An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size.

Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

Permeation of tetracyclines through membranes of liposomes and Escherichia coli.

Uptake of tetracycline (tc), 2-tetracyclinonitrile (CN-tc), and 9-(N, N-dimethylglycylamido)-6-demethyl-6-deoxytetracycline (DMG-DMDOT) by liposomes containing Tet repressor (TetR) and by Escherichia coli cells overexpressing TetR was examined. TetR specifically binds to tetracyclines, enhances their fluorescence and thereby allows selective detection of tetracyclines that have crossed the membranes. Analysis of the diffusion of tc and DMG-DMDOT into liposomes yielded permeation coefficients of (2.4 +/- 0.6) x 10-9 cm.s-1 and (3.3 +/- 0.8) x 10-9 cm.s-1, respectively. Similar coefficients were obtained for uptake of these tetracyclines by E. coli, indicating that diffusion through the cytoplasmic membrane is the rate-limiting step. The permeation coefficients translate into half-equilibration times of approximately 35 +/- 15 min and explain how efflux pumps can mediate resistance against tetracyclines. Furthermore, diffusion of CN-tc into liposomes was at least 400-fold slower than that of tc, indicating that the carboxamide group at position C2 is required for efficient permeation of tc through lipid membranes and thereby explaining the lack of antibiotic activity of CN-tc.

Nasal deformity and microform cleft lip in parents of patients with cleft lip.

OBJECTIVE: To describe subtle nasal deformities and microform cleft lips in parents whose children have complete cleft lip deformities. DESIGN: Clinical analyses of three parents whose children had complete cleft lips. Subtle nasal deformities and microform cleft lips were identified. SETTING: An institutional general hospital: Manuel Gea González Cleft Lip and Palate Clinic in Mexico City, Mexico. PATIENTS: The study first examined the parents of all complete and incomplete cleft lip-palate patients who were seen from March 1994 to February 1997 by the authors (n = 1000). We identified three patients, each of whom had one parent who showed signs of subtle nasal deformity and microform cleft lip. INTERVENTIONS: None for the parents. Interventions in the children with cleft lips and palates were known. MAIN OUTCOME MEASURES: Qualitative photographic analyses were performed. Nostril symmetry, septal deviation, nasal floor position, and orbicularis oris malinsertions were carefully examined. RESULTS: Three of the evaluated parents had one alar cartilage caudally displaced and a deviated septum. One parent's nasal floor was depressed. Two parents also had evidence of a minimal orbicularis oris muscle fissure located in the upper lip. CONCLUSION: Genetic evaluations of children with complete and incomplete cleft lips might also include thorough evaluation of their parents. Although small in size, this study of three case histories identified nasal and lip deformities in the patients' parents.

Maxillary growth in children after early facial bipartition.

Facial osteotomies performed in young children are frequently associated with growth deficiencies, especially at the middle third of the face. This problem may be more severe when the initial deformity is associated with alveolar and palatal clefts. Orbital hypertelorism is a major congenital malformation requiring early correction. The resection of the ethmoid tissues located between the orbit and the medialization of the orbital skeleton through the intracranial approach modifies the exaggerated interorbital distance but does not correct the vertical shortness at the midline of the face. Also this procedure interferes with the sagittal growth of the maxilla possibly resulting from the horizontal osteotomy across the maxillae. The medial rotation of the two halves of the face performed by the intracranial approach or the subcranial approach simultaneously corrects the orbital hypertelorism and elongates the nose and the central segment of the face. Our experience with this procedure in infants and young children is analyzed. A series of nine patients with orbital hypertelorism associated with median and paramedian clefts underwent correction by hemifacial rotation. All patients were monitored from 6 to 10 years (mean, 7 years) and demonstrated normal sagittal growth of the maxillae.

Endurance exercise in the presence of heart disease.

Although patients with heart disease have successfully completed marathon runs, the immediate cardiac effects of similar and greater distance endurance exercise competition are unknown. Two such cases are presented, demonstrating that vigorous exercise and extreme levels of fitness are not precluded in the cardiac patient.

Unilateral hyperlucent lung (Swyer-James syndrome) after severe Mycoplasma pneumoniae infection.

An 11-year-old girl contracted pneumonia with consolidation of the left lower lobe, infiltrates in the lingula and left upper lobe, and a large left pleural effusion, accompanied by a Mycoplasma complement-fixation titer increasing to 1:16,384. Serial chest radiographs demonstrated resolution of the pneumonia and effusion, followed by development of a hyperlucent left lower lobe. This diagnosis was supported by abnormalities discovered by chest cinefluoroscopic examination and lung scans of ventilation and perfusion. Unilateral hyperlucent lung should be considered as a possible sequel to severe Mycoplasma pulmonary infection.

Changing erythrocyte populations in juvenile chronic myelocytic leukemia: evidence for disordered regulation.

Fetal and adult erythrocyte characteristics were studied serially in a 30-mo-old female with juvenile chronic myelocytic leukemia. On presentation the erythrocytes exhibited predominantly fetal characteristics as indicated by 69% hemoglobin F (HbF), 1.1% hemoglobin A2 (HbA2), absent I antigen, and fetal levels of the erythrocyte enzymes, carbonic anhydrase I and II, glucose-6-phosphate dehydrogenase, hexokinase, pyruvate kinase, and lactate dehydrogenase; 100% of the erythrocytes present contained HbF. However, Orskov-Jacobs-Stewart hemolysis demonstrated that at least one adult characteristic was present. Seven months later HbF was 17%; I antigen and carbonic anhydrase I had increased to adult levels. The number of cells containing HbF had decreased to 30%. Further studies indicated that at least three new populations of red cells were present after 7 mo which had not previously been detected. Two of these populations exhibited a mixture of both fetal and adult characteristics. Such findings suggested that an ongoing disturbance of regulatory mechanisms was responsible for the variable expression of fetal versus adult erythrocyte characteristics.