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Biomedical subjects

M Max

Publications and source records attributed to M Max.

36 records · Page 2Linked to original sources

Light-dependent activation of rod transducin by pineal opsin.

The pineal gland expresses a unique member of the opsin family (P-opsin; Max, M., McKinnon, P. J., Seidenman, K. J., Barrett, R. K., Applebury, M. L., Takahashi, J. S., and Margolskee, R. F. (1995) Science 267, 1502-1506) that may play a role in circadian entrainment and photo-regulation of melatonin synthesis. To study the function of this protein, an epitope-tagged P-opsin was stably expressed in an embryonic chicken pineal cell line. When incubated with 11-cis-retinal, a light-sensitive pigment was formed with a lambdamax at 462 +/- 2 nm. P-opsin bleached slowly in the dark (t1/2 = 2 h) in the presence of 50 mM hydroxylamine. Purified P-opsin in dodecyl maltoside activated rod transducin in a light-dependent manner, catalyzing the exchange of more than 300 mol of GTPgammaS (guanosine 5'-O-(3-thiotriphosphate))/mol of P-opsin. The initial rate for activation (75 mol of GTPgammaS bound/mol of P-opsin/min at 7 microM) increased with increasing concentrations of transducin. The addition of egg phosphatidylcholine to P-opsin had little effect on the activation kinetics; however, the intrinsic rate of decay in the absence of transducin was accelerated. These results demonstrate that P-opsin is an efficient catalyst for activation of rod transducin and suggest that the pineal gland may contain a rodlike phototransduction cascade.

Animals↗

[Perspectives in mechanical ventilation in ARDS].

Despite more than 25 years of extensive research, the mortality of ARDS patients remains high. The inflammatory process within the lung and the associated gas exchange disturbances require an aggressive ventilatory regimen, which itself may harm the lung. Therapeutic measures which are used to reduce iatrogenic damage to the lung are pressure controlled mechanical ventilation in combination with PEEP and permissive hypercapnia, dehydration and extracorporeal gas exchange. At present, new strategies such as intratracheal instillation of surfactant, partial liquid ventilation and inhalation of nitric oxide (NO) are being evaluated. Surfactant reduces the surface tension, forming a monomolecular layer at the air/tissue interface. It thereby decreases the forces necessary to expand the alveoli and prevents alveoli with small diameter from collapsing. In ARDS, a disturbance of surfactant synthesis, function and re-uptake is the rationale for treatment with exogenous surfactant. Initial clinical results suggest a limited positive effect independently of the surfactant preparation used, the dose and the application mode. Experience with partial liquid ventilation with perfluorocarbons in ARDS has also been reported. Perfluorocarbons are liquids with a high binding capacity for oxygen and carbon dioxide. During normal mechanical ventilation with gas, repetitive doses of perfluorocarbons are instilled into the lungs up to a volume equal to the functional residual capacity. The liquid is pushed into collapsed alveoli and keeps them open by reducing the surface tension. First clinical studies have demonstrated the possible improvement in pulmonary gas exchange. In ARDS, inhalation of NO may cause a predominantly selective vasodilation in blood vessels of ventilated lung regions, resulting in an increase in PaO2 and a decrease in pulmonary artery pressure. The effect of NO on the pulmonary vasculature also induces a reduction in right ventricular afterload and also in pulmonary capillary pressure, which may lead to a faster resolution of pulmonary edema. However, in spite of the promising results of these new strategies, further studies are needed to evaluate their influence on morbidity and mortality.

Combined Modality Therapy↗

Partial liquid ventilation with small volumes of FC 3280 increases survival time in experimental ARDS.

