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Biomedical subjects

C Kane

Publications and source records attributed to C Kane.

At least 37 records · Page 2Linked to original sources
PubMed1996

Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder of childhood associated with inappropriate hypersecretion of insulin by the pancreas. The pathogenesis of the condition has hitherto remained controversial. We show here that insulin-secreting cells from a homogeneous group of five infants with PHHI lack ATP-sensitive K+ channel (KATP) activity. As a consequence, PHHI beta-cells are spontaneously electrically active with high basal cytosolic Ca2+ concentrations due to Ca2+ influx. Our findings define the pathogenesis of this disease as a novel K+ channel disorder.

ATP-Binding Cassette Transporters↗
PubMed1996

Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus-response coupling of insulin release.

1. Microfluorimetry techniques with fura-2 were used to characterize the effects of efaroxan (200 microM), phenotolamine (200-500 microM) and idazoxan (200-500 microM) on the intracellular free Ca2+ concentration ([Ca2+]i) in mouse isolated islets of Langerhans. 2. The imidazoline receptor agonists efaroxan and phentolamine consistently elevated cytosolic Ca2+ by mechanisms that were dependent upon Ca2+ influx across the plasma membrane; there was no rise in [Ca2+]i when Ca2+ was removed from outside of the islets and diazoxide (100-250 microM) attenuated the responses. 3. Modulation of cytosolic [Ca2+]i by efaroxan and phentolamine was augmented by glucose (5-10 mM) which both potentiated the magnitude of the response and reduced the onset time of imidazoline-induced rises in [Ca2+]i. 4. Efaroxan- and phentolamine-evoked increases in [Ca2+]i were unaffected by overnight pretreatment of islets with the imidazolines. Idazoxan failed to increase [Ca2+]i under any experimental condition tested. 5. The putative endogenous ligand of imidazoline receptors, agmatine (1 microM-1 mM), blocked KATP channels in isolated patches of beta-cell membrane, but effects upon [Ca2+]i could not be further investigated since agmatine disrupts fura-2 fluorescence. 6. In conclusion, the present study shows that imidazolines will evoke rises in [Ca2+]i in intact islets, and this provides an explanation to account for the previously described effects of imidazolines on KATP channels, the cell membrane potential and insulin secretion in pancreatic beta-cells.

Adrenergic alpha-Antagonists↗
PubMed1996

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.

Blood Glucose↗
PubMed1996

Activation of ATP-dependent K+ channels and inhibition of insulin release: effect of BPDZ 62.

The present study was undertaken to characterize the effects of BPDZ 62, an original pyridothiadiazine derivative structurally related to both diazoxide and pinacidil, on ionic and secretory events in the rat pancreatic islet cells. BPDZ 62 increased the rate of 86Rb outflow from islets perfused in the presence or absence of extracellular glucose. These effects persisted in the absence of extracellular Ca++ but were abolished by glibenclamide. Such data support the view that BPDZ 2 activates ATP-sensitive K+ (K(ATP)) channels. This proposal was substantiated by the finding that the drug enhanced the flow of current through K(ATP) channels in excised inside-out membrane patches. BPDZ 62 markedly decreased 45Ca uptake, 45Ca outflow and insulin output from islets incubated in the presence of 16.7 mM glucose. By contrast, the drug did not affect the increase in 45Ca outflow and 45Ca uptake mediated by K+ depolarization. In single B cells, BPDZ 62 inhibited the glucose but not the KCl-induced rise in [Ca++]i. It is concluded that the inhibitory effect of BPDZ 62 on the insulin-releasing process results from the activation of K(ATP) channels leading to a decrease in Ca++ influx and [Ca++]i. Last, BPDZ 62 was shown to be five times more potent than diazoxide at inhibiting the insulin-releasing process. This suggests that BPDZ 62 could be a valuable pharmacological tool for further characterization of B-cell K(ATP) channels.

Adenosine Triphosphate↗
PubMed1995

Frequency of Travel of Adults Infected with HIV.

