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PubMed2001

Essential role of a fast persistent inward current in action potential initiation and control of rhythmic firing.

In spinal motoneurons in an in vivo preparation, we investigated the relationship between a fast persistent inward current located in or near the soma and the capacity of these cells to fire rhythmically. The fast persistent current could be markedly reduced by prolonged depolarization. Modest reductions resulted in profound changes in the slope of the frequency-current relationship. At greater reduction levels, rhythmic firing failed and could not be restored by increasing injected current. However, fully formed spikes still occurred in a slow, uncoordinated fashion, suggesting that the fast inactivating Na(+) currents that generate the spike itself remained unchanged. Consequently, the fast persistent inward current, which may be primarily generated by persistent Na(+) channels, appears to be essential for initiation of spikes during rhythmic firing. Additionally, it appears that the fast persistent current plays a major role in setting the frequency-current gain.

Action Potentials↗
PubMed2001

Are all older adults with persistent pain created equal? Preliminary evidence for a multiaxial taxonomy.

BACKGROUND: Persistent pain is grossly undertreated in older adult sufferers, despite its high prevalence in this age group. Because of its multidimensional impacts, including depression, sleep disruption and physical disability, patients with persistent pain often benefit from interdisciplinary pain clinic treatment. This treatment is expensive, however, and may not be required by all patients. The Multiaxial Assessment of Pain (MAP) has demonstrated value in predicting response to treatment in younger adults with persistent pain. OBJECTIVE: To examine the feasibility of a MAP taxonomy for community-dwelling adults age 65 years or older. PARTICIPANTS AND PROCEDURES: One hundred eight subjects with persistent pain (mean age 73.8 years, SD=8.4 years) were interviewed and data collected on demographics, pain intensity, depressive symptoms, sleep disruption, pain interference with performance of basic and instrumental activities of daily living, frequency of engagement in advanced activities of daily living, cognitive function and comorbidity. A subset of these subjects underwent physical capacities testing, including maximal isometric lift strength, dynamic lifting endurance, timed chair rise and balance. RESULTS: Analyses derived three primary clusters of patients. Cluster 1 (24%) reported less intense pain, less depression and sleep disruption, and higher activity levels. Cluster 3 (30%) suffered from more pain and were more functionally disabled. Cluster 2 (46%) had characteristics of cluster 1 and cluster 3, but with some characteristics that were clearly unique. CONCLUSIONS: While these results are preliminary and require further validation, they indicate that older adults are heterogeneous in their response to persistent pain. Future studies should be performed to examine whether the MAP taxonomy is applicable to older adults regardless of medical diagnosis. Ultimately, this information may have meaning with regard to both treatment prescribing, and the design and interpretation of intervention studies.

Aged↗
PubMed2004

Identifying children with persistent asthma from health care administrative records.

BACKGROUND: Investigation into the origins of asthma is contingent on definitions of asthma, which can differentiate asthma from transient wheezing syndromes in children. OBJECTIVES: This research was undertaken to develop a definition for asthma derived from health care administrative records, which would identify children with persistent asthma. PATIENTS AND METHODS: Using population-based, health care administrative data, children with possible asthma were identified as having one or more physician visits or hospitalizations for asthma or bronchitis diagnoses from January 1995 to December 1995, or, in the absence of asthma-like diagnoses, one or more prescriptions for asthma prophylaxis drugs or ketotifen concomitant with a beta-agonist, or two or more prescriptions for beta-agonists. RESULTS: The likelihood of persistent asthma, defined as repeated health care and prescription use for asthma from 1996 to 1998, was assessed for various asthma markers and risk factors in 29,198 children with possible asthma. Children with asthma prescription drugs or asthma health care use not limited to the winter season were three to six times more likely than children without these characteristics to have persistent asthma. The likelihood of persistent asthma was elevated to a substantial degree in the presence of both of these markers. CONCLUSIONS: The inclusion of these measures in a diagnosis-based definition improves the ability to identify persistent asthma in children.

