Genomic insight into the amino acid relations of the pea aphid, Acyrthosiphon pisum, with its symbiotic bacterium Buchnera aphidicola.

The pea aphid genome includes 66 genes contributing to amino acid biosynthesis and 93 genes to amino acid degradation. In several respects, the pea aphid gene inventory complements that of its symbiotic bacterium, Buchnera aphidicola (Buchnera APS). Unlike other insects with completely sequenced genomes, the pea aphid lacks the capacity to synthesize arginine, which is produced by Buchnera APS. However, consistent with other insects, it has genes coding for individual reactions in essential amino acid biosynthesis, including threonine dehydratase and branched-chain amino acid aminotransferase, which are not coded in the Buchnera APS genome. Overall the genome data suggest that the biosynthesis of certain essential amino acids is shared between the pea aphid and Buchnera APS, providing the opportunity for precise aphid control over Buchnera metabolism.

Cytochrome c oxidase-associated Leigh syndrome: phenotypic features and pathogenetic speculations.

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.

Adverse events following immunization: assessing probability of causation.

The Monitoring System for Adverse Events Following Immunization of the Centers for Disease Control collects data on events temporally related to immunization. Occasionally, reports are received of neurologic disturbances temporally related to receipt of vaccine. Most of these disturbances are events that regularly occur in the absence of immunization. It is then difficult to determine whether the relationship between the immunization and illness is causal or coincidental. We developed a method to assess causation of serious neurologic events by probability theory. By combining epidemiologic information on disease incidence with specific elements of the patient history, an estimate of the odds of vaccine causation can be derived, based on rational assumptions rather than observer bias. The result is not a diagnosis but an estimate of probability.

Brain death in children: characteristic common carotid arterial velocity patterns measured with pulsed Doppler ultrasound.

The clinical criteria for brain death in children remain controversial. An accepted confirmatory test for brain death is the documented absence of intracranial blood flow, the most common methods being arteriography and radionuclide cerebral angiography. We correlated the common carotid arterial blood velocity patterns measured by pulsed Doppler ultrasound in 32 brain-dead infants and children with results of their clinical examinations and, whenever possible, with radionuclide cerebral angiography. A distinct, characteristic carotid arterial blood velocity waveform indicating absent cerebral blood flow appeared in 19 of the 23 brain-dead patients 4 months of age or older. The velocity patterns of the other four older children were similar, but not identical, to the characteristic waveform. The remaining nine brain-dead patients were infants 4 months of age or younger. These infants had velocity waveforms different from those of healthy infants, but also were totally different from the characteristic brain death pattern of older children. No patient had the characteristic brain death waveform without being clinically brain dead. Measurement of carotid arterial blood velocity with pulsed Doppler ultrasound is a repeatable, noninvasive, portable test useful for confirmation of brain death in children.

Antigenic analysis of hematopoiesis. IV. The My-11 hematopoietic cell surface antigen is expressed by myelomonocytic and lymphoid, but not erythroid, progenitor cells.

The anti-My-11 murine monoclonal antibody reported on in this work identifies a KG-1a cell surface glycoprotein with apparent molecular mass of 210,000 daltons. Peripheral blood B-lymphocytes, and a novel subset of T-lymphocytes (not coinciding with helper or cytotoxic subsets) express My-11 antigen; granulocytes, red cells, and platelets are antigen negative. In normal bone marrow, lymphoid progenitors (TdT positive) and most granulocyte-monocyte progenitors express My-11, but erythroid and multilineage progenitors are My-11 negative. Approximately half of acute leukemia blast cell specimens are My-11 positive. The My-11 antigen distinguishes between lymphohematopoietic cells on the basis of lineage, and assists in the purification of hematopoietic progenitor cells and the subclassification of leukemias and normal lymphocytes.

Sialylated glycolipid antigens on human leukemic cell lines.

Many granulocyte-specific mouse monoclonal antibodies recognize the carbohydrate sequence 3-fucosyllactosamine, Ga 1 beta 1-4[Fuc alpha 1-3]GlcNAc, which occurs in cell-surface glycolipids and glycoproteins. In general, these antibodies bind to blast cells from most patients with acute myeloblastic leukemia, but not to those with acute lymphocytic leukemia. Neuraminidase treatment, however, increases exposure of this antigen on both myeloid and lymphoid cells. In the present study, the glycolipids from 13 lymphoid and nonlymphoid human cell lines were examined for the presence of unsialylated and sialylated 3-fucosyllactosamine sequences using a thin-layer chromatography immunostaining method. Nine of the cell lines were also tested by indirect immunofluorescence both before and after neuraminidase treatment. None of the six B-cell and T-cell lines had detectable neutral or sialylated glycolipid antigen. In contrast, six out of seven and five out of seven nonlymphoid cell lines had neutral and sialylated glycolipid antigens, respectively. These results agreed, in general, with those found by indirect immunofluorescence. They also represent the first direct demonstration of these sialylated glycolipids on human leukemic cells. Thus, in some cases increased antibody binding to neuraminidase-treated cells can be explained by the presence of sialylated glycolipid antigen.