Background: Little is known about the frequency and pattern of travel in the HIV-infected population. Method: A test questionnaire administered to patients cared for at a public hospital HIV clinic examined the frequency, destinations, and motivations for travel of persons with HIV disease. Results: Of 89 persons surveyed, 46% had traveled within the preceding 2 years within the United States for a minimum of 1 week, or to a foreign destination. Forty patients (45%) had traveled to a mean of 3.4 destinations within the United States for an average trip duration of 16 days. In addition, 18 patients (20%) had traveled to at least one foreign country for an average of 20 days. Of the 25 foreign destinations that were specified, 15 (60%) were in lesser developed countries. Patients stated that they undertook 30% of their trips because they thought it was their last chance to travel. At the time of completion of the survey, the majority of those patients who had traveled were severely immunosuppressed (median CD4+ count, 120/mm3). Conclusions: These data provide information by which the clinician can anticipate the health care needs of patients who travel and develop appropriate travel medicine guidelines. (J Travel Med 2:85-88, 1995)

Journal Article↗
PubMed1994

Transient bacteremia due to Mycobacterium avium complex in patients with AIDS.

It is generally assumed that Mycobacterium avium complex (MAC) bacteremia, once it develops, is unremitting. On the basis of this presumption, changes in the level of mycobacteremia are used to gauge therapeutic response. In 7 (12%) of 60 patients enrolled in a prospective trial of MAC bacteremia and AIDS, bacteremia became undetectable before the initiation of antimycobacterial therapy. Patients with transient bacteremia reported fewer and shorter symptoms and survived longer than those with sustained bacteremia (59 vs. 31 weeks; P = .022). There was no difference in the duration of AIDS, CD4+ cell count, hematocrit, or body weight between groups. Two additional patients with transient bacteremia were identified outside this study setting. Despite disappearance of detectable mycobacteremia and subsequent administration of antimycobacterial agent(s), bacteremia once again became detectable in 6 patients 4-45 weeks after their negative pretreatment cultures. Patients with disseminated MAC may have fluctuating levels of mycobacteremia that become undetectable in the absence of antimycobacterial therapy.

AIDS-Related Opportunistic Infections↗
PubMed1993

Fetal ACTH and blood pressure responses to thromboxane mimetic U-46619.

This study was performed to test the hypothesis that thromboxane A2 stimulates increases in fetal adrenocorticotropic hormone (ACTH), vasopressin, or renin secretion and affects fetal cardiovascular function by an action on the fetal central nervous system. We infused a stable synthetic analogue of thromboxane A2, U-46619, into one common carotid artery or inferior vena cava or infused saline into one common carotid artery in chronically catheterized fetal sheep between 127 and 140 days gestation. We found that intracarotid but not intravenous infusions of U-46619 at a rate of 750 ng/min stimulated increases in fetal plasma ACTH concentration. Infusions of U-46619 at both sites increased fetal blood pressure; the infusion into the carotid arterial blood produced a more rapid increase in blood pressure and a significant decrease in central venous pressure. None of the infusions altered plasma vasopressin concentration or plasma renin activity, blood gases, hematocrit, or plasma cortisol concentration. We conclude that thromboxane A2 stimulates fetal ACTH, but not vasopressin or renin, secretion via an action within the area perfused by carotid arterial blood. Thromboxane A2 increases blood pressure via an action at the fetal central nervous system, as well as via a direct vasoconstrictor action in the systemic circulation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Family management of schizophrenia: a comparison of behavioral and supportive family treatment.

This paper reports a comparison of behavioral and supportive family treatment for family management of schizophrenia. The family project applied two psycho-educational approaches to a highly "treatment resistant" population of young adults afflicted with chronic mental illness. The study compares and contrasts the effects of behavioral and supportive family management programs on clinical outcomes. Clinical improvements were associated with both family interventions. Discussion is provided on the relevance of this work to the growing body of evidence concerning the efficacy of psychoeducational family intervention for the management of schizophrenia.

Adolescent↗
PubMed1990

Isolation and characterization of renin-expressing cell lines from transgenic mice containing a renin-promoter viral oncogene fusion construct.