The aim of this study was to determine the prolonged effects of sequential doses of a highly purified perfluorocarbon (FC 3280) on gas exchange and survival time in experimental acute respiratory distress syndrome (ARDS). The study was prospective, randomized and controlled. Twelve pigs (body weight 30 +/- 5 (mean +/- SD) kg) were surfactant-depleted by repetitive lung lavages, reducing arterial oxygen tension (Pa,O2) to 6.9 +/- 1.6 kPa (52 +/- 12 mmHg) (mean +/- SD) at an inspired oxygen fraction (Fi,O2) of 1.0. They were then randomized to receive partial liquid ventilation by sequential intratracheal application of 7.5 mL.kg-1 FC 3280 at 30 min intervals to a cumulative dose of 15 mL.kg-1 (treatment group), or to receive no further treatment (control group). Haemodynamics and gas exchange were assessed at 30 min intervals after instillation, and hourly afterwards in both groups until death. In the treatment group, Pa,O2 was 8.9 +/- 4.4 kPa (67 +/- 33 mmHg) after 7.5 mL.kg-1 FC 3280 and 14.1 +/- 9.9 kPa (106 +/- 74 mmHg) after 15 mL.kg-1 FC 3280 (NS). In the control group, gas exchange remained unchanged. Haemodynamics were stable in the treatment group and deteriorated in the control group. Peak airway pressures and dynamic compliance were not significantly affected in the treatment group. Mean survival time was 8.2 +/- 4.5 h in the treatment group and 1.8 +/- 1.4 h in the control group (p < 0.05). Upon histological examination, both study groups were not significantly different in total lung injury scores. We conclude that partial liquid ventilation with small volumes of FC 3280 provides improvement in gas exchange and increases survival time in experimental acute respiratory distress syndrome.

Animals↗

Pineal opsin: a nonvisual opsin expressed in chick pineal.

Pineal opsin (P-opsin), an opsin from chick that is highly expressed in pineal but is not detectable in retina, was cloned by the polymerase chain reaction. It is likely that the P-opsin lineage diverged from the retinal opsins early in opsin evolution. The amino acid sequence of P-opsin is 42 to 46 percent identical to that of the retinal opsins. P-opsin is a seven-membrane spanning, G protein-linked receptor with a Schiff-base lysine in the seventh membrane span and a Schiff-base counterion in the third membrane span. The primary sequence of P-opsin suggests that it will be maximally sensitive to approximately 500-nanometer light and produce a slow and prolonged phototransduction response consistent with the nonvisual function of pineal photoreception.

Amino Acid Sequence↗

Host defence capacities of pulmonary surfactant: evidence for 'non-surfactant' functions of the surfactant system.

The most well characterized function of pulmonary surfactant is its ability to reduce surface tension at the alveolar air-liquid interface, thereby preventing lung collapse. However, several lines of evidence suggest that surfactant may also have 'non-surfactant' functions: specific components of surfactant (proteins and phospholipids) may interact with different alveolar cells, inhaled particles and micro-organisms modulating pulmonary host defence systems. SP-A, the most abundant surfactant protein, binds to alveolar macrophages via a specific surface receptor with high affinity [128]. Such binding effects the release of reactive oxygen species from resident alveolar macrophages if SP-A is properly presented to the target cell. SP-A also stimulates chemotaxis of alveolar macrophages [142], and serves as an opsonin in the phagocytosis of herpes simplex virus [161] Candida tropicalis [138] and various bacteria [137]. In addition, SP-A enhances the uptake of particles by monocytes and culture-derived macrophages [140] and improves bacterial killing. SP-D, another hydrophobic surfactant-associated protein, might interact with alveolar macrophages as well, stimulating the release of oxygen radicals [148], while for the hydrophilic surfactant proteins SP-B and SP-C no macrophage interactions have been described so far. SP-A and SP-D are members of the so-called 'collectins', pattern recognition molecules involved in first line defence. While some surfactant proteins appear to stimulate certain macrophage defence functions, surfactant phospholipids seem to inhibit those of lymphocytes. Suppressed lymphocyte functions include lymphoproliferation in response to mitogens and alloantigens, B cell immunoglobulin production and natural killer cell cytotoxicity. Concerning surfactant's phospholipid composition phosphatidylglycerol is more suppressive than phosphatidylcholine on a molar basis [38]. Bovine surfactant has an immunosuppressive effect on the development of hypersensitivity pneumonitis in a guinea pig model [150]. Despite these interesting observations, several important questions concerning the interactions of surfactant components with pulmonary host defence systems remain unanswered. Sufficient host defence in the lungs works through various humoral-cellular systems in conjunction with the specific anatomy of the airways and the gas exchange surface--how does the surfactant system fit into this network? Surfactant and alveolar cells are both altered during lung injury--is there a relationship between alveolar cells from RDS patients and the endogenous surfactant isolated from such patients? How does exogenous surfactant as used for substitution therapy modulate the defence system of the host? Some of those artificial surfactants have been shown to inhibit the endotoxin-alveolar macrophages, PMNs and monocytes including IL-1, IL-6 and TNF [139,152].(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Abdominal incision endometriomas.

