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Biomedical subjects

A M Saunders

Publications and source records attributed to A M Saunders.

At least 127 records · Page 7Linked to original sources

A linkage map of mouse chromosome 8: further definition of homologous linkage relationships between mouse chromosome 8 and human chromosomes 8, 16, and 19.

Using an interspecific cross, a mouse chromosome 8 linkage map spanning 72 cM has been defined by the segregation of restriction fragment length variants. Linkage and genetic distance were established for 10 loci by analysis of 114 meiotic events and indicated the following gene order: (centromere)-Insr-3.5 cM-Plat-26.3 cM-Crryps/Mel/Jund-3.5 cM-Junb/Ucp-10.5 cM-Mt-1-27.2 cM-Acta2-0.9 cM-Aprt. These data provide further definition of mouse chromosome 8 linkage relationships and the relationship between segments of this chromosome and human chromosomes 8, 16, and 19.

Animals↗

Mediastinal mass following esophageal surgery.

In this Radiology Rounds, the authors report the computed tomographic findings of a patient with an infected esophageal mucocele that formed within one month after repair of a perforated paraesophageal hiatus hernia. The patient was a 78-year old male.

Aged↗

A molecular genetic linkage map of mouse chromosome 7.

The homology between mouse chromosome 7 and human chromosomes 11, 15, and 19 was examined using interspecific backcross animals derived from mating C3H/HeJ-gld/gld and Mus spretus mice. In an earlier study, we reported on the linkage relationships of 16 loci on mouse chromosome 7 and the homologous relationship between this chromosome and the myotonic dystrophy gene region on human chromosome 19. Segregation analyses were used to extend the gene linkage relationships on mouse chromosome 7 by an additional 21 loci. Seven of these genes (Cyp2a, D19F11S1h, Myod-1, Otf-2, Rnu1p70, Rnu2pa, and Xrcc-1) were previously unmapped in the mouse. Several potential mouse chromosome 7 genes (Mel, Hkr-1, Icam-1, Pvs) did not segregate with chromosome 7 markers, and provisional chromosomal assignments were made. This study establishes a detailed molecular genetic linkage map of mouse chromosome 7 that will be useful as a framework for determining linkage relationships of additional molecular markers and for identifying homologous disease genes in mice and humans.

Animals↗

The syntenic relationship of proximal mouse chromosome 7 and the myotonic dystrophy gene region on human chromosome 19q.

The syntenic relationship of the myotonic dystrophy (DM) gene region on human chromosome 19q and proximal mouse chromosome 7 was examined using an interspecific backcross between C3H/HeJ-gld/gld mice and Mus spretus. Segregation analyses were used to order homologs of nine human loci linked with the DM gene. Their order from the centromere was Prkcg, [Apoe, Atpa-2, Ckmm, D19S19h, Ercc-2], Cyp2b, Mag, Lhb. Two other murine loci, D7Rp2 and Ngfg, were also positioned within this interval. Homologs for five human chromosome 11 and 15 loci (Calc, Fes, Hras-1, Igflr, Tyr) were localized within an 18-cM span telomeric to Lhb. Comparison of the gene orders indicates an inversion extending from Prkcg through the interval between Mag and Lhb. This study establishes a detailed map of proximal mouse chromosome 7 that will be useful in identifying and determining whether new human chromosome 19 probes are linked to the DM region.

Animals↗

The beta-phosphoro[35S]thioate analogue of UDP-Glc is efficiently utilized by the glucose phosphotransferase and is relatively resistant to hydrolytic degradation.

The beta-phosphoro[35S]thioate analogue of UDP-glucose ((beta-35S)UDP-Glc) is utilized with approximately the same efficiency as the parent compound by the UDP-glucose:glycoprotein glucose-1-phosphotransferase (glucosyltransferase), which catalyzes the transfer of alpha Glc-1-P from UDP-Glc to mannose-containing oligosaccharides on acceptor glycoproteins. The same endogenous acceptor glycoproteins are labeled by the glucosyltransferase using [beta-32P]UDP-Glc and (beta-35S)UDP-Glc. However, in liver homogenates, incorporation from [beta-32P]UDP-Glc ceases to increase after about 4 min of incubation, while incorporation from (beta-35S)UDP-Glc persists for at least 1 h. This difference is due to an approx. 10-fold slower hydrolytic rate for the phosphorothioate analogue than for the parent compound, a finding similar to previous work showing that a variety of nucleases and phosphodiesterases are less efficient in cleaving phosphorothioate DNA than the native polymer.

Animals↗

Flow cytometric analysis of lymphocyte phenotypes in AIDS using monoclonal antibodies and simultaneous dual immunofluorescence.

