Biomedical subjects
Publications and source records attributed to K Miller.
It is generally accepted that corneal grafts in hypervascular and sclerosed host corneas have little chance of success. At the end of a three-month postoperative immunosuppression period using the new immunosuppressant Cyclosporin A, full incorporation of transplants was achieved in 10 out of 11 high-risk patients. Patients were observed over a period of between 3 and 15 months, the median being 9 months.
Deficiency of Antithrombin III (AT III), which is one of the main inhibitors of blood coagulation, may lead to severe thrombosis and embolism. The authors detected AT III deficiency in two patients with retinal vessel occlusion. Both patients were otherwise healthy. One had recurrent retinal vein thrombosis, the other cilioretinal occlusion. To the authors' knowledge, only one case of retinal vessel occlusion with AT III deficiency has been reported in literature. Furthermore, in the patients reported here retinal vessel occlusion may have been caused by AT III deficiency, which has considerable therapeutic and prophylactic consequences for patients with this disorder. AT III should therefore be determined in retinal vessel occlusion of unknown cause.
We report the status of obstetric education in physical therapy curricula. A questionnaire was sent to 83 accredited physical therapy education programs. Of the respondents from 69 programs, 47 (68%) included a specific unit or information on obstetrics in their program. The reporting programs averaged 7.5 hours for obstetric education. The unit was required in 45 of the 47 programs. Topics covered included anatomy and physiology, psychology, labor and delivery sequence, relaxation techniques, breathing techniques, prenatal and postpartum exercises, body mechanics, nutrition, fetal development, and birthing alternatives. Fifty-three percent of the units were taught by a physical therapist and combination of other professionals including a nurse, physician, nutritionist, psychiatric social worker, physiologist, or anatomist. We present behavioral objectives, required readings, and audiovisual aids used in the units.
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The capacity of tartrazine to initiate reaginic antibody production was investigated in inbred rats. Parenteral administration of tartrazine, when covalently linked to a protein carrier and presented in association with carrageenan, resulted in the production of a transient tartrazine-specific reaginic antibody. This response could be enhanced by a secondary challenge, but declined rapidly and thereafter could not be re-elicited.
Extracorporeal shock-wave lithotripsy (ESWL) has now been in clinical use for more than 4 years. In October 1983, the second kidney lithotripter in the world was installed in our department and, from then until October 1984, 800 treatments were performed on 733 patients. Our results confirm the promising reports published by the Munich group. Furthermore, it was possible to extend the range of indications by combining ESWL with percutaneous procedures, such as percutaneous nephrolithotomy and ureteroscopy. As a result only 7% of all patients who were referred to our hospital with urinary stones (4% of renal stone patients and 15% of those with ureteral stones) had to undergo open surgery.
Antegrade ureteroscopy, using the 11-French ureteroscope via a percutaneous transrenal access, provides safe and easy endoscopic exploration of the ureter above the level of the iliac vessels. The technique has proven to be reliable and effective for the removal of obstructing proximal ureteral calculi: all of the 22 patients who underwent antegrade ureteroscopy were stone-free after treatment. Since the introduction of this new technique in our department, no more open surgery has been required to manage ureteral calculi.
The association between alkylating agent exposure and acute nonlymphocytic leukemia in humans indicates that myeloid cells may be particularly susceptible to mutagenic damage. Alkylating agent mutagenesis is frequently mediated through formation and persistence of a particular DNA base adduct, O6alkylguanine, which preferentially mispairs with thymine rather than cytosine, leading to point mutations. O6alkylguanine is repaired by O6alkylguanine-DNA alkyltransferase (alkyltransferase), a protein that removes the adduct, leaving an intact guanine base in DNA. We measured alkyltransferase activity in myeloid precursors and compared it with levels in other cells and tissues. In peripheral blood granulocytes, monocytes, T lymphocytes, and B lymphocytes, there was an eightfold range of activity between individuals but only a twofold range in the mean activity between cell types. Normal donors maintained stable levels of alkyltransferase activity over time. In bone marrow T lymphocytes and myeloid precursors, there was an eightfold range of alkyltransferase activity between donors. Alkyltransferase activity in the two cell types was closely correlated in individual donors, r = 0.69, P less than 0.005, but was significantly higher in the T lymphocytes than the myeloid precursors, P less than 0.05. Liver contained the highest levels of alkyltransferase of all tissues tested. By comparison, small intestine contained 34%, colon 14%, T lymphocytes 11%, brain 11%, and myeloid precursors 6.6% of the activity found in liver. Thus, human myeloid precursors have low levels of O6alkylguanine-DNA alkyltransferase compared with other tissues. Low levels of this DNA repair protein may increase the susceptibility of myeloid precursors to malignant transformation after exposure to certain alkylating agents.
The distribution of cell surface receptors for transferrin-iron and epidermal growth factor (EGF) on the surface of cultured epithelioid (A431) cells has been identified by immunocytochemical electron microscopy. The patterns of movement displayed by these two receptor populations as they transfer to their sites of internalization on the cell surface are different. The movement of recycling transferrin receptors over the surface is ligand-independent whereas EGF receptors are more stable residents and remain monodisperse until they bind ligand. Prior to uptake transferrin receptors cluster, predominantly within existing clathrin-coated pits while the aggregates formed by EGF ligand-receptor complexes induce new membrane invaginations. These results are discussed in relation to receptor populations concerned with constitutive, high capacity uptake processes and receptors involved in signal transduction.
