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Biomedical subjects

L Johnson

Publications and source records attributed to L Johnson.

At least 361 records · Page 20Linked to original sources

The screening of Duchenne muscular dystrophy patients for submicroscopic deletions.

We have probed the DNA of 156 Duchenne muscular dystrophy (DMD) patients, representing 140 kindreds, with cloned DNA sequences derived from Xp21 and known to show deletions in some DMD patients. Sixteen cases showed a deletion, as defined by lack of hybridisation to one or more of the four probes used. However, two of these cases were brothers, so 15 independent deletions (10.7%) are represented. The deletion map is compatible with the suggested order for the sites of the probes used in the study, that is, telomere----pERT87.15----pERT87.8----pERT87.1----pX J1.1----754----centromere. Further mapping of these deletions and characterisation of the deletion breakpoints should facilitate more accurate molecular localisation of the gene or genes which, when mutated, are responsible for causing DMD.

Chromosome Deletion↗

Linkage studies in Duchenne and Becker muscular dystrophies.

We have studied the inheritance of four cloned DNA sequences which recognise restriction fragment length polymorphisms on the short arm of the X chromosome in families with Becker and Duchenne muscular dystrophy. We have confirmed linkage of two probe loci to the disease loci and have combined our results with those previously published to give a maximum lod score of 11.642 at a recombination fraction of 0.15 for DXS41 (probe 99.6), and a maximum lod of 15.84 at a recombination fraction of 0.15 for DXS84 (probe 754). Linkage of these diseases to the loci defined by the pERT87 probes and probe pXJ1.1 has also been studied, giving maximum lod scores of 8.634 and 5.118 at recombination fractions of 0.02 and 0.00 respectively. The information obtained using these polymorphic DNA markers, combined with pedigree and CK data, can be used to give more accurate genetic counselling to women at risk in Becker and Duchenne families.

DNA↗

Characterization of the testicular abnormality in 5 alpha-reductase deficiency.

The testes of five phenotypic women (from four families) with 5 alpha-reductase deficiency were studied. In one of the patients, the enzyme deficiency was similar in the testis and epididymis and in fibroblasts cultured from the labia majora. In testes from four of the patients, the concentrations of the 5 alpha-reduced steroids dihydrotestosterone and 3 alpha-androstanediol were less than 10% of those in normal subjects. We conclude that the testis is involved in 5 alpha-reductase deficiency. Impaired spermatogenesis was evident in testicular biopsies from all five subjects, and in two, sperm production, as estimated in testicular homogenates, was less than 10% of normal. The extent to which spermatogenic arrest is due to 5 alpha-reductase deficiency or testicular maldescent is not clear.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Annual cycle of the Sertoli cell population in adult stallions.

Stereological methods were employed in two experiments with adult stallions: to confirm seasonal variation in number of Sertoli cells and to characterize the annual cycle of the Sertoli cell population. In the first experiment, testes from 28 adult (4-20 years old) horses obtained in the non-breeding season (December-January) were compared to testes from 28 adult horses in the breeding season (June-July). Sertoli cell numbers were calculated from the nuclear volume density, parenchymal volume, and volume of an individual Sertoli cell nucleus determined by reconstruction of serial sections or from average height and width measurements. The number of Sertoli cells per testis was significantly greater in the breeding season. In a second experiment involving 43-48 adult horses in each 3-month period, the Sertoli cell population was higher (P less than 0.05) in May-July than other periods and higher (P less than 0.01) than in November-January. These combined studies confirm seasonal differences in the Sertoli cell numbers per testis and define the annual cycle of the Sertoli cell population in adult stallions.

Animals↗

Concentrations of prolactin, luteinizing hormone and follicle stimulating hormone in pituitary and serum of horses: effect of sex, season and reproductive state.

Pituitary and serum from 86 male or female horses of various reproductive states were collected in the normal breeding season (summer) and in the nonbreeding season (winter) at a commercial slaughterhouse. Concentrations of prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassay. Concentrations of pregnant mare serum gonadotropin and reproductive steroids in serum and gross appearance of the reproductive tract and gonads were used to catagorize reproductive state. Concentrations of PRL were higher (P less than .01) in summer than in winter in pituitary and serum of mares, stallions and geldings. In summer, mares had higher (P less than .01) concentrations of PRL in serum than stallions. In mares, concentrations of LH in pituitary were higher (P less than .05) in summer than in winter. Concentrations of LH in serum were higher (P less than .01) in summer than in winter in mares and geldings, higher (P less than .01) in mares than in stallions in summer, higher (P less than .01) in geldings than in stallions in summer and higher (P less than .01) in mares with low serum progesterone (P) concentrations than in mares with high P concentrations in summer. Concentrations of FSH in pituitary and serum did not differ between summer and winter for any type of horse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Timentin versus piperacillin in the therapy of serious urinary tract infections.

