Work on your theories!
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Breast Neoplasms↗
Biomedical subjects
M Baum
Publications and source records attributed to M Baum.
The role of the spleen in the leucocytosis of exercise: consequences for physiology and pathophysiology.
Thirteen patients after splenectomy and 13 control subjects participated in the study. The splenectomy was caused in all cases by accidents, none of the participants had had hematological disorders. All of them exercised to exhaustion on a cycle ergometer, beginning with 1 Watt/kg body weight (b.w.) and increasing 0.5 W/kg b.w. every 5 min. Blood samples were taken before and immediately after exercise. The following lymphocyte subsets were determined: CD14+/CD45+, CD3+, CD20+/CD23+, CD4+/CD25+, CD8+, CD16+/CD56+/CD3-. Furthermore, sIL2-R, neopterin and IGG and IGM were measured. The control group exercised more intensively and reached significantly higher levels of lactic acid and catecholamines (adrenaline and noradrenaline). Under conditions of rest all white blood cell counts were higher in the patients group, levels of significance were reached by lymphocyte and B-cell count. B-cells also showed a significantly higher expression of the CD23 antigen. IGM, s-IL2-R and neopterin levels were not significantly different between the two groups. After exercise all cell counts increased significantly, between the two groups no significant differences were seen. We conclude that the pattern of white blood cell mobilization is unchanged after splenectomy, especially natural-killer cell (the subset most sensitive to catecholamines and exercise) mobilization is not impaired. Therefore the importance of the spleen as storage tissue for white blood cells seems to be low with reference to the exercise induced leucocytosis. The elevated expression of the CD23-antigen might indicate a higher activation level of the B-cell system.
Adult↗
Human herpesvirus type 8 DNA sequences in cell-free plasma and mononuclear cells of Kaposi's sarcoma patients.
Human herpesvirus (HHV) type 8 has been detected in both classical and AIDS-related Kaposi's sarcoma, body-cavity lymphomas, and other types of tumors. HHV-8 has also been detected in DNA from peripheral blood mononuclear cells (PBMC) of some Kaposi's sarcoma patients and more readily in B cell fractions derived from panned cell subpopulations. Two patients were followed using several methods; in situ hybridization, solution-based polymerase chain reaction (PCR), and in situ PCR. HHV-8 was intermittently detected in plasma, and detection correlated with detection in PBMC. In situ PCR demonstrated HHV-8 sequences in both peripheral blood B lymphocytes and, to a lesser extent, T lymphocytes. HHV-8 may undergo periods of viremia while at other times it is undetectable and infects circulating B cells and some T cells.
Adult↗
Glucocorticoids regulate NHE-3 transcription in OKP cells.
OKP cells express NHE-3, an amiloride-resistant Na+/H+ antiporter, which is likely an isoform responsible for apical proton secretion by the proximal tubule. We have previously shown that an amiloride-resistant Na+/H+ antiporter in OKP cells is regulated by dexamethasone, a synthetic glucocorticoid. The purpose of the present study was to examine the mechanism for the glucocorticoid-mediated increase in Na+/H+ antiporter activity. Incubation of OKP cells with 10(-6) M dexamethasone resulted in a two- to threefold increase in NHE-3 mRNA abundance. This increase was seen after 4 h of incubation with dexamethasone, a time course similar to that found for Na+/H+ antiporter activity. To examine the mechanism for the increase in NHE-3 mRNA abundance, mRNA half-life and in vitro transcription experiments were performed. NHE-3 mRNA had a half-life of 8 h in control and dexamethasone-treated cells. The rate of in vitro transcription was 1.8-fold greater when OKP cells were treated with dexamethasone. These data suggest that the glucocorticoid-mediated increase in Na+/H+ antiporter activity is due to an increase in NHE-3 gene transcription.
Animals↗
Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates.
Intracellular cystine loading by use of cystine dimethyl ester (CDME) results in a generalized inhibition in proximal tubule transport due, in part, to a decrease in intracellular ATP. The present study examined the importance of phosphate and metabolic substrates in the proximal tubule dysfunction produced by cystine loading. Proximal tubule intracellular phosphorus was 1.8 +/- 0.1 in control tubules and 1.1 +/- 0.1 nmol/mg protein in proximal tubules incubated in vitro with CDME P < 0.001). Infusion of sodium phosphate in rabbits and subsequent incubation of proximal tubules with a high-phosphate medium attenuated the decrease in proximal tubule respiration and prevented the decrease in intracellular ATP with cystine loading. Tricarboxylic acid cycle intermediates have been shown to preserve oxidative metabolism in phosphate-depleted proximal tubules. In proximal tubules incubated with either 1 mM valerate or butyrate, there was a 42 and 34% reduction (both P < 0.05) in the rate of oxygen consumption with cystine loading. However, tubules incubated with 1 mM succinate or citrate had only a 13 and 14% P = NS) reduction in the rate of oxygen consumption, respectively. These data are consistent with a limitation of intracellular phosphate in the pathogenesis of the proximal tubule dysfunction with cystine loading.
