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Re-evaluation of birth weights at high altitude. Study of babies born to mothers living at an altitude of 3,100 meters.

Babies born at altitudes above 2,700 meters have been reported to be below normal birth weight and small for gestational age (SGA). In a study of a specific community (Leadville, Colorado, altitude 3,100 meters) over a period of 14 months (ending November, 1978), 215 newborn infants were found to be appropriate for gestational age (AGA), with the entire group having a mean birth weight (3.16 kilograms) similar to that of newborn infants in Denver, Colorado (3.12 kilograms). This study from a community with a stable population indicates that babies born at high altitude are AGA. The increased morbidity which does occur for these babies is not due to SGA factors.

Altitude↗

Central core degeneration after tenotomy in soleus muscles of hyperthyroid rats.

Tenotomy of the rat soleus muscle is followed by a central degeneration of slow, fatigue-resistant muscle fibers. Previous experiments showed that fast, fatigable fibers of the gastrocnemius when transformed to slow, fatigue-resistant fibers by cross-reinnervation also develop lesions after tenotomy. The experiments described in this communication were carried out to discover whether the susceptibility of fibers to lesions was determined by their fiber type or the nature of their innervation. Rats were rendered hyperthyroid by the administration of sodium 3,3',5-triiodo-L-thyronine (T3) for 7 to 10 weeks. Tenotomy of the soleus muscles was then carried out and the experimental and contralateral muscles were removed and stained for myosin ATPase activity after a further 2 weeks. The hyperthyroid state of each animal was confirmed by the assay of succinate dehydrogenase activity of liver and the contralateral muscle. After acid preincubation, whole muscle fiber type counts of contralateral muscles showed a statistically significant change from a predominantly acid-stable population of fibers to acid-labile fibers. In addition, many fibers of intermediate staining properties were seen. When the experimental muscles were examined, all three varieties of fiber showed central degeneration. The nature of the fiber type change induced by T3 and the role that innervation might play in this is discussed. It was concluded that the susceptibility of fibers to the lesions that follow tenotomy is dependent on the nature of their innervation rather than their fiber type.

Animals↗

Peripheral nerve segments promote consistent long-term survival of adrenal medulla transplants in the brain.

Patients with Parkinson's disease have received intracerebral transplants of autologous adrenal medulla in the attempt to counteract their severe motor dysfunctions. Unfortunately, in the majority of cases, clinical improvement has not persisted and there has been extremely poor survival of the grafts. Based on the recent observations of long-term viability of adrenal medulla grafts in the interior of transected peripheral nerves, adrenal medulla/peripheral nerve complexes were constructed in the brain to promote extended viability of chromaffin cells. A three-step, time-dependent transplantation procedure is described that results in a 100% survival rate of the adrenal medulla graft. The grafts consist of a stable population of approximately 2.0 x 10(3) chromaffin cells that survive for at least 6 months (longest time point studied): Immunoreactivity to catecholamine-related enzymes (tyrosine hydroxylase, dopamine beta-hydroxylase) and the low-affinity NGF receptor (192-IgG) are expressed by the chromaffin cells. The ultrastructural characteristics of the cells are normal and comparable to their in vivo counterparts. Construction of these peripheral nerve/adrenal medulla complexes evidently improves local conditions in and around the grafts, enabling the chromaffin cells to remain viable. This new methodology achieves the goal of reliable and extended survival of the adrenal medulla graft after intracerebral transplantation. The enhanced longevity now provides an opportunity to reevaluate the efficacy of the adrenal medulla transplant to ameliorate the functional disorders associated with striatal dopamine depletion, especially over long time periods.

Adrenal Medulla↗

Comparative studies of Iodo-bead and chloramine-T methods for the radioiodination of human alpha-fetoprotein.

Human alpha-fetoprotein (h-AFP) of iodination grade was radiolabeled with Na125I by chloramine-T (conventional method) and by Iodo-bead (solid-phase method) in our laboratory under standard and varied conditions, such as quantity of h-AFP and volume of the reaction mixture. We have slightly modified the chloramine-T method and developed a protocol for the Iodo-bead method of iodination. Our results show that while the chloramine-T method yields radiolabeled h-AFP of apparently 40% higher specific radioactivity (SR) than those of the Iodo-bead method, the latter appears to be a simpler, more controllable and milder method, giving rise to a more stable population of [125I]h-AFP. This is supported by the results of radioactive counting of [125I]h-AFP collected from a Sephadex G-50 column after radioiodination, storage stability and immunoreactivity with anti-h-AFP.

Chloramines↗

Current views on the ontogeny of macrophages and the humoral regulation of monocytopoiesis.