General surgeons frequently are asked to evaluate masses appearing in abdominal incisions. The differential diagnosis of these masses is extensive, including suture granulomas, hernias, abscesses, and malignant tumors. When evaluating masses in or near cesarean section scars, endometrioma should also be considered in the differential diagnosis. The presence of endometriomas in and around cesarean section scars clearly has been established in the obstetrics/gynecology literature, with the reported incidence ranging from 0.03 to 0.4 per cent. However, the presence of only two case reports in the general surgery literature suggests underappreciation of this pathologic entity by general surgeons. It also indicates that endometrioma commonly may not be considered in the differential diagnosis of masses detected in or near cesarean scars. Cesarean scar endometriomas are diagnosed by clinical history, with surgical excision as the primary mode of therapy.

Abdomen↗

Circadian and daily rhythms of melatonin in the blood and pineal gland of free-running and entrained Syrian hamsters.

The aim of this study was to develop a radioimmunoassay for the measurement of endogenous circulating melatonin concentrations in the Syrian hamster, and then to determine the effect of various photic manipulations upon this endocrine signal. In experiment 1, pineal-intact or pinealectomized adult male Syrian hamsters, housed under a long photoperiod (LD; 16 h light:8 h darkness) for 2 weeks, were then either maintained on LD or transferred to a short photoperiod (SD; 8 h light:16 h darkness) for a further 8 weeks. The profile of serum melatonin concentrations was determined from blood samples taken by cardiac puncture at intervals over a 24-h period. Radioimmunoassay revealed that daytime concentrations were at or below the limit of sensitivity of the assay (< or = 50 pmol/l). Under both photoperiods, the concentration of melatonin in the serum of pineal-intact animals rose 4-5 h after the onset of darkness, and the peak amplitude of the melatonin rhythm was not significantly different between the SD- or LD-housed animals (200-250 pmol/l). Premature exposure of animals to light during the dark phase of LD caused a precipitous decline in circulating concentrations to daytime values within 15 min and they remained there for several hours. In animals which experienced an uninterrupted night on either LD or SD, the most striking difference in the rhythm of endogenous melatonin secretion was the duration. Animals housed under LD had high levels until the start of the light period, a peak duration of 3.7 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of melatonin production by light, darkness, and temperature in the trout pineal.

The pineal gland of the rainbow trout, Salmo gairdneri, when kept under in vitro perifusion culture conditions, displays a consistently elevated level of melatonin production in darkness (Gern and Greenhouse 1988). Upon light exposure melatonin production falls and stabilizes at a new lower level that is dependent upon the irradiance of the stimulus. To achieve the maximal response for each irradiance, the duration of the stimulus must exceed 30 min. The response amplitude is maximally sensitive to photons presented over durations of 30-45 min; is very insensitive to shorter light exposures; and is maintained with no evidence of adaptation over longer exposures. Temperature plays a role in regulation of melatonin production both in darkness and during light exposure; increased temperature increases melatonin production in darkness and also increases the sensitivity of the response to light. The action spectrum for the response is best fit by the Dartnall nomogram for a vitamin A1 based rhodopsin with peak sensitivity near 500 nm. The possible adaptive significance of control of melatonin synthesis by light and temperature is considered.

Animals↗

Excitatory amino acid receptors may mediate the effects of light on the reproductive system of the golden hamster.