Adenosine Triphosphate↗
Ontogeny of the extracellular calcium-sensing receptor in rat kidney.
We recently cloned extracellular Ca(2+)-sensing receptors (CaRs) from bovine parathyroid and rat kidney that play key roles in Ca2+ homeostasis. Inactivating mutations of the CaR in the inherited human disorder, familial hypocalciuric hypercalcemia, cause reduced responsiveness of the parathyroid to extracellular Ca2+ (Cao2+), as well as abnormally avid renal tubular reabsorption of both Ca2+ and Mg2+ in the distal tubule, suggesting an important role for the CaR in regulating parathyroid hormone (PTH) secretion and renal handling of divalent cations. High Cao2+ also inhibits vasopressinstimulated adenosine 3',5'-cyclic monophosphate accumulation in the medullary thick ascending limb (MTAL) and water reabsorption in the collecting duct (CD) and modulates various other aspects of renal function. The relevance of the CaR to these processes, however, is uncertain. Reduced responsiveness of vasopressin-and PTH-mediated actions on the kidney have been described in the newborn that could potentially reflect effects of the CaR on these aspects of renal function. To define further the role of the CaR in regulating renal function, including the above-mentioned changes during the perinatal period, therefore, we have studied its ontogeny in rat kidney. Northern and Western blot analyses, as well as immunohistochemistry with CaR-specific probes, demonstrate that there is little prenatal expression of the extracellular Ca(2+)-sensing receptor, except in large tubules and branching ureteric buds of developing nephrons. Postnatally, CaR mRNA and protein increase markedly during the 1st wk, related principally to expression of the receptor in the developing TAL and, to a lesser extent, in the CD. The level of expression of the receptor remains nearly constant after postnatal day 14. These results demonstrate that the perinatal increases in expression of CaR mRNA and protein parallel its tissue-specific renal expression. Furthermore, it is possible that some of the previously described changes in renal handling of divalent cations and water in the perinatal and immediate postnatal period are related, in part, to the increasing levels of expression of the CaR and resultant inhibitory effects on the actions of PTH and antidiuretic hormone on the developing nephron.
Aging↗
Developmental changes in rabbit juxtamedullary proximal convoluted tubule water permeability.
The mammalian proximal tubule reabsorbs the bulk of the glomerular filtrate in a nearly isosmotic fashion due to the high osmotic water permeability (Pf) of this segment. Although the characteristics of proximal tubule water transport have been studied in the adult proximal tubule, little is known about the neonatal segment. The present study directly measured the Pf and diffusional water permeability (PDW) of neonatal (10 +/- 2 day old) and adult rabbit juxtamedullary proximal convoluted tubules (PCT) using in vitro microperfusion. The Pf of neonatal juxtamedullary PCT was greater than the Pf of adult juxtamedullary PCT. In contrast, the PDW was not different between the two groups. The Pf and PDW values of both neonatal and adult tubules were inhibited to the same degree by p-chloromercuribenzene sulfonate and had identical activation energies. The transepithelial reflection coefficients of NaCl and NaHCO3 were also found to be similar in both the neonatal and adult proximal tubules. Thus neonatal and adult juxtamedullary PCT have many characteristics of water transport that are identical; however, neonatal Pf is three to five times that of the adult value. This difference in Pf with identical PDW values may give an insight into the transepithelial pathway for water movement in the neonatal tubule.
Aging↗
Quack cancer cures or scientific remedies.
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Breast Neoplasms↗
Maturation of rabbit proximal convoluted tubule chloride permeability.