Adolescent↗
PubMed2001

Simultaneous microsurgical spermatic vein ligation and sclerotherapy. a combined procedure for the treatment of recurrent or persistent varicocele.

OBJECTIVES: Microsurgical ligation as well as antegrade sclerotherapy have been established in varicocele treatment. The aim of this study was to evaluate whether a combination of microsurgery and sclerotherapy can provide a safe and effective treatment of varicocele recurrence or persistence. METHODS: Nine patients with recurrent or persistent varicoceles were operated by means of the combination method. Under microscopic control varix veins were ligated selectively preserving lymphatics and arteries. Ectopic veins as a possible source for varicocele persistence or recurrence were also ligated. Finally, an intraoperative venography with subsequent sclerotherapy was performed through one of the dissected veins. RESULTS: Despite difficult anatomical situations after previous surgical interventions, the operations were performed successfully without any complications. Clinical controls showed varicocele disappearance without damage of the testis. No varicocele recurrence or persistence was observed. CONCLUSIONS: This method combines the advantages of both methods. Precision of the microsurgical technique is combined with velocity of sclerotherapy. Thus, it may represent an interesting alternative to conventional operation methods especially in the treatment of recurrent or persistent varicoceles.

Combined Modality Therapy↗
PubMed1978

Induction of persistent estrus by constant light: effects of neonatal constant light and Harderian gland function.

The effect of constant light on the age at onset of persistent estrus was compared in rats exposed to constant light since birth (LL-0) and those exposed beginning at 70 days of age (LL-70). Persistent estrus occurred about 27 days later in the LL-0 rats than in the LL-70 rats. Exposure to LL for just the 1st 15 days of life (LL-0-15) and then subsequent exposure to LL at 71 days also delayed the induction of persistent estrus. Neonatal injection of a Harderian gland (HG) homogenate to LL-0-15 rats reduced the age of vaginal opening and 1st estrus and reduced the delayed onset of persistent estrus caused by the neonatal LL. Harderianectomy of LL-0 or hematoporphyrin injections in LL-0-15 rats had no effect on the onset of LL-induced persistent estrus.

Animals↗
PubMed1988

Pituitary gonadotropin-releasing hormone binding sites in persistent estrous rats.

Pituitary gonadotropin-releasing hormone (GnRH) binding sites were studied in persistent estrous rats. For comparison females at different stages of the estrous cycle, ovariectomized animals, and intact males were examined. Persistent estrus was induced by a hypothalamic knife cut, administering testosterone to neonatal rats, or by constant illumination. Rats showing spontaneously such alteration were also used in the experiment. Besides pituitary GnRH-binding sites, the GnRH content of the median eminence and plasma luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone concentrations were determined. Pituitary GnRH receptors changed during the estrous cycle with the highest concentrations observed on proestrus. In rats in persistent estrus, pituitary GnRH-binding sites varied between proestrous and estrous values of cyclic females. Ovariectomy resulted in a significant increase in receptors. Depending on how the persistent estrous syndrome was induced, very different amounts of GnRH were found in the median eminence of the various groups. Our data indicate that the GnRH-binding sites on pituitary cells of persistent estrous rats are in essence not changed.

Animals↗
PubMed1983

Serum bile acid levels in children with chronic persistent hepatitis and chronic aggressive hepatitis.

A statistical study was carried out to determine if fasting serum bile acid levels are clinically useful in differentiating children with chronic persistent hepatitis from children with chronic aggressive hepatitis. Serum bile acid levels were determined in 27 patients with chronic aggressive hepatitis, 41 with chronic persistent hepatitis and 55 control children. Several other biochemical tests of liver function were also determined in these children. There were significant differences in the mean fasting serum bile acid levels between chronic hepatitis patients and control children (p less than 0.001). These levels were significantly higher for the chronic aggressive group than the chronic persistent hepatitis group (p less than 0.001). Other biochemical 'hepatic function' tests did not show statistically different values between these two groups. Using stepwise discriminant analysis for the biochemical 'liver function' tests studied, only serum bile acid levels are able to distinguish statistically between chronic aggressive hepatitis and chronic persistent hepatitis children. These data suggest that fasting serum bile acid levels may have clinical utility in identifying children with asymptomatic chronic hepatitis and differentiating between chronic aggressive hepatitis and chronic persistent hepatitis children.

