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Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 559 records · Page 31Linked to original sources

Effects of monoclonal antibodies to bovine and Paracoccus denitrificans cytochromes c on reactions with oxidase, reductase and peroxidase.

The effects of monoclonal antibodies to bovine and Paracoccus denitrificans cytochromes c (Kuo, L.M. and Davies, H.C. (1983) Mol. Immunol. 20, 827-838) in the reactions of the cytochromes c with cytochrome c oxidase, reductase and peroxidase were studied. Spectrophotometric assays were employed, under conditions where binding of cytochrome c to the enzymes appears to be rate-limiting. Less than stoichiometric amounts of antibodies to P. denitrificans cytochrome c added to the cytochrome rendered some of it nonoxidizable or nonreducible by the P. denitrificans membrane-bound electron transport system and decreased the rate constant with the remaining cytochrome c. The antibodies appear to affect both electron transport reactions (blocking effects) with the oxidase and reductase and binding effects (effects on rate constants) and to distinguish between the two. Different ratios of antibody site to cytochrome c gave different extents of blocking of the reductase as compared with the oxidase reaction. Differences were also apparent in the effect of these antibodies on the reaction of yeast peroxidase and the oxidase with the P. denitrificans cytochrome c. Antibodies to bovine and P. denitrificans cytochromes c had considerably less effect on the reactions of the bovine cytochrome with bovine oxidase and reductase. One antibody was inhibitory to the oxidase reaction with bovine cytochrome c, but not to that with the reductase. Also, an antibody which inhibited the oxidase reaction had no effect on the reaction with yeast peroxidase. The data give evidence that the interaction areas on cytochrome c for oxidase and reductase and peroxidase are not identical, although they may be nearby.

Animals↗

Effective treatment of advanced multiple myeloma refractory to alkylating agents.

Twenty-nine patients with advanced refractory multiple myeloma were treated with intermittent high-dose dexamethasone in combination with four-day infusions of vincristine and doxorubicin. Rapid and marked tumor-mass reduction (greater than 75 per cent) was noted in 14 of 20 patients whose disease was resistant to alkylating agents and in 3 of 9 patients with additional resistance to doxorubicin--a result far superior to those in previous trials with similar patients. In responsive patients, remissions were of excellent quality, and survival was significantly longer than in unresponsive patients.

Alkylating Agents↗

Focal osteomalacia due to low-dose diphosphonate therapy in Paget's disease.

Transiliac bone biopsies carried out on 13 patients with Paget's disease to evaluate the effects of low-dose diphosphonate (disodium etidronate) therapy showed focal osteomalacia in the 9 patients in whom post-therapy specimens were taken through pagetic bone. Active bone resorption persisted in 5 of these. A mineralisation defect not amounting to osteomalacia--ie, osteoid of increased thickness but of normal extent--was present in the 4 specimens taken through non-pagetic bone. Although 9 patients experienced symptomatic improvement, 2 suffered fissure fractures in affected lower limbs. In Paget's disease, the combination of osteomalacia and continuing active resorption within a lytic lesion may increase the risk of fracture in a weight-bearing bone. It is suggested that although disodium etidronate often provides effective pain relief it should be administered with caution until the optimum dose and duration of therapy are further evaluated.

Aged↗

Initiation of DNA synthesis in quiescent Swiss 3T3 and 3T6 cells by lanthanum.

La3+ stimulated quiescent Swiss 3T3 and 3T6 cells to enter the DNA-synthesizing S phase of the cell cycle. La3+ and insulin interacted synergistically to increase DNA synthesis. A brief exposure of the cells to soluble LaCl3 optimally stimulated entry into S. La3+ was similar to A13+ in its mitogenic properties (J. Cell. Physiol. 118, 298, 1984), but La3+ was 10 times more potent than A13+.

Aluminum↗

The superior mesenteric artery. The critical factor in the pouch pull-through procedure.