We constructed transgenic mice containing a renin-promoter SV40 T antigen fusion transgene with the intention of inducing neoplasia in renin-expressing cells and isolating renin-expressing cell lines in vitro. We examined six kidney tumors from mice representing three different transgenic lines and found they expressed their endogenous renin gene. Initially, five nonclonal kidney tumor-derived cell lines were established which expressed their endogenous renin gene in addition to the transgene. They retained active renin intracellularly and constitutively secreted an inactive form of renin (prorenin). One of these cell lines was cloned to homogeneity. This line maintained high level expression of renin mRNA throughout 3 months of continuous culture. Although the cells contained an equal proportion of active and inactive renin, the species constitutively secreted into the media was predominantly (95%) prorenin. However, active renin secretion was stimulated 2.3- and 4.6-fold by treatment with 8-bromo-cAMP after 4 and 15 h, respectively. In addition, the presence of multiple secretory granules was confirmed by ultrastructural analysis. These cells, which express renin mRNA and can regulate secretion of active renin, should provide an excellent tool for studying renin gene regulation and secretion. Furthermore, these mice should provide a useful source for the establishment of renin-expressing cell lines from a variety of renin-expressing tissues.

Animals↗
PubMed1990

Peripheral chemoreceptor control of fetal renin responses to hypoxia and hypercapnia.

The renin response to hypoxia in late gestation fetal sheep has been well characterized. However, the renin response to asphyxia--the combination of hypoxia and hypercapnia--has not been extensively studied. The purpose of this study was to determine 1) the interaction of hypoxia and hypercapnia in the control of renin secretion in late gestation fetal sheep and 2) the role of peripheral arterial chemoreceptors therein. Chronically catheterized fetal sheep (intact or sinoaortic denervated) were exposed to hypoxia and/or hypercapnia for 30 minutes. Hypercapnia alone had no effect on plasma renin activity or aldosterone but did result in a significant increase in angiotensin II. Hypercapnia combined with hypoxia resulted in a significant increase in renin activity, angiotensin II, and aldosterone. Sinoaortic denervation attenuated the renin and angiotensin II responses to hypercapnia plus hypoxia. The increase in renin and angiotensin II in response to hypercapnia with or without concomitant hypoxia strongly correlated with the magnitude of the decrease in arterial pH in intact fetuses only. Hypoxia alone and in concert with hypercapnia increased mean arterial pressure and decreased heart rate in intact but not sinoaortic denervated fetuses. We conclude that 1) hypercapnia more potently increases plasma renin activity than does hypoxia in late gestation fetal sheep, 2) arterial pH may be the relevant signal perceived by the peripheral arterial chemoreceptors for the control of the renin-angiotensin system during asphyxia, and 3) the cardiovascular response to hypoxia is mediated, in part, by peripheral arterial chemoreceptors.

Aldosterone↗
PubMed1985

Obstructive uropathy associated with endometriosis.

Although endometriosis involving the urinary tract is uncommon, it is responsible for considerable morbidity. A review of eight cases at two Ottawa teaching hospitals from 1979 to 1983 revealed obstructive uropathy in seven patients. There was permanent loss of kidney function in two, ovarian remnant syndrome in two, and patient and family history of renal disease in three. The diagnosis of endometriosis was not made before operation in four patients. Endometriosis was localized in four patients and generalized in the remaining four, while four patients had significant uterosacral nodularity. The conclusion reached after study of this small but important population is that physicians should have a heightened awareness of this uncommon but serious manifestation of the disease. Earlier diagnosis might be achieved on the basis of a high index of suspicion and careful physical and pelvic examination. The liberal use of intravenous pyelography even in cases of minimal endometriosis is urged. Intensive and prolonged follow-up of all patients with the diagnosis of endometriosis is recommended until the menopause has been reached. Treatment of obstructive uropathy requires meticulous surgical intervention and we recommend ovarian ablation with adjuvant hormonal therapy in most circumstances.

Adult↗