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Biomedical subjects

L A Johnson

Publications and source records attributed to L A Johnson.

At least 163 records · Page 9Linked to original sources

Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. III. Impaired dendritic differentiation of basket and stellate cells.

The effects of zinc deficiency and undernutrition on the dendritic differentiation of basket and stellate cells were studied in 21-day-old rats. A morphometric analysis of the dendritic branching of basket and stellate neurons was used that took into account the cell's position in the molecular layer. Zinc deficiency and undernutrition during the suckling period impaired the dendritic differentiation of cerebellar basket and stellate cells. The effects of zinc deficiency were not due totally to the reduced food intake of lactating dams. In the lower 65-75% of the molecular layer of zinc-deficient (ZD) pups, the dendritic field area, the total dendritic length and the number of branches per interneuron were reduced by 45-61%. In the lower 50-60% of the molecular layer, undernutrition reduced the dendritic field area, the total dendritic length and the number of branches per neuron by 32-44%. A comparison of ZD and undernourished (pair-fed) pups indicated that the dendritic field area and total dendritic length of neurons of ZD animals were 43% and 30% smaller in the lower half of the molecular layer. The number of branches per neuron was not significantly different between ZD and undernourished animals. The area of the soma was unaffected by dietary treatment. A delay in the onset of dendritic differentiation and a retarded rate of dendritic growth were considered possible mechanisms for the impaired dendritic differentiation.

Aging↗

Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections.

In a randomized comparative study, 116 patients with acute bacterial infections were treated with timentin (ticarcillin plus clavulanic acid) or a comparative agent (piperacillin for respiratory or urinary tract infections, and moxalactam for soft tissue infections). There were 91 clinically evaluated infections (timentin, 46; piperacillin, 29; moxalactam, 16). Twelve patients were bacteremic. A satisfactory clinical response occurred in all 46 patients treated with timentin and in 42 of the 45 treated with a comparative agent. Two clinical failures were due to superinfection (a Staphylococcus aureus pneumonia in the piperacillin group and an enterococcal skin infection in the moxalactam group), and one clinical failure was due to a primary S. aureus skin infection (moxalactam group). One wound isolate of Pseudomonas aeruginosa developed resistance to timentin during therapy (despite clinical improvement). Adverse reactions were uncommon but did include one patient treated with timentin who developed unexplained hallucinations.

Acute Disease↗

Neocarzinostatin versus m-AMSA or doxorubicin in hepatocellular carcinoma.

Sixty-one of 76 patients entered on a prospective randomized trial of neocarzinostatin ( NCZ ) versus m-AMSA or doxorubicin were eligible for analysis. Among these 61 patients at least one episode of severe toxicity was documented in 39% of patients on NCZ and 58% on m-AMSA. Fifty-one of the 61 patients were previously untreated with chemotherapy. Among these 51 patients objective response was documented in two of 25 patients treated with NCZ , none of 17 treated with m-AMSA, and one of nine treated with doxorubicin. Among previously untreated North American and European (NA/E) patients the median survival times were: NCZ 11 weeks and m-AMSA 12 weeks. The data on South African (SA) patients with similar entrance criteria entered on earlier Eastern Cooperative Oncology Group trials were analyzed with that from the randomized trial and show that for SA patients the median survival times were: NCZ , 11 weeks (31 patients); m-AMSA, 13 weeks (33 patients); and doxorubicin, 15 weeks (29 patients).

Aminoacridines↗

Carcinoids: the association of histologic growth pattern and survival.

There are five generally accepted carcinoid histologic growth patterns, i.e., insular, trabecular, glandular, undifferentiated, and mixed. To determine their possible prognostic significance, a panel of pathologists studied the growth patterns of 138 carcinoids collected from an Eastern Cooperative Oncology Group carcinoid advanced stage disease chemotherapy investigation. Survival times were measured from date of initial pathologic diagnosis of carcinoid disease to date of either death or last follow-up. Significant differences were observed in survival times between the five major growth patterns (P less than 0.001). Within the mixed growth pattern group, significant differences in survival time were also observed (P approximately 0.05). In decreasing order of median survival time in years, the growth patterns ranked as follows: mixed insular plus glandular, 4.4; insular, 2.9; trabecular, 2.5; mixed insular plus trabecular, 2.3; three pooled low incidence rate mixed growth patterns, 1.4; glandular, 0.9; and undifferentiated, 0.5. Histologic growth patterns are recommended as a stratification factor in future studies of this disease.

