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Biomedical subjects

J W Simon

Publications and source records attributed to J W Simon.

At least 37 records · Page 2Linked to original sources

cDNA cloning of Brassica napus malonyl-CoA:ACP transacylase (MCAT) (fab D) and complementation of an E. coli MCAT mutant.

The GenBank database was searched using the E. coli malonyl CoA:ACP transacylase (MCAT) sequence, for plant protein/cDNA sequences corresponding to MCAT, a component of plant fatty acid synthetase (FAS), for which the plant cDNA has not been isolated. A 272-bp Zea mays EST sequence (GenBank accession number: AA030706) was identified which has strong homology to the E. coli MCAT. A PCR derived cDNA probe from Zea mays was used to screen a Brassica napus (rape) cDNA library. This resulted in the isolation of a 1200-bp cDNA clone which encodes an open reading frame corresponding to a protein of 351 amino acids. The protein shows 47% homology to the E. coli MCAT amino acid sequence in the coding region for the mature protein. Expression of a plasmid (pMCATrap2) containing the plant cDNA sequence in Fab D89, an E. coli mutant, in MCAT activity restores growth demonstrating functional complementation and direct function of the cloned cDNA. This is the first functional evidence supporting the identification of a plant cDNA for MCAT.

Acyl-Carrier Protein S-Malonyltransferase↗

Crystallization of the NADP-dependent beta-keto acyl carrier protein reductase from Escherichia coli.

The NADP-dependent beta-keto acyl carrier protein reductase (BKR) from E. coli has been crystallized by the hanging-drop method of vapour diffusion using poly(ethylene glycol) of average molecular weight 1450. The crystals belong to the hexagonal space group P6122 or P6522 with unit-cell dimensions a = b = 67.8, c = 355.8 A. Calculated values for Vm and consideration of the packing suggest that the asymmetric unit contains a dimer. BKR catalyses the first reductive step in the elongation cycle of fatty-acid biosynthesis. It shares extensive sequence homology with the enzyme which catalyzes the second reductive step in the cycle, enoyl acyl carrier protein reductase (ENR), and thus provides an opportunity to study the evolution of enzyme function in a metabolic pathway. The structure determination will permit the analysis of the molecular basis of its catalytic mechanism and substrate specificity.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗

Normal reading despite limited eye movements.

Many investigators have demonstrated that poor readers exhibit abnormal eye movements during reading. An association between defective vergence, accommodation, and poor reading skills has also been noted by some investigators. Children who are poor readers have been subjected to therapeutic interventions on the basis of the assumption that improving their eye movements, as part of a multifaceted program of "vision therapy," will yield commensurate improvement in reading performance. This approach has been controversial, and other authors have expressed opposing views. We report the ophthalmologic and reading assessments of two children with Möbius' syndrome who were average to above-average readers despite essentially absent horizontal eye movements.

Adolescent↗

Superior oblique damage from the traction suture at cataract surgery.

A 41-year-old woman underwent uneventful phacoemulsification and posterior chamber lens implantation in the right eye. Approximately a month later similar surgery was performed in the left eye. The surgery was performed with the patient under retro-bulbar anesthesia with a combination of bupivacaine (Marcaine) 0.75% and lidocaine (Xylocaine) 4% administered through a lower lid injection. Immediately after the patch was removed, the patient was aware of constant vertical diplopia. Over the ensuing 6 months the symptom worsened. Orbital computed tomography showed no abnormalities.

Adult↗

Corneal edema after pediatric cataract surgery.

INTRODUCTION: We have encountered idiopathic corneal edema in four patients (five eyes) after pediatric lensectomy. This problem has not been previously described in the pediatric ophthalmology literature. METHODS: Clinical and operative records were reviewed. The children, who ranged in age from 15 months to 6 years, underwent apparently uncomplicated limbal lensectomy without lens implantation. After surgery, all received subconjunctival hydrocortisone (12.5 mg) and 2 to 4 drops daily of topical prednisolone acetate. The corneal edema developed between 2 and 14 days after surgery. RESULTS: The condition cleared in all patients during a 5- to 14-day course of intensive topical steroids. No sequelae have been apparent. Final visual acuities are 20/30 or better in the three children (four eyes) old enough for recognition acuity testing. The fifth eye has excellent central fixation. CONCLUSIONS: We suspect that the corneal decompensation was a manifestation of sterile inflammation. Two of the children had a history of iritis. Difficulty measuring cellular response at the slit-lamp examination and instilling eyedrops at home may have contributed to the complication. Postoperative corneal decompensation can be responsive to topical steroids, which we now prescribe more intensively even in apparently quiet eyes.

