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Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 415 records · Page 23Linked to original sources

Rapid identification of calbindin-D28k cyanogen bromide peptide fragments by plasma desorption mass spectrometry.

Chicken intestinal calbindin-D28k is an intracellular protein which is believed to have a fundamental role in vitamin D-mediated transport of calcium. A mapping approach based on 252Cf plasma desorption mass spectrometry (PD mapping) was used to screen the DNA-deduced sequence of calbindin-D28k for sequence changes and post-translational modifications. In the PD mapping experiment, purified calbindin-D28k was cleaved with cyanogen bromide and the resulting peptides were subjected to PD mass spectrometric analysis either as a mixture or as high-performance liquid chromatography isolated fractions. The DNA-derived primary structure of calbindin-D28k was confirmed by rapid PD mass spectral identification of the CNBr peptide fragments, and the nature of the N-terminal blocking group was readily determined to be an acetyl group. The relatively non-destructive nature of the PD mass spectrometric analysis allowed the mapping of the N-terminal peptide through an additional in situ V8 protease enzymatic reaction.

Amino Acid Sequence↗

Cerebral glucose metabolic rates in obsessive compulsive disorder.

Brain metabolism was measured with positron emission tomography and [18F] 2-fluoro-2-deoxyglucose in normal subjects and in patients with obsessive compulsive disorder (OCD) while they performed a continuous auditory discrimination task designed to evaluate the functional localization of sustained attention. Data on 8 nondepressed patients with OCD were compared with 30 normal volunteers. We observed significantly higher normalized regional metabolism both in the right orbital frontal cortex (p = 0.002, two-tailed t test) and in the left anterior orbital frontal cortex (p = 0.017, one-tailed t test) and in patients with OCD as compared to normal controls. We observed no normalized glucose metabolic differences in basal ganglia structures in patients with OCD as compared to our normal controls. There were no statistical differences in global glucose metabolic values between the OCD and the control group. Our findings are consistent with the findings of Baxter et al. (Arch Gen Psychiatry 44:211-218, 1987). Regions in the parietal cortex also appear to show differences in this preliminary study.

Adult↗

Evidence for common alterations in cerebral glucose metabolism in major affective disorders and schizophrenia.

Regional glucose metabolic rates were measured in affectively disordered patients during the performance of auditory discrimination. Those regions previously observed as abnormal in schizophrenia were examined to see if similar alterations might be associated with affective disorder. The abnormalities observed in the mid-prefrontal cortex, an area that appears to be an important biologic determinant of the sustained attention required of subjects in this task, are similar to those previously observed in schizophrenia. Moreover, the abnormalities do not appear to relate directly to symptomatology or the subject's performance. The authors discuss the possibility that this abnormality may reflect dysfunction in the integrating component of the attention network critical for the maintenance of goal-directed behavior and thus represent a psychosis vulnerability factor in some patients.

Acoustic Stimulation↗

The unproven utility of the preoperative urinalysis: economic evaluation.

The clinical effectiveness of the preoperative urinalysis is unproven, yet it is routinely obtained before surgery. To determine if the routine urinalysis might be economically beneficial, we evaluated its cost-effectiveness and cost-benefit. In the setting of elective clean-wound, non-prosthetic knee procedures, we estimated that: (1) nearly U.S. $7,000,000 is spent annually on preoperative urinalyses and associated costs; (2) given the best estimate of the increase in risk of wound infection attributable to urinary tract infection, 4.58 wound infections may be prevented annually, at a cost of $1,500,000 per wound infection prevented; (3) the cost of treating additional cases of wound infection, given no preoperative urinalysis, is approximately five hundred-fold less than the cost of screening with routine urinalyses. We conclude that the routine preoperative urinalysis is clinically and economically unsound before clean-wound, non-prosthetic knee surgery and probably before other types of clean-wound surgery. For this relatively inexpensive test, aggregate costs are disproportionately high and appear to outweight clinical benefits.

Aged↗

An evaluation of the biocompatibility of a glass ionomer-silver cement in rat connective tissue.

Pellets of a glass ionomer-silver cement and a zinc oxide-eugenol cement were implanted into the soft tissues and bones of 30 rats. Following experimental periods of 14, 30, and 80 days, the animals were killed and tissue sections were prepared. The responses to each of the materials initially and at 30 days consisted of mild inflammation. No severe inflammatory responses were noted in any of the groups. By 80 days, although mild inflammation persisted, the materials appeared to be well tolerated. Bone apposition occurred in the glass ionomer-silver cement group; the zinc oxide-eugenol group produced fibrosis.

