Search PubMed⌕ Search

Biomedical subjects

L Hood

Publications and source records attributed to L Hood.

At least 343 records · Page 19Linked to original sources
PubMed1981

Microchemical instrumentation.

A number of cell surface molecules of great theoretical and practical importance simply cannot be obtained in amounts sufficient for molecular analysis using conventional methods and instrumentation. Because of our interest in such studies, we began about eight years ago to explore the possibility of developing new instrumentation for the sequence analysis of very small quantities of polypeptide chains. These efforts have led to the development of two microsequenators which employ one thousandth to one ten-thousandth the material used in the original sequenator described by Per Edman. In addition, in conjunction with the explosion of recombinant DNA techniques, we also have begun to develop instrumentation for the sequence analysis and synthesis of DNA molecules. In this paper we describe briefly several new instruments that have been developed at Caltech. We believe this new instrumentation in conjunction with the recombinant DNA and hybridoma technologies will provide unique opportunities to analyze cell-surface molecule in the years ahead.

Amino Acid Sequence↗
PubMed1981

Serological and biochemical characterization of rat (RT1) class II molecules with restricted mouse anti-Ia sera.

Murine anti-Ia sera were tested for their reactivity with rat peripheral lymphocytes. Extensive cross-reactions were observed in a complement-dependent cytotoxicity assay. In the majority of strain combinations, these reactions were specific for B cells. We demonstrated by absorption analyses that (1) the reaction was specific, (2) B cells from all rat strains reacted with anti-I-Ek serum, and (3) the anti-I-A sera defined five new specificities. These antisera can also immunoprecipitate class II (Ia-like) molecules from radiolabeled, detergent-solubilized cell extracts. The rat equivalents of molecules encoded in the I-A and I-E subregions in mice can be isolated from all rat strains studied. The alpha and beta subunits of the rat class II molecules were polymorphic when analyzed by sodium dodecyl sulfate (SDS) polyacrylamide electrophoresis. This observation allows the characterization of rat alloantisera or monoclonals of unknown specificity by comparing them to the defined reactivity of the mouse anti-Ia sera.

Absorption↗
PubMed1981

Tryptic peptide map analyses of mouse transplantation antigens.

Tryptic peptide map analyses of five K- and three D-gene products of various H-2 haplotypes are presented. These data support earlier sequence studies and demonstrate that the variations in allelic gene products of the K or D loci are scattered throughout much of the polypeptide chains. Furthermore, the K allelic gene products are no more closely related to one another than they are to the D allelic gene products. This apparent lack of K-ness and D-ness places interesting constraints on the genetic organization and evolutionary history of the genes encoding the transplantation antigens.

Amino Acids↗
PubMed1981

A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains.

We have isolated about 30 to 40 different BALB/c mouse sperm DNA genomic clones that hybridize to cDNA clones encoding proteins homologous to transplantation antigens. One of these clones (27.1) was selected for sequence because it was polymorphic in Southern blot analysis of the DNAs from BALB/c and CBA mice. A fragment of 5.7 kilobases of this clone was completely sequenced and found to contain a pseudogene whose sequence is highly homologous to the sequences of known transplantation antigens. Pseudogene 27.1 is split into eight exons that correlate with the structurally defined protein domains of transplantation antigens. Using Southern blot hybridization on the DNAs of different inbred mouse strains, we mapped the pseudogene to the Qa-2,3 region, a part of the Tla complex on chromosome 17 that is adjacent to the major histocompatibility complex. The Qa2,3 region encodes lymphoid differentiation antigens homologous to the transplantation antigens in size, in peptide map profiles and in their association with beta2-microglobulin. These mapping studies suggest that gene 27.1 may be a pseudogene for eigher a Qa antigen or an as yet undefined transplantation antigen. Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library.

Base Sequence↗
PubMed1981

Antibody diversity: somatic hypermutation of rearranged VH genes.

The immune response to phosphorylcholine in BALB/c mice has been well characterized. Amino acid sequence analyses of heavy-chain variable (VH) regions from 19 myeloma and hybridoma immunoglobulins binding phosphorylcholine show that 10 are identical (the prototype T15 VH sequence) and 9 are distinct variants differing by one to eight residues. A T15 VH DNA probe was used to isolate four closely related members of the T15 VH gene family, including one encoding the T15 VH sequence, from a sperm genomic library. A comparison of the protein and germline VH sequences suggested that most of the immune response to phosphorylcholine is derived from the T15 germline VH gene segment. The variant heavy chains from the M167 and M603 alpha immunoglobulins differ in their VH protein sequences from T15 by eight and three residues, respectively. We analyzed the somatic variability in and around the coding regions of these two variant VH genes by comparing them with the corresponding regions of the appropriate germline gene segments. The somatic variation has three properties: it is extensive and is found in flanking as well as coding sequences (for example, at least 44 substitutions for the M167 sequence and 10 substitutions for the M603 sequence); in the coding regions, it includes many silent as well as replacement substitutions; and it is focal in nature and centered around the rearranged VH genes. Although the mutations extend into the neighboring upstream and downstream flanking sequences, sequences approximately 5 kb upstream and downstream from the VH genes show no substitutions. Moreover, the associated heavy-chain constant genes (C alpha) from both variant alpha genes are unaltered, indicating that a closely linked and coexpressed gene is unmutated. We conclude that this somatic variation is generated by a special hypermutational mechanism highly localized in its site of execution and highly restricted in its time of operation during B-cell development.

