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Biomedical subjects

G Rogers

Publications and source records attributed to G Rogers.

At least 73 records · Page 4Linked to original sources

Attenuation of growth hormone gene expression in desensitized somatotropes.

The effects of GRF-induced desensitization of somatotropes on GH gene expression were investigated on pituitary cells derived from male rats. Pretreatment of monodispersed cells for 18 hr with GRF abolished both the acute release of GH and the stimulation of GH gene expression in response to a subsequent 4 hr challenge with GRF. Concomitant preincubation with GRF and SS resulted in restoration of the ability of GRF to stimulate release of GH but not to augment GH gene expression. These results demonstrate that desensitization by GRF affects both the release of GH and GH gene expression, whereas the resensitizing effects of SS appear to be directed exclusively at the release mechanism.

Animals↗

Cultivation of murine hair follicles as organoids in a collagen matrix.

Techniques are described for the isolation and cultivation of functionally intact mouse hair follicles. Follicles were isolated by collagenase digestion of dermis from 5-day-old mice and purified by differential centrifugation and filtration. Purified follicles were cultured in a Type 1 collagen matrix using Medium 199 and 8% fetal calf serum as the basic nutrient. Viability of follicles was maintained in culture since the cultures incorporated thymidine into DNA and methionine into proteins for at least 7 days. Furthermore, follicles isolated from the collagen matrix after 7 days could reattach to a plastic culture substrate or be further cultivated in a fresh collagen matrix. Functional integrity of cultured follicles was maintained since some follicle-specific cytoskeletal proteins were synthesized in vitro, and follicles isolated from the collagen matrix after 7 days formed a haired skin when recombined with dermal fibroblasts and grafted to a skin site on nude mice. Only a minority of follicles appeared to produce a mature hair shaft in vitro by morphologic criteria, however, and synthesis of the total complement of hair proteins was not observed. Cholera toxin was a strong mitogen for cultured follicles, whereas epidermal growth factor was slightly mitogenic. Epidermal growth factor stimulated the release of a Type 1 collagenase by follicle cells, however. This model system provides an opportunity for the systematic analysis of factors required for the induction of hair growth and the underlying physiology of hair follicle development. This model should also be useful for studying the role of the hair follicle in skin carcinogenesis.

Animals↗

Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise.

This study was undertaken to gain insight into the mechanisms responsible for the hypoferremia occurring after severe exercise. To this end, 18 athletes who were competing in a 160-km triathlon involving canoeing, cycling, and running were evaluated before the race, immediately after the finish, and thereafter at 30 min, 24 h, and 48 h. The evaluation included plasma iron, total iron-binding capacity, lactoferrin, ferritin, haptoglobin, cortisol, various enzymes, and white cell count. The cortisol, white cell count, and lactoferrin were significantly increased immediately after the race, while the plasma iron and transferrin saturation were significantly decreased. There was a 40% but nonsignificant rise in the plasma ferritin at the completion of the race, while the C-reactive protein was raised by nearly 300% at 24 h. In contrast, haptoglobin declined significantly by 24 h but was normal again 24 h later. Quantitative considerations suggested that the lactoferrin was not responsible for removing transferrin iron from circulation and hence causing the hypoferremia. Instead, it seemed more likely that the iron-related changes were occurring as part of an acute phase response initiated by muscle injury.

Acute-Phase Proteins↗

The response of runners to arduous triathlon competition.

As very few of the competitors in a triathlon are truly specialist in more than one of the three disciplines, high levels of physical (and mental) stress may result during the course of the event. We investigated some of the physiological responses occurring in runners participating in an "Iron Man" triathlon consisting of canoeing (20 km), cycling (90 km) and running (42 km), in that sequence. Twenty-one male entrants volunteered as subjects for the study. Prior to the competition, maximal oxygen consumption (VO2max) was determined. Basal venous blood samples were collected on the day prior to the competition and post-exercise venous blood samples were collected within 5 minutes of completion of the race. Serum iron was significantly reduced from a mean basal value of 20.6 mumol X l-1 to a mean value of 8.4 mumol X l-1 after the race. Cortisol levels showed a 3 fold increase after the race. Gross VO2max (l X min-1) and mass standardised VO2max (ml X min-1 X kg-1) were both negatively correlated to cortisol levels after the race (p less than 0.05). Total performance time was not related to gross VO2max (l X min-1) but was well correlated to mass corrected VO2max (ml X min-1 X kg-1). The marked fall in serum iron may have been related to heavy sweating or prelatent iron deficiency. Chronic iron deficiency (without frank anaemia) can impair physical performance, although we were unable to show any significant correlation between serum iron level after the race and time taken to complete the event.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship of spinal cord blood flow to vascular anatomy during thoracic aortic cross-clamping and shunting.