Animals↗

Eicosanoids and multistage carcinogenesis in NMRI mouse skin: role of prostaglandins E and F in conversion (first stage of tumor promotion) and promotion (second stage of tumor promotion).

When applied to NMRI mouse skin in vivo, phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) have been found to induce two early waves of prostaglandin E2 (PGE2) synthesis after 15 and 90 min and a delayed accumulation of prostaglandin F2 alpha (PGF2 alpha) after 2 h. With respect to PGF2 alpha formation different activities of both agents were observed, in that TPA but not RPA induced additional PGF2 alpha waves after 4 and 17 h. Functionally, PGE2 was previously shown to be an endogenous mediator of the TPA- or RPA-induced epidermal hyperproliferation and hyperplasia. A functional role of PGF2 alpha could be attributed to the post-initiation stages of tumor development in initiated mouse skin, i.e. the conversion stage (stage I of tumor promotion) elicited by two TPA applications and the promotion stage (stage II of promotion) brought about repetitive RPA treatments. PGF2 alpha, appearing as one distinct biosynthetic wave 3-4 h after TPA application seems to be critically involved in the conversion steps since (i) inhibition of its accumulation by indomethacin led to an inhibition of tumor formation, (ii) the inhibitory effect of indomethacin could be reversed by PGF2 alpha and (iii) RPA was not able to give rise to the accumulation of PGF2 alpha 4 h after application as obtained by TPA treatment. Moreover, RPA-induced promotion of DMBA- and TPA-treated mouse skin was inhibited by indomethacin. The inhibitory effect of indomethacin on papilloma formation was again reversed by PGF2 alpha treatment concomitant with RPA.

Animals↗

Retirement of fighter pilots with incidentally detected illnesses: a decision analytic model.

Decisions regarding professional fitness after an incidental detection of a clinical disorder are often problematic. The added risk of an occupational error related to the detected disorder may be smaller than the risk of an error due to lack of experience if a veteran is replaced by a novice. In this paper, we examine the choice between grounding or granting a waiver to an experienced fighter pilot with an incidental finding of premature ventricular contractions. The decision considers the probability of sudden incapacitation during flight and of pilot error-related air accidents in novices and veterans. Although deliberately biased in favor of grounding the veteran, the analysis indicates that the risk of sudden death or incapacitation in an experienced fighter pilot with an incidentally detected illness should be increased ten-fold to 46-fold to justify his or her replacement by a novice. In the specific case considered, the analysis suggests that the risk of an air accident due to sudden death or incapacitation of a veteran with incidentally detected premature ventricular contractions is similar to the estimated added risk of an error-related air accident if she or he is grounded and replaced by a novice. When reliable data on the frequency of human error by age and experience become available, the proposed model may be applied to other situations in which trained professionals develop a potentially disabling disease.

Accidents, Aviation↗

[Polygraphic studies of newborn infants at risk using acoustic stimulation close to and above the threshold level].

16 newborns were investigated by means of polygraphy (EEG, respirography, heart rate, psychogalvanic reflex and behavioural observations). They were acoustically stimulated (125, 750, 15000 and 3000 Hz, with stepwise increase of the intensity by 10 dBA) during the period of quiet sleep. Partial vegetative reactions appeared in 11 newborns between a stimulation intensity of 30 to 50 dBA. Changes of breathing were initially observed. A further increase of intensity caused reactions in heart rate, psychogalvanic reflex and also body movements. The EEG and behavioural states were never changed at this level of intensity. Reactions in these parameters were recurrently observable if stimulation intensity was higher than 80 dBA. Only half of all stimulations were followed by reactions. The results verify decreased threshold intensity to evoke partial vegetative reactions in newborns at risk and the same sequence of additional reactions in EEG and behavioural states as in healthy newborns following increasing stimulation intensity.

Acoustic Stimulation↗

[Familial circumscribed plantar keratosis with sensorineural hearing loss and sporadic CHILD syndrome].

The authors report a case of siblings in whom circumscribed plantar keratoderma developed during early childhood. The keratotic areas increased with age and also affected the dorsal aspects of the digital joints. In addition, a markedly progressive disturbance in sound perception occurred in both children from age 4 onwards. This observation confirms the concept proposed by Blanchet-Bardon et al. that focal palmoplantar keratoderma with sensorineural hearing loss constitutes a distinct entity. In addition, the younger sister was affected with the CHILD syndrome. She suffered from linear ichthyosiform nevus with ipsilateral ectrodactyly. The simultaneous occurrence of the two syndromes is probably purely coincidental.

