On the question of an internal secretion from the human ovary.
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Biomedical subjects
Publications and source records attributed to J Oliver.
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Fluid and electrolyte shifts occurring during human spaceflight have been reported and investigated at the level of blood, cardiovascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90% of cerebrospinal fluid (CSF) and which are involved in brain homeostasis. Rats flown aboard space shuttles were sacrificed either in space (SLS-2 experiment, on flight day 13) or 4-8 hours after landing (SLS-1 and SLS-2 experiments). Quantitative autoradiography performed by microdensitometry and image analysis, showed that lateral and third ventricle choroid plexuses from rats flown for SLS-1 experiment demonstrated an increased number (about x 2) of binding sites to natriuretic peptides (which are known to be involved in mechanisms regulating CSF production). Using electron microscopy and immunocytochemistry, we studied the cellular response of choroid plexuses, which produce cerebrospinal fluid (CSF) in brain lateral, third and fourth ventricles. We demonstrated that spaceflight (SLS-2 experiment, inflight samples) induces changes in the choroidal cell structure (apical microvilli, kinocilia organization, vesicle accumulation) and protein distribution or expression (carbonic anhydrase II, water channels,...). These observations suggested a loss of choroidal cell polarity and a decrease in CSF secretion. Hindlimb-suspended rats displayed similar choroidal changes. All together, these results support the hypothesis of a modified CSF production in rats during long-term (9, 13 or 14 days) adaptations to microgravity.
Recent evidence supports a role for thymosin beta 4 (T beta 4) in the inhibition of murine hematopoietic stem cell proliferation. This supposition results from studies in which the N-terminal tetrapeptide derived from native T beta 4 was administered to mice and appeared to prevent CFU-S recruitment into DNA synthesis. The importance of this observation was the concomitant ability of the tetrapeptide to prevent cytosine arabinoside (ara-C) toxicity in mice given LD50 doses of this drug. In the present study, we have extended these observations by demonstrating that whole synthetic T beta 4 is more effective than the N-terminal tetrapeptide in protecting mice from the toxicity of ara-C. This observation supports the hypothesis that T beta 4 is the biologically important parent molecule for this activity. To determine if inhibition of cell cycle progression also occurs in committed human bone marrow progenitors treated with T beta 4, we have investigated the effects of synthetic T beta 4 on proliferating and unstimulated enriched human bone marrow. In short-term liquid cultures studied sequentially over 1-7 days, T beta 4 failed to inhibit cell proliferation, but maintained the proliferative effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on days following maximum stimulation (days 5-7). No effect was noted before the fifth day in culture, nor did T beta 4 exert any demonstrable effect in the absence of added GM-CSF. Any observable effect of T beta 4 required that it be present in the cultures on or before day 3 of GM-CSF stimulation. These results suggest that an additional effect of T beta 4 is the stimulation of a subpopulation of committed human bone marrow precursor cells to become more sensitive to the growth-promoting activity of GM-CSF, thereby enhancing myelopoiesis. It is of interest that the N-terminal peptide of T beta 4 is a shared sequence with tumor necrosis factor alpha, which is also known to have a similar stimulatory capacity. We, therefore, postulate that the growth enhancement noted in short-term cultures is mediated by the region containing these shared sequences.
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Poly(ADP-ribose) polymerase (PARP) is a zinc-finger DNA binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these lesions, the immediate poly(ADP-ribosylation) of nuclear proteins converts DNA interruptions into intracellular signals that activate DNA repair or cell death programs. To elucidate the biological function of PARP in vivo, the mouse PARP gene was inactivated by homologous recombination to generate mice lacking a functional PARP gene. PARP knockout mice and the derived mouse embryonic fibroblasts (MEFs) were acutely sensitive to monofunctional alkylating agents and gamma-irradiation demonstrating that PARP is involved in recovery from DNA damage that triggers the base excision repair (BER) process. To address the issue of the role of PARP in BER, the ability of PARP-deficient mammalian cell extracts to repair a single abasic site present on a circular duplex plasmid molecule was tested in a standard in vitro repair assay. The results clearly demonstrate, for the first time, the involvement of PARP in the DNA synthesis step of the base excision repair process.