Anti-Inflammatory Agents↗

Primary infratarsal lower eyelid retractor lysis to prevent eyelid retraction after inferior rectus muscle recession.

PURPOSE: To evaluate a procedure to prevent lower eyelid retraction, which may occur after inferior rectus muscle recession surgery as a direct consequence of the intimate anatomic connections between the inferior rectus muscle and lower eyelid retractors. METHODS: We evaluated the technique of primary infratarsal lower eyelid retractor lysis on 12 eyelids of ten patients undergoing inferior rectus muscle recession of 3 mm or more. Indications for surgery included restrictive strabismus related to Graves' ophthalmopathy, orbital blowout fracture, and orbital fibrosis syndrome. RESULTS: For the 12 eyes, inferior rectus muscle recession ranged from 3 to 10 mm (mean, 5.3 mm). Postoperatively there was no significant change in mean lower eyelid position (P > .82), and no patient developed inferior scleral show. CONCLUSION: Primary infratarsal eyelid retractor lysis is an effective technique for preventing lower eyelid retraction after inferior rectus muscle recession strabismus surgery.

Aged↗

Cerebellar astrocytoma manifesting as isolated, comitant esotropia in childhood.

PURPOSE: We encountered a 4 1/2-year-old girl with gradual onset of intermittent, comitant esotropia in the absence of diplopia and other neurologic findings. METHODS: Because of the patient's relatively advanced age and lack of response to hyperopic correction for accommodative esotropia, computed tomography of the head was performed. RESULTS: A large cerebellar astrocytoma was identified and successfully resected. After strabismus surgery, fusion was reestablished. CONCLUSIONS: The onset of comitant esotropia in an older child may indicate an underlying neurologic disorder.

Astrocytoma↗

Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase.

BACKGROUND: Enoyl acyl carrier protein reductase (ENR) catalyzes the NAD(P)H-dependent reduction of trans-delta 2-enoyl acyl carrier protein, an essential step in de novo fatty acid biosynthesis. Plants contain both NADH-dependent and separate NADPH-dependent ENR enzymes which form part of the dissociable type II fatty acid synthetase. Highly elevated levels of the NADH-dependent enzyme are found during lipid deposition in maturing seeds of oilseed rape (Brassica napus). RESULTS: The crystal structure of an ENR-NAD binary complex has been determined at 1.9 A resolution and consists of a homotetramer in which each subunit forms a single domain comprising a seven-stranded parallel beta sheet flanked by seven alpha helices. The subunit has a topology highly reminiscent of a dinucleotide-binding fold. The active site has been located by difference Fourier analysis of data from crystals equilibrated in NADH. CONCLUSIONS: The structure of ENR shows a striking similarity with the epimerases and short-chain alcohol dehydrogenases, in particular, 3 alpha,20 beta-hydroxysteroid dehydrogenase (HSD). The similarity with HSD extends to the conservation of a catalytically important lysine that stabilizes the transition state and to the use of a tyrosine as a base--with subtle modifications arising from differing requirements of the reduction chemistry.

Amino Acid Sequence↗

Crystallization of the NADH-specific enoyl acyl carrier protein reductase from Brassica napus.

The tetrameric, NADH-dependent enoyl acyl carrier protein reductase from developing seeds of Brassica napus (oil seed rape) has been crystallized from solutions containing ammonium sulphate as the precipitant in the presence of NAD+ or NADH using the hanging drop method of vapour diffusion. The crystals belong to the tetragonal system and are in space group P4(2)2(1)2 with cell dimensions a = b = 70.5 A, c = 117.8 A. Considerations of the possible values of Vm indicate that the asymmetric unit contains a single subunit. The crystals are resistant to radiation damage and X-ray diffraction photographs taken with synchrotron radiation show measurable reflections to beyond 1.9 A resolution. Determination of the structure of this enzyme will advance the understanding of the mechanisms of lipid biosynthesis in plants and provide an opportunity to study the interactions between this enzyme and its acyl carrier protein substrate.

Brassica↗

Studies on wheat acetyl CoA carboxylase and the cloning of a partial cDNA.