Simultaneous dual immunofluorescence and flow cytometry was used to study sixteen lymphocyte phenotypes in 209 men including: healthy homosexuals, lymphadenopathy patients (LAN), and AIDS patients. Significant differences between the distribution of lymphocytes in healthy homosexuals and healthy heterosexuals were decreased percentages of helper/inducer T cells (Leu 3), increased cytotoxic/suppressor T cells (Leu 2), and consequently a decreased Leu 3/Leu 2 ratio. The increased Leu 2 cells were identified as functionally cytotoxic subset Leu 2+ 15- phenotype rather than suppressor cells which are Leu 15+. Leu 2 and Leu 3 bearing cells exhibited an excess of membrane-bound immunoglobulins which were easily elutable at 37 degrees C. An increased percentage of an HLA-DR framework determinant bearing T cells were also detected. Within the NK cell family, Leu 7 cells were moderately increased and the functionally unidentified Leu 2+ 7+ population was strikingly elevated. LAN or AIDS patients were compared to healthy homosexual controls. Lower percentages of Leu 3 cells and higher percentages of Leu 2 cells were evident in LAN patients. These subsets were similar in LAN and AIDS patients. The increase in Leu 2+ cells was due to the Leu 2+ 15- cytotoxic subset. Fewer T cells had immunoglobulin in LAN and AIDS. A definite increase in Leu 2+ DR+ cells but not Leu 3+ DR+ cells occurred in AIDS compared to LAN or healthy controls. NK cell changes already present in healthy homosexuals persisted in LAN and AIDS patients. No differences in the distribution of B cells was detected in any intergroup comparisons. Changes in monocytes or pan-T cells were relatively insensitive measures of immunologic alterations among any of the groups. These results indicate many of the changes in lymphocyte subsets seen in AIDS and LAN subjects are already present in a carefully screened population of healthy homosexuals in San Francisco. Many of the changes in Leu 2 and NK family of cells suggest a possible adaptive response to viral or neoplastic challenge. Whether these interesting phenotypic alterations relate to functional changes in response to such challenge of the identified subsets waits further investigation.

Acquired Immunodeficiency Syndrome↗

Sources of physiological variation in differential leukocyte counting.

A statistical analysis is provided on the diurnal and day-to-day variations of individuals in order to validate the usefulness of high precision differential counts. There is a significant within-day variability that interferes with monitoring of individual patients unless a constant time of day is chosen for sampling. An experiment with endotoxin illustrates possible changes that can be monitored with highly precise counts, and several examples are given of monitoring patients over the course of an illness. Conclusions are that all the cell types of the differential respond independently to a variety of physiological and pathological stimuli. Information obtained will be as valuable as the care with which sample acquisition and other factors are controlled.

Basophils↗

Distinctive lymphocyte subpopulation abnormalities in patients with congenital coagulation disorders who exhibit lymph node enlargement.

The majority of patients with congenital clotting disorders who use clotting factor concentrate exhibit lymphocyte subpopulation abnormalities. A subset of these patients develop lymph node enlargement (LNE), part of the spectrum of clinical disease associated with the acquired immune deficiency syndrome (AIDS). It is therefore important to determine if these patients with LNE exhibit specific immune alterations suggestive of early infection with the AIDS agent. We used one- and two-color immunofluorescence to distinguish the lymphocyte subpopulation alterations associated with concentrate use from those associated with LNE. Patients who use concentrate had elevated levels of Leu-2+ (T suppressor phenotype) cells and Leu-7+ (phenotype of some natural killer) cells. These increased levels were largely caused by a dramatic (2.6-fold) increase in the number of lymphocytes co-expressing Leu-2 and Leu-7 (2+7+). A dose-response effect between amount of concentrate infused during the preceding year and level of 2+7+ cells was observed. Concentrate recipients, as a group, also showed increased levels of T cells expressing Dr antigen (T+Dr+ phenotype, characteristic of activated or immature T cells) and cells expressing the T10 antigen (phenotype of some null cells and activated/immature T cells). Patients with LNE showed a further increase in T10+ cells as well as a distinctive decrease in Leu-3+ (T helper phenotype) lymphocytes. All LNE patients exhibited either low Leu-3+ levels, high T10+ levels, or both. Thus, concentrate use was associated with increased levels of Leu-2+ (particularly 2+7+) cells and T+Dr+ cells, whereas LNE was associated with decreased levels of Leu-3+ cells and high levels of T10+ cells.

Acquired Immunodeficiency Syndrome↗

A rapid spot test for urinary methylmalonic acid collected on ion-exchange filter paper.

We developed a rapid, accurate method to detect pathologic amounts of methylmalonic acid (MMA) in urine samples, which can be applied to simplify and improve the accuracy of screening for methylmalonic acidemia. Urine is collected on DEAE-cellulose paper and air-dried. Six mm discs are punched from the dried paper and placed in a multi-well tray; non-anionic substances interfering with the assay are rinsed from the discs; and a color reaction using diazotized p-nitroaniline is carried out in situ on the disc. Of 407 urine samples blindly tested, all 83 samples from nine patients with methylmalonic acidemia gave positive results. None of the other urine specimens from normal individuals or patients with a variety of organic acidemias gave positive results. This method should allow accurate and inexpensive mass screening for methylmalonic acidemia in newborn or infant screening programs.