Aged↗

Quantification of the X- and Y-chromosome-bearing spermatozoa of domestic animals by flow cytometry.

The relative content of DNA in spermatozoa presumed to be the X- and Y-chromosome-bearing gametes from bulls, boars, rams and rabbits and the amount of DNA in spermatozoa of cockerels was determined by flow cytometry. Differences in the relative content of DNA and proportions of the presumed X- and Y-sperm populations in cryopreserved semen from Holstein, Jersey, Angus, Hereford and Brahman bulls were also determined. Spermatozoa were washed by centrifugation using a series of dimethyl sulfoxide solutions made in isotonic sodium citrate, fixed in ethanol, treated with papain and dithioerythritol to loosen the chromatin structure and remove cellular organelles, and stained quantitatively for DNA with the fluorochrome 4'-6-diamidino-2-phenylindole (DAPI). Approximately 5000 stained sperm nuclei, which were nonviable due to the removal of other cellular organelles during the washing procedure, were measured for DNA in an epi-illumination flow cytometer. A single distinct peak for cockerel spermatozoa and two symmetrical, overlapping peaks for species with X- and Y-spermatozoa were seen. This and other evidence strongly supports the interpretation that the peaks represent the X- and Y-sperm populations. The content of DNA in sperm nuclei from cockerels, bulls, boars, rams and rabbits, as determined by fluorescence flow cytometry, corresponded to biochemical estimates of DNA per sperm cell. Analyses of the bimodal histograms by computer-fitting two Gaussian distributions to the data showed the means of the peaks differed by 3.9, 3.7, 4.1 and 3.9% for bulls, boars, rams and rabbits, respectively. In four replicate analyses of semen from 25 bulls representing 5 breeds, the average population of sperm nuclei in the Y-peaks ranged from 49.5 to 50.5% for all breeds. The X-Y peak differences did not vary within each breed, but were significantly different when the breeds were compared. Spermatozoa from Jersey bulls had larger X-Y peak differences (P less than 0.001) than spermatozoa from Holstein, Hereford, and Angus bulls; spermatozoa from Brahman bulls had smaller X-Y differences (P less than 0.004). It is suggested from the evidence obtained in these studies that flow cytometry can be used to assess the proportion of X- and Y-spermatozoa in semen of domestic animals and is thereby applicable to verification of the effectiveness of enrichment techniques for X- or Y-spermatozoa.

Animals↗

Cimetidine-induced interstitial nephritis with response to prednisone therapy.

Acute renal failure developed in a patient after she received cimetidine therapy. A renal biopsy specimen showed acute interstitial nephritis. Withdrawal of cimetidine therapy led to improvement of renal function. Rechallenge with cimetidine occurred during prednisone therapy. Renal function continued to improve, but worsened when the treatment with these steroids was discontinued.

Acute Disease↗

Use of boar spermatozoa for artificial insemination. II. Fertilizing capacity of fresh and frozen spermatozoa in gilts inseminated either at a fixed time or according to Walsmeta readings.

A fertility trial was conducted comparing two methods of defining the optimum time to inseminate frozen boar semen. One hundred sixty-four gilts were inseminated, one-half at a fixed insemination time of 32 to 34 h after calculated onset of estrus and the remainder were inseminated on the basis of changes in the vaginal mucosal electrical resistance. Inseminations were made when the instrument (an inversely scaled ohmmeter) reading fell between 54 to 64 on a scale of 1 to 100. Both fresh and frozen boar semen were used. Pregnancy rates and live embryos/gilts from inseminations made at the fixed time and inseminations made on the basis of ohmmeter readings did not differ significantly for either fresh of frozen-thawed spermatozoa. Pregnancy rates and number of live embryos/gilt were significantly higher for gilts inseminated with fresh spermatozoa than for those inseminated with frozen-thawed spermatozoa (82%, 11.6 vs 61%, 8.2, respectively). Inseminations were conducted from January to September. Pregnancy rates were significantly higher for inseminations made for the first quarter or the year (January, February and March) than for inseminations made for the third quarter (July, August and September). No benefit was derived from using an ohmmeter to time insemination with frozen-thawed boar spermatozoa.

