvalEchinococcus multilocularis

Using surgical techniques, 70Meriones unguiculatus were infected by implantation of 0.15–0.20 g of larvalEchinococcus multilocularis tissue into the subcutis of the neck region. In 64 of 65 animals necropsied, the transplants had increased in size and weight and reached an average weight of 4.1 g at the end of the experiment 12 weeks post infection (p.i.). MetastaticEchinococcus lesions developed in the regional lymph nodes and in the lungs; in 18 animals the parasite proliferated into the thoracic cavity. Of 41 animals examined 10 and 12 weeks p.i., 88% had multiple or single metastatic lung lesions, the first being observed 6 weeks p.i. Typical cysts and protrusions (buds) of the germinal layer were detected in samples of parasite tissue before and after transplantation to experimental animals, as well as in lymph nodes and lungs in which metastases had developed. Similar structures were found in liver sections of two patients with alveolar echinococcosis.It is concluded that the spread of the parasite from the subcutis of the neck region to the draining lymph nodes and the lungs had taken place via the lymph and blood system. The possible role of the buds in metastases formation is discussed.     

Anti-CD3-induced changes in protein kinase C isozymes expression in human CD4+ and CD8+ T lymphocytes

In order to determine whether there is a differential expression and activation of PKC isozymes between CD4+ and CD8+ T cells, peripheral blood mononuclear cells were stimulated with anti-CD3 monoclonal antibody (moAb) for various time intervals and the expression of calcium-dependent PKC isozymes (, , ) and calcium-independent PKC isozymes (, , ) was analyzed with dual color flow cytometry, using anti-PKC isozyme antibodies and anti-CD4 or anti-CD8 antibodies. The basal fluorescence intensity of all PKC isozymes was comparable between CD4+ T cells and CD8+ T cells. Following activation with anti-CD3 moAb a marked increase in the fluorescence intensity of all PKC isozymes in both CD4+ and CD8+ T cells, albeit to a different extent and with different kinetics was observed. Among all PKC isozymes studied, the least striking changes were observed in PKC isozyme and the most striking changes were observed in PKC- isozyme. Laser-based confocal microscopic studies confirmed that the increase in fluorescence intensity of PKC isozymes following anti-CD3 moAb stimulation, as measured by flow cytometry was accompanied by the translocation of PKC isozymes from cytosol to the plasma membrane. This study demonstrates a differential effect of anti-CD3 moAb on the expression of PKC isozymes between CD4+ and CD8+ T cells and suggests that flow cytometry can be used to study the translocation of PKC isozymes from cytosol to the plasma membrane.     

Pharmacological characterization of P2X7 receptors in rat peritoneal cells

Objective and design: P2X₇ receptor activation by ATP results in the release of IL-1 and IL-18. Prolonged stimulation can lead to pore formation and cell death. In this study we pharmacologically characterized P2X₇ receptors on rat peritoneal cells (RPC) and on 1321N1 cells transfected with rat P2X₇ receptor (1321rP2X₇-11).Materials and methods: RPC were isolated from rats by lavage. P2X₇ agonist induced pore formation in RPC was measured by EtBr uptake. P2X₇-stimulated pore formation and Ca⁺⁺ influx in 1321rP2X₇-11 cells were measured by a fluorometric imaging plate reader. The effects of pyridoxal phosphate-6-azo phenyl –2-4-disulfonic acid (PPADS) on pore formation and Ca⁺⁺ influx were examined in both RPC and 1321rP2X₇-11. P2X₇-mediated IL-1 release in RPC and the effect of PPADS were determined.Results: RPC express functional P2X₇ receptors that were activated by ATP analogs with a rank order of potency of 2- 3-O-(4-Benzoylbenzoyl) adenosine 5-triphosphate (BzATP) > ATP > ,-methylene ATP. Activation of P2X₇ receptors by BzATP was inhibited by PPADS. Similar results were also obtained in 1321rP2X₇-11 cells. Activation of P2X₇ receptors on RPC resulted in IL-1 secretion, which was inhibited by PPADS.Conclusions: RPC express functional P2X₇ receptors that form pores and mediate the release of IL-1.Received 20 July 2004; returned for revision 9 September 2004; accepted by N. Boughton-Smith 5 November 2004     

Changing patterns of eye-head coordination during 6 h of optically reversed vision

Summary 1) This study investigates the early development of adaptive changes in oculomotor function associated with coordinated eye-head tracking of the optically reversed image of an earth-fixed target seen through horizontally reversing dove prism goggles attached to the skull. 2) Two tasks comprised a) fixation of a single target during head rotation which causes the seen target's image to move in the direction of head motion by an amount exactly equal to the head movement itself (the 1-Target task), and b) change of gaze onto a displaced target with head free to move (2-Target task). 3) The 1-Target task requires the eyes to move in a direction opposite to that of the normal vestibulo-ocular reflex (VOR). The 2-Target task is identical, except that reorientation onto the new target calls for an initial saccadic eye movement in a direction opposite to that of the ensuing head movement, which is contrary to the normal pattern of eye-head coordination during gaze shifts. 4) Eye (EOG) and head (potentiometer) movements were continuously recorded (0–250 Hz) in an apparatus which permitted sudden, unexpected, electromagnetic braking of the head movement, either just before or during the intended manuvre. 5) Early adaptive strategies employed reduction of VOR gain, rearrangement of timing, amplitude and shape of catch-up saccades and the introduction of centrally programmed eye movements uncovered by the braking manuvres. 6) All of these phenomena were detectable in an initial series of 60 trials, in which the total exposure to visual-vestibular conflict was less than 30 s. They became more systematized and more marked after 6 h of active reversed vision experience. 7) Specifically, mean VOR gain, measured within the first 80 ms of head movement (deemed free of visuomotor influence), became markedly attenuated (25% in the first test series; 66% after 6 h of active visionreversed exercise). In addition (not included in the above percentages) there were numerous occasions of complete absence of measurable VOR during head rotation, in both the first and final test series. 8) In the 1-Target task, the latency of the first catch-up saccade (re onset of head movement) tended to offset residual VOR by becoming shortened to the point of synchrony with head movement onset. This saccade (not present in control tests) continued to occur on those occasions when the head was unpredictably prevented from moving, and when head movements were made in the dark. 9) Sometimes these initial saccades began normally, but glissaded in a graded manner into a smooth pursuitlike trajectory, resembling the classical glissade associated with pulse-step mismatch in the saccade generating system. 10) All these events represent embryo facsimilies of more advanced adaptive manuvres seen in an earlier study extending over 19 days of reversed vision experience. 11) It is concluded that the adaptive process is a multifactorial one, exhibiting idiosyncracy in individuals and from time to time. Some phenomena appear in embryo form within seconds of exposure to the new condition. Others, such as progressive VOR gain attenuation, introduction of central programming and advanced strategies of the glissade type, developed more slowly over the 6 h period of these experiments.