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.Background:
The management of traumatic optic neuropathy remains controversial. This retrospective study presents the results of 19 cases of indirect optic neuropathy where surgical decompression represented the primary mode of treatment.
Methods:
Nineteen patients (20 optic nerves) with traumatic optic neuropathy underwent primary surgical decompression. The surgery was performed using the transethmoidal technique.
Results:
The extent of bony optic canal injury documented during surgery indicated that this had been underestimated in this series by CT findings. Vision improved in eight patients, five of whom had had no light perception preoperatively.
Conclusion:
Primary surgical decompression of the optic nerve within 48 h of injury produces beneficial results. Testing of visual acuity 6 weeks after surgery does not serve as a reliable predictor of final outcome.

Human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type II (HTLV-2) use a similar mechanism for -1 translational frameshifting to overcome the termination codon in viral RNA at the end of the gag gene. Previous studies have identified two important RNA signals for frameshifting, the slippery sequence and a downstream stem-loop structure. However, there have been somewhat conflicting reports concerning the individual contributions of these sequences. In this study we have performed a comprehensive mutational analysis of the cis-acting RNA sequences involved in HIV-1 gag-pol and HTLV-2 gag-pro frameshifting. Using an in vitro translation system we determined frameshifting efficiencies for shuffled HIV-1/HTLV-2 RNA elements in a background of HIV-1 or HTLV-2 sequences. We show that the ability of the slippery sequence and stem-loop to promote ribosomal frameshifting is influenced by the flanking upstream sequence and the nucleotides in the spacer element. A wide range of frameshift efficiency rates was observed for both viruses when shuffling single sequence elements. The results for HIV-1/HTLV-2 chimeric constructs represent strong evidence supporting the notion that the viral wild-type sequences are not designed for maximal frameshifting activity but are optimized to a level suited to efficient viral replication.

The Zab domain of the editing enzyme ADAR1 binds tightly and specifically to Z-DNA stabilized by bromination or supercoiling. A stoichiometric amount of protein has been shown to convert a substrate of suitable sequence to the Z form, as demonstrated by a characteristic change in the CD spectrum of the DNA. Now we show that Zab can bind not only to isolated Z-forming d(CG)(n) sequences but also to d(CG)(n) embedded in B-DNA. The binding of Zab to such sequences results in a complex including Z-DNA, B-DNA, and two B-Z junctions. In this complex, the d(CG)(n) sequence, but not the flanking region, is in the Z conformation. The presence of Z-DNA was detected by cleavage with a Z-DNA specific nuclease, by undermethylation using Z-DNA sensitive SssI methylase, and by circular dichroism. It is possible that Zab binds to B-DNA with low affinity and flips any favorable sequence into Z-DNA, resulting in a high affinity complex. Alternatively, Zab may capture Z-DNA that exists transiently in solution. The binding of Zab to potential as well as established Z-DNA segments suggests that the range of biological substrates might be wider than previously thought.

Cholesteryl ester storage disease and Wolman disease are rare autosomal recessive lipoprotein-processing disorders caused by mutations in the gene encoding human lysosomal acid lipase. Thus far we have elucidated the genetic defects in 15 unrelated CESD patients. Seven were homozygotes for the prevalent hLAL exon 8 splice junction mutation which results in incomplete exon skipping, while eight probands were compound heterozygotes for E8SJM and a rare mutation on the second chromosome. In this report, we describe the molecular basis of CESD in three compound heterozygous subjects of Czech and Irish origin. RFLP and DNA sequence analysis revealed that they were heteroallelic for the common G(934)-->A substitution in exon 8 of the hLAL gene and a mutation which, if inherited on both alleles, would be expected to result in complete loss of enzyme activity and to cause Wolman disease. In patients A. M. and J. J., two nucleotide deletions in exons 7 and 10 were detected, involving a T at position 722, 723, or 724 and a G in a stretch of five guanosines at positions 1064;-1068 of the hLAL cDNA. Both mutations result in premature termination of protein translation at residues 219 and 336, respectively, and in the production of truncated, inactive enzymes. Subject D. H., in contrast, is a compound heterozygote for the Arg(44)-->Stop mutation previously described in a French CESD proband. Combined with data in the literature, our results demonstrate that compound heterozygosity for a mutation causing Wolman disease is common among cholesteryl ester storage disease patients.

BACKGROUND: Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS: To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. METHODS: Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. RESULTS AND CONCLUSIONS: Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.