Macrophages do not constitute a stable population but are constantly renewed by an influx of monocytes and by local division of immature mononuclear phagocytes that have also recently arrived in the tissues. The calculated mean turn-over time of tissue macrophages lies between four and six days. During an inflammatory response the production of monocytes in the bone marrow is increased. This process is regulated by a humoral factor, FIM, which is formed and secreted by tissue macrophages. The response of monocyte precursors to FIM is under genetic control.

Animals↗

The two-sex problem with persistent unions: a generalization of the birth matrix-mating rule model.

The birth matrix-mating rule (BMMR) model solves the two-sex problem of classical stable population theory by allowing births to adjust to changes in a population's age-sex composition. To avoid complications the BMMR model assumes that unions last for only a single period. This paper drops that assumption and presents the BMMRPU (BMMR persistent unions) model. To establish the existence of equilibrium in the BMMRPU model, the existence proof used in the BMMR model is supplemented by a fixed-point argument.

Age Factors↗

APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method.

Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.

Anticoagulants↗

High incidence of primary gastric lymphoma in northeastern Italy.

We previously noted an extraordinarily high number of cases of primary gastric lymphoma (PGL) in northeastern Italy. We have now formally compared the incidence in Feltre, Italy, with that in three similar communities in the UK. Each community has a stable population served by a single endoscopy unit and histopathology laboratory. There were 13 times more cases of PGL in Feltre in 1986-91 than in the UK communities (66 vs 5 per 100,000 per 5 years). The incidence of gastric adenocarcinoma was also substantially higher in Feltre than in the UK (270 vs an average of 82 per 100,000 per 5 years), as was the prevalence of gastritis associated with Helicobacter pylori infection (87% of 1343 gastric biopsy samples in 1991).

Humans↗

Endothelial cell adhesion to vascular prosthetic surfaces.

Improving the long term patency of small diameter prosthetic grafts remains an important but elusive objective in vascular surgery. In pursuit of a non-thrombogenic surface, we have cultured human-adult endothelial cells, examined their adhesive properties and their ability to colonize the inner surface of a Dacron graft. To examine cell adhesion, endothelial cells were labelled with 111In-oxine and inoculated onto prosthetic wells previously prepared with either cold insoluble globulin (CIG), 1% gelatin, alginate or left untreated as a control. At 100 min, mean percentage adhesion to CIG and gelatin precoated wells was 86.0 +/- 9.9% (+/- SD) and 81.6 +/- 2.9% respectively, whereas alginate at 57.5 +/- 7.5% and the control well at 48.3 +/- 9.9% showed significantly less adhesion. Further experiments examined the adhesion of Indiumoxine labelled endothelial cells to Dacron graft (2 cm X 6 mm ID) placed in an in vitro arterial circuit. An immediate loss of approximately 20% of the cells occurred within the first 30 s, whereafter, a stable population were adherent to the graft material. By 102 min, 73.4 +/- 1.8% of cells remained attached when exposed to tissue culture medium, but only 64.1 +/- 6.9% after exposure to blood. Cultured human adult endothelial cells adhere most effectively to prosthetic surfaces precoated with CIG or gelatin, and remain attached following exposure to shear forces.

Alginates↗

Differentiation induction therapy of myelodysplastic syndromes.

Myelodysplastic syndromes are a heterogenous group of haemopoietic stem cell disorders characterized by dysplastic haematopoiesis and a defective maturation of a slowly expanding or sometimes of a stable population of haemopoietic progenitors. Defective maturation, which may involve one or more of the marrow cell lineages is regarded as the central pathophysiological feature of myelodysplastic syndromes. Patients with myelodysplastic syndromes respond poorly to conventional cytotoxic chemotherapy, frequently developing a prolonged marrow aplasia. The alternative and more appropriate form of therapy is differentiation induction therapy. The results of few preliminary clinical studies in myelodysplastic patients showed that a combination of differentiating agents is superior to single agent differentiation therapy. An extensive pre-clinical screening of the response of fresh cells from myelodysplastic patients in primary culture is needed to establish the optimal doses and conditions for significant synergies between various differentiating agents followed by large controlled randomized clinical trials based on differentiation induction therapy for patients with myelodysplastic syndromes.

Cell Differentiation↗

Dysplastic nevi can be diagnosed and graded reproducibly: a longitudinal study.

BACKGROUND: Poor interobserver reproducibility in diagnosing and grading dysplastic melanocytic nevi is often cited as evidence against the ability of pathologists to recognize such an entity. OBJECTIVE: We attempted to examine the diagnostic profiles of melanocytic lesions of two dermatopathologists in a stable population base. METHODS: All 2600 melanocytic neoplasms were diagnosed at Stanford University Medical Center during the past 4 years by one dermatopathologist from 1987 to 1989 and a different dermatopathologist in 1990 and 1991. The two independently evaluated these lesions unaware of the other's criteria. RESULTS: The diagnostic profile of the two pathologists shows a striking degree of similarity: 76.7% versus 75.3% of all nevi were diagnosed as acquired melanocytic nevi, 8.8% versus 12.0% were diagnosed as mildly dysplastic, 7.0% versus 6.8% as moderately dysplastic, and 2.7% versus 1.6% as severely dysplastic. CONCLUSION: Our findings suggest that the two pathologists are using reproducible criteria for diagnosing and grading dysplastic nevi.

