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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 1,207 records · Page 67Linked to original sources
PubMed1981

Serum and milk alkaline phosphatase in human lactation.

Serum and milk alkaline phosphatase (AP) values are reported for the first 16 weeks of lactation. Serum levels at all stages are elevates above normal-pregnant controls. Sequential milk AP values are reported for the first time. Heat inactivation and phenylalanine inhibition studies would suggest that serum AP in lactation is composed of bone and liver isoenzymes, but it shows an increase in the rate at which enzymatic activity is lost when frozen, indicating that lactation serum AP is largely a different isoenzyme. Electrophoresis demonstrates several AP "slow" bands of unknown origin in lactation serum.

Alkaline Phosphatase↗
PubMed1981

A position effect in the control of transcription at yeast mating type loci.

The two mating type loci MATa and MAT alpha each produce two mRNAs that are transcribed in opposite and diverging directions from central promoters. Silent copies of MATa (HMRa) and MAT alpha (HML alpha) contain identical DNA sequences throughout the transcribed region, yet are not transcribed. It is concluded that sequences to the left of HMRa (and probably HML alpha) must somehow affect transcription initiated at the centre of each locus 700 to 1,400 base pairs away. A possible mechanism for this position effect is discussed.

Base Sequence↗
PubMed1981

Confirmation of the assignment of genes of human immunoglobulin heavy chains to chromosome 14 by analysis of Ig synthesis by man-mouse hybridomas.

Hybridomas were produced by fusing the NS1 mouse myeloma line, which does not produce mouse heavy chain Ig, with human peripheral B lymphocytes from a normal individual. Two vigorously growing colonies from this fusion were found to secrete human Ig heavy chains and were recloned. Two secondary clones, which secreted human chains, were again recloned. Among the tertiary clones, two were identified which produced intracellular human Ig chains, but did not secrete immunoglobulin. These tertiary clones were recloned, generating 6 quaternary clones which failed to produce human Ig heavy chains, and 15 quaternary clones which produced intracellular Ig chains. Hybrid clones from each successive subcloning were examined for their human chromosomal content and only those clones which were found to be individually chromosomally distinct, a total of 56 clones in all, were used to analyze the segregation of human chromosomes and human Ig heavy chain synthesis. Results of this study indicate concordant segregation of human Ig heavy chain synthesis and chromosome 14. These studies therefore confirm the previous assignment by C. M. Croce et al. (Proc. Natl. Acad. Sci. USA 1979. 76: 3416) of the genes for human Ig heavy chains to chromosome 14.

Alleles↗
PubMed1981

The fine structural relationship between Theileria schizonts and infected bovine lymphoblasts from cultures.

The fine structure of Theileria-lymphoblast relationship was studied using cultured bovine lymphoblastoid cells infected with Theileria parva, T lawrencei, or T. annulata. The major findings of this study were: (1) the presence of a very active Golgi complex with the associated annulate lamelae; (b) the presence of cytoplasmic microtubules which joined the parasites and host cell centriole during lymphoblast mitosis; and (c) the absence of morphological evidence to suggest that the host cell developed a reaction to the parasitic presence. The significance of these findings is discussed.

Animals↗
PubMed1981

Litomosoides carinii infection in cotton-rats: evolution of microfilaraemia before and after treatment with diethylcarbamazine and suramin.

The activity of diethylcarbamazine (DEC) and suramin (S) on Litomosoides carinii filariasis was assessed by the study of microfilaraemia in 30 cotton-rats (Sigmodon hispidus). DEC (per os) and S (injected subcutaneously) were administered alone or in combination, at doses of 50 mg/kg/day for five consecutive days. 15 rats were treated at day 91 after infection and 15 others at day 184. The immediate but temporary efficacy observed with DEC was in contrast to the delayed and long-lasting effect of S. With combined therapy there was neither antagonism nor synergism. The demonstration of an apparently smaller reduction of parasitaemia in the rats treated with DEC before the plateau phase of the microfilaraemia was consistent with the lack of action of this drug on microfilariae outside the blood system.

Animals↗
PubMed1981

The sequence of the DNAs coding for the mating-type loci of Saccharomyces cerevisiae.