Animals↗
PubMed1981

Three cDNA clones encoding mouse transplantation antigens: homology to immunoglobulin genes.

We constructed cDNA libraries from poly(A)+ RNA isolated from cell lines of two different inbred strains of mice, and screened the libraries with a cDNA clone encoding a human transplantation antigen. Three cDNA clones were identified, sequenced and found to encode amino acid sequences highly homologous to portions of a known mouse transplantation antigen. Comparison of the cDNA sequences of mouse transplantation antigens with the constant region domains of the mouse immunoglobulin mu gene reveals a striking homology, which suggests that the two genes share a common ancestor. Antibody genes undergo DNA rearrangement during B cell differentiation that are correlated with their expression. In contrast, DNA blots with these cDNA probes suggest that the genes for the transplantation antigens are not rearranged in the genomes of liver or embryo cells, which express these antigens, as compared with sperm cells, which do not express these antigens. In Bam Hl-digested liver DNAs from different inbred strains of mice, 10-15 bands of hybridization were found. Accordingly, the genes encoding the transplantation antigens appear to constitute a multigene family with similar gene numbers in different mice.

Amino Acid Sequence↗
PubMed1981

Is the CSF lactate measurement useful in the management of children with suspected bacterial meningitis?

The role of the cerebrospinal fluid lactate measurement was evaluated for the management of children with suspected bacterial meningitis. Although CSF lactate can be precisely measured, it provided no additional information over that which can be obtained from a CSF cell count. Reliance on the CSF lactate concentration alone would have increased the number of children being treated unnecessarily with antibiotics. There was neither clinical nor experimental evidence to suggest that the test should be used in the early diagnosis of meningitis. In patients with equivocal clinical and CSF findings, it failed to differentiate bacterial from nonbacterial infection. The data do not support the view that the measurement of CSF lactate has significant role in the management of children with suspected meningitis.

Adolescent↗
PubMed1981

The temporal course of the masking of tinnitus as a basis for inferring its origin.

For patients with tinnitus and sensorineural hearing loss, the intensity of broad-band noise required to mask the tinnitus increases by as much as 45 dB during a 30-minute period if the patient is exposed to noise. In contrast, the intensity required to mask an external tone remains nearly constant. Some speculations which might account for this result are offered. Excess neural activity is posited to be the physiological determinant of tinnitus and to be central, generated in the brainstem postsynaptic to the eighth nerve.

Auditory Threshold↗
PubMed1981

Porcine pituitary dynorphin: complete amino acid sequence of the biologically active heptadecapeptide.

The full primary structure of the very potent opioid peptide dynorphin, from porcine pituitary, has been determined. It is (H)Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln(OH). The synthetic peptide with this sequence behaves identically to natural dynorphin in a number of ways, and it has the same potency in the guinea pig ileum myenteric plexus--longitudinal muscle bioassay. The potency is accounted for by the first 13 residues.

Amino Acid Sequence↗
PubMed1981

Nucleotide sequence of a human immunoglobulin C gamma 4 gene.

We report the nucleotide sequence of a gene encoding the constant region of a human immunoglobulin gamma 4 heavy chain (C gamma 4). These data represent the first complete sequence determination of a human CH gene. As expected from structural studies of mouse C gamma genes, the coding sequences for the CH domains and hinge segment are separated from one another by intervening DNA sequences. Comparison with genomic sequences of the mouse C gamma 1, C gamma 2a, and C gamma 2b genes shows conservation of the sequences in the constant region domains and the 3' untranslated region surrounding the presumed site of poly(A) addition.

Amino Acid Sequence↗
PubMed1981

An immunoglobulin VH pseudogene.

In the course of studying the members of the T15 group of VH gene segments, some of which participate in the immune response to phosphorylcholine in the mouse, we identified a VH gene segment that contains three mutations preventing its expression. The mutations are an in-frame stop codon, a 4-base insertion which causes a termination codon to be shifted into the reading frame, and a modification of the recognition elements involved in the joining of VH and D gene segments during variable region formation. This pseudogene, which is 88-96% homologous to the other members of the T15 VH gene group, is probably of relatively recent origin and will presumably be deleted from the VH gene family eventually. We suggest that pseudogenes can only arise in multigene families and that the occurrence of pseudogenes will be a relatively frequent phenomenon in these families. Because the antibody gene families are made up of multiple gene elements, undergo two types of DNA rearrangements during differentiation, and employ several different RNA splicing mechanisms for expression, there are many different ways a particular antibody gene segment may become a pseudogene.

Animals↗