Animals↗

Use of boar spermatozoa for artificial insemination. III. Fecundity of boar spermatozoa stored in Beltsville liquid and Kiev extenders for three days at 18 C.

A field trial was conducted on several hundred farms in The Netherlands to compare the fertilizing capacity of boar spermatozoa stored for 1, 2, or 3 d at 18 C in either Kiev or Beltsville liquid extender (BL-1). Two storage volumes (25 and 100 ml) were used. Twelve Dutch Landrace boars, all in routine commercial artificial insemination service, provided the semen in twice-a-week collections. Over an 8-wk period in March and April, 1979, 2,849 sows and gilts were inseminated. Farrowing rates were higher (P less than .0001) with Kiev extender than with BL-1 extender (69.3 vs 60.5%) when semen was used over a 3 d period. The volume at which the semen was extended and stored had no effect on any parameter. Farrowing rate declined significantly when semen stored at 18 C for more than 2 d was used (74.5% vs 64.7% with semen stored for 1 and 3 in Kiev extender; 65.9% vs 52.7% with semen stored for 1 and 3 d in BL-1 extender). The farrowing rate, total number of pigs/litter and live pigs/litter were significantly higher for sows than for gilts inseminated with similar extended semen. On the basis of the results of this trial, Kiev extender appears to be more suitable as a diluent for liquid semen than does BL-1. AI with semen extended and stored for 3 d at 18 C can be expected to result in a lower farrowing rate than AI with semen stored for 1 or 2 d.

Animals↗

Fertility of stallions with abnormalities of the sperm acrosome.

During a 2-year period, 7 stallions were identified as having ejaculated spermatozoa characterized by a high incidence (27-74%) of acrosomal abnormalities. The most frequent abnormality of the acrosome was the 'knobbed sperm' defect which was observed in nigrosin--eosin, Giemsa, and haematoxylin and eosin stained semen smears under light microscopy, in buffered formal--saline and in glutaraldehyde-fixed wet mounts under phase contrast and differential interference microscopy, and in glutaraldehyde-fixed spermatozoa with electron microscopy and scanning electron microscopy. The defect was visible as a flattened apical ridge, tongue-like flap at the apical surface of the acrosome, or a bead-like protrusion from the apical ridge. A cystic swelling on the acrosomal surface was also seen in some electron micrographs of knobbed spermatozoa. Crater defects of the sperm nucleus were also present in the spermatozoa of 3 of 4 stallions examined by phase contrast, differential interference and electron microscopy. All the stallions sired foals; they achieved a pregnancy rate that ranged from 12.5 to 100% per oestrous cycle.

Acrosome↗

Use of spermatozoa for artificial insemination. I. Fertilizing capacity of fresh and frozen spermatozoa in sows on 36 farms.

A field trial was conducted on 36 farms in the Netherlands to compare the fertilizing capacity of fresh and frozen-thawed boar spermatozoa. Four-hundred and fifty-one sows were artificially inseminated with semen than that had been frozen and thawed according to the Beltsville Method or diluted in Kiev extender and inseminated on the day of collection. Twelve boars of the Dutch Landrace and Dutch Large White breeds were used. Farrowing rates, total number of pigs per litter and number of live pigs per litter were higher (P less than .0001) for sows inseminated with fresh semen than for sows inseminated with frozen-thawed semen (79.1%, 10.6 and 9.9 vs 47.0%, 7.4 and 7.1, respectively). Farrowing rates for sows inseminated with frozen-thawed semen were higher when semen from Dutch Large White boars was used than when semen from Dutch Landrace boars was used (58.6 vs 40.9%); the pattern reversed for insemination with fresh semen (76.5 vs 81%). Boar differences based on farrowing rate ranged from 62 to 92% for fresh semen and from 29 to 72% from frozen semen. There was no inseminator effect or farm effect on farrowing rate. On the basis of these results, frozen semen used for artificial insemination under practical circumstances can be expected to result in a farrowing rate about 30 percentage points lower and a litter size about three pigs smaller than does fresh semen.

