Rare craniofacial clefts: Tessier no. 4 clefts

A major difficulty in understanding rare craniofacial clefts arises from the fact that previous reports have focused on a single case or have grouped together different types of rare clefts. Less than 50 Tessier no. 4 clefts have been reported. This paper examines our experience with eight patients treated primarily or secondarily for Tessier no. 4 clefts. A treatment plan is recommended. The primary early concern is protection of the eye. Early correction of soft-tissue deformities should include skin, muscle, and lining of the orbit, cheek, and oral cavity. Contrary to the dictum that all soft tissue must be preserved, the medial portion of the upper lip from the cleft to the philtral ridge must be resected to prevent poorly camouflaged scars, muscle deficiency, and macrostomia. Bone grafting should be undertaken at an early age using calvarial bone. Late operations will be necessary for correction of medial and lateral canthal position, epiphora, lower eyelid skin deficiency, and further bony augmentation.     

Unilateral exophthalmos caused by an anterior ethmoidal meningoencephalocele.

A case of unilateral enophthalmos in a 1-year-old child is presented. This was caused by a meningoencephalocele that originated in the anterior cranial fossa and protruded into the orbit through a bony defect at the junction of the frontal and ethmoid bones at the site of the anterior ethmoid canal. This meningoencephalocele was reduced, and the dura was repaired with a temporalis fascia graft. A split calvarial bone graft was inserted into the floor of the orbit, and lateral canthal ligament elevation completed the operative correction.     

Hydrodynamic multibead modeling: problems, pitfalls, and solutions. 1. Ellipsoid models

The shape of macromolecules can be approximated by filling models, if both hydrodynamic and scattering properties should be predicted. Modeling of complex biological macromolecules, such as oligomeric proteins, or of molecule details calls for usage of many beads to preserve the original features. However, the calculation of precise values for structural and hydrodynamic parameters has to consider many problems and pitfalls. Among these, the huge number of beads required for modeling details and the choice of appropriate volume corrections for the calculation of intrinsic viscosities are pestering problems to date. As a first step to tackle these problems, various tests with multibead models (ellipsoids of different axial ratios) were performed. The agreement of the predicted molecular properties with those derived from whole-body approaches can be used as evaluation criteria. Modification of previously available versions of García de la Torre’s program HYDRO allows hydrodynamic modeling of macromolecules composed of a maximum of about 11,000 beads. Moreover, application of our recently suggested “reduced volume correction” enables a fast and efficient anticipation of intrinsic viscosities. Correct parameter predictions were obtained for all models analyzed. The data obtained were compared to the results of calculations based on HYDRO programs available to the public. The calculations revealed some unexpected results and allowed founded conclusions of general importance for precise calculations on multibead models (e.g., the requirement of calculations in the double-precision mode).     

Significance of structural chromosome aberrations in human sperm: analysis of induced aberrations

Summary A significant increase in the incidence of structural chromosome anomalies has been observed in the sperm of patients treated with radio and/or chemotherapy for different types of cancer when analyzed by the interspecific fertilization of hamster eggs. The analysis of these aberrations shows that while in controls only 9.4% of structural abnormalities are of the stable type, in treated patients this figure increases to 39.3%, thus indicating that the anomalies have not been produced during the fertilization of the hamster egg. However, it is possible that part, or even most, of the breaks appear as a result of a reduced repair capacity of sperm chromosomes in the cytoplasm of the hamster egg.     

Correction of lower eyelid ptosis in the anophthalmic orbit with an autogenous ear cartilage graft

We describe the correction of lower eyelid ptosis in patients with an anophthalmic orbit, using ear cartilage grafts. This procedure has been particularly useful in the scarred or previously reconstructed lower eyelid.     

Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns

Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.     

Re-absorption of chlorophyll fluorescence in leaves revisited. A comparison of correction models.

The application of correction methods to account for re-absorption of chlorophyll fluorescence emission in leaves is subject to a number of controversies in the literature. These uncertainties lead to high discrepancies in the corrected spectral distribution of fluorescence and consequently in the interpretation of related physiological features of plants, according to the chosen method used in the process of correction. In this research, three correction methods, based on transmittance and/or reflectance measurements on leaves, were analysed comparatively. One method gave high values for the corrected fluorescence ratio between 685 nm and 737 nm (F685/F737 approximately 7 to 20 according to the different species of leaves). The two other methods were found to give similar results with corrected fluorescence ratios around a value of two (F685/F737 approximately 2). While the first method was developed in the light of empirical considerations, the latter two models are based upon defined physical approaches depicting interaction between light and matter. The theoretical basis of these methods, the validation methodologies used to support them and the similarity in the spectra corrected by light re-absorption for both models, all showed that they should be treated as confident and suitable approximations to solve the problem of light re-absorption in leaves.     

