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Biomedical subjects

M C Young

Publications and source records attributed to M C Young.

At least 55 records · Page 3Linked to original sources

170H-progesterone rhythms in congenital adrenal hyperplasia.

Serial blood spot and saliva samples were collected at home by 18 patients being treated for congenital adrenal hyperplasia to determine the circadian rhythm of 170H-progesterone as an index of therapeutic control. There was a strong correlation between the magnitude of the circadian fall and a single morning measurement of the plasma testosterone concentration taken near the time of the 170H-progesterone rhythm samples. Poor control in pubertal girls produced an exaggerated circadian fall in 170H-progesterone concentrations that were raised at all sampling times. Optimal control (plasma testosterone 1.5-2.5 nmol/l) was associated with blood spot and salivary 170H-progesterone concentrations at 0800 hours of between 30-70 nmol/l and 260-1000 pmol/l, respectively, falling thereafter to less than 10 nmol/l and less than 150 pmol/l, respectively. Similar results were obtained in prepubertal patients. Nomograms have been constructed to interpret the daily profiles of blood spot or salivary measurements of 170H-progesterone, or both. The analysis of 170H-progesterone circadian rhythms is useful in monitoring treatment in patients with congenital adrenal hyperplasia, particularly those who may be overtreated.

17-alpha-Hydroxyprogesterone↗

Androstenedione rhythms in saliva in congenital adrenal hyperplasia.

Serial samples of saliva were collected at home by 17 patients being treated for congenital adrenal hyperplasia to determine the circadian rhythm of androstenedione as an index of therapeutic control. Single samples of blood for measurement of plasma testosterone, 170H-progesterone, and androstenedione concentrations were collected from these and a further seven patients for comparison. Plasma androstenedione concentrations showed a close correlation with plasma concentrations of 170H-progesterone and testosterone. There was a strong correlation between the salivary androstenedione profiles and plasma testosterone concentrations in pubertal girls. Concentrations of androstenedione in saliva decreased during the day but remained raised at each sampling time in relation to plasma testosterone concentrations. Salivary androstenedione profiles are shown as nomograms to distinguish the degree of therapeutic control. The concentration of androstenedione, measured in plasma or saliva, is an alternative marker to monitor control of treatment in congenital adrenal hyperplasia. The measurement in saliva is a useful index of androgen production when blood sampling is difficult.

Adolescent↗

Thoracic outlet syndrome with congenital pseudarthrosis of the clavicle: treatment by brachial plexus decompression, plate fixation and bone grafting.

Although a number of cases of congenital pseudarthrosis of the clavicle have been described in the literature, they provide little direction for the treatment of this condition when it is associated with thoracic outlet syndrome. The authors describe their experience with such a case in a 20-year-old woman. Symptoms of pain in the ulnar distribution of the right forearm and discoloration of the hand with abduction of the extremity had developed over 3 years. The radial pulse was obliterated by abduction of the arm. Exploration of the brachial plexus revealed a constricting band arising from the distal fragment of the clavicle running to the first rib which, together with the mass of the pseudarthrosis, comprised the thoracic outlet. The patient was successfully treated by division of the fibrous band, reduction of the clavicle, internal fixation with a plate and iliac crest bone grafting. At follow-up the patient had a full range of motion in the shoulder and was asymptomatic.

Adult↗

Congenital murine polycystic kidney disease. I. The ontogeny of tubular cyst formation.

In the current study, the ontogeny of tubular cyst formation was studied in the CPK mouse, a murine strain with autosomal recessive polycystic kidney disease. Utilizing the technique of intact nephron microdissection in addition to standard light and transmission electron microscopy, the earliest morphologic alterations in CPK kidneys were localized in fetal tissue at 17 days of gestation to the distal portion of developing proximal tubules. During disease progression, from birth to 21 days of postnatal age, there was a shift in the site of cystic nephron involvement from proximal tubule to collecting tubules without involvement of other nephron segments. Cysts were enlarged tubular segments which remained in continuity with other portions of the nephron and were not associated with abnormalities in the overall pattern of nephron growth or differentiation. Analysis suggested that alterations in transtubular transport in abnormally shortened proximal tubular segments of juxtamedullary nephrons may have pathogenic importance in the early stages of cyst formation, and that epithelial hyperplasia and cytoskeletal alterations may have a role in progressive proximal tubular cystic enlargement. Cellular hyperplasia of epithelial walls of normally formed tubules was a prominent feature of cyst formation and progressive enlargement in collecting tubules. Such data form the basis for future studies into specific pathophysiological processes which may be operative in specific nephron segments during different stages of cyst formation in the CPK mouse.