The critical factor in ileal pouch pull-through operations is the length of the superior mesenteric artery. The pouch must reach the dentate line and have adequate blood supply. A series of cadaver and morgue studies were performed to evaluate the two most popular pouches of the "J" and "S" configurations. The "S" pouch generally reaches 2 to 4 cm more caudad than the "J" pouch. If necessary, however, the "J" pouch can be lengthened 2 to 4 cm by cutting the branch vessel under tension to the pouch, sparing vessels to either side and the marginal arcade. The "S" pouch procedure always sacrifices the ileocecal artery, but the "J" pouch procedure does not necessarily do so. The greatest caudad reach is available when the ileum is cut flush with the cecum. To verify a rule of thumb for reaching the dentate line with the pouch, the length of the superior mesenteric artery (SMA) origin to the inferior margin of the symphysis pubis and the SMA to dentate line were compared. If the tip of the pouch or conduit reached 6 cm below the symphysis pubis, all pouches reached the dentate line.

Cadaver↗

Hormonal and haemodynamic responses to upper abdominal surgery during isoflurane and balanced anaesthesia.

The purpose of the study was to compare the protective role of different anaesthetic techniques against surgical stress. Sixty patients undergoing elective laparotomy were randomly divided into six groups of ten patients each: Group I was given 0.65 MAC nitrous oxide (66 per cent inspired) and 0.65 MAC isoflurane (0.75 per cent end-expired); Group II was given 0.65 MAC nitrous oxide and 1-1.2 MAC isoflurane (1.2-1.4 per cent end-expired); Group III was given the same anaesthetic management as patients in Group I but with the addition of fentanyl (2 micrograms X kg-1) before the skin incision and 1/8 of the initial dose every 15 minutes during surgery; Group IV was treated as patients in Group I with an additional infusion of lidocaine (30 micrograms X kg-1 X min-1); Groups V and VI were given 0.65 MAC of nitrous oxide and fentanyl, 7.5 and 15 micrograms X kg-1, respectively, before skin incision with 1/8 of the initial dose every 15 minutes during the operation; diazepam, 5 mg IV each hour of surgery, was given to prevent intraoperative awareness. Cortisol concentration was determined by radioimmunoassay method and catecholamines were measured by high performance liquid gas chromatography in blood samples taken at different stages perioperatively. All patients had satisfactory haemodynamic courses of anaesthesia. Statistically significant increases in both epinephrine and norepinephrine concentrations were observed during the immediate postoperative period in Group I patients only. Haemodynamic stability was maintained despite a two- to three-fold increase in cortisol which occurred during the operation and immediate postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells.

Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with 45Ca2+, myo-[2-3H]inositol, or 32Pi. The efflux of 45Ca2+ was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of 45Ca2+ lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated 45Ca2+ release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of external Ca2+ had no effect on AII-stimulated 45Ca2+ release. Depolarization with high external K+ only slightly increased 45Ca2+ efflux and had no effect on AII-induced 45Ca2+ release. AII had no effect on the initial rate of 45Ca2+ influx. These results indicate that the rapid 45Ca2+ efflux evoked by AII is probably due to the release of 45Ca2+ sequestered intracellularly rather than to an increase in the Ca2+ permeability of the plasma membrane. AII provoked rapid increases in the levels of phosphatidic acid and phosphoinositides in the cells. These increases in phospholipids were associated with increases in phospholipase C-generated inositol phosphates (tri-, di-, and mono-). It appears that AII simultaneously increases phosphoinositide hydrolysis and synthesis in vascular smooth muscle, and both phospholipid effects may contribute to inositol triphosphate generation, which was sufficiently rapid to have a role in intracellular Ca2+ mobilization.

Angiotensin II↗

Reproducible production of protective human monoclonal antibodies by fusion of peripheral blood lymphocytes with a mouse myeloma cell line.

The production of monoclonal antibodies of human origin may represent a significant advance in immunotherapy for disease in humans. Although human monoclonal antibody has been produced from human lymphocytes by fusion with human myeloma cell lines or by Epstein-Barr viral transformation, fusion of postimmunization human lymphocytes with a mouse myeloma cell line is a relatively simple and reproducible alternative. Mouse-human hybrid cell lines were obtained in 205 (53%) of the microtiter wells initially seeded. Thirty-one (15%) of these hybrid cell lines secreted antibody of predefined specificity. Cloning was attempted with eight of the hybrid cell lines, and long-term antibody production was established in four of the lines: two hybridomas secreted antibody to the capsule of Haemophilus influenzae type b, one secreted antibody to tetanus toxoid, and one secreted antibody to diphtheria toxin. The production of mouse-human hybridomas appears to be a reliable method for obtaining human monoclonal antibody of predefined specificity.