No satisfactory explanation exists as to why paraplegia occurs despite distal aortic perfusion during thoracic aortic operations. We studied the hemodynamics, paraplegia rate, and spinal cord blood flow with radioactive microspheres in 17 male adult baboons, with particular reference to the arteria radicularis magna. The groups consisted of control animals, subjected to cross-clamping for 60 minutes, and animals with aorto-aortic shunts operational for 60 minutes. There were no significant left ventricular hemodynamic advantages with shunting. Shunting significantly increased lumbar spinal cord blood flow (p = 0.0009), which correlated with the distal aortic mean pressure (r = 0.59, p = 0.008). However, lower thoracic spinal cord blood flow did not increase during shunting (p = 0.2) and did not correlate with the distal aortic pressure (r = 0.11, p = 0.64). This is due to the vascular anatomy of the anterior spinal artery, which was, as in man, smaller above (0.278 mm) than below (0.744 mm) the entry of the arteria radicularis magna. Resistance to flow, as calculated by Poiseuille's equation, was 51.7 times greater up the anterior spinal artery as compared with down this artery. The vascular anatomy explains the absence of paraplegia in one baboon in the cross-clamp group and paraplegia in one baboon in the shunt group. Thus, distal aortic perfusion protects the spinal cord below the arteria radicularis magna but not above it.

Animals↗

Toluene embryopathy.

Three children with microcephaly, central nervous system dysfunction, minor craniofacial and limb anomalies, and variable growth deficiency were born to women who inhaled large quantities of pure toluene throughout pregnancy. The features in our patients were reminiscent of the patterns of malformation previously described following in utero exposure to alcohol, certain anticonvulsants, and hyperphenylalaninemia. It is possible that there is a variable and nonspecific teratogenic phenotype characterized by alterations in growth, development, and morphogenesis. Careful evaluation and monitoring of infants exposed to toluene in utero are needed to determine the significance of our findings.

Abnormalities, Drug-Induced↗

Accelerated wound healing with stapled enteric suture lines. An experimental study comparing traditional sewing techniques and a stapling device.

The healing of 3-cm longitudinal colotomies closed with either Czerny-Lembert suture lines (CLSL) or TA-30 staple lines (SSL) were studied in 28 mongrel dogs using bursting strength (BS) measurements. Dogs from each group were sacrificed on postoperative days (POD) 1 through 7. Mean BS for the SSL in all 14 dogs was 165 mmHg +/- 64 and for CLSL 80 mmHg +/- 49 (DF = 13; t = 5.5672; p less than 0.00005 for matched pairs). For POD 2 through 5, BS of the SSL was 154 mmHg +/- 42, three times greater than the BS of the CSLS, which was 54 mmHg +/- 33 (DF = 7; t = 5.6289; p less than 0.0004 for matched pairs). BS of the SSL increased linearly from the first day of surgery: BS (mmHg) = 26 (POD) + 61 (n = 14; r = 0.838; p less than 0.01). BS of the CLSL followed the traditional pattern of wound healing dropping to a nadir after 3 days and then increasing linearly: BS (mmHg) = 32 (POD) - 72 (n = 10; r = 0.834; p less than 0.01). Microscopic examination revealed a greater inflammatory response to the CSLS than the SSL. Differences were most marked from 2 to 4 days following operation. Thus, the SSL healed more rapidly than the CLSL as measured by BS. The SSL healed with a negligible Lag Period of wound healing entering directly into the Period of Fibroplasia.

Animals↗

Delayed onset of infectious mononucleosis associated with acquired agammaglobulinemia and red cell aplasia.

In 1974, an 11-year-old white boy with the X-linked lymphoproliferative syndrome developed hyper-IgM after becoming infected with Epstein-Barr virus. However, he failed to develop normal immune responses against the virus. In December 1981, when red cell aplasia occurred, he was given packed erythrocytes and gammaglobulin. Nine weeks later, acute infectious mononucleosis developed. Concurrently, his T4/T8 helper/suppressor ratio decreased from 2.7 to 0.2, and IgM antibodies to Epstein-Barr virus appeared. Subsequently, circulating B cells became undetectable in his blood, and agammaglobulinemia appeared. Red cell aplasia abated transiently. This patient's course was complicated by Haemophilus influenzae and Mycobacterium tuberculosis pneumonias, and red cell aplasia and agammaglobulinemia have persisted. Epstein-Barr virus acting as a slow virus probably induced the red cell aplasia and agammaglobulinemia because of the aberrant immune responses to Epstein-Barr virus. Immunodeficient responses to Epstein-Barr virus should be sought in other patients with the diseases documented in our patient.

Agammaglobulinemia↗

Regression in malignant melanoma.

A multiple stepwise logistic regression analysis shows that histologic regression is more likely to be found in a malignant melanoma that is level III or less, more than 10 mm in diameter, associated with solar elastosis, located on an anatomic area other than the head or neck, and when there are areas of whiteness clinically. Although patients with malignant melanomas displaying signs of regression histologically have a slightly better 5-year disease-free survival, this may be attributed to a difference in tumor thickness.