1. In five intact rabbits beta-adrenoreceptor blockade (i.v. propranolol), and combined cardiac blockade (i.v. propranolol plus i.v. methscopolamine sulphate) revealed that spectral power of heart rate (HR) variability at low frequencies (LF:0.0625-0.1875 Hz) was modulated predominantly by the sympathetic nervous system and power at high frequencies (HF:0.4373-0.5625 Hz) by vagal influences. 2. In 16 rabbits resting power of HR at LF and changes in LF power in response to maximal treadmill exercise were examined prior to and after 4 and 6 weeks of doxorubicin treatment (1 mg/kg twice weekly). 3. The development of doxorubicin-induced congestive heart failure (CHF) was accompanied by a progressive increase in resting LF power [control, 8.5 +/- 2.1; 4 weeks, 13.4 +/- 1.8; 6 weeks, 21.9 +/- 3.5 (beats/min)2, P < 0.005]. 4. Power spectral analysis (PSA) of HR variability in the immediate post-exercise period showed no change from resting values in normal rabbits [5.3 +/- 1.4 vs 8.5 +/- 2.1 (beats/min)2, P > 0.05] whereas CHF rabbits showed falls in LF power after 4 weeks [4.6 +/- 1.0 vs 13.4 +/- 1.8 (beats/min)2, P < 0.005] and 6 weeks [6.5 +/- 2.4 vs 21.9 +/- 3.5 (beats/min)2, P < 0.005] of doxorubicin treatment. 5. It was concluded that PSA of HR variability reflects the autonomic regulation of sinus node function in conscious rabbits. In doxorubicin-treated animals, the rise in LF power reflects increased sympathetic activity as CHF develops. However, the apparent paradoxical fall in LF power with exercise in these animals underscores the need for caution in interpretation of PSA profiles.
Deep-frozen, aseptically collected and processed allogeneic cancellous bone was implanted in eight dogs during the surgical repair of diaphyseal long bone fractures and in two dogs during arthrodeses. A combined allogeneic and autogeneic cancellous bone graft was used in two fractures with a segmental bone loss of more than 5 cm. Bone union occurred in five fractures and in both arthrodeses. Failure of fixation occurred in two dogs with nonunion fractures and in a third dog with an open, infected fracture. Biopsies from the fracture sites were obtained from these dogs following failure of their fracture fixation. The cancellous bone graft appeared to be in the process of normal incorporation in each case. Failure of fixation was attributed to technical or case management errors or both, in each of the three fractures that failed to achieve bony union. Frozen allogeneic cancellous bone grafts were effectively incorporated when used in the primary repair of fractures and arthrodeses. Combined autogenous and allogeneic cancellous bone grafts may be particularly useful in the repair of fractures with large segmental diaphyseal bone defects. The use of allogeneic cancellous bone grafts in nonunion fractures requires further investigation before it can be recommended.
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We reviewed the efficiency of bracing in 85 patients with anterolateral rotatory instability (ALRI). We were able to compare 18 patients using an antirotational brace with 67 using the AC brace (J. E. Hanger, Montreal, Canada). We found the AC brace to offer better overall stability, 71% compared to 50%.
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Horse mares carrying mule foals were immunized during the last trimester of pregnancy with whole acid-citrate-dextrose-anticoagulated donkey blood to experimentally induce neonatal alloimmune thrombocytopenia. Thrombocytopenia occurred in the neonatal mule foals born to immunized horse mares within 24 hours after ingestion of their dams' colostrum. Mule foals born to mares not immunized with donkey blood did not develop thrombocytopenia. These findings suggest that antibodies may have been directed against a donkey platelet antigen present in the mule foals but not present in their dams. The objectives of this study were to determine whether anti-platelet antibody could be detected in mule foals with experimentally induced neonatal alloimmune thrombocytopenia, to identify any platelet proteins recognized by serum antibody in these foals, and to determine if platelet function was altered by sera from these mule foals. An indirect enzyme-linked immunosorbent assay demonstrated significantly higher absorption at 1:200 of platelet-bindable immunoglobulin G in serum from thrombocytopenic mule foals, compared with nonthrombocytopenic mule foals. Sera from thrombocytopenic and nonthrombocytopenic mule foals produced similar binding patterns in western immunoblots with donkey platelet proteins separated on sodium dodecyl sulfate polyacrylamide gels. Maximal platelet aggregation and relative slope of aggregation in response to collagen were significantly inhibited after incubation with sera from thrombocytopenic mule foals. These results suggest that mule foals with induced alloimmune thrombocytopenia have serum antibodies that bind to platelets and may compete with collagen binding sites to impair platelet aggregation.