Dysplastic Nevus Syndrome↗

The myelodysplastic syndromes.

The myelodysplastic syndromes constitute a fascinating model for monoclonal premalignant disorders. Haemopoiesis is 'dysplastic' with inefficient maturation of a slowly expanding or sometimes of a stable population, of blood cell precursors. About one third of the patients evolve into acute leukaemia, the result of either a progressive expansion of the original clone or a new mutation producing a more malignant subclone. The majority of patients suffer from the results of bone-marrow insufficiency, with pancytopenia and possibly immune deficiency. Characteristic karyotype anomalies involving mainly chromosomes 5, 7 and 8 are seen in half the patients. These same chromosomes are known to carry different oncogenes. The myelodysplastic syndrome occurs mainly in the aged and there is a moderate male preponderance. The incidence is still unknown but is probably similar to that of acute leukaemia. The etiology is also unknown; however, a secondary myelodysplastic syndrome precedes acute myeloid leukaemia, as a late consequence of chemo- and radio-therapy in treated Hodgkin's disease. This suggests that environmental mutagens might also be involved in primary myelodysplastic syndromes. Treatment remains highly unsatisfactory but a few recent developments improve prognosis, at least in the younger patient.

Humans↗

The migration of larval Toxocara canis in mice. II. Post-intestinal migration in primary infections.

Following oral infection of NIH mice with Toxocara canis embryonated eggs the L2 pass the visceral phase of migration during te first week of infection. Larvae reach the liver and lungs and peak in number in these organs 2 and 3 days after infection, respectively. Larvae are then dispersed throughout the body and enter the myotropic--neurotropic phase by the 7th day of infection. Larvae injected directly into the brain are capable of migrating into the viscera and musculature. Considerable pathology occurs due to larval migrations, especially through the liver and lungs, and both acute and chronic disease are recorded. Studies of infections extending over a year show that the number of recoverable larvae declines gradually with periods of stable populations. On Days 3, 4 and 5 after infection, larvae were demonstrable in the faeces of infected mice. Prenatal infection was observed in a third of the offspring of mice infected the same day as conception.

Animals↗

Dermal-epidermal interactions.

The dermal papilla is established as a permanent and stable population of specialized fibroblasts that first appear as a cellular aggregate that interacts with the epidermis to ensure follicle development. Our experimental findings strongly suggest that thereafter the papilla, in association with the confluent lower dermal sheath, continues to interact with the follicular epidermis with the papilla cells, which retain their aggregative property, undergoing cyclic changes in size and synthetic activities in phase with the hair cycle. In these activities, the lower follicle dermis appears to act as a functional unit that retains key embryonic characteristics throughout the lifetime of the follicle, re-enacting its inductive influence over follicular epidermis to regulate the profound morphogenetic changes that occur during successive hair cycles and to determine the physical characteristics of the fibers produced. While epidermal mitotic inhibitors have been suggested as a controlling mechanism in the hair cycle, we have argued that the papilla provides potent factors that stimulate epidermal proliferation in the hair germ to initiate, and then sustain, anagen and also follicle morphogenesis. Our recent findings with cocultures of dermal papilla and epidermal cells, which demonstrated that papilla cells enhance epidermal cell attachment and proliferative activity, reinforces this supposition. Thus, it may prove that the intrinsically determined aspect of the hair cycle reflects and is dependent on an intrapapillary cycle of events. Furthermore, we have suggested that at another level of interaction the dermal component of the follicle may mediate the influence of systemic factors, which are known to modify this innately programmed pattern of follicle behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Prognostic use of echocardiography 1 year after a myocardial infarction.