Animals↗

Osteochondral disruption of the second metatarsal: a variant of Freiberg's infraction?

A case of Freiberg's Infraction of the second metatarsal is presented. The metatarsal head was resected and its pathology proved very informative. Necrotic bone was not found, but a shearing type of separation was identified at the level of "tidewater mark" in the articular cartilage and was the major observation. This suggested the possibility that in adults Freiberg's Infraction rather than true avascular necrosis may be in fact the result of a shearing-compression type of injury occurring at the interface between mineralized and nonmineralized articular cartilage (tidewater mark). An anatomical examination of metatarsophalangeal joints in cadavers showed that during walking at the "toe off" position, the toes dorsiflex to force the metatarsal head into plantar flexion. The proximal phalanges ride dorsally over the metatarsal heads producing a shearing force that would support our interpretation of the observations made in the case presented.

Ankle Injuries↗

Site of protein digestion in steers fed sorghum grain diets. I. Effect of level of feed intake.

Two digestion trials were conducted with seven crossbred, abomasally cannulated yearling steers (400 kg) to study the effect of level of feed intake on the site and extent of feed and microbial protein digestion. Steers, in a crossover design experiment, were fed an 81.5% steam-processed flaked (SPF) sorghum grain diet at either 95% (four steers) or 75% (three steers) of their ad libitum intakes. At the end of the first trial, steers were switched to the opposite treatment. Dysprosium (31 to 32 micrograms/g) was used as an external marker. Feed, abomasal contents and fecal grab samples were taken at 12-h intervals advancing by 2 h each day over a 6-d total fecal collection period. Organic matter (OM) intakes were 6,102 and 4,570 g for the two treatments. Higher level of intake increased (P less than .05) quantities of OM, crude protein and trichloroacetic acid precipitable protein entering the small intestine, digested post-ruminally and digested in the total tract. The higher level of intake decreased (P less than .05) the percentage of bacterial protein (BP) present in the abomasum and percent post-ruminal BP digestion; however, the amounts of BP and non-BP entering the small intestine and digested post-ruminally were greater (P less than .05) in steers fed 95% ad libitum. Most of the feed protein was degraded in the rumen with both treatments. Predicted true feed protein digestibilities were 91.1 and 91.7% for 95 and 75% of ad libitum intakes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Site of protein digestion in steers fed sorghum grain diets. II. Effect of grain processing methods.

Seven crossbred, abomasally fistulated yearling steers (400 kg) were used in two digestion trials (crossover design) to study the effect of processing sorghum grain on the site and extent of feed and microbial protein digestion. Steers were fed an 81.5% sorghum grain diet in which the grain was either dry-rolled (DR; four steers) or steam-processed, flaked (SPF; three steers). At the end of the first trial steers were switched to the opposite treatment. Dysprosium (21 to 23 micrograms/g of feed) was used as a digesta marker. Feed, abomasal contents and fecal grab samples were collected at 12-h intervals during a 6-d total fecal collection period. Organic matter (OM) intake for SPF and DR grain diets averaged 6,426 and 6,787 g/d, respectively. Compared with DR, SPF increased (P less than .05) the apparent total digestibility and ruminal digestibility of OM. Trichloroacetic acid precipitable protein consumed by the steers was lower (P less than .05) for SPF than the DR treatment. Processing method had no effect on ruminal digestion of crude protein (CP), bacterial protein (BP) synthesis, quantity of CP entering the small intestine or on total digestion of feed protein. There was a trend for increased total and post-ruminal digestion of CP with the SPF diet. Post-ruminal digestion of BP was increased (P less than .05) by SPF grain as compared with DR. Percentage of non-BP digested ruminally, post-ruminally or in the total tract was not significantly affected by processing method.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Induction of IgG and IgE synthesis in normal B cells by autoreactive T cell clones.