Adolescent↗
PubMed2003

Synergistic effect of persistent Chlamydia pneumoniae infection, autoimmunity, and inflammation on coronary risk.

BACKGROUND: Given the role of chronic infections, autoimmunity, and inflammation in atherosclerosis, we studied the joint effect of chronic Chlamydia pneumoniae infection, persistently elevated human heat-shock protein 60 (hHsp60) antibodies, and C-reactive protein (CRP) on coronary risk. METHODS AND RESULTS: The participants for this prospective nested case-control study were obtained from the Helsinki Heart Study, during which 241 nonfatal myocardial infarctions or coronary deaths occurred among 4081 dyslipidemic middle-aged men. Serum samples taken at baseline and 3 to 6 months before the coronary events that occurred during the 8.5-year period were analyzed for antibodies to C pneumoniae and hHsp60 and the CRP concentration. Compared with persistently low levels, the risk of coronary events was 2-fold for persistently elevated immunocomplex (IC)-bound and/or serum IgA antibodies to C pneumoniae (OR, 1.96; 95% CI, 1.14 to 3.36) and also for serum IgA antibodies to hHsp60 (OR, 2.11; 95% CI, 1.08 to 4.13). The risks associated with elevated antibodies were much higher when CRP was also elevated. Compared with low or transiently elevated levels, the risk of coronary events, with adjustment for age and smoking, was 4.5-fold for persistently elevated CRP and C pneumoniae IC/IgA antibodies together (OR, 4.47; 95% CI, 1.84 to 10.83) and was similar for CRP and hHsp60 IgA antibodies together (OR, 4.36; 95% CI, 1.53 to 12.39). CONCLUSIONS: Persistently but not transiently elevated C pneumoniae IC/IgA and hHsp60 IgA antibodies, especially when present together with an elevated CRP level, predicted coronary events.

Autoantibodies↗
PubMed2000

Differential pacing for distinguishing block from persistent conduction through an ablation line.

BACKGROUND: Because complete linear conduction block is necessary to minimize the recurrence of reentrant tachycardias such as typical atrial flutter, we investigated a simple technique to recognize a persistent gap or complete linear block. METHODS AND RESULTS: We prospectively evaluated cavotricuspid isthmus conduction in 50 patients (age 63+/-8 years, 43 men) after radiofrequency ablation. The distal and proximal bipoles of a quadripolar catheter placed close to the ablation line were successively stimulated during recording from the ablation line. We hypothesized that because the initial and terminal components of local potentials reflected activation at the ipsilateral and contralateral borders of the ablation lesion, a change to a more proximal pacing site without moving the catheter would prolong the stimulus to the initial component timing, whereas the response of the terminal component would depend on the presence of block or persistent conduction. A shortening or no change in timing of the terminal component would indicate block, whereas lengthening would indicate persistent gap conduction. The results were compared with previously described criteria for isthmus block. Ninety-two sites were assessed: 17 before and 75 after the achievement of complete isthmus block. The timing of the initial component was delayed by 19+/-9 ms, and the terminal component was advanced by 13+/-8 ms after block and delayed by 12+/-9 ms in case of persisting conduction. The sensitivity, specificity, and positive and negative predictive values for linear block were 100%, 75%, 94%, and 100%, respectively. CONCLUSIONS: An accurate assessment of isthmus block or persistent isthmus conduction is possible with this technique of differential pacing.

Aged↗
PubMed1998

Low-level expression of a mutant coxsackieviral cDNA induces a myocytopathic effect in culture: an approach to the study of enteroviral persistence in cardiac myocytes.