Primary and secondary orbit surgery: the transconjunctival approach

The transconjunctival approach to the orbit is underutilized because of concern regarding inadequate exposure and higher postoperative rates of lower eyelid shortening and ectropion. All patients who had a transconjunctival incision performed for orbital surgery over the last 6 years (1990 to 1996) were studied. Patients who had a transconjunctival blepharoplasty were excluded. A total of 35 patients, average age 32 years, had 45 transconjunctival incisions performed. Lateral canthotomy or cantholysis was not done. Operations fell into three categories: fracture plating alone, 10 (22 percent); split-calvarial bone graft placement with or without plating, 26 (58 percent); and orbital decompression, 9 (20 percent). The overall incidence of ectropion was 6.7 percent (3 of 45). One patient (2 percent) had transient ectropion, and two patients (4 percent) had persistent ectropion, which required surgical correction. Ectropion occurred only in those lower eyelids that had a previous transcutaneous incision (3 of 18 = 17 percent). None occurred in those eyelids that had no prior incision or only a previous transconjunctival incision. The transconjunctival approach without a lateral canthotomy provides safe access to the orbit in eyelids that have not had a previous transconjunctival incision.     

Calculation of the g-factors of hemoproteins with the crystal field theory. Development of a 3-term model

A 3-term crystal field model is used for the calculation of the magnetic properties of ferric hemoproteins. This model includes the high spin term (6A1), the low spin term (2T2) and the quartet term (4T1). The pertubation matrix between these 3 terms caused by spin orbit coupling and ligand fields of cubic, axial and rhombic symmetry are evaluated. The g-factor of the low spin cytochrome P-450 LM2 from rabbit liver are calculated using this 3-term model and the results are compared with those from the usual 1-term model. Contrary to the 1-term model, no orbital moment correction factor is necessary. That means that the orbital moment correction factor with value > 1 simulates some term interaction, predominantly with the quartet term. The g-factors of the high spin cytochrome P-450 LM4 were also calculated by means of the 3-term model and compared with a spin hamilton treatment. A good agreement between the spin hamilton parameters derived from the experimental g-factors and those calculated by the 3-term model were obtained. For hemoproteins with strongly mixed spin states the 3-term model is also useful, contrary to 1-term models or spin hamiltonians which are completely incorrect. The 3-term model is a minimal model to describe all typical magnetic properties of low spin and high spin ferric hemoproteins with the smallest number of terms.     

Stability and activity of a phenol oxidase from the ligninolytic fungus Pleurotus ostreatus

Three different phenol oxidases produced by the basidiomycete fungus Pleurotus ostreatus have been isolated and their main structural, enzymatic and physico-chemical properties characterized. Studies have forcaused on the most abundantly secreated of these proteins, a copper-e nzyme specific towards ortho-diphenol substrates. This protein was purified to homogeneity and part of its primary structure determined by direct protein sequencing. The ingluence of pH, temperature and presence of water-soluible or water-insoluble organic solvents on the activity and stability of the enzyme were also investigated. These data can be used for applying bioarectors to problems of environmental concern such as waste-water treatment Correspondens to: G. Sannia     

Why it's time for a national health program in the United States.

The United States lacks a coherent national health program. Current programs leave major gaps in coverage and recently have become more restrictive. Influential policies that have failed to correct crucial problems of the health-care system include competitive strategies, corporate intervention, and public-sector cutbacks with bureaucratic expansion. A national health program that combines elements of national health insurance and a national health service is a policy that would help solve current health-care problems. Previous proposals for national health insurance contained weaknesses that would need correction under a national program. Based on the experiences of other economically advanced countries, a national health program could provide universal entitlement to health care while controlling costs and improving the health-care system through structural reorganization. Current proposals for a national health program contain several basic principles dealing with the scope of services, copayments, financing, cost controls, physician and professional associations, personnel and distribution, prevention, and participation in policy making. Support for a national health program is growing rapidly. Such a program would help protect all people who live in this country from unnecessary illness, suffering, and early death.     