Human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) is essential for the intralysosomal metabolism of cholesteryl esters and triglycerides taken up by receptor-mediated endocytosis of lipoprotein particles. The key role of the enzyme in intracellular lipid homeostasis is illustrated by two lysosomal storage diseases inherited as autosomal recessive traits. Wolman disease, associated with deficient hLAL activity, leads to massive intracellular substrate accumulation and is always fatal in early infancy. Cholesteryl ester storage disease (CESD), in contrast, is characterized by very low levels of enzymic activity sufficient to allow survival of the affected patients into adulthood. In order to elucidate the underlying molecular defects in Wolman disease, we have characterized the hLAL gene in two female Wolman patients of German and Turkish origin by SSCP and DNA sequence analysis. Our results demonstrate that the German proband was compound heterozygous for an 8-bp deletion in exon 3 and a 2-bp deletion in exon 4 of the hLAL gene. These frameshift mutations lead to protein truncation at amino acid positions 24 and 116 and to complete loss of hydrolytic activity. The Turkish proband, in contrast, was homozygous for a G(1064)-->T substitution in exon 10 of the hLAL gene which converts the completely conserved glycine (GGG) residue at position 321 of the mature enzyme to tryptophan (TGG). In vitro expression of the hLAL(Gly(321)-->Trp) cDNA construct revealed that the amino acid replacement results in a more than 99% reduction of neutral lipid hydrolysis.The mutations provide new insights into the molecular basis of Wolman disease which is apparently more heterogeneous at the genetic level than cholesteryl ester storage disease.-Lohse, P., S. Maas, P. Lohse, A. C. Sewell, O. P. van Diggelen, and D. Seidel. Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease.

Grain sorghum [Sorghum bicolor(L.) Moench] plants characteristically exhibit an increase in the areas of successively older leaves on the shoot up to a maximum value, followed thereafter by a decrease in leaf areas. Data from 2 yr of field studies were used to develop empirical functions relating average areas of successive leaves. These functions were representative for a number of published data sets and exhibited the following characteristics: (i) an early exponential phase of leaf area increase apparently terminated by the onset of intraplant competition; (ii) a transition between two linear phases of leaf area increase that appears to be invariant among years, cultivars, and treatments; and (iii) a final phase of decreasing leaf areas that is apparently sensitive to interplant competition and reproductive growth. Data from the literature and studies involving water stress, plant population, and N fertilizer application effects indicate that, while reproductive organ growth may affect some aspects of leaf area development, the onset and severity of intraplant and interplant competition may be more important factors determining individual leaf areas.

Pre-mRNAs for brain-expressed ionotropic glutamate receptor subunits undergo RNA editing by site-specific adenosine deamination, which alters codons for molecular determinants of channel function. This nuclear process requires double-stranded RNA structures formed by exonic and intronic sequences in the pre-mRNA and is likely to be catalyzed by an adenosine deaminase that recognizes these structures as a substrate. DRADA, a double-stranded RNA adenosine deaminase, is a candidate enzyme for L-glutamate-activated receptor channel (GluR) pre-mRNA editing. We show here that DRADA indeed edits GluR pre-mRNAs, but that it displays selectivity for certain editing sites. Recombinantly expressed DRADA, both in its full-length form and in an N-terminally truncated version, edited the Q/R site in GluR6 pre-mRNA and the R/G site but not the Q/R site of GluR-B pre-mRNA. This substrate selectivity correlated with the base pairing status and sequence environment of the editing-targeted adenosines. The Q/R site of GluR-B pre-mRNA was edited by an activity partially purified from HeLa cells and thus differently structured editing sites in GluR pre-mRNAs appear to be substrates for different enzymatic activities.

An understanding of the optical properties of plant leaves is basic to the application of remote sensing to agriculture. This study was conducted to demonstrate the effects of pigments on light reflectance, transmittance and absorptance spectra of corn (Zea maysL.) leaves. Three treatments were used to produce corn seedlings with different pigmentations. Normal seedlings contained the natural complement of colored pigments (predominantly chlorophylls and carotenoids). Etiolated seedlings (grown in the dark) contained carotenoids but not chlorophylls. Albino seedlings, produced by treating seeds with fluridone (l‐methyl‐3‐phenyl‐5‐[3‐(trifluromethyl) phenyl]‐4(1H)‐ pyridinone) contained no colored pigments. The morphology and histology of seedlings in the three treatments were basically similar, except that the leaves of the etiolated seedlings were characteristically elongated. Pigments did not affect leaf reflectance, transmittance, and absorptance spectra at infrared (< 2500 nm) wavelengths. Over most of the visible waveband, albino leaf reflectance was the same as the maximum observed at infrared wavelengths. The leaf absorptance spectrum of the etiolated seedlings at ultraviolet (> 350 nm) and visible wavelengths resembled the in vitro absorptance spectrum of β‐carotene masked by the background absorptance of the unpigmented albino system. Because fluridone‐induced albino seedlings can be used to separate the contributions of pigments from leaf structure and water content, they represent a potentially important tool in studying leaf optical properties.