Wheat germ acetyl CoA carboxylase (ACCase) was purified by liquid chromatography and electroelution. During purification bovine serum albumin (BSA) was used to coat Amicon membranes used to concentrate partially pure ACCase. Despite further SDS-PAGE/electroelution and microbore HPLC steps BSA remained associated. This presented serious protein sequencing artefacts which may reflect the affinity of BSA for fatty acids bound to ACCase. To avoid these artefacts the enzyme was digested in gel with Endoproteinase LysC protease without the presence of BSA, and the resulting peptides blotted and sequenced. A partial cDNA (1.85 kb) encoding ACCase from a wheat embryo library was cloned, which hybridised to a 7.5 kb RNA species on northern blot of wheat leaf poly(A)+ RNA. The partial cDNA therefore represents about 0.25 of the full-length cDNA. The clone was authenticated by ACCase peptide sequencing and immuno cross-reactivity of the overexpressed clone. The derived amino acid sequence showed homology with both rat and yeast ACCase sequences (62%). Antibodies raised against wheat acetyl CoA carboxylase were specific for a 220 kDa protein from both wheat embryo and leaf. In addition, by using a novel quick assay for ACCase that utilised 125I-streptavidin, we showed the major biotin containing protein to be 220 kDa in both leaf and germ. This is in marked contrast to the previously published molecular mass of 75 kDa allocated to wheat leaf ACCase.

Acetyl-CoA Carboxylase↗

Development of object vision in infants with permanent cortical visual impairment.

We examined 30 infants in whom cortical visual impairment was diagnosed during their first year of life to ascertain prognostic factors for the development of object vision, defined as the ability to recognize faces or hand-held toys. All patients were followed up for a minimum of 12 months. The most common causes of cortical visual impairment in the 30 infants were hydrocephalus in nine infants (30.0%), birth asphyxia or neonatal hypoxia in eight infants (26.7%), intracranial hemorrhage with or without hydrocephalus in seven infants (23.3%), and meningitis in five infants (16.7%). Lack of development of object vision was associated only with hypoxia (P = .013). Findings on ophthalmic examination, an abnormality in the visual pathway on computed tomographic or magnetic resonance scan, and seizures, hydrocephalus, intracranial hemorrhage, meningitis, cerebral palsy, developmental delay, prematurity, microcephaly, and hearing deficit, did not appear to be risk factors for the lack of development of object vision.

Brain Diseases↗

Variable expression of albinism within a single kindred.

We studied the albinotic characteristics in 13 members of a white family (age range, 2 to 73 years), which were graded according to severity and were correlated with visual acuity. Clinical, electrophysiologic, and biochemical characteristics of this family do not fit any known category of human albinism. The degree of heterogeneity in expression of albinotic features was unexpected. The correlation between visual acuity and nystagmus was particularly strong. The brown-haired propositus had severe skin involvement, iris transillumination, fundus hypopigmentation, and foveal hypoplasia. He had no manifest nystagmus, however, and his visual acuity was nearly normal. These observations suggest that nystagmus imposes a visual deficit beyond that related to foveal hypoplasia alone.

Adolescent↗

Glaucoma after pediatric lensectomy/vitrectomy.

Glaucoma after pediatric cataract surgery, once well recognized, now occurs only rarely after modern lensectomy/vitrectomy. The authors performed directed glaucoma evaluations of 34 eyes of 26 children. Based on intraocular pressures of 26 mmHg or greater, glaucoma was diagnosed in 8 (24%) eyes of 7 (27%) children. Glaucoma was found more commonly among children followed more than 60 months and was diagnosed up to 105 months after surgery. Typically, the glaucoma was open angle and asymptomatic. Four children had had previously normal pressures recorded. With longer follow-up, it is likely that more children will be diagnosed with glaucoma after lensectomy/vitrectomy procedures. The authors believe such patients should be followed as glaucoma suspects for the rest of their lives.

Cataract Extraction↗

Functional eyelid pulling in children.

Five children (three girls and two boys, aged 3 1/2 to 9 1/2 years) were referred by their pediatricians for evaluation of intermittent pulling on their eyelids. All the children were free of systemic disease. One child wore spectacles for accommodative esotropia but no child had evidence of an acute ocular disorder. The duration of symptoms before examination ranged from one to 13 months. None of the parents were able to identify temporally related stressful events. Reassurance alone was given to both parents and children; eyelid pulling resolved in all cases within two weeks. In only the youngest patient did eyelid pulling recur and no child developed other symptoms during a follow-up of six to 15 months. Following resolution, parents believed their children pulled on the eyelids to gain attention or because their eyes were initially irritated and they then developed a "bad habit." Children said they did it to "look funny" or because their "eyes were not opening enough."

Attention↗