During the course of generating tetanus toxoid (TT)-specific T cell clones frm an HLA-DR2,7 donor, four clones were obtained which proliferated in the presence of autologous monocytes alone without the addition of TT antigen. This proliferation was specifically inhibited by anti-HLA-DR framework mouse monoclonal antibody, and appeared to be HLA-DR-restricted. Two of the clones proliferated in response to HLA-DR2-bearing monocytes, and the other two clones proliferated in response to HLA-DR7-bearing monocytes. The capacity of these four autoreactive human T cell helper clones to induce IgE synthesis in B cells was studied. All four clones stimulated autologous peripheral blood B cells to synthesize IgE and IgG antibody. Induction of IgE synthesis in B cells by the autoreactive T cell clones followed the same pattern of HLA-DR restriction which governed the proliferative response of these clones. These results suggest that the interaction of autoreactive helper T cells with B cell HLA-DR antigens may be important in the activation of IgE immune responses in humans.

B-Lymphocytes↗

Induction of IgE synthesis in normal human B cells. Sequential requirements for activation by an alloreactive T cell clone and IgE-potentiating factors.

Two human alloreactive T cell clones were established from a one-way mixed lymphocyte culture involving two nonatopic donors, and were assessed for their capacity to induce IgE synthesis by B cells obtained from the original stimulator. The two alloreactive T cell clones studied induced IgG but not IgE synthesis in normal B cells. However, one of the two clones, clone 2H6, induced IgE synthesis in the presence of supernatants from T cell lines derived from patients with the hyper-IgE syndrome (HIE), and enriched for T cells bearing receptors for IgE. These supernatants by themselves caused no IgE synthesis in nonatopic B cells. The potentiating factors in these supernatants were shown to bind to IgE. Time sequence experiments indicated that interaction of the B cells with the alloreactive clone 2H6 renders them responsive to the action of the IgE-potentiating factors. These results indicate that induction of IgE synthesis in normal B cells involves at least two sequential T cell derived signals. Furthermore, T cell clones are heterogenous in their capacity to provide these signals.

B-Lymphocytes↗

Percutaneous bone marrow grafting of fractures and bony defects. An experimental study in rabbits.

Since bone marrow has been shown to contain osteoprogenitor cells, an experiment was devised to test its effects when injected percutaneously into osteotomies and 2-cm bony defects produced in rabbit radii. The parameters tested included callus volume, breaking load, tensile strength, and cross-sectional area of callus at the fracture or bony defect site. At two weeks postgrafting callus volume was significantly higher (p less than 0.01) in the grafted radii than in the contralateral saline controls. By four weeks all four parameters were significantly greater in the bone marrow grafted radii than in the contralateral saline controls. Serial radiographs and histology confirm this advanced fracture healing in the grafted bones. The earlier and more abundant callus, at the bone marrow grafted sites, was felt to provide earlier and greater stability, resulting in decreased early healing time when contrasted with the saline controls. Similarly, the bony defects that were grafted with bone marrow united by a bony bridge, whereas the saline controls did not. Percutaneous bone marrow grafting is a simple semi-invasive technique that may have potential clinical applications.

Animals↗

Trichostasis spinulosa.

Trichostasis spinulosa is a common disorder of follicular hyperkeratosis that is often confused clinically with similar disorders, such as keratosis pilaris and eruptive vellus hair cysts. Six patients from the UTMB dermatology clinic who had trichostasis spinulosa are presented. Two of the six also had keratosis pilaris and one had eruptive vellus hair cysts. The present study was undertaken to compare and contrast the clinical presentation and histopathologic appearance of these three disorders. The results of the study and review of the literature revealed differences in distribution of lesions and microscopic appearance of follicular and histopathologic material.

Adult↗

Secretion of IgE-specific potentiating factors by human Fc epsilon R+ T cell lines.

In the present study, Fc epsilon R+ and Fc epsilon R- T cells were isolated from patients with the hyper-IgE syndrome and maintained in long-term cultures with interleukin 2. Supernatants from the Fc epsilon R+ but not from the Fc epsilon R- T cell lines enhanced IgE but not IgG synthesis in B cells derived from patients with allergic rhinitis. There was, however, no induction of IgE synthesis in B cells from nonatopic donors. The IgE-potentiating factors bound to IgE-Sepharose but not to IgG-Sepharose. The target B cells for these IgE binding factors appear to be preactivated IgE-bearing B cells.

B-Lymphocytes↗

A human T cell lymphoma secreting an immunoglobulin E specific helper factor.