Chromatography, Gas↗

Within-day physiologic variation of leukocyte types in healthy subjects as assayed by two automated leukocyte differential analyzers.

The physiologic within-day (700-2200 h) variation of leukocyte-type concentrations in blood as determined for 21 healthy young adults is reported. All blood specimens were obtained in duplicate such that the within-batch analytic variation, as well as the pertinent biologic sources of variation, was able to be determined. All specimens were analyzed on each of two automated leukocyte differential systems: Hemalog-D Differential System and the Hematrak-240 Analyzer. On the basis of a comparison of the performances of the two analyzers, it was decided to report the neutrophil and the lymphocyte values as measured on both systems, the monocyte values as measured on teh Hematrak only, and the eosinophil and basophil values as measured on the Hemalog-D only. The intrasubject within-day physiologic variations for the cell on the Hemalog-D and Hematrak, respectively, in terms of coefficient of variation wee as follows: neutrophils 19.4% and 19.6%; lymphocytes, 13.8% and 17.5%. For monocytes, as measured on the Hematrak, it was 13.4%. For eosinophils and basophils, as measured on the Hemalog-D, it was 27.2% and 8.3%, respectively. There was a consistent group-specific diurnal variance that amounted to more than 40% of the total within-day variance, both for lymphocytes and for eosinophils. The within-day physiologic variation of the cell type concentrations for eight of the volunteers was compared with that of the plasma cortisol concentrations, as determined on specimens derived from the same veni-puncture sessions. The decrease in plasma cortisol values was in most instances associated with decreases in eosinophils and increases in neutrophils. For total leukocytes and neutrophils, the mean concentration for smokers was significantly higher than that for nonsmokers.

Adult↗

White blood cells: what to do beyond measurement.

A commercial pattern recognition device is described. Although its main function is in automating differential white blood cell counts, it is capable of simultaneously developing profiles on neutrophils and lymphocytes. These profiles are more or less independent of conventional morphologic classification. Although their clinical meaning is still to be verified, the profiles appear to be good flags for a number of illnesses, including inflammations and possibly some malignancies.

Humans↗

Mixed malignant tumour of the lung.

A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed.

Adenocarcinoma↗

Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers.

The authors determined mean day-to-day (daily over five days), mean week-to-week (weekly over five weeks) and mean hour-to-hour (800 h, 1100 h, 1400 h) physiologic intra-individual variation of concentration values of leukocyte cell types, platelet count, and erythrocyte values (hematocrit, hemoglobin) for a group of 20 healthy adult volunteers. Total leukocyte counts and concentration values of leukocyte cell types were determined in duplicate on the Hemalong-DTM Automated Leukocyte Differential Cell Counter to minimize analytic variation. The data sets were analyzed according to an analysis of variance model. The mean physiologic hour-to-hour and week-to-week intra-individual variations in terms of % coefficient of variation included: hemoglobin, 2.5, 2.2; hematocrit, 2.6, 2.7; platelets, 1.6, 6.6; total leukocyte count, 9.4, 15.7; neutrophils, 12.9, 26.0; lymphocytes, 10.3, 13.2; monocytes, 18.6, 19.3; eosinophils, 19.9, 26.9; basophils, 7.4, 15.0; large unstained cells, 13.7, 16.0; "high-peroxidase" cells, 32.7, 25.7. Hour-to-hour variation was partitioned into random diurnal variation, group-consistent diurnal variation, and subject-specific unique individual variation. Subject-specific diurnal variation contributed greatly and statistically significantly to total diurnal variation for many of the leukocyte cell types--especially in the case of eosinophils, where it represented more than half of total diurnal variation.

Adult↗

The automation of cytochemical methods for automated cytophotometers.

The development of an automated differential white blood cell counter is reviewed. After the red cells have been lysed, the white cells are counted by staining and passing through an electro-optical chamber in liquid suspension, surrounded by a laminar, or sheath, stream. Staining procedures were made specific for each type of leukocyte, and separate channels were used for counting each type. Staining intensity and characteristics of the various types of blood cells are discussed. They relate to enzyme levels and the effect on differentiation and identification of the cells. Since reasons for some of the design features are not obvious, discussion of the relevant problems is included. Several applications that go beyond routine differential counting are described.

Basophils↗

The presentation of three-dimensional reconstructions from serial sections.

A simple and effective way is described for showing particular structures in serial sections. By using waterproof inks and acetate sheets supported on a frame immersed in water and illuminated from beneath, the information from up to sixty sections can be easily visualized. This technique is particularly useful for displaying enclosed structures and by a suitable choice of colours enables special emphasis to be given to selected components. The information can be recorded simply through stereo photography.

Models, Structural↗