Animals↗

Balanced rearrangements of the autosomes: results of a longitudinal study of a newborn survey population.

Thirty-six infants were identified by cytogenetic screening at birth as having balanced rearrangements of their autosomes, and 30 of them took part in a longitudinal study of their development, together with four of their affected sibs. With the exception of one child with a de novo reciprocal translocation who died, all children attended normal schools. Congenital malformations and short stature were present in only one child who had a de novo reciprocal translocation. The IQ scores of the 10 children with de novo translocations were significantly lower than those of the 20 children with familial translocations, but there were children in the de novo group of above average intelligence. Children with familial reciprocal translocations had significantly higher IQ scores than both the Robertsonian translocations and the controls, but the numbers in each category were small and a variety of different chromosomes were involved.

Adult↗

Relationship between the home environment and sensorimotor development of Down syndrome and nonretarded infants.

Thirteen Down syndrome and 19 nonretarded infants participated in a prospective, longitudinal study designed to investigate the effect of the home environment on sensorimotor development as assessed by infant tests and direct observation of behavior. The present paper is concerned with the age span from 6.5 to 24 months. The two groups did not differ on measures of the social environment obtained at 6.5 months but differed on such measures at 17 months. At 6.5 months, the amount of tactile stimulation, encouragement of postural control, and level of social stimulation were all related to concurrent test performance in both groups; characteristics of the inanimate environment were of longer-term predictive significance among the Down syndrome babies. At 17 months, mothers' referential speech was related to the developmental pattern from 6.5 to 24 months for the Down syndrome children. The Down syndrome children tended to explore objects as a solitary activity, whereas exploration was done within the interactional situation by the nonretarded subjects. An attempt at multiple prediction demonstrated the usefulness of an interactional approach, showing the joint predictive value of language behavior and mothers' referential speech. Of special concern was how slowness of development among Down syndrome children may be a factor producing changes in maternal behavior.

Adolescent↗

Amyloidosis in multiple myeloma or without apparent cause.

Thirty-two patients with primary amyloidosis (AL) either due to multiple myeloma or without apparent cause were studied. The most common manifestations were carpal tunnel syndrome and nephrosis. Rectal biopsy specimens showed amyloid infiltrates in 65% (15 of 23) of the patients studied, but virtually all biopsies of normal skin were negative. lambda Light chains were present in 75% (21 of 28) of patients with a monoclonal gammopathy. The median survival time was 14 months after histologic diagnosis, following a median delay of seven months from the recognition of disease by a physician. An earlier diagnosis would have been possible in most of the patients if the initial findings of amyloidosis had been recognized and evaluated definitively. The prognosis remains poor, because effective therapy is not available.

Amyloidosis↗

Neural crest cells: the role of extracellular matrix in their differentiation and migration.

This paper describes a two-pronged approach to the problem of skull development, tackling on the one hand cyto-differentiation and on the other, pattern formation and morphogenesis through the parameter of migration. Although clearly there are a number of questions still to be answered, it does seem that extracellular matrices are implicated in both aspects of the system. Cell interactions leading to chondrogenic differentiation are apparently matrix-mediated and the presence of type II collagen at the site of the interaction might indicate that it, possibly together with unidentified matrix molecules, has a causal role in such interactions. NC cell locomotion can be arrested by epithelially-derived matrix components causing an aggregation phenomenon. relationship between these two aspects of skull development may be closer than we've indicated. However, initially it will be necessary to define the full range and individual functions of the matrix components present during the events described.

Animals↗

The incidence of monoclonal proteins during 7 years of screening in a District General Hospital.

The aim of this study was to assess the incidence of monoclonal proteins, during a 7-year period, in the population served by a typical District General Hospital. 183,300 sera were electrophoresed and 804 monoclonal proteins were detected. Various biochemical prognostic criteria, such as the concentration of monoclonal protein, incidence of Bence-Jones protein and the presence of reduced polyclonal immunoglobulins, were studied in an attempt to assess the benign or malignant nature of the monoclonal protein. In this study, 75% of the patients with monoclonal proteins fulfilled at least one of these criteria, demonstrating the importance of long-term monitoring.

Adolescent↗