In a comparative study, 47 patients received Timentin, a combination of ticarcillin plus clavulanic acid, or piperacillin to treat serious urinary tract infections. Thirty-nine infections in 38 patients were clinically evaluable (21 in the Timentin-treated group and 18 in the piperacillin-treated group). These included pyelonephritis (10 in the Timentin-treated group and five in the piperacillin-treated group), bladder infections with sepsis (11 in the Timentin-treated group and 11 in the piperacillin-treated group) and bladder infections without fever (two in the piperacillin-treated group). The addition of clavulanic acid to ticarcillin greatly enhanced the susceptibility of five of the 28 evaluable pathogens in the Timentin-treated group (two Escherichia coli isolates, two Staphylococcus aureus isolates, and one Klebsiella pneumoniae isolate). The minimal inhibitory concentrations at which 50 and 90 percent of the bacterial growth was inhibited were 4 and 64 micrograms/ml, respectively, for Timentin, and 4 and 32 micrograms/ml, respectively, for piperacillin. All evaluable patients had a satisfactory symptomatic response at the end of the trial. Of 28 evaluable pathogens treated with Timentin, 18 were eradicated up through the one-week post-therapy evaluation period; of 27 evaluable pathogens treated with piperacillin, 18 were eradicated up through the same time period. Eradicated pathogens included E. coli (six of 13 in the Timentin-treated group and six of 11 in the piperacillin-treated group), other Enterobacteriaceae (three of three in the Timentin-treated group and eight of 10 in the piperacillin-treated group), Pseudomonas aeruginosa (two of four in the piperacillin-treated group), enterococcus (two of three in the Timentin-treated group and two of two in the piperacillin-treated group), staphylococcal species (four of five in the Timentin-treated group), and other organisms (three of four in the Timentin-treated group). Resistance did not develop in any of the persisting pathogens. Adverse effects thought possibly to be related to the study drugs were minimal and included rash in one Timentin-treated patient and diarrhea in another.

Adult↗

Use of monoclonal antibodies to analyse the expression of a multi-tubulin family.

We have used a panel of monoclonal antibodies in a study of the expression of multiple tubulins in Physarum polycephalum. Three anti-beta-tubulin monoclonal antibodies, DM1B, DM3B3 and KMX-1 all reacted with the beta 1-tubulin isotypes expressed in both myxamoebae and plasmodia. However, these antibodies showed a spectrum of reduced reactivity with the plasmodial beta 2-tubulin isotype - the competence of recognition of this isotype was graded DM1B greater than KMX-1 greater than DM3B3. The anti-alpha-tubulin monoclonal antibody, YOL 1/34 defined the full complement of Physarum alpha-tubulin isotypes, whilst the anti-alpha-tubulin monoclonal antibody, KMP-1 showed a remarkably high degree of isotype specificity. KMP-1 recognises all of the myxamoebal alpha 1-tubulin isotypes but only recognises 3 out of the 4 alpha 1-tubulin isotypes expressed in the plasmodium (which normally focus in the same 2D gel spot). KMP-1 does not recognise the plasmodial specific alpha 2-tubulin isotype. This monoclonal antibody reveals a new level of complexity amongst the tubulin isotypes expressed in Physarum and suggests that monoclonal antibodies are valuable probes for individual members of multi-tubulin families.

Antibodies, Monoclonal↗

Evidence for a conformational change in deglycosylated glycoprotein hormones.

Removal of long-chain asparagine-linked carbohydrates leads to loss of receptor-effector coupling in gonadotropin target tissue. This implies a direct interaction between carbohydrate and cell membrane components. To examine other mechanisms by which carbohydrate could activate post-receptor events, we have used sequence-specific and conformation-specific alpha-subunit radioimmunoassays as probes for conformational changes in deglycosylated choriogonadotropin and follitropin. Immunoreactivity of either hormone was enhanced 8-13-fold after removal of carbohydrate by anhydrous hydrogen fluoride. Removal of sialic acid alone had little effect on reactivity. Based on the specificity of the antisera, the effect could be localized to a region in the amino-terminus remote in the linear sequence from actual sites of carbohydrate attachment. The results suggest that a conformational change in the alpha-subunit could account, at least in part, for the observed effects of deglycosylation on glycoprotein hormone action.

Amino Acid Sequence↗

The nature of immunity to Snyder-Theilen fibrosarcoma virus induced tumors in cats.