It has been proposed that remotely sensed information from satellites could complement the performance of crop growth models. A study was conducted to determine how a model could effectively utilize satellite data and if model estimates of crop yield could be significantly improved by satellite data. A simple model was developed for simulating growth and yield of grain sorghum [Sorghum bicolor(L.) Moench] on an individual‐field basis. The model contained three state variables (stage of development, green leaf area index [GLAI], and aboveground dry mass) and utilized daily meteorological observations. When available, GLAI values for target fields could be used to adjust the initial values of the state variables until a “best fit” of the observed data was iteratively achieved by the simulation. GLAI values could be obtained by ground‐based measurements, but satellite observations were demonstrated to be an appropriate source of data for initializing the model. The model was developed and verified using data from 10 fields observed in Central Texas in 1976. The model was tested using a completely independent data set containing yield and satellite observations from 37 fields in South Texas in 1973, 1975, 1976, and 1977. Without using the initializing procedure, the average yield for the 37 fields was underestimated by approximately 30%. Use of satellite‐derived GLAI data to initialize the same simulations resulted in a 2% overestimate of average yield. The results of this study confirm the usefulness of the initializing procedure and satellite data to improve model estimates of crop yield.

The mammalian RNA-specific adenosine deaminases DRADA/dsRAD (alias ADAR) and RED1 (alias ADARB1) have been implicated in the site-selective editing of brain-expressed pre-mRNAs for glutamate receptor subunits and of antigenomic RNA of hepatitis delta virus. These enzymes are expressed in many if not all tissues, predicting an as yet unappreciated significance for adenosine deamination-mediated recoding of gene transcripts in the mammalian organism. We now report the molecular cloning of cDNA for RED2 (alias ADARB2), a third member of the RNA-specific adenosine deaminase family in the rodent. RED2 is closely sequence-related to RED1 but appears to be expressed only in the brain, where expression is widespread reaching highest levels in olfactory bulb and thalamus. RED2 further differs from RED1 in having a 54-residue amino-terminal extension which includes an arginine-rich motif. Different from DRADA and RED1, recombinantly expressed RED2 did not deaminate adenosines in extended synthetic dsRNA or in GluR-B pre-mRNA. However, a chimera of RED1 and RED2 edited the GluR-B Q/R and R/G sites with moderate efficiency. Our data suggest that RED2 may edit brain-specific transcripts with distinct structural features.

The interim results of a multicentered clinical trial with the combination therapy Pilogel®/topical ß-blocker (twice daily) in patients with primary open angle glaucoma or ocular hypertension are discussed. Six patients were treated with Pilogel® and a topical ß-blocker for one month. Four out of six patients responded well to the combination therapy. Most patients experienced some difficulty in applying the gel and their eyelids stuck together on awakening. In two patients a superficial punctate keratitis was observed. We found an average decrease in intra-ocular pressure (IOP) of 22.5% 22.5 hours after Pilogel® administration, but there was some tendency towards higher evening values compared to morning values. In view of the appearance of a corneal haze as described by Johnson et al. during long-term treatment, longer follow-up is necessary.

Tropodiaptomus turkanaesp. nov.is described from Lake Turkana (formerly Lake Rudolph), Kenya. After years of confusion withT. banforanus,the identity of this taxon as an endemic of Lake Turkana is established. The species is described, and its relationship with otherTropodiaptomusspecies discussed.

In neurons of the mammalian brain primary transcripts of genes encoding subunits of glutamate receptor channels can undergo RNA editing, leading to altered properties of the transmitter-activated channel. Editing of these transcripts is a nuclear process that targets specific adenosines and requires a double-stranded RNA structure configured from complementary exonic and intronic sequences. We show here that the two independent editing sites in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR-B pre-mRNA are edited with positional accuracy by nuclear extract from HeLa cells. Nucleotide analysis by thin layer chromatography of the edited RNA sequences revealed selective adenosine to inosine conversion, most likely reflecting the participation of double-stranded RNA adenosine deaminase. Our results predict the presence of inosine-containing codons in other mammalian mRNAs.