Biomedical subjects
M Harris
Publications and source records attributed to M Harris.
Hypothalamic-pituitary function of children with acute lymphocytic leukemia after three forms of central nervous system prophylaxis. A retrospective study.
The hypothalamic-pituitary function of 93 children, who had received central nervous system (CNS) prophylaxis as part of their therapy for acute lymphocytic leukemia (ALL), and who remained in continuous complete remission, was evaluated retrospectively. Treatment regimens included--Group I: 31 subjects, intrathecal methotrexate (IT MTX); Group II: 31 subjects, IT MTX plus 2400 rad cranial irradiation; and Group III: 31 subjects, IT MTX and intravenous intermediate-dose methotrexate. Serum thyroid-stimulating hormone (TSH) and T4 levels were normal. All participants had normal adrenocorticotropic hormone (ACTH) secretion as assessed by plasma cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) excretion of pubertal and postpubertal patients (N = 37) was appropriate, except for one subject from Group I who had an abnormally high output of gonadotropins, and one from Group II who had abnormally low levels. Growth hormone (GH) responses were subnormal after sequential arginine-insulin stimulation as follows--Group 1: 3 of 31 patients; Group II: 6 of 25 patients; and Group III: 2 of 29 patients. Nevertheless, all children had normal linear growth. It was concluded that the three forms of CNS prophylaxis evaluated had no long-term adverse effect on TSH and ACTH secretion. FSH-LH production appears to be normal, but final judgment must await follow-up studies because 60% of the patients were prepuberteral or still receiving chemotherapy. Eleven patients had subnormal GH responses after pharmacologic stimulation of the pituitary, but long-term linear growth was unaffected.
A cluster of Pallister-Hall syndrome cases, (congenital hypothalamic hamartoblastoma syndrome).
We report on three infants with hand anomalies and congenital hypopituitarism. In two of the cases, a hypothalamic tumor was found; the third infant died without postmortem brain studies. Family history in the first case suggested possible familial recurrence; the mother's sister had died at 17 hr of age with polydactyly, microglossia, and flat nasal bridge (no autopsy done). Our second case was born by cesarean section after a pregnancy complicated by extremely low maternal estriols. At birth, hypopituitarism was diagnosed, a cranial CT scan was read as normal, and hormonal replacement was begun with thyroxine, hydrocortisone, and growth hormone. At 11.5 mo of age she developed seizures; and a repeat CT scan showed a mass extending beneath the hypothalamus. This tumor was removed surgically at 12 mo, the first successful treatment of this disorder. Our third possible case had a bifid epiglottis, hypopituitarism, and hand anomalies. A CT scan at birth failed to reveal a mass in the hypothalamus. This child died from complications of untreated hypopituitarism, and no neuropathology studies were done. These three cases were conceived between March 10th and April 17th in three different years in three geographically contiguous counties of Vermont. Clustering in time and space and possible familial recurrence, in one of these cases, suggest a possible gene/environment interaction.
Homer's Odyssey: a psychological journey.
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Induction and reversion of asparagine auxotrophs in CHO-K1 and V79 cells.
Two asparagine-dependent clones (2002-103 and 2002-109) were obtained from CHO-K1 cells by treatment with EMS followed by a BrdU-black light selection procedure; an additional ASP- clone (2293-343) was isolated similarly from V79-56 cells. All three clones show a low rate of spontaneous reversion which is increased somewhat by exposure to EMS. Two of the variant clones (2002-103 and 2002-109) are converted in high frequency to asparagine independence by treatment with 5-azacytidine, while 2293-343 cells show no significant induction after similar exposure. All three ASP- clones were found by hybrid analyses to belong to the same complementation group. Treatment of hybrids constructed between 2002-103 or 2002-109 X 2293-343 with 5-azacytidine resulted in high-frequency induction of asparagine independence. Thus, the potential for response to 5-azacytidine in such hybrids by reversion to asparagine independence is dominant or codominant, with no suppressor effect in hybrids from the nonresponsive parent line.
Simultaneous induction of epigenetic variants.
Epigenetic changes at one, two, or three loci were induced with 5-azacytidine in CHO-K1 cells, using markers (proline dependence, asparagine dependence, and thymidine kinase deficiency) which respond by high-frequency reversion to wild-type states. The observed incidence of dual or triple revertants was compared with the frequency expected by chance as the product of single frequencies measured separately for the markers involved. Values observed for dual reversions consistently exceeded levels predicted by this purely stochastic model, and for triple reversion the divergence was 1000-fold. Coordinate responses could account for this disparity, if minority cell types with higher reactivity to 5-azacytidine exist in target cell populations. To test this hypothesis, single colonies were isolated under nonselective conditions from a mass culture of CHO-K1 cells that had been treated with 5-azacytidine. These clones showed wide and reproducible differences in competence for reversion from proline dependence to independence. Our data thus suggest that simultaneity of epigenetic changes depends on random events which are modulated by a mosaic of inductive potentials within individual cells of the reacting system.
Mucosal destruction and regeneration of the colon by local hyperthermia. An experimental preliminary study.
An experimental model has been developed to produce colonic mucosal destruction followed by regeneration. The canine model consists of a defunctioned portion of the large intestine which has been subjected to water at a temperature of 125 degrees F for 7 hours. Colonic specimens were harvested at different periods of up to six weeks and studied macro- and microscopically. It has been shown that it is possible to achieve significant mucosal destruction and regeneration. Possible adaptation to clinical states is presented and discussed.
Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma.