Child↗

Intracellular localization of the calcium- and calmodulin antagonist fendiline.

Microautoradiograpic studies of mouse heart sections were performed to evaluate intracellular localization of the antianginal drug fendiline (Sensit). 15 microCi 3H-fendiline/g b. w. (0.5 mg/kg b.w.) were injected intravenously. 10 min p.a. the heart was removed and either frozen in acetone/dry ice or, after perfusion in situ with dextran 40 and formaldehyde, fixed in formaldehyde. Frozen, paraffin-embedded, and semithin epoxy resin sections were prepared and coated with Ilford K2 emulsion. After 7 to 30 days exposure and development in amidol silver grains were counted above cells, nuclei and extracellular space. The results show that fendiline is able to enter myocardial cells.

Animals↗

The therapeutic efficacy of an anti-IL-2 receptor monoclonal antibody correlates with an increase in serum soluble IL-2 receptor levels.

We tested the capacity of three rat monoclonal antibodies (MoAb), recognizing different epitopes on the L chain of mouse interleukin-2 receptor (IL-2R), to block delayed-type hypersensitivity (DTH) and local graft-versus-host reaction (GVHR). Furthermore, we investigated the effect of IL-2R-targeted immunotherapy on serum soluble IL-2R levels by ELISA technique. Following administration of AMT-13 MoAb, in sufficient amounts to suppress both DTH (60-90% inhibition) and local GVHR (55-70% inhibition), an increase in soluble IL-2R levels up to 12-fold was observed. In contrast, the administration of 7D4 MoAb did not show any immunosuppressive effect in vivo and even decreased the soluble IL-2R levels. The third anti-IL-2R MoAb AMT45-20 had an intermediate effect. AMT45-20 MoAb marginally suppressed the DTH as well as local GVHR (15-35% inhibition) and induced only a slight increase in soluble IL-2R levels (up to 4-fold). Both cyclosporin A, a conventional immunosuppressive drug, and the anti-L3T4 MoAb, which defines the entire T helper cell subset, suppressed GVH and DTH response but did not increase the soluble IL-2R serum levels. The increased concentration of soluble IL-2R in the serum of successfully treated mice may be due to destruction of IL-2R-positive cells by anti-IL-2R-targeted immunotherapy and seems to be a sensitive indicator for the success of such a therapy.

Animals↗

Regulation of protein synthesis in rabbit reticulocyte lysate. Glucose 6-phosphate is required to maintain the activity of eukaryotic initiation factor (eIF)-2B by a mechanism that is independent of the phosphorylation of eIF-2 alpha.

Previous studies from other laboratories, using rabbit reticulocyte lysate filtered through Sephadex G-25 or G-50, have demonstrated that glucose 6-phosphate is required to maintain active rates of translation, but its mechanism of action is currently unsettled. We have tested whether glucose 6-phosphate is required to prevent activation of the hemin-controlled translational repressor and the phosphorylation of the smallest or alpha subunit of eukaryotic initiation factor 2 (eIF-2). We have found that antibody to the hemin-controlled translational repressor can completely restore protein synthesis in reticulocyte lysate, filtered through Sephadex G-25, that is incubated in the absence of hemin and presence of glucose 6-phosphate, but cannot restore protein synthesis in such lysate incubated in the presence of hemin and absence of glucose 6-phosphate. We have also found, using a modification of the method of Matts and London [1984) J. Biol. Chem. 259, 6708-6711) to measure the ability of gel-filtered lysate to dissociate and exchange GDP from eIF-2.GDP, that this endogenous eIF-2B activity is reduced to the same low level in the presence of hemin and absence of glucose 6-phosphate as it is in the absence of hemin and presence of glucose 6-phosphate. Although there is a low level of phosphorylation of eIF-2 alpha in gel-filtered lysate given hemin but no glucose 6-phosphate, it cannot account for the loss of eIF-2B activity, since this phosphorylation is removed by antibody to the hemin-controlled translational repressor or isocitrate, which do not restore protein synthesis or eIF-2B activity, and not by fructose 1,6-diphosphate, which does partially restore protein synthesis and eIF-2B activity. These findings suggest that sugar phosphates may exert a direct effect on eIF-2B and may be required for its proper function. Additional support for this conclusion is our finding that protein synthesis and eIF-2B activity in partially hemin-deficient lysate can be restored by high levels of glucose 6-phosphate or fructose 1,6-diphosphate without a reduction in the level of phosphorylated eIF-2 alpha, suggesting that such levels of sugar phosphate may permit restoration of normal function with a limiting amount of eIF-2B.

Animals↗