Seasonal regulation of reproduction occurs in golden hamsters (Mesocricetus auratus) in response to changes in day length (photoperiod). We report here the results of experiments designed to evaluate whether excitatory amino acid neurotransmission is involved in mediating the effects of light on reproduction. We found that MK-801, a specific antagonist of the N-methyl-D-aspartate subclass of excitatory amino acid receptors, blocked the stimulatory action of short pulses of light on gonadal function in hamsters maintained in short days. Furthermore, MK-801 also inhibited the light-induced decline in pineal melatonin content. These findings suggest that excitatory amino acids may mediate the effects of light on the reproductive system.

Amino Acids↗

Surface area sized of intravitreal iron wires: their effects on the electroretinograms of rats.

UNLABELLED: The electroretinogram (ERG) was recorded 20 times over a period of 360 days in 26 albino-rats with implanted intravitreal iron wires ranging in size between 0.15 and 1.2 mm2. RESULTS: (i) The a- and b-wave amplitudes decreased rapidly within one day after iron wire implantation. During the following week the amplitudes recovered to some extent. In the course of the next few months the a- and b-wave amplitudes of the eyes implanted with the largest iron wires (1.2 mm2) decreased steadily to about 20% by the end of the observation time, whereas in the groups containing smaller iron wires the electroretinographic changes were limited. (ii) Implantation of equally-sized glass splinters reduced the a- and b-wave amplitudes to 65-75% in comparison to the intact fellow eye. Fast recovery of both potentials to 83-93% followed within two weeks. The mean values of the a-wave amplitudes reached nearly 100%, those of the b-wave 90-95% in the next month.

Animals↗

The organization of retinal projections to the diencephalon and pretectum in the cichlid fish, Haplochromis burtoni.

The organization of retinofugal projections was studied in a cichlid fish by labelling small groups of retinal ganglion cell axons with either horseradish peroxidase or cobaltous lysine. Two major findings resulted from these experiments. First, optic tract axons show a greater degree of pathway diversity than was previously appreciated, and this pathway diversity is related to the target nuclei of groups of axons. The most striking example is the formation of the medial optic tract. Fibers that will become the medial optic tract move abruptly away from their neighbors, at about the level of the optic chiasm, and coalesce at the dorsomedial edge of the marginal optic tract. The medial optic tract projects to the thalamus, the dorsal pretectum, and the deep layer of the optic tectum. The axial optic tract is a group of fibers which segregates from the most medial portion of the marginal optic tract, at about the level of the optic chiasm. The axial tract stays medial to the marginal optic tract for a few hundred microns and then curves laterally to rejoin the marginal optic tract. At least some axial trat axons terminate in the suprachiasmatic nucleus. Within the marginal optic tract, retinal ganglion cell axons from a given retinal quadrant are always segregated into at least two groups. The smaller group projects to the superficial pretectal nucleus. The larger group projects to the superficial layer of the optic tectum. Second, each nontectal retinal termination site receives a unique pattern of retinal input. Within the pretectum the parvocellular superficial pretectal nucleus receives a highly retinotopically organized input from all retinal regions; the basal optic nucleus receives a roughly retinotopically organized input from all retinal regions; the dorsal pretectum receives an input from all retinal regions; and the central pretectal nucleus receives input only from the ventral hemiretina. Within the diencephalon the thalamus receives an input from all retinal regions, but this input is not retinotopically organized; the suprachiasmatic nucleus receives input from the region of central retina that lies just dorsal to the optic nerve head, via the axial optic tract. The accessory optic nucleus receives input from the dorsal hemiretina.

Animals↗

Acute hypercalcemic crisis.

Although hypercalcemia may be caused by extraparathyroid disease and controlled with various medications, acute hypercalcemic crisis is a surgical emergency. All nonperative measures are directed toward diagnosis of hyperparathyroidism and preparation for operation. Parathyroidectomy is indicated even in the absence of definite evidence of a functioning parathyroid tumor in patients when nonoperative methods fail. Prompt medical therapy and timely surgical intervention will result in success in the vast majority of patients with hypercalcemic crises.

Acute Disease↗