Anti-My-28, an antigranulocyte mouse monoclonal antibody, binds to a sugar sequence in lacto-N-neotetraose.

Anti-My-28 is an IgM kappa monoclonal antibody produced by a hybridoma prepared from spleen cells of a mouse immunized with normal human granulocytes. By immunofluorescence it binds to human granulocytes but not to monocytes and lymphocytes. However, after treating cells with neuraminidase, the antibody also binds to lymphocytes and monocytes and to many leukemic cell lines and patient leukemic blast cells. Anti-My-28 binds to several neutral glycolipids and desialylated gangliosides of leukocytes and erythrocytes as detected by radioimmunoassay and immunostaining of thin-layer chromatograms. It recognizes a sugar sequence in lacto-N-neotetraose, Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc. This tetrasaccharide occurs in the glycolipids paragloboside and sialosylparagloboside, and its distal trisaccharide sequence is found in higher glycolipids and in glycoproteins.

Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells.

The anti-My-10 mouse monoclonal antibody was raised against the immature human myeloid cell line KG-1a and was selected for nonreactivity with mature human granulocytes. Anti-My-10 immunoprecipitated a KG-1a cell surface protein with an apparent Mr of approximately 115 kD. We describe the binding of this antibody to human hematopoietic cell types and show that My-10 is expressed specifically on immature normal human marrow cells, including hematopoietic progenitor cells. My-10 is also expressed by leukemic marrow cells from a subpopulation of patients. Thus, this antibody allows the identification and purification of hematopoietic progenitor cells from normal human marrow and the subclassification of leukemia.

Validity of the Peabody Picture Vocabulary Test-Revised with mentally retarded adults.

Investigated the validity of using the PPVT -R with mildly mentally retarded adults. The PPVT -R, PPVT , and WAIS-R were administered to 21 Ss, and WAIS scores were obtained from client files. Results indicated that the revised Peabody tended to yield significantly lower estimates of functioning than did the other measures. Implications are discussed.

Congenital diencephalic and brain stem damage: neuropathologic study of three cases.

Neuropathologic findings and clinical features of three patients with congenital brain stem damage are reported. All of the infants were premature (32 - 36 weeks' gestation) and experienced respiratory difficulty in the immediate postnatal period. One infant was moribund at deliver, dying 3 h after birth. In two infants who survived for 12 and 16 days, detailed neurologic examinations demonstrated multiple cranial nerve palsies with absence of facial expression. Autopsies revealed similar changes in the brains of all three infants: bilateral symmetrical lesions were found predominantly in the thalamus and brain stem. Histological features common to all three cases included prominent basophilic mineralized neurons, neuronal loss astrocytosis and axonal spheroids. Necrosis was observed in two cases. These changes are most compatible with one or more episodes of total asphyxia during fetal life. This study supports the hypothesis that, in some cases, Möbius' syndrome is the result of intrauterine asphyxia.

Simultaneous analysis of cell surface antigens and cell morphology using monoclonal antibodies conjugated to fluorescent microspheres.

A new method for simultaneous analysis of cell surface antigens and cell morphology using monoclonal antibodies conjugated to fluorescent microspheres ('immunospheres') is described. Wright's staining was performed on cells after reaction with immunospheres, and a direct correlation of cell surface antigen expression and cell morphology was made. Mild formalin fixation of cells inhibited phagocytosis of microspheres, which is a potential source of confusion in the analysis of cell surface binding. Rapid, accurate analysis of cell surface antigen expression in single cell suspensions of heterogeneous human hematopoietic and lymphoid cell populations was facilitated by this method.

Reliability of ultrasound in diagnosis of intracerebral hemorrhage and posthemorrhagic hydrocephalus: comparison with computed tomography.

Subependymal and intraventricular hemorrhage are frequent complications of the high risk preterm infant. It has been stated recently that ultrasound may be used to diagnose intraventricular hemorrhage. A comparative prospective study of ultrasound scan (US) with a commercially available B-mode real time linear array US machine and the computed tomography (CT) scan was undertaken to determine the accuracy of US in diagnosing the presence and quantity of subependymal and intraventricular hemorrhage and in following infants with hemorrhage for the development of progressive hydrocephalus. There were 101 patients followed with serial US examination for evidence of subependymal and/or intraventricular hemorrhage. CT correlation was obtained on each patient. The US examination correlated with the CT scan in 77 of these 101 patients. The demonstration of hydrocephalus by US in eight infants with postthemorrhagic hydrocephalus was reliable, and the correlation with CT scan was excellent.