Humans↗

Reconstitution of a tandem Co- and post-translational processing pathway with rat liver subcellular fractions.

Previously we showed that smooth microsomes from a variety of tissues effectively cleaved, sequestered, and "core" glycosylated nascent chains of secretory proteins. To further characterize the role of smooth membranes in the biosynthesis of secretory polypeptides, rat liver smooth microsomes were separated into smooth endoplasmic reticulum and Golgi fractions. Membranes of the smooth endoplasmic reticulum cleaved the signal peptide of pre-placental lactogen, attached the high mannose core to the alpha subunit of chorionic gonadotropin, and sequestered the processed proteins. None of these processing steps were performed by Golgi membranes. However, processing of asparagine-linked oligosaccharides and the coincident addition of terminal sugars was performed by Golgi but not by smooth endoplasmic reticulum membranes. The properties of this post-translational reaction are very similar to those described for the reactions in vivo. These observations demonstrate that the enzymes for co-translational (pre-protein processing) and posttranslational (oligosaccharide maturation) processing events are localized in the endoplasmic reticulum and Golgi apparatus, respectively. This functional differentiation of Golgi and endoplasmic reticulum membranes is an important feature of the secretory process in eukaryotic cells. Restriction of the recognition and transport of nascent secretory proteins to the endoplasmic reticulum establishes the polarity necessary for the ordered sequence of post-translational steps involved in the synthesis and maturation of secretory proteins.

Animals↗

Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): update on studies of the registry.

Analyses of 100 subjects with the X-linked lymphoproliferative syndrome (XLP) in 25 kindreds revealed four major interrelated phenotypes: infectious mononucleosis, malignant B-cell lymphoma, aplastic anemia, and hypogammaglobulinemia. Eighty-one of the patients died. Two male subjects were asymptomatic but showed immunodeficiency to Epstein-Barr virus (EBV). Seventy-five subjects had the infectious mononucleosis phenotype and concurrently, 17 subjects of this group had aplastic anemia. All subjects with aplastic anemia died within a week. Aplastic anemia did not accompany hypogammaglobulinemia or malignant lymphoma phenotypes. Hypogammaglobulinemia had been detected before infectious mononucleosis in three subjects, after infectious mononucleosis in five subjects, and was not associated with infectious mononucleosis in 11 boys with hypogammaglobulinemia. In nine subjects infectious mononucleosis appeared to have evolved into malignant lymphoma; however, the majority of patients with malignant lymphoma showed no obvious antecedent infectious mononucleosis. One subject had infectious mononucleosis following recurrent malignant lymphoma. Twenty-six of 35 lymphomas were in the terminal ileum. Results of immunologic and virologic studies of 15 survivors revealed combined variable immunodeficiency and deficient antibody responses to EBV-specific antigens. Mothers of boys with XLP exhibited abnormally elevated titers of antibodies of EBV. Subjects of both sexes with phenotypes of XLP should be investigated for immunodeficiency to EBV. Persons with inherited or acquired immunodeficiency may be vulnerable to life-threatening EBV-induced diseases.

Agammaglobulinemia↗

Immune deficiency in the X-linked lymphoproliferative syndrome. I. Epstein-Barr virus-specific defects.

Eleven males with XLP were evaluated for EBV-specific antibodies during periods of 2 to 7 yr. Variable responses to EBV-specific antigens were found. All 11 patients had subnormal anti-EBNA titers, which probably reflected a T cell deficiency. The patients showed four different patterns in their anti-VCA response: 1) two boys who had experienced malignant lymphoma mounted no antibodies at all; 2) two patients showed intermittent anti-VCA titers; 3) four males had persistently elevated anti-VCA titers; and 4) three patients showed normal anti-VCA titers. ADCC against EBV-infected cells was abnormally low in six patients and was elevated in two patients given gamma-globulin. ADCC titers did not correlate with anti-VCA titers. However, most patients with XLP failed to effect regression of autologous EBV-infected lymphoblastoid cell lines, indicating a deficiency in long-lived T cell-mediated immunity to EBV.

Antigens, Viral↗

Time course and disposition of methazolamide in human plasma and red blood cells.

Methazolamide was determined in plasma, whole blood, and urine by a GLC-mass spectrometric method. Temporal patterns of methazolamide concentrations in plasma and red blood cells were obtained following single- and multiple-dose oral administration of the drug. The nonlinearity in the binding of the drug to the red blood cell carbonic anhydrase was evident from a comparison of plasma and red blood cells concentrations. The drug was cleared slowly from the red blood cells. The binding constants to the two isoenzymes of carbonic anhydrase were determined from the plasma and red blood cell concentrations and were in agreement with those determined by previous measurements. The half-life of elimination was 7.5 hr. The urinary recovery of unchanged drug was approximately 25% of the administered dose.

Carbonic Anhydrases↗