Enteric pythiosis was diagnosed in nine dogs in Oklahoma. Eight dogs had anorexia and weight loss. Two of these dogs had diarrhea; two dogs exhibited vomiting and diarrhea; and one dog had vomiting. One dog presented with dysphagia. Seven dogs had either a palpable or radiographically visible abdominal mass. These seven dogs had localized regions of mucosal ulceration and thickened gastric or intestinal walls with some involvement of the adjacent mesentery or omentum. Two dogs had enlarged regional mesenteric lymph nodes. One dog that presented with dysphagia had an oropharyngeal mass involving the larynx and cranial esophagus. Microscopically, there was transmural chronic sclerosing and granulomatous to pyogranulomatous inflammation with arteritis. Pythium spp. were identified in all specimens by immunohistochemistry.
A four-year-old, sexually intact, male dachshund was diagnosed with pulmonary blastomycosis. Itraconazole was administered for 60 days, and the dog was considered to be disease-free at three- and 12-month reevaluations. Two years following discontinuation of itraconazole, the dog developed a granuloma of the cranial vena cava resulting in chylothorax and cranial vena caval obstruction. To the authors' knowledge, this is the first case of a blastomycotic granuloma involving the vena cava reported in the dog. Blastomycosis should be considered as a differential diagnosis for both chylothorax and cranial vena caval syndrome in the dog.
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INTRODUCTION: When we consider the importance of cardioembolism in the aetiology of cerebral ischaemia in young adults, echocardiography, both transthoracic and transesophageal, becomes of increasing diagnosis importance. We analyze its usefulness and contribution to the reduction in the number of cerebral ischemias of unknown origin. PATIENTS AND METHODS: We selected persons aged between 14 and 45 years who had had cerebral ischaemia during the period between January 1991 and April 1998. The protocol for the diagnosis of stroke in young persons was applied to all of them together with transthoracic echocardiography whenever there was the possibility of embologenous cardiopathy followed by transesophageal echocardiography when the transthoracic echocardiography was not diagnostic. RESULTS: In 114 identified cases, 98 transthoracic echocardiographs were done, of which 14 were diagnostic, together with 32 transesophagic echocardiograms, which showed nine cases of embologenous cardiopathy not detected on transthoracic echography. The most frequent diagnoses were: prolapsed mitral valve (14); patent foramen ovale (8); mitral stenosis (5) and interauricular septal aneurysm (4). A total of 31 patients were diagnosed as having a previously unrecognized cardioembolic origin of their illness. CONCLUSIONS: The diagnostic usefulness of transthoracic echography was 22.45% (9.18% were false negatives), and 28.12% for transesophagic echocardiography. These reduced the diagnosis of ischaemia of unknown origin by 32.69% and 20% respectively. Besides, in 75% of the patients with a patent foramen ovale and 100% of those with interauricular septal aneurysms, no other possible cause for their condition was found. Transthoracic echocardiography is a technique to be recommended in all cases of cerebral ischaemia of unknown origin in young adults. Its usefulness may be enhanced by transesophagic ultrasonography when diagnosis cannot be definitely made on transthoracic echosonography alone.
From 1975 to 1988 we have operated 117 patients with left arterial thrombosis associated with rheumatic mitral valve disease. Seventy-seven were female and 40 male, with ages ranging from 22 to 69 years. In 75 cases (64.1%) the valvular lesion was mitral stenosis. Embolic antecedents were present in 38 cases (32.4%) and 95 patients (81.1%) were in class III or IV of the NYHA functional classification. In 48 cases we performed a mitral commissurotomy and in 51 cases mitral valve replacement, associated to left artrial thrombectomy. In the remaining 18 patients we made other valve procedures. The hospital mortality was 15 cases (12.8%), eight because low cardiac output, four because severe brain injury and three because posterior atrioventricular sulcus disruption. In 41.1% of the survivors there was serious hospital complications, standing out the incidence of 8 cases of transient neurologic accidents. We have followed 98 of the 102 hospital survivors between 10 and 140 months (mean 57 months). Three patients died in the follow-up, two of them during a reintervention because bioprosthesis disfunction and the third one during a reintervention because prosthetic infective endocarditis. Nine additional patients were reoperated because recidivant valvular lesions or because prosthetic disfunction, and two patients suffered embolic events during the follow-up. The antithrombotic therapy was abandoned in 19.6% of patients. At present 73.6% are in functional class I and 26.3% in class II. The association of left atrial thrombosis with with mitral valve disease induce a surgical morbimortality greater than usual for isolated valvular lesions, being mandatory a watchfull surgical technic.(ABSTRACT TRUNCATED AT 250 WORDS)