Chloride transport in the rabbit proximal convoluted tubule (PCT) has components of active, transcellular, and passive, paracellular transport. The preferential reabsorption of bicarbonate and organic solutes by the early proximal tubule leaves the luminal fluid with a higher chloride concentration than that in the peritubular capillaries. Previous studies have suggested that solute permeability of the paracellular pathway may be higher in the neonatal PCT and that the neonatal proximal tubule reabsorbs solutes by passive mechanisms to a greater extent than the adult segment. A higher chloride permeability would provide a mechanism for the greater rate of passive NaCl transport by the neonatal proximal tubule. The purpose of the present in vitro microperfusion study was to directly examine the chloride permeability of neonatal and adult PCT. Superficial and juxtamedullary, neonatal and adult PCT were perfused with a high chloride perfusate without organic solutes, simulating late proximal tubular fluid, at 20 degrees C, and bathed in a serum-like albumin solution. Chloride concentrations in the perfusate and the collected fluid were measured by electrometric titration. Neonatal juxtamedullary PCT chloride permeability (PCl) was significantly lower than adult juxtamedullary PCT PCl (0.15 +/- 0.25 x 10(-5) cm/s versus 5.23 +/- 0.57 x 10(-5) cm/s, p < 0.001). The PCl of neonatal superficial PCT was not different from that of adult superficial PCT (0.81 +/- 0.48 x 10(-5) cm/s versus 0.05 +/- 0.62 x 10(-5) cm/s). Thus, there is a maturational increase in juxtamedullary PCT PCl, whereas superficial PCT PCl remains very low. The passive diffusion of chloride in neonatal PCT is extremely low and is not a mechanism to explain a higher rate of passive NaCl transport in this segment.
Animals↗
Breast cancer--a challenge to the contemporary paradigm.
There is much triumphalism about the apparent progress in the diagnosis and management of breast cancer and yet the impact on mortality from this disease in both the United States of America and Europe has been quite trivial. The early results of adjuvant systemic therapy have been sustained out of 15 to 20 years, which presumably accounts for the majority of the mortality reductions we are seeing, yet it is my impression that progress has slowed down, if not plateaued. For that reason it is time to reconsider our prejudices and recognize that we will need another conceptual revolution before there is the next important incremental step forward. It is here proposed that the current concepts on the initiation and progress of micrometastases are wrong and that we need to develop a new paradigm based on our current knowledge of cell and molecular biology which recognizes that occult metastases that ultimately are the cause of breast cancer mortality are complex organisms, maintained in the state of dynamic equilibrium. This equilibrium can be perturbed by 'premature' surgery, so that the whole concept of 'early diagnosis' and prompt treatment might be fundamentally flawed. Therapeutic interventions that may control rather than 'cure' breast cancer using biological specific modalities rather than non-specific cytotoxic drugs could provide some of the answers. An even more radical challenge to the contemporary paradigm is suggested. Perhaps not all metastases are cellular phenomena, maybe in vivo transfection by endogenous retroviral-like particles allows breast cancer to escape destruction by chemotherapy?
Breast Neoplasms↗
Nephrocalcinosis is associated with renal tubular acidosis in children with X-linked hypophosphatemia.
BACKGROUND: X-linked hypophosphatemia is characterized clinically by rickets and growth retardation. Therapy of this disorder with phosphate and vitamin D often produces nephrocalcinosis. The long-term effects of nephrocalcinosis on renal function in patients with X-linked hypophosphatemia are unknown. The purpose of this study was to evaluate the prevalence of glomerular and tubular disorders in patients with X-linked hypophosphatemia who developed nephrocalcinosis. METHODS: The creatinine clearance and the prevalence of renal tubular acidosis were compared in 19 patients with X-linked hypophosphatemia and nephrocalcinosis with 15 patients with X-linked hypophosphatemia without nephrocalcinosis. RESULTS: Sixteen of the 19 patients (84%) with nephrocalcinosis had a hyperchloremic metabolic acidosis compared with one of the 13 patients without nephrocalcinosis (P < .01). The serum bicarbonate of patients with nephrocalcinosis was 20.0 +/- 0.7 as compared to 24.5 +/- 0.6 mmol/L in patients without nephrocalcinosis (P < .01). The urinary anion gap was positive in all patients with acidosis (+62.1 +/- 13.3 mmol/L). The creatinine clearance was 125 +/- 6 mL/min/1.73 m2 in patients with nephrocalcinosis and 124 +/- 7 mL/min/1.73 m2 in those without nephrocalcinosis. CONCLUSION: Therapy of X-linked hypophosphatemia is often associated with nephrocalcinosis. Nephrocalcinosis is associated with renal tubular acidosis in patients with X-linked hypophosphatemia.
Acidosis, Renal Tubular↗
Pneumocystis carinii pneumonia in infants after heart transplantation.