The complete sequences of the yeast a mating-type locus, MATa, and of the silent alpha cassette, HML alpha, have been determined. A segment of 642 nucleotides is unique to MATa, and a corresponding segment of 747 nucleotides is unique to MAT alpha. The major mRNAs (a1, a2, alpha 1 and alpha 2) encoded by MATa and MAT alpha have been aligned with the DNA sequence. The a1 mRNA is encoded entirely within the a-specific DNA sequence. The a2 mRNA, which is transcribed divergently from a1 mRNA, is encoded in a region common to both Mata and Mat alpha. The alpha 1 and alpha 2 mRNAs are also transcribed divergently and have their 5' starts about 240 nucleotides apart within the alpha-specific sequence. The amino acid sequences of the MAT proteins have been predicted from the DNA sequences. An unanticipated conclusion is that the a1 protein, containing 148 amino acids, results from readthrough of a UGA at codon 45. Polymorphic forms of the homologous outer segments of the HML alpha, MAT alpha, MATa and HMRa sequences suggest that the boundaries of the segments involved in mating-type switching are immediately adjacent to the a-specific and alpha-specific sequences.

Base Sequence↗
PubMed1981

In vitro mutation analysis of the mating-type locus in yeast.

The mating-type locus (MAT) of Saccharomyces cerevisiae is a complex locus that codes for the regulators of cell type. Two unique messages are transcribed from each MAT allele. Using the in vitro mutagenesis technique whereby synthetic oligonucleotides containing restriction sites (linkers) were inserted into plasmids, we have constructed a series of mutations in cloned DNA containing either the MATa or MAT alpha locus. The new restriction site associated with each "linker" mutation has allowed the mutation to be mapped and sequenced. We have complemented genetically defined mutations (mata1, mat alpha 1 and mat alpha 2) with plasmids containing these in vitro mutations by yeast transformation, thereby mapping the genes onto the DNA sequence. MATa1 has been localized to the MATa unique region (Ya) from which the a1 message is transcribed. We find no function for the other MATa message by using our complementation assay. MAT alpha 1 maps to the MAT alpha unique (Y alpha) and adjacent (Z) region from which the alpha 1 message is transcribed. MAT alpha 2 maps to the other major message found in the common (X) region of the MAT alpha loci. Although most linker mutations that have a mutant phenotype appear to disrupt the translated portion of each gene, two mutations may disrupt transcription.

Chromosome Mapping↗
PubMed1981

The natural history of retinopathy in insulin-dependent juvenile-onset diabetes.

We determined the cross-sectional natural history of retinopathy by prospective study of 461 insulin-dependent juvenile-onset diabetics. In so doing, we compared the sensitivity of ophthalmoscopy, photography, and fluorescein angiography in detecting retinopathy. Photography was far more reliable than ophthalmoscopy in detecting early retinopathy and equivalent to angiography. Retinopathy was not present at diagnosis of diabetes. After a lag period, the prevalence of retinopathy rose in sigmoidal fashion, reaching 50% at just over seven years duration, and asymptotically approaching 90% at 17--50 years. Proliferative retinopathy was first seen at 13 years duration, and its prevalence rose to 26% at 26--50 years. From the natural history we computed the dimensions of a proposed clinical trial to test the effect of tight metabolic control in prevention of retinopathy.

Diabetes Mellitus, Type 1↗
PubMed1981

Idiopathic inflammatory orbital pseudotumor in childhood. II. Results of diagnostic tests and biopsies.

Twenty-nine patients with pediatric orbital pseudotumor underwent a wide variety of diagnostic tests including biopsies. The following abnormalities were discovered: peripheral blood eosinophilia (9/29 patients); elevated ESR (17/27); elevated antinuclear antibody titres in the Tolosa-Hunt variant (2/2); hypercomplementemia (2/3); and mild CSF pleocytosis (2/6). Thyroid function tests were normal in nine patients so studied. B-mode ultrasonography performed on 12 patients displayed abnormalities in all cases (some combination of Tenonitis, myositis, perioptic inflammation, or mass effect). Computed tomography in seven patients provided higher resolution confirmation of these findings. Orbital bone changes and serious sinus disease were absent on routine radiographic studies. Biopsies performed on 16 patients disclosed mild lymphocytic inflammation in all cases, fibrosis and tissue eosinophilia in 9 biopsies (6 correlating with peripheral blood eosinophilia). Nine biopsies demonstrated a lipogranulomatous response to damaged fat cells. A true vasculitis or extensive lymphoid hyperplasia was not identified in any biopsy specimen.

Child↗
PubMed1981

Deletion mapping of sequences essential for in vivo transcription of the iso-1-cytochrome c gene.