Mothers of a population-based series of 86 children with osteosarcoma or chondrosarcoma were traced and their health status or cause of death ascertained. There were 6 cases of breast cancer among these mothers and 6 other cancers. Risk of breast cancer was approximately three times that expected, and appeared to be highest in mothers of boys and in mothers of children under the median age at diagnosis. The mothers who developed breast cancer were relatively young at diagnosis compared with population data. Risk of other malignancies in the mothers was not in excess of expectation. These findings are in line with those reported for breast cancer risk in mothers of children with soft tissue sarcomas, and provide further indications of a genetic component in the aetiology of these cancers.
Anti-inflammatory effects of ultrasound therapy: evidence for a major placebo effect.
The value of therapeutic ultrasound (US) for reducing inflammation was tested in a double-blind controlled study in 150 patients following surgical removal of impacted lower third molars. Facial swelling, trismus, pain and serum C-reactive protein (CRP) were significantly reduced in the US-treated groups and in a placebo group ('mock' US) compared with an untreated control group. The majority of the anti-inflammatory activity was attributable to the placebo effect, and the highest intensity of US (1.5 W.cm-2) was consistently less beneficial than the lower intensities (0.1 and 0.5 W.cm-2) and the mock US.
The ultrastructure of medullary, atypical medullary and non-medullary carcinomas of the breast.
Three medullary, eight atypical medullary and four non-medullary carcinomas of the breast were studied by transmission electron microscopy. Detailed comparison of a number of structural, cytoplasmic and nuclear features failed to confirm previous suggestions that medullary carcinoma cells have a distinctive ultrastructure. Electron microscopy is thus unlikely to be useful in the differential diagnosis of the tumours, nor does it suggest a basis for the good prognosis of medullary carcinoma.
Immunohistochemical detection of ras oncogene p21 product in benign and malignant mammary tissue in man.
The monoclonal antibody RAP-5 generated against a synthetic peptide corresponding to amino acid positions 10-17 of the ras p21 protein was used in an immunohistochemical study of the expression of ras in normal, benign, and malignant breast epithelium in man. The staining intensity and intracellular distribution of RAP-5 was similar in the three epithelial populations and extended to other tissue elements including myoepithelial cells, smooth muscle, myelin, capillary endothelium, and stromal fibroblasts, as well as sebaceous glands and sweat glands overlying the breast. These results suggest that RAP-5 recognises a normal cellular component, the expression of which is not more enhanced in hyperplastic or neoplastic conditions. The detection of mutant forms of p21 exclusively expressed in malignant tumours requires that alternative reagents be developed.
Improved serodiagnosis of tuberculosis using two assay test.
An antigen capture immunoassay was developed for the detection of mycobacterial antigens in sera from patients with tuberculosis. The assay was evaluated together with an antibody measuring enzyme immunoassay in a clinical trial for serodiagnosis of tuberculosis. Sensitivity of the antibody assay for active pulmonary tuberculosis, including relapsed infections, was 75%, and specificity with other lung diseases was 97%. Sensitivity for extrapulmonary tuberculosis was 84.5% and specificity 84%. Sensitivity of the antigen assay for active tuberculosis was 45% with no false positive reactions. Combination of the results from the two assays increased total sensitivity to 96.5% with a positive predictive value of 0.81 and a negative value of 0.98. The two assay test was relatively simple to perform and offered improved serological diagnosis of tuberculosis over a single antibody test.
Clostridial myonecrosis in association with etoposide therapy presenting as severe thigh pain.
The case is described of a 68 year old man who was immunosuppressed as a result of receiving chemotherapy for small cell lung cancer and who presented with severe right thigh pain. This proved to be due to clostridial myonecrosis with none of the classical clinical features of clostridial infection. This is believed to be the first reported case of spontaneous clostridial infection associated with etoposide administration.
Psychiatric and nonpsychiatric indicators for rehospitalization in a chronic patient population.
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Spinal cord injuries.
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Amianthoid fibres in muscle tissue associated with temporomandibular joint ankylosis.
The masseter and temporalis muscles were studied ultrastructurally in 3 patients having extra and intra-articular ankylosis of the TMJ. Amianthoid fibres (thick collagen fibres) varying from 280-430 nm in diameter were found in the connective tissue of both muscles. These fibres appeared to form by fusion of collagen fibrils of normal thickness rather than representing an active dynamic process. The presence of amianthoid fibres in these muscles may account for the restricted mouth opening associated with TMJ ankylosis and could be of some value in future management of this condition.
Intralobular stromal fibroblasts in the resting human mammary gland: ultrastructural properties and intercellular relationships.
The intralobular stroma of the resting human mammary gland was studied by thin-sectioning transmission electron microscopy on tissue obtained from reduction mammoplasty or adjacent to fibroadenomas. The arrangement of delimiting fibroblasts around the epithelium and their possession of contacts as shown by earlier studies were confirmed. Observations on other ultrastructural aspects show these cells to have abundant rough endoplasmic reticulum, a well developed Golgi apparatus and vesicles considered to contain collagen-precursor, and conflict with earlier data. The fine structure of those fibroblasts without close epithelial proximity has been described for the first time and was similar to that of delimiting fibroblasts. Other features applicable to both categories of fibroblast included: variation in overall staining intensity, structures resembling hemi-desmosomes, simple junctions, and close juxtapositions of cell surfaces forming 'contacts' with other fibroblasts as well as with mononuclear cells (lymphocytes, plasma cells, mast cells, macrophages). These cell contacts have not been documented previously. Contacts were structurally undifferentiated, forming spaces 20-50 nm wide which were occluded by lanthanum nitrate. Intralobular stromal cells were therefore organised into a kind of reticulum. The possible functions of this network are discussed. The concept of the epithelial-stromal junction is re-assessed in the light of these observations.