A study of the response of rat and hamster to nitrogen dioxide (NO2) under identical conditions has been undertaken. Exposure to 20 parts/IO6 NO2 for 24 h produced a mild cytotoxic effect on the terminal bronchiole and proximal alveoli in the rat, whereas the hamster developed a moderate to severe bronchiolitis and alveolitis. Electron microscopic examination of tissue sections showed accumulation of surfactant in lamellar bodies of the alveolar type II cell in the rat but not in the hamster, whereas in the hamster Clara cells were observed in mitosis. Increased levels of surfactant isolated from whole lung homogenates by sucrose gradient centrifugation were found in both rat and hamster. In contrast surfactant isolated from bronchiolo-alveolar lavage was increased only in the hamster. The results suggest that caution must be exercised in the choice of animal model in investigations aimed at the understanding of the toxicological effects of nitrogen dioxide in man.
Studies were carried out on the mechanisms by which B lymphocytes are polyclonally activated to secrete antibodies during visceral leishmaniasis. Crude extracts of Leishmania donovani, the aetiological agent of this disease, of Leishmania mexicana amazonensis, the etiological agent of cutaneous leishmaniasis, and of Herpetomonas muscarum, a related non-pathogenic organism, all contain components which cause strong in vitro polyclonal activation of hamster spleen cells leading to the production of antibodies. However, in vivo, only hamsters infected with L. donovani develop hypergammaglobulinaemia due to B cell polyclonal activation. Hamsters injected with the crude extracts of leishmania or infected with L. mexicana amazonensis do not manifest these alterations in their B cell response. Furthermore spleen cells of hamsters infected with L. donovani became unresponsive to stimulation with the T cell mitogen phytohaemagglutinin (PHA) by day 10 of infection, whereas their response to concanavalin A (Con A) was preserved. The decreased lymphocyte response to PHA coincided with the augmentation of the PFC/spleen ratio. In contrast, spleen cells from hamsters infected with L. mexicana amazonensis, responded normally to both mitogens throughout the course of infection. These results suggest that the hypergammaglobulinaemia present in visceral leishmaniasis may be the consequence of an inbalance of regulatory T cells, possibly associated with a direct stimulation of hamster B cells by L. donovani components.
Three-dimensional stereofluoroscopic pictures of the kidney and renal calyces were first used for percutaneous renal surgery with a laboratory prototype equipment. The grid-controlled X-ray tube provides sequential images, which are separated into pairs by digital image processing and storage and can be seen on a 3-D display unit. This method allows exact and rapid puncture of a suitable calyx for percutaneous nephrolithotomy, shortens the learning process for the endourologist, reduces the radiation exposure, and thus makes the method safer.
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Administration of 3-hydroxymethylfuran-N-ethylcarbamate (HFC) to female hamsters via the jugular vein under pentobarbitone anaesthetic at 20 mg per kg body weight produced pronounced necrosis of the Clara cells without apparent morphological effect on other cell types as judged by transmission electron microscope examination. The surfactant material recoverable by minimal lavage followed by purification by sucrose gradient ultracentrifugation increased, reaching a maximum around 48 h after treatment. At this time static pressure/volume measurements on isolated lungs indicated an increase in airway surface compliance. Lavageable surfactant phospholipid composition was examined by 31P nuclear magnetic resonance (n.m.r.). The distribution of phospholipids between the various classes was unchanged by HFC treatment. No change in the total lung surfactant pool size was seen. These results are discussed in relation to the possible roles of the Clara cell in influencing airway surfactant levels.
A family with two independent reciprocal translocations t(3;19) and t(16;22) is described. The proband, a 4-week-old male, was phenotypically conspicuous with multiple congenital anomalies. Cytogenetic examination revealed a balanced reciprocal translocation (3;19) and a supernumerary small marker chromosome. His mother carried two balanced reciprocal translocations, the one found in the proband and a reciprocal translocation (16;22). The maternal grandmother and a maternal uncle were identified as carriers of a single translocation (16;22). The findings in the family members permitted the identification of the proband's marker chromosome as a derivative chromosome 22 resulting in partial trisomy 16 and 22.
The human hepatoma cell line PLC/PRF/5 produces tumours and lung metastases in nude athymic mice. Here we describe how detection of hepatitis B virus surface antigen, a marker of these cells, as led to identification of pancreatic and muscle metastases. The antigen was shown in the tissues, and antigen-producing PLC/PRF/5 cells were isolated from them. The number of cells detectable by this method is between 5 and 10 million. The principle used here may be adaptable be useful in studying micrometastasis formation in other systems.
Inbred rats fed diets containing 150 ppm dioctyltin dichloride (DOTC) demonstrated a progressive reduction in thymic weight. This was accompanied by a decrease in both the number of circulating lymphocytes and their ability to respond to mitogenic stimulation. Morphologically the thymuses from treated animals showed a loss of cortical thymocytes and a marked vacuolation of the reticular epithelial cells (REC). After return to normal diet for 4 weeks vacuolated REC were still present and PHA-induced lymphocyte blastogenesis remained low. Adrenalectomy failed to alter the atrophic action of DOTC on the thymus and although administration of hydrocortisone alone produced thymic atrophy, no damage to the REC was observed. The results show that thymic atrophy resulting from DOTC administration differs from that induced by steroids and lends support for the hypothesis that DOTC acts selectively on the thymus in such a way that the humoral function of the organ may be affected.