Although the reported incidence of Pneumocystis carinii pneumonia after heart transplantation in adults ranges from 3% to 40%, data are lacking regarding the incidence in the pediatric heart transplantation population. A retrospective review was performed on 152 infants (0 to 12 months of age) undergoing transplantation from November 1985 through December 1993 who survived at least 6 months after heart transplantation. Patients did not receive postoperative Pneumocystis carinii prophylaxis. Ten episodes (7%) were diagnosed in four neonates and six infants. The mean postoperative time to Pneumocystis carinii diagnosis was 5 months (range 3 to 9 months). Features of Pneumocystis carinii included hypoxia and tachypnea (10 of 10), progressive interstitial infiltrates (8 of 10), and persistent right middle lobe consolidation (1 of 10). Pneumocystis carinii was diagnosed with the use of bronchoscopy in eight cases and by open lung biopsy in two cases. Mean CD4 count available on five patients at the time of Pneumocystis carinii diagnosis was 413/mm3 (range 158 to 1358); 5 of 37 patients receiving antithymocyte induction had Pneumocystis carinii versus 5 of 115 patients who did not receive induction (p = 0.05). Patients were at increased risk for the development of Pneumocystis carinii if they had more than two episodes of rejection during the first year after heart transplantation (p = 0.04). All cases were successfully treated with trimethoprim/sulfamethoxazole. The incidence of Pneumocystis carinii in infant heart transplantation recipients is approximately 7% and appears most frequently in the first 6 months after the operation. Increased risk for Pneumocystis carinii may be related to early antithymocyte induction and increased episodes of rejection.
Anti-Infective Agents↗
Screening for breast cancer, time to think--and stop?
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Breast Neoplasms↗
Breast Cancer: A Revolutionary Concept.
In this paper we trace the evolution of paradigms concerning the nature of breast cancer and their therapeutic consequences. There is no doubt that the conceptual revolution of about 20 years ago has led to modest gains in survival following the use of adjuvant systemic therapy and the quality of survival by demonstrating the safety of conservative surgical regimens. At the same time, there seems to be a plateau in progress. The results of adjuvant systemic therapy are not as good as anticipated and there are a number of other inconsistencies within the conventional model of biological predeterminism that remain to be explained. We offer up an alternative paradigm that suggests that not all metastases are due to cellular dissemination with late onset local and distant recurrence resulting from a transfection phenomenon, whereby subcellular particles shed by the primary cancer cell are taken up by wandering cells of the monocyte macrophage system and transported to distant sites where the local mesenchymal cells are transfected with the genetic information that activates components of the genome to instruct these plastic cells to express the phenotypic picture of a dedifferentiated breast duct epithelial cell. Such a conceptual revolution will open up the way for a new program of research and the development of therapies based on anti-viral rather than cytotoxic drugs.
Journal Article↗
Screening for breast cancer. Informed consent may increase non-attendance rate.
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Breast Neoplasms↗
Value of mammography for women aged 40-49.
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Adult↗
Catecholamines, lymphocyte subsets, and cyclic adenosine monophosphate production in mononuclear cells and CD4+ cells in response to submaximal resistance exercise.
We examined the effect of 30 min of submaximal resistance exercise on free and sulphoconjugated plasma catecholamine concentrations determined by high performance (-pressure) liquid chromatography separation, the distribution of circulating lymphocytes quantified by flow cytometry, and isoproterenol induced cyclic adenosine monophosphate (cAMP) production in mononuclear cells (MNL) and CD4+ cells. Venous blood samples were taken before, immediately after and 45 min after exercise. Resistance exercise increased free plasma adrenaline (A) and noradrenaline (NA) concentrations, whereas sulphoconjugated catecholamine concentrations remained unchanged. Exercise induced leucocytosis and lymphocytosis was predominantly manifested by an increase in the number of total lymphocytes, monocytes, CD3+, CD8+ cells and CD3- CD16/CD56+ cells. Redistribution resulted in a decrease in the CD4+:CD8+ ratio. The total number and distribution of lymphocytes returned to baseline after 45-min rest. An exercise-induced increase in the number of CD3- CD16/CD56+ cells was significantly correlated with the increase in plasma NA (r = 0.66; P = 0.035), indicating a NA dependent process of redistribution. The cAMP-production in MNL was significantly elevated after resistance exercise, when cells were stimulated with 1 mumol.1(-1) isoproterenol [pre-exercise 16.5 (SD 3.3); postexercise 21.6 (SD 9.8); 45 min postexercise 10.7 (SD 2.8)]. The cAMP production in CD4+ cells was not affected by exercise. Therefore, it is discussed whether redistribution is responsible for the exercise induced increase in cAMP production in MNL.
Adult↗
Stimulation of growth hormone secretion in children with X-linked hypophosphatemia.
X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8 +/- 0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225 +/- 38 ng/ml and IGF binding protein-3 was 3.0 +/- 0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response to L-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.
Adolescent↗