Surgical management of the anophthalmic orbit, part 2: post-tumoral

Ablative surgery for tumors of the globe and its adnexal structures is frequently the cause of major orbitofacial deformity. Radiotherapy compounds the problem because it suppresses skeletal growth in the growing patient and induces a contraction of the remaining soft tissues in the orbit. Goals for reconstruction in these patients include the restoration of orbital structures to allow the fitting of an ocular prosthesis and the correction of distorted orbitofacial relationships. The authors present a series of 53 patients (mean age, 29 years; 28 male) who were treated over the past 18 years by composite reconstruction of the post-tumoral anophthalmic orbit. The follow-up ranged from 5 months to 18 years (mean, 7.75 years). Four patients were treated primarily (immediate reconstruction after tumor ablation), and 49 were treated secondarily (mean oncological follow-up since ablative surgery, 14.8 years). Twenty-eight patients underwent orbital enucleation (including three bilateral cases), 23 underwent orbital exenteration, and two underwent evisceration. Forty-two patients received radiotherapy, including 20 enucleation patients, 15 exenteration patients, and seven others in whom details of primary therapy were incomplete. A staged reconstruction was undertaken in each case; it considered, in turn, the bony orbital volume (orbital remodeling and cranial bone grafts), orbital contents (implant, temporalis muscle transposition, cranial bone grafts, and dermafat grafts), conjunctival sac (mucosal and skin grafts), ocular prosthesis, eyelids (local flaps and skin grafts), and additional procedures to restore orbitofacial symmetry. The authors conclude that the long-term results of post-tumoral orbital reconstruction are favorable, and they particularly recommend the use of autogenous tissues in irradiated orbits.     

R&D of long-term life support system by using electrochemically activated biofilm reactor of aquatic animals for space examinations.

We have developed the long-term life support system that enables the experiment of aquatic animals breeding for 90 days or more for the future experiments in orbit. In order to enable long-term breeding of wide aquatic animals, it is necessary to remove nitrate produced by biological nitrification. Then, we examined a denitrification method to use an electrochemical reaction of biofilm-electrode reactor. In this research, we have not kept the aquatic animals actually but imitated breeding of five goldfish. The ammonia of about 250 ppm was added in breeding water through 90 days. As a result, neither ammonia nor nitrite accumulated 0.1 ppm and nitrate could be suppressed to about 10 ppm.     

Chemical inactivation of Escherichia coli 30-S ribosomes by iodination. Identification of proteins involved in tRNA binding.

30-S ribosomal subunits are inactivated by iodination for both enzymic fMet-tRNA and non-enzymic Phe-tRNA binding activities. This inactivation is due to modification of the protein moiety of the ribosome. Reconstitutions were performed with 16-S RNA and mixtures of total protein isolated from modified subunits and purified proteins isolated from unmodified subunits. This allowed identification of the individual proteins which restore tRNA binding activity. S3, S14 and S19 were identified as proteins involved in fMet-tRNA binding. S1, S2, S3, S14 and S19 were identified as proteins involved in Phe-tRNA binding. Modified particles shown normal sedimentation constants and complete protein compositions both before and after reconstitution. This suggests that the loss of activity is due to modification of one or more of the actual binding sites located on the 30-S subunit and that restoration of activity is due to structural correction at this site rather than to correction of an assembly defect.     

Structural and Nonstructural Proteins of an Arbovirus

Purified Semliki Forest virus (SFV) contains three structural proteins while its core (nucleocapsid) contains two of these proteins. To identify all of the proteins synthesized under virus direction, cells were infected with SFV in the presence of actinomycin D and guanidine. Cell protein synthesis was markedly and irreversibly inhibited under these conditions; virus growth was reversibly inhibited by guanidine and began when the cells were washed to remove the guanidine. When cells were treated with guanidine for 4 hr after virus infection and then were washed, five major proteins were produced early in infection. Three of these proteins corresponded to virus structural proteins. None of these five proteins was a major protein of uninfected cells or of virus-infected cells which had been incubated with partially purified interferon before infection. Late in infection, three major proteins, the virus structural proteins, were produced.     

Optimizing the delivery systems of chimeric RNA.DNA oligonucleotides.