An 8-yr-old nonallergic girl with non-Hodgkin's lymphoma had markedly elevated serum IgE at presentation (greater than 10,000 IU/ml), negative skin tests to a battery of 24 common allergens, and no evidence of parasitic infestation. Serum levels of IgG, IgA, and IgM were normal. Remission after cytotoxic chemotherapy was accompanied by a marked reduction in serum IgE levels (to less than 200 IU/ml) with no change in the level of serum IgG, IgM, or IgA. Recurrence of the lymphoma 7 mo after remission was accompanied by an isotype specific rise in serum IgE (to 3,850 IU/ml). Isoelectric focusing revealed that the IgE was polyclonal. Phenotypic analysis of the lymphoma obtained during relapse revealed all (greater than 98%) cells to be T3+, T4+, and T8+. Incubation of lymphoma cells with human myeloma IgE followed by immunosorbent purified fluorescein tagged goat anti-human IgE (anti-IgE PS-adsorbed over IgE ADZ) stained 25% of the cells. In contrast, less than 1% of the cells were stained after incubation with human IgG followed by fluorescein conjugated goat anti-human IgE. Supernatants from lymphoma cells (5 X 10(6)/ml, 48 h) enhanced IgE production in B cells derived from four patients with allergic rhinitis (mean +/- SD picograms per milliliter of net IgE 930 +/- 320 in unstimulated cultures versus 2,450 +/- 650 in cultures stimulated with lymphoma supernatants; P less than 0.01) but did not induce IgE synthesis in B cells from two normal subjects that synthesized no IgE spontaneously. Lymphoma supernatants failed to enhance IgG synthesis by B cells of both allergic and nonallergic subjects. These results indicate that a T cell lymphoma comprised of cells bearing Fc receptors for IgE with a phenotype characteristic of immature T cells (i.e., T3+, T4+, T8+) exhibited IgE specific helper function. This lymphoma may represent the monoclonal expansion of a subpopulation of IgE specific helper T cells.

Antigens, Differentiation, T-Lymphocyte↗

Production of IgE-potentiating factor in man by T cell lines bearing Fc receptors for IgE.

The regulation of human IgE production in vitro by soluble T cell factors was examined. T cells were isolated from the peripheral blood of 2 patients with the hyper-IgE syndrome on the basis of their expression of Fc receptors for human IgE (Fc epsilon R). The T cells were incubated with human myeloma IgE (10 micrograms/ml), washed, reacted with immunosorbent-purified goat anti-human IgE conjugated with fluorescein isothiocyanate, and then separated into Fc epsilon R+ and Fc epsilon R- T cells on the fluorescence-activated cell sorter. Fc epsilon R+ T cells and Fc epsilon R- T cells were propagated in culture using supernatants of phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) and irradiated autologous PBMC. Supernatants of Fc epsilon R+ T cell lines but not of Fc epsilon R- T cell lines selectively enhanced IgE synthesis in cultures of B cells obtained from patients with allergic rhinitis but not from normal nonallergic subjects. The surface phenotype of the Fc epsilon R+ T cell line was predominantly T3+, T4+, Ia+ with few (15%) T8+ cells. Two T cell clones were grown from the Fc epsilon R+ T cell line by limiting dilution (0.3 cells/well). These clones possessed the T4+ helper/inducer phenotype and secreted IgE-enhancing factor(s). The IgE-enhancing factor(s) which had affinity for insolubilized human IgE was sensitive to treatment with trypsin and neuraminidase, and had as its target an IgE-bearing B cell. These results suggest that a subset of human T cells bearing an Fc epsilon R secretes an IgE-binding glycoprotein which selectively enhances IgE synthesis by IgE-bearing B cells.

Adult↗

Identification of high-affinity phorbol ester receptor in cytosol of EL4 thymoma cells: requirement for calcium, magnesium, and phospholipids.

A specific high-affinity phorbol ester binding component has been identified in the cytosol of an EL4 mouse thymoma line by using conditions similar to those for demonstrating activity of a calcium/phospholipid-dependent protein kinase. Specific binding is absolutely dependent on acidic phospholipids (maximal binding at 96 micrograms of phosphatidylserine per ml or 200 micrograms of phosphatidylinositol per ml) and is greatly enhanced by addition of calcium (0.5 mM) and magnesium (75 mM). Scatchard analysis of the cytosolic binding component indicated a Kd of 4.2 +/- 2.5 nM with 1.8 +/- 0.6 x 10(4) sites per cell compared to a Kd of 11.9 +/- 4.4 nM and 4.1 +/- 1.0 x 10(4) sites per cell for the membrane receptor. Consistent with the existence of at least two phorbol ester binding sites in EL4 cells was the observation of curvilinear Scatchard plots for binding to whole homogenates. The cytosolic binding showed the same order of potency for binding phorbol ester analogs as has been observed for intact cells. These results further support the similarity between phorbol ester receptors and the calcium/phospholipid-dependent protein kinase and suggest that the cytosolic receptor may be involved in subsequent phorbol ester effects in EL4 cells including loss of the kinase activity from the cytosol and production of T-cell growth factor.

