Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs.

GRP1 and the related proteins ARNO and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. Here we show the PH domains of all three proteins exhibit relatively high affinity for dioctanoyl phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P(3)), with K(D) values of 0.05, 1.6 and 1.0 micrometer for GRP1, ARNO, and cytohesin-1, respectively. However, the GRP1 PH domain was unique among these proteins in its striking selectivity for PtdIns(3,4, 5)P(3) versus phosphatidylinositol 4,5-diphosphate (PtdIns(4,5)P(2)), for which it exhibits about 650-fold lower apparent affinity. Addition of a glycine to the Gly(274)-Gly(275) motif in GRP1 greatly increased its binding affinity for PtdIns(4,5)P(2) with little effect on its binding to PtdIns(3,4,5)P(3), while deletion of a single glycine in the corresponding triglycine motif of the ARNO PH domain markedly reduced its binding affinity for PtdIns(4,5)P(2) but not for PtdIns(3,4,5)P(3). In intact cells, the hemagglutinin epitope-tagged PH domain of GRP1 was recruited to ruffles in the cell surface in response to insulin, as were full-length GRP1 and cytohesin-1, but the PH domain of cytohesin-1 was not. These data indicate that the unique diglycine motif in the GRP1 PH domain, as opposed to the triglycine in ARNO and cytohesin-1, directs its remarkable PtdIns(3,4,5)P(3) binding selectivity.

Amblyopia and visual acuity in children with Down's syndrome.

BACKGROUND/AIMS: Amblyopia in people with Down's syndrome has not been well investigated. This study was designed to determine the prevalence and associated conditions of amblyopia in a group of home reared children with Down's syndrome. METHODS: All children in the study group underwent an evaluation of visual acuity. In addition, previous ophthalmological records were reviewed, and a subgroup of children was examined. For the purposes of this study, amblyopia was defined quantitatively as a difference of two Snellen acuity lines between eyes or if unilateral central steady maintained (CSM) vision and a clear fixation preference was observed. A high refractive error was defined as a spherical equivalent more than 3 dioptres and astigmatism more than 1.75 dioptres. Anisometropia was defined as a difference of at least 1.5 dioptres of sphere and/or 1.0 dioptre of cylinder between eyes. 68 children with Down's syndrome between the ages of 5 and 19 years were enrolled in the final study group. RESULTS: Amblyopia was observed in 15 (22%) of 68 patients. An additional 16 (24%) patients had bilateral vision less than 20/50. Strabismus, high refractive errors, and anisometropia were the conditions most commonly associated with decreased vision and amblyopia CONCLUSION: This study suggests that the prevalence of amblyopia is higher than previously reported. Fully 46% of these children with Down's syndrome had evidence of substantial visual deficits. These patients may be at higher risk for visual impairment and should be carefully examined for ophthalmological problems.

Relative efficacy of the argon green, argon blue-green, and krypton red lasers for 10-0 nylon subconjunctival laser suture lysis.

BACKGROUND AND OBJECTIVE: To determine the optimal wavelength for subconjunctival laser suture lysis. MATERIALS AND METHODS: 130 black monofilament 10-0 nylon sutures were sewn subconjunctivally into the bare sclera of enucleated rabbit globes. The lowest energy levels facilitating laser suture lysis were determined for the argon green (514.5 NM), argon blue-green (488.0 NM, 514.5 NM), and krypton red (647.1 NM) wavelengths. In addition, absorption spectroscopy was performed on the suture material and conjunctiva using the Perkin Elmer W/VIS Lambda 2 spectrometer. RESULTS: Krypton red produced the fewest buttonhole defects, and it was also the most efficient energy source for suture lysis (P = 0.0001) under nontenectomized conjunctiva. Absorbance spectra studies revealed peak absorbance at 628 NM for the 10-0 nylon suture material. CONCLUSIONS: Based on animal and absorption spectroscopy studies, krypton red may be a safer and more efficient wavelength for subconjunctival laser suture lysis.

Prognostic importance of ophthalmic manifestations in childhood leukaemia.

In order to assess the systemic prognosis of children with leukaemic ocular involvement, 63 of 131 patients admitted to hospital with acute leukaemia were evaluated ophthalmically. A total of 28 of 63 showed ophthalmic involvement and were followed up for up to 84 months. Twenty seven of 28 patients (96.4%) died within 28 months after the onset of ocular involvement and within 83 months after the onset of leukaemia. The 5 year survival rate of patients with ophthalmic manifestations was 21.4% (6/28). This survival rate was significantly lower than that of those who lacked ophthalmic manifestations (16/35: 45.7%, p < 0.05). All of the patients with ophthalmic manifestations had either bone marrow relapse or central nervous system leukaemia. The prognosis was related to risk factors such as central nervous system leukaemia or bone marrow relapse in most cases.

Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age.