Special oligonucleotides for targeted gene correction have attracted increasing attention recently, one of which is the chimeric RNA.DNA oligonucleotide (RDO) system. RDOs for targeted gene correction were first designed in 1996, and are typically 68 nucleotides in length including continuous RNA and DNA sequences (RNA is 2'-O-methyl-modified). They have a 25 bp double stranded region homologous to the targeted gene, two hairpin ends of T loop and a 5 bp GC clamp, that give the molecule much greater stability [Fig. 1]. One mismatch site in the middle of the double-stranded region is designed for targeted gene therapy. RDOs have been used recently for targeted gene correction of point mutations both in vitro and in vivo, but many problems must be solved before clinical application. One of the solutions is to optimize the delivery vectors for RDOs. To date, few RDO delivery systems have been used. Therefore, new vectors should be tried for RDO transfer, such as the use of nanoparticles. Additionally, different kinds of modifications should be applied to RDO carrier systems to increase the total correction efficiency in vivo. Only with the development of delivery systems can RDOs be used for gene therapy, and successfully applied to functional genomics.     

Intrinsic viscosity of bead models for macromolecules and nanoparticles

The calculation of the intrinsic viscosity by means of classical treatments of bead models, typically composed of a number of identical beads, presents some problems when applied to models where the beads are unequal and their number is not very large. A correction to this problem was proposed 10 years ago (García de la Torre and Carrasco in Eur Biophys J 27:549–557, 1998). This so-called volume correction, which consisted of adding a term proportional to the volume of the model, was proved to be rigorous in physico-mathemathical terms, and produced improved results in some circumstances, but not always. Recently, the volume correction is being reconsidered so that with some deduced or empirical modifications, it can allow for safer predictions of the intrinsic viscosity. This paper contributes a discussion and further improvements of that correction for the intrinsic viscosity.     

Prions: an evolutionary perspective.

Studies in both prion-due diseases in mammals and some non-Mendelian hereditary processes in yeasts have demonstrated that certain proteins are able to transmit structural information and self-replication. This induces the corresponding conformational changes in other proteins with identical or similar sequences. This ability of proteins may have been very useful during prebiotic chemical evolution, prior to the establishment of the genetic code. During this stage, proteins (proteinoids) must have molded and selected their structural folding units through direct interaction with the environment. The proteinoids that acquired the ability to propagate their conformations (which we refer to as conformons) would have acted as reservoirs and transmitters of a given structural information and hence could have acted as selectors for conformational changes. Despite the great advantage that arose from the establishment of the genetic code, the ability to propagate conformational changes did not necessarily disappear. Depending on the degree of involvement of this capacity in biological evolution, we propose two not mutually exclusive hypotheses: (i) extant prions could be an atavism of ancestral conformons, which would have co-evolved with cells, and (ii) the evolution of conformons would have produced cellular proteins, able to transmit structural information, and, in some cases, participating in certain processes of regulation and epigenesis. Therefore, prions could also be seen as conformons of a conventional infectious agent (or one that co-evolved with it independently) that, after a longer or shorter adaptive period, would have interacted with conformons from the host cells.     

Oxidative damage to DNA in mammalian chromatin.

Efforts have been made to characterize and measure DNA modifications produced in mammalian chromatin in vitro and in vivo by a variety of free radical-producing systems. Methodologies incorporating the technique of gas chromatography/mass spectrometry have been used for this purpose. A number of products from all four DNA bases and several DNA-protein cross-links in isolated chromatin have been identified and quantitated. Product formation has been shown to depend on the free radical-producing system and the presence or absence of oxygen. A similar pattern of DNA modifications has also been observed in chromatin of cultured mammalian cells treated with ionizing radiation or H2O2 and in chromatin of organs of animals treated with carcinogenic metal salts.     

Antipyretic activity of prazosin.

Thermal responses to prazosin (0.75 mg/kg, i.v. as a bolus injection or 3 h infusion) were investigated in febrile rabbits (treated with E. coli lipopolysaccharide, PLPS) at 3 ambient temperatures (Ta) of 5, 19, 28 degrees C. The drug produced antipyresis which increased with the simultaneous drop of Ta. This antipyretic activity was accompanied by an inhibition of heat production or enhanced elimination of heat, depending on Ta. It is suggested that antipyresis produced by prazosin is mainly due to the effector part of the thermoregulatory system.