Animals↗

Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma.

To evaluate the treatment of advanced islet-cell carcinoma, we randomly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil. Each regimen was given in five-day courses. The most frequent toxic effects were nausea and vomiting, mild and reversible renal toxicity, and bone-marrow depression with the combination regimen. The combination had advantages over streptozocin alone in overall rate of response (63 vs. 36 per cent) and in rates of complete response (33 vs. 12 per cent). There was no evidence of a preferential response among types of functional tumors. Objective responses were generally of long duration (median, 17 months) and of substantive clinical benefit. Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone (medians, 26 and 16 1/2 months), but this difference is not statistically significant. In spite of gastrointestinal side effects, streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma.

Adenoma, Islet Cell↗

2-hydroxyestradiol-17 alpha and 4-hydroxyestradiol-17 alpha, catechol estrogen analogs with reduced estrogen receptor affinity.

2-Hydroxyest radiol-17 alpha and 4-hydroxyestradiol-17 alpha, the catechol derivatives of estradiol-17 alpha, have reduced affinity for hypothalamic, pituitary, and uterine estrogen receptors, but retain a potency for interaction with catechol-0-methyltransferase equal to that of the natural, 17 beta-hydroxy catechols. This dissociation of receptor binding and catecholamine interactions may allow the use of the 17 alpha catechols as a probe for the mechanism of action of the catechol estrogens.

Amygdala↗

Regulation of purine de novo synthesis in cultured human fibroblasts: the role of P-ribose-PP.

Procedures for assaying the rate of purine de novo synthesis in cultured fibroblast cells have been compared. These were (i) the incorporation of [(14)C]-glycine or [(14)C]formate in alpha-N-formylglycinamide ribonucleotide (an intermediate in the purine synthetic pathway) and (ii) the incorporation of [(14)C]-formate into newly synthesised cellular purines and purines excreted by the cell into the medium. Fibroblast cells, derived from patients with a deficiency of hypoxanthine phosphoribosyltransferase (HPRT-) (EC 2.4.2.8) and increased rates of purine de novo synthesis, were compared with fibroblasts from healthy subjects (HPRT+). Fetal calf serum, which was used to supplement the assay and cell growth medium, was found to contain sufficient quantities of the purine base hypoxanthine to inhibit purine de novo synthesis in HPRT+ cells. This inhibition was the basis of differentiation between HPRT- and HPRT+ cells. In the absence of added purine base, both cell types had similar capacities for purine de novo synthesis. This result contrasts with the increased rates of purine de novo synthesis reported for a number of human HPRT- cells in culture but conforms recent studies made on human HPRT- lymphoblast cells. The intracellular concentration and utilisation of 5-phosphoribosyl-1-pyrophosphate (P-Rib-PP), a substrate and potential controlling factor for purine de novo synthesis, were determined in HPRT- and HPRT+ cells. The rate of utilisation of P-Rib-PP in the salvage of free purine bases was far greater than that in purine de novo synthesis. Although HPRT- cells had a 3-fold increase in P-Rib-PP content, the rate of P-Rib-PP generation was similar to HPRT+ cells. Thus, in fibroblasts, the concentration of P-Rib-PP appears to be critical in the control of de novo purine synthesis and its preferential utilisation in the HPRT reaction limits its availability for purine de novo synthesis. In vivo, HPRT+ cells, in contrast to HPRT- cells, may be operating purine de novo synthesis at a reduced rate because of their ability to reutilise hypoxanthine.

Adenine↗