Animals↗

[Humoral and cell-mediated immunities in epileptic patients (author's transl)].

Humoral and cell-mediated immunities were studied in 50 epileptic patients receiving phenytoin treatment and in 20 normals. The mean serum concentrations of IgG, IgA and IgM showed no significant difference between these two groups; however, abnormally low serum IgA (less than 125 mg/dl) was found in 10 patients (10/50, 20%) and in one of them serum IgA was less than 50 mg/dl (1/50, 2%). The serum IgA was related neither to the duration of phenytoin therapy nor to the serum concentration of the drug. The mean serum C3 value was lower in the patient group than in the normals. The mean percentages of T cells, Tmu cells, T gamma cells and monocytes were also lower in the patients, especially in those with serum level of phenytoin over 20 micrograms/ml. These data indicate that phenytoin can suppress the cell-mediated immunity, whereas certain genetic factors, in addition to the effect of phenytoin, may contribute to the change of serum immunoglobulin levels in the epileptics. The incidence of positive antinuclear antibody among the epileptics was 18%, which was much higher than that in the general population. The occurrence of autoantibody did not correlate with the serum concentration of phenytoin.

Adolescent↗

Immune suppression to nucleosides: differences between NZB and NZW mice.

Previous studies (Y. Borel and M.C. Young, Proc. Natl. Acad. Sci. USA 1980 77: 1593) have shown that one can raise nucleic acid-specific suppressor T cells which diminish either the T-dependent immune response in vivo or the T-independent immune response in vitro. The results presented here confirm and extend these observations in several different strains of mice. Administration of nucleoside-modified spleen cells diminishes antibody-forming cells to nucleoside in mice immunized with nucleoside linked to keyhole limpet hemocyanin (KLH), Immune suppression was obtained in all strains except SJL and NZW, which are known to be high responders to denatured DNA. Both the primary and secondary immune responses were suppressed in C57BL/6 mice. Autologous cells exhibit a different ability to function as carriers. Spleen cells are the most effective, and to a certain extent, thymus cells. In contrast, bone marrow cells and red cells fail to induce immune suppression. A strain difference was found between NZB and NZW mice in their susceptibility to immunosuppression by nucleoside-modified spleen cells. Whereas NZB mice are high responders to nucleoside-KLH, they were easily suppressed by nucleoside coupled to spleen cells. In contrast, NZW mice, although relatively low responders to nucleoside-KLH, were not suppressed by administration of nucleoside coupled to spleen cells. Both male and female (NZB X NZW) F1 mice appeared to behave like the NZW parental strain and were resistant to immunosuppression by nucleoside-modified spleen cells. The significance of this observation for the pathogenesis of murine systemic lupus erythematosus is discussed.

Adenosine↗

Effect of 2- versus 6-day collections for the determination of ruminal and postruminal digestion in steers.

Abomasally fistulated steers (500 kg) were used to determine the effect of length of collection period (2 vs 6 days) on total, ruminal and postruminal digestibilities of organic matter, starch and protein. Twice daily, four steers were fed steam-processed flaked grain and three steers were fed dry-rolled sorghum grain in an 82% grain diet. Dysprosium was used as an indicator. Abomasal and fecal samples were collected at 12-hr intervals for 6 days or every 4 hr for 2 days, providing 12 samples per collection period. Nutrient contents of feed, abomasal and fecal samples were similar during both collection periods. Except for total digestibility of crude protein in the dry-rolled grain diet, ruminal, postruminal and total digestibilities of organic matter, starch and protein did not differ between the 2- and 6-day collection periods. Standard deviations for nutrient concentration and digestion coefficients were similar for the two collection periods within both the steam-processed flaked and dry-rolled treatments. Results indicate that sampling six times daily for 2 days provided representative samples for partitioning organic matter, starch and protein digestibilities in abomasally fistulated steers that had been adapted to collection procedures.

Abomasum↗