Snyder-Theilen fibrosarcoma virus (ST-FeSV) induced tumors evoked a vigorous immune response in adolescent cats. The response was characterized histologically by a lymphoid and histiocytic cell infiltrate beginning around the 9th day post inoculation. Hyperemia edema, hemorrhage, and necrosis of the tumors occurred shortly thereafter. Gross regression of the tumors commenced around the 15th day. Viable fibrosarcoma cells could be recovered as almost pure cultures from tumors biopsied on the 9th day. Biopsies taken between days 9 and 15 contained progressively fewer tumor cells and increasing numbers of lymphoid cells, histiocytes, giant cells, and normal fibroblasts. Tumor cells in such mixed cultures did not replicate as fast as normal and died out within 7 to 14 days. Viable tumor cells were not recovered from biopsies taken after day 15. Fibrosarcoma regression was associated with the appearance of tumor cell specific cytotoxic lymphocytes and antibodies in the blood. Cell mediated immunity, as determined by a chromium release assay, consisted of both antibody dependent and independent mechanisms. Fluorescent and complement dependent cytolytic antibodies were detected in the blood at the same time as cytotoxic lymphocytes, but persisted after regression. In a preliminary experiment, serum from tumor regressor cats was injected into susceptible kittens, and the kittens were then challenged with ST-FeSV transformed fibroblasts or whole FeSV. Immune serum did not prevent the appearance of initial growth of tumors, but did slow their subsequent growth and increased the rate of regression. Immune serum had a much more dramatic inhibitory effect on the accompanying retrovirus infection.

Animals↗

Vitamin E and retinopathy of prematurity. Follow-up at one year.

Five hundred forty-five infants weighing less than 1501 g at birth were entered into a randomized, prospective study to determine the effect of high serum levels (5 mg/dL) of vitamin E used prophylactically to try to prevent or alter the natural course of retinopathy of prematurity (ROP) and its sequel, retrolental fibroplasia (RLF). Three hundred twenty-eight infants were available for the one- to two-year eye examination. Although there was a trend (P = 0.072) toward less severe RLF among vitamin E-treated infants, the incidence of RLF was 11/162 (6.8%) in the placebo treated (P) infants, and 12/166 (7.2%) in the vitamin E-treated (E) infants. The incidences of hyperopia, myopia, anisometropia, strabismus and amblyopia were also similar in both the P and E groups.

Cicatrix↗

On the subject of subjects: suggestions for describing subjects in language intervention studies.

Recent child language intervention literature was analyzed to determine the content and consistency of subject descriptions. The amount and type of descriptive information varied widely both within and among journals. In view of the potential importance of such descriptions and the apparent lack of standards for acceptability, suggestions were developed and forwarded as a working model for describing language-handicapped children in intervention studies.

Adolescent↗

Characterization of a pigment-dispersing hormone in eyestalks of the fiddler crab Uca pugilator.

A pigment-dispersing hormone (PDH) from eyestalks of the fiddler crab Uca pugilator has been purified by gel filtration, ion-exchange chromatography, partition chromatography, and reversed-phase liquid chromatography. Based on automated gas-phase sequencing and subsequent identification of carboxyl-terminal amide, we have assigned the primary structure of this peptide as Asn-Ser-Glu-Leu-Ile-Asn-Ser-Ile-Leu-Gly-Leu-Pro-Lys-Val-Met-Asn-Asp-Ala-NH (2). We have confirmed the sequence by synthesizing this peptide and demonstrating that the synthetic PDH and the native PDH display identical chromatographic behavior and biological activity. This hormone is a member of a family of invertebrate neuropeptides that includes a light-adapting/pigment-dispersing octadecapeptide hormone from the prawn Pandalus borealis. In assays for melanophore pigment dispersion in destalked fiddler crabs, Uca PDH was 21-fold more potent than Pandalus PDH. These two hormones share a hexapeptide core sequence (residues 5-10: -Ile-Asn-Ser-Ile-Leu-Gly-) as well as the amino- and carboxyl-terminal residues but differ at positions 3, 4, 11, 13, 16, and 17. These results point to speciesrelated or group-specific structural differences among crustacean PDHs.

Journal Article↗

Hyperprolactinemia inhibits development of Leydig cell tumors in aging Fischer rats.

In inbred CDF (Fischer 344) male rats autopsied at the age of 18-24 months, testicular tumors were present in 24 of 36 control animals but in none of 28 males rendered hyperprolactinemic by transplantation of anterior pituitaries from adult females under the renal capsules. In another experiment, microscopically detectable Leydig cell adenomas were present in each of 11 control animals at the age of 14.5 months but in none of 11 males in which hyperprolactinemia was induced by treatment with diethylstilbestrol. Development of testicular tumors had initially little effect on basal and hCG-stimulated plasma testosterone and androstenedione levels but eventually led to atrophy of the seminal vesicles. Incubated tumor tissue produced large quantities of progesterone and responded to hCG in vitro by an increase in progesterone but not testosterone secretion. Daily sperm production and epididymal sperm reserves were significantly reduced already during early stages of Leydig cell tumor development. We propose that hyperprolactin prevents development of Leydig cell tumors by suppression of plasma LH levels and suggest that age-related reductions in gametogenic and steroidogenic functions of the testes in Fischer rats are due to development of Leydig cell tumors rather than to aging per se.

Age Factors↗