Head injury in the youngest age group is distinct from that occurring in older children or adults because of differences in mechanisms, injury thresholds, and the frequency with which the question of child abuse is encountered. To analyze some of these characteristics in very young children, the authors prospectively studied 100 consecutively admitted head-injured patients 24 months of age or younger who were drawn from three institutions. Mechanism of injury, injury type, and associated injuries were recorded. All patients underwent ophthalmologic examination to document the presence of retinal hemorrhages. An algorithm incorporating injury type, best history, and associated findings was used to classify each injury as inflicted or accidental. The results confirmed that most head injuries in children younger than 2 years of age occurred from falls, and while different fall heights were associated with different injury types, most household falls were neurologically benign. Using strict criteria, 24% of injuries were presumed inflicted, and an additional 32% were suspicious for abuse, neglect, or social or family problems. Intradural hemorrhage was much more likely to occur from motor vehicle accidents and inflicted injury than from any other mechanism, with the latter being the most common cause of mortality. Retinal hemorrhages were seen in serious accidental head injury but were most commonly encountered in inflicted injury. The presence of more serious injuries associated with particular mechanisms may be related to a predominance of rotational rather than translational forces acting on the head.

Ophthalmic manifestations of pulmonary diseases.

Patients suffering from pulmonary diseases often have ophthalmic manifestations, some of which may be critical and disabling. The purpose of this article is to discuss the ophthalmologic manifestations of pulmonary diseases. This is achieved by describing a typical ophthalmologic examination, starting with the external structures and ocular adnexae and proceeding through the structures of the eye, including the retina, optic nerve, and orbit.

Diagnosis of diabetic eye disease.

The correct diagnosis of proliferation diabetic retinopathy is essential, because it is a treatable disease and missing the diagnosis can lead to the patient becoming blind. We examined the ability of internists and ophthalmologists to diagnose proliferative retinopathy under optimal conditions. Twenty-three physicians performed retinal examinations on ten diabetic patients and one normal patient with dilated pupils. Physician examiners were members of a university medical center and included 10 internists, 2 diabetologists, 4 senior medical residents, 4 general ophthalmologists, and 3 ophthalmologists who were subspecialists in retinal disease. Correct diagnosis was determined separately by the consensus of three ophthalmologists specializing in retinal disease, who reviewed seven-view stereo fundus photographs and medical charts. Of a possible 483 individual eye a examinations, 438 were completed. The overall error rate was 61%. The error rate for missing the diagnosis of proliferative retinopathy varied from 0% for retinal specialists to 49% for internists, diabetologists, and medical residents. We conclude that potentially serious mistakes in diagnosis are currently made by the physicians who care for most diabetic patients. Experience and specialized knowledge lessen that the error rate. Further education or greater use of referrals may be necessary to provide optimal patient care.

Computerized axial tomography in inflammatory pseudotumor of the orbit.

Although thyrotoxicosis and orbital complications of acute ethmoid or frontal sinusitis are among the most common causes of unilateral exophthalmos, inflammatory pseudotumor is frequently accompanied by progressive acute unilateral proptosis. Because the associated chemosis, scleral erythema, and ophthalmoplegia constitute a spectrum of clinical findings present in numerous inflammatory orbital disorders and systemic diseases, the diagnosis of inflammatory pseudotumor is one of exclusion, often requiring orbital biopsy. Four patients without evidence of sinusitis, endocrinopathy, collagen vascular disease, or Wegener's granulomatosis are described. The diagnosis of orbital pseudotumor was disclosed by computed axial tomography, thus avoiding orbitotomy. The finding of scleral and choroidal thickening with enhancement following intravenous contrast injection represents a select group of patients with orbital pseudotumor and differentiates them from patients with endocrine exophthalmopathy or neoplasms. This noninvasive technique is extremely valuable because early diagnosis is critical for successful treatment. All four patients responded dramatically to high-dose corticosteroid therapy. In the absence of significant clinical response, however, Wegener's granulomatosis, lymphoma, and rhabdomyosarcoma, especially in younger patients, must be carefully excluded. Orbital exploration or decompression or both are used when proptosis, headache, or orbital pain does not resolve promptly, visual acuity deteriorates, or the diagnosis remains unknown.

Effect of lateral cervical cord lesions on the respiratory rhythm of anaesthetized, decerebrate cats after vagotomy.

1. The lateral cervical cord of vagotomized, anaesthetized cats was superficially lesioned at the C3 or the C7 level before or after midcollicular decerebration.2. These cord lesions eliminated the inhibition of diaphragmatic discharge caused by chest compression. Previous work (Remmers, 1973) indicates that this change can be attributed to loss of reflex inhibition of inspiratory activity by intercostal afferents, probably as a result of interruption of tracts ascending in the lateral columns.3. Decerebrate cats with bilateral cervical cord lesions displayed abnormal respiratory patterns, ranging from apnoea to apneusis.4. The results are consistent with the hypothesis that the lateral columns carry proprioceptive feed-back from intercostal mechanoreceptors which promotes rhythmic breathing in the anaesthetized decerebrate cat.