Comparison of lumbar puncture with computed tomography scan as an indicator of intracerebral hemorrhage in the preterm infant.

Computed tomography (CT) scan is the most accurate method for diagnosing intracerebral hemorrhage in the high-risk preterm infant. The present study was undertaken to evaluate lumbar puncture (LP) as a reliable means of diagnosing such hemorrhages. Forty eight infants less than 35 weeks gestation, requiring intensive care, were evaluated by CT scan at 48 to 96 hours of life, and serial LPs were performed. The initial LP preceded the CT scan by one to four hours and repeat LPs were done three and five days later if the initial CT scan revealed intracerebral hemorrhage. The initial LP was successfully performed in 28 of 48 infants. Of these 48 infants, 15 had hemorrhage by CT scan. The initial LP was consistent with the diagnosis on scan in eight of these 15. In the other seven infants, initial LP was normal in three, traumatic in one, and unsuccessful in three. The second LP was consistent with hemorrhage in four of the latter seven. Thus, in only eight of 15 infants, in whom CT scans revealed intracerebral hemorrhage, was the initial LP useful in confirming the diagnosis. Furthermore, LPs showed bloody cerebrospinal fluid in 10 of 18 infants whose CT scans were normal. At the present time LP cannot be considered a reliable means of identifying infants with subependymal-intraventricular hemorrhage.

Hereditary spinal arachnoid cysts, distichiasis, and lymphedema.

Familial congenital spinal arachnoid cysts causing progressive paraplegia are reported in two adolescent siblings as part of a hereditary syndrome. The other features of this unusual dominantly inherited disorder include double rows of eyelashes, partial ectropion of the lower eyelids, and acquired late-onset lymphedema of the lower extremities. The siblings' mother, who had roentgenographic evidence of a similar intraspinal lesion, was free of neurological symptoms but had the other characteristic features. Surgical treatment of the arachnoid cysts improves the progressive paraplegia.

Intraventricular hemorrhage in the high-risk preterm infant: incidence and outcome.

To determine the incidence of subependymal (SEH) or intraventricular hemorrhage (IVH) and its short-term outcome, infants of less than 35 weeks' gestation who required intensive care were evaluated and computerized tomographic scans obtained. If the scans showed blood, serial scans were followed until the hemorrhage had resolved and ventricle size was stable. Hemorrhage was quantitated; Seventy-seven of 191 (40.3%) infants were shown to have SEH, IVH, or both; 22 of them (28%) died, and hemorrhage was thought to be the primary cause of death in 17. Fifty-five survivors (71%) with SEH, IVH, or a combination of the two had serial follow-up scans. Six had SEH alone; 49 had IVH. Severe progressive hydrocephalus developed in 12 (22%) infants. Thirty-seven (75.5%) die not show progressive hydrocephalus. The degree of hemorrhage in these 37 was mild in 14, moderate in 13, and marked in 10. Of those with progressive hydrocephalus, hemorrhage was marked in 8 and moderate in 4. Hydrocephalus resolved spontaneously in 4 of the 12. Medical treatment (repeated lumbar punctures) was successful in 3, but failed in 4. Hydrocephalus was managed by shunt surgery in 5. This study revealed that the quantity of blood is prognostically important with regard to both survival (p less than 0.001) and development of progressive hydrocephalus (p less than 0.05). Furthermore, hydrocephalus, even if progressive, may not necessitate surgical management;

Recurrent meningitis due to an intracranial epidermoid.

The association of intracranial dermoids and epidermoids and recurrent meningitis is usually related to the presence of dermal sinuses that allow bacterial entry. Epidermoid cysts rarely discharge their contents into subarachnoid space to cause meningitis, except after surgical removal. We describe a child who had 10 separate episodes of chemical meningitis between age 13 months and her death at age 2 years 9 months. Death was caused by an intra-axial epidermoid in the ventral pons which had ruptured into the subarachnoid space, as shown at autopsy. There was no evidence of sinus tracts, and radiographic studies revealed no mass.

Toxic encephalopathy related to antihistamine-barbiturate antiemetic medication.

A toxic encephalopathy characterized by depressed level of consciousness, marked irritability, and ataxia developed in seven children, 5 years of age and younger, following administration of an antiemetic combination of pentobarbital and pyrilamine maleate. Three of the seven patients were given a dosage of medication and exceeding the manufacture's recommendation. All seven patients recovered without sequelae.