BACKGROUND: Left ventricular (LV) and right ventricular (RV) function are known predictors of morbidity and mortality after an acute myocardial infarction (MI). However, the prognostic use of a late evaluation of cardiac function after an MI remains unclear. METHODS: We analyzed echocardiograms obtained 1 year after MI in patients with LV dysfunction at baseline (ejection fraction [EF] < or = 40%) from 291 patients enrolled in the SAVE echocardiographic substudy who did not develop heart failure (HF) or a recurrent MI during this first year. Left ventricular EF and RV fractional area change were assessed. RESULTS: After a median follow-up of 22 months after the 1-year echocardiogram, a low LVEF (< 30%) at 1 year was associated with an increased risk of death and/or HF (hazards ratio [HR] 2.7, 95% CI 1.3-5.3). Presence of RV dysfunction was also associated with an increased risk of death (HR 8.9, 95% CI 3.5-22.1), development of HF (HR 7.1, 95% CI 3.4-15.0), and the composite end point of death or HF (HR 7.6, 95% CI 4.1-14.2). In multivariate analyses, both low LVEF and RV dysfunction remained independently predictive of the composite end point of death or HF. Patients with biventricular dysfunction were at the greatest risk of death and/or HF (HR 19.4, 95% CI 8.2-46.0) in follow-up. CONCLUSIONS: In a stable population of survivors of MI, impaired LV and RV function at 1 year after MI are independently and additively predictive of increased risk of HF or death.

Female↗

Spontaneous switch from Agamma- to beta-globin promoter activity in a stable transfected dual reporter vector.

Here it is analyzed the expression of a mini locus dual reporter construct composed by a micro-LCR and by the promoters for (A)gamma- and beta-globin gene, each one linked to a different Luciferase, in stably transfected GM979 cells for as long as 1-2 years from transfection. The transfected GM979 cells rapidly (within 1 month) evolved into a stable population which expresses constant levels of reporters for more than a year of continuous bulk culture. No silencing of the inserted construct was observed over time. In contrast, after 1 month, the reporter activity (both from (A)gamma- and beta-promoter) expressed per cell increased over time. The analysis of the Luciferase contained in single cell clones indicated that the higher reporter activity was due to increased gene expression per cell rather than to clonal selection of the most expressing clones. Since the activity driven by the beta-promoter increased 10-fold more than that driven by the (A)gamma one, the ratio between (A)gamma-driven/((A)gamma-driven + beta-driven) reporter activity in the cells decreased after 1 month and became similar to the gamma/(gamma + beta) globin mRNA ratio expressed by adult erythroid cells. Moreover, although both cells from early and late bulk culture responded to incubation with butyric acid, a known inducer of fetal globin gene expression, by increasing the reporter activity driven by the (A)gamma-promoter, only cells from late bulk culture decreased, as normal primary erythroblasts do, the activity of the reporter driven by the beta-promoter. These results suggest that the rapid changes in activity driven by the (A)gamma- and beta-globin promoters occurring during the first month after transfection may represent a novel in vitro model to study epigenetic regulation of the (A)gamma- and beta-promoter during the fetal to adult hemoglobin switch and confirm GM979 cells stably transfected with the dual reporter construct as a reliable assay for automated screening of chemical inducers of fetal globin gene activation.

Animals↗

Microglandular hyperplasia: a model for the de novo emergence and evolution of endocervical reserve cells.

BACKGROUND: Microglandular hyperplasia (MGH) of the cervix in human beings is associated early with gland proliferation and terminates in mature squamous metaplasia. Using antibodies to basal cell markers, we analyzed biopsies with MGH to profile the distribution and evolution of reserve cells and their relationship to these epithelial components. DESIGN: Serial sections of 24 MGHs were subdivided into (1) early MGH with microacinar proliferation, abundant subnuclear vacuoles, and a paucity of supporting stroma and (2) late MGH with more prominent supporting stroma and/or squamous metaplasia. Serial sections were stained with antibodies to p63, bcl-2, and keratin-5. RESULTS: Three patterns of p63 staining were observed corresponding to the age of the MGH: (1) scattered staining of columnar cells, (2) focal subcolumnar staining in a reserve cell distribution, and (3) linear subcolumnar arrays of p63-positive reserve cells that in some MGHs expanded into a squamous metaplasia. Early acinar proliferations showed weak and focal columnar cell staining followed by focal subcolumnar p63-positive cells. In late lesions, p63 staining was compartmentalized to the extraglandular (or subcolumnar) areas. Stainings of p63, bcl-2, and keratin-5 were concordant. Staining for keratin 14, which localizes to squamous cells, was variable. CONCLUSIONS: The immunohistochemical profile in MGH indicates that reserve cells are created in adulthood during specialized columnar proliferations. This columnar to reserve cell transition may produce a stable population of reserve cells or a transition to squamous metaplasia. Similar patterns are seen in cervical neoplasia, suggesting a link between benign and neoplastic cervical epithelial differentiation.

Biomarkers↗

Harvesting induced fluctuations: insights from a threshold management policy.

In this work, it is shown that in a deterministic context, a threshold policy can induce cyclic behavior in an otherwise exploited stable population. These dynamics ensue as a result of the combination of the degree of harvesting pressure and more protective threshold densities. Virtual equilibrium in variable structure systems plays a determinant role in this dynamical outcome.

Animals↗