The 5' termini of yeast CYC1 RNA molecules have been mapped, by nuclease S1 digestion of mRNA . DNA duplexes, to seven locations from 29 to 93 base pairs upstream from the initiating ATG codon. When the CYC1 gene is introduced into yeast in plasmid YEp13, substantially the same transcripts are made. Using this system to study in vivo gene expression, we measured the capacity of enzymatically produced DNA deletions to form the normal set of RNAs. Four regions of 5'-flanking DNA were identified as functional. Sequences within the region -242 to -139 are required for maximal CYC1 transcript formation; their deletion reduces transcription by a factor of 15 but does not change the pattern of 5' ends observed. Deletion of the sequence between -242 and -99 does not further change the overall transcript level but does affect the specificity of CYC1 mRNA starting. A deletion that extends from -242 to -75 causes both an additional shift in the pattern of 5' ends observed and a further large decrease (factor of 10--20) in CYC1 RNA level. Deletions that extend from -242 to -43, and particularly two deletions that extend still closer to the initiating ATG, cause the appearance of an abundant transcript which starts upstream of position -1078 and of minor transcripts starting in the region -325 to -245.

Base Sequence↗
PubMed1981

Regional gene assignment of human porphobilinogen deaminase and esterase A4 to chromosome 11q23 leads to 11qter.

The regional gene assignments for human porphobilinogen deaminase (PBGD; EC 4.3.1.8) and esterase A4 (ESA4; EC3.1.1.1) chromosome 11 have been determined with somatic cell hybridization and immunologic, electrophoretic, and cytogenetic techniques. Dimethyl sulfoxide-induced erythroid differentiation of hybrid clones derived from the fusion of tetraploid Friend murine erythroleukemia (2S MEL) cells deficient in thymidine kinase and human Lesch--Nyhan fibroblasts (HLN) deficient in hypoxanthine phosphoribosyltransferase (HPRT-; EC 2.4.2.8) were examined for expression of human PBGD, ESA4, and lactate dehydrogenase A (LDHA; EC 1.1.1.27). Human PBGD was detected by rocket immunoelectrophoresis with rabbit anti-human PBGD IgG and by isoelectric focusing. The human chromosome complement of each clone was determined by cytogenetic and enzyme marker analyses. Of the five primary 2S MEL--HLN clones examined, three were positive for human PBGD. These were subcloned to yield a total of 10 secondary, tertiary, or quaternary clones. Analyses of these subclones permitted the regional assignment of human PBGD and ESA4 to the long arm of chromosome 11. Finer regional assignment of the loci for human PBGD and ESA4 was facilitated when two 2S MEL (HPRT-)--human fibroblast (HX/11) hybrids, each containing the X chromosome--autosome translocation (der11), t(X;11)(q25-26;q23) as the only human chromosome, were examined for expression of human PBGD, ESA4, and LDHA. One clone, HX/11-2, contained the intact X/11 translocated chromosome; in the other, HX/11-3, 11p was deleted, and the human X/11 derivative was translocated onto a mouse chromosome. HX/11-2 expressed human LDHA, but HX/11-3 did not, verifying that the latter human 11/X derivative did not include 11pter leads to 11p12; PBGD and ESA4 were not detected in either hybrid. These results confirm the location of the gene for human PBGD on chromosome 11 and establish the assignment of the loci for PBGD and ESA4 in the region 11q23 leads to 11qter.

Ammonia-Lyases↗
PubMed1981

Lacrimal gland adenoid cystic carcinoma: intracranial and extracranial en bloc resection.

Adenoid cystic carcinoma of the lacrimal gland is a rare tumor, although it is the malignancy most frequently arising in the gland. Treatment has been unsuccessful generally, with a 15-year survival of less than 20 percent. Our experience with this tumor in a 61-year-old woman has led to a proposal for therapeutic management based on awareness of the lesion's natural history, an understanding of regional anatomy, and familiarity with therapies reported in the literature. The feasibility of adequate tumor ablation is determined from preoperative evaluation, including CT scan, initial exploratory craniotomy, and frozen-section examination of the cranial nerves transversing the orbit. Once resectability is confirmed, "curative" intracranial and extracranial en bloc resection is performed, including the tumor, the lacrimal gland, and all contiguous structures. The defect is immediately resurfaced with and "ice cream cone" forehead flap in anticipation of adjuvant radiotherapy. An orbital prosthesis is fitted as soon as the radiation reaction subsides, and a postablative CT scan is obtained as the baseline for follow-up. It remains to be seen whether this application of the technology of CT scanning and the techniques of craniofacial surgery will improve the prognosis for adenoid cystic carcinoma arising in the lacrimal gland.

Carcinoma, Adenoid Cystic↗