BACKGROUND: Enteroviral ribonucleic acids have been identified in heart muscle of a subset of patients with myocarditis and dilated cardiomyopathy as well as in a mouse model of persistent coxsackievirus B3 (CVB3) infection, suggesting that persistent viral infection along with activation of an immune response may contribute to the pathogenesis of ongoing cardiac disease and dilated cardiomyopathy in certain patients. It is still not known whether persistence of the viral genome contributes to the pathogenesis of dilated cardiomyopathy. METHODS AND RESULTS: To determine whether low-level enteroviral gene expression similar to that observed with viral persistence can induce myocytopathic effects without formation of infectious virus progeny, the full-length infectious cDNA copy of CVB3 was mutated at the VP0 maturation cleavage site. This prevented formation of infectious virus progeny. In myocytes transfected with this mutated cDNA copy of the viral genome, both positive- and negative-strand viral RNAs were detected, demonstrating that there was replication of the viral genome by the RNA-dependent RNA polymerase. The level of viral protein expression was found to be below limits of detection by conventional methods of protein detection, thus resembling restricted virus replication. Nonetheless, the CVB3 mutant was found to induce a cytopathic effect in transfected myocytes, which was demonstrated by inhibition of cotransfected MLC-2v luciferase reporter activity and an increase in release of lactate dehydrogenase from transfected cells. CONCLUSIONS: This study demonstrates that restricted replication of enteroviral genomes in myocytes in a pattern similar to that observed in hearts with persistent viral infection can induce myocytopathic effects without generation of infectious virus progeny.

Animals↗
PubMed2004

Persistent lowering of pressure by transplanting kidneys from adult spontaneously hypertensive rats treated with brief antihypertensive therapy.

Kidney function is critical in determining the level of arterial pressure and in the pathogenesis of hypertension. Important evidence comes from studies in which the level of blood pressure is dictated by the donor when kidneys are transplanted between genetically hypertensive and normotensive rats. We have hypothesized that pharmacotherapy modifies specific properties of the kidney, particularly the vasculature, such that after kidney transplantation, there are persistent changes in the level of arterial pressure. Consistent with previous studies, a 2-week aggressive treatment of adult (15 weeks) spontaneously hypertensive rats with an angiotensin-converting enzyme inhibitor (enalapril) combined with a low-salt diet induced a persistent change in the kidney and a decrease in arterial pressure (18%). These persistent changes in arterial pressure could be completely transferred to untreated adult spontaneously hypertensive rats by kidney transplantation (ie, pressure in untreated rats was decreased after transplantation of a kidney donated from a previously treated rat). Further, the importance of kidney-specific changes was demonstrated by finding that the treatment-induced lowering of arterial pressure was completely reversed by transferring an untreated kidney into a previously treated rat. The specific treatment-induced changes to the kidney included a decrease in structurally based renal vascular resistance that was similar to the persistent lowering of arterial pressure. These data provide evidence for a link between the treatment-induced changes in kidney vascular structure and the persistent lowering of arterial pressure. The findings also suggest that a key pharmacotherapeutic target in hypertension should be kidney-specific changes, such as renal vascular structure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Prevalence, persistence, and clinical significance of masked hypertension in youth.

Masked hypertension, an elevated daytime ambulatory blood pressure in the presence of a normal office blood pressure, confers an increased cardiovascular risk to adults. We investigated the prevalence, persistence, and clinical significance of masked hypertension in children and adolescents. We enrolled 592 youths (6 to 18 years old). Youths with masked hypertension (n=34) and a random sample of the normotensive participants (n=200) were followed-up. In a nested case-control study, we compared echocardiographic left ventricular mass among cases with persistent masked hypertension and normotensive controls. At baseline, mean age was 10.2 years; 535 youths were normotensive on office and daytime ambulatory blood pressure measurement (90.4%), and 45 had masked hypertension (7.6%). Compared with normotensive controls, participants with masked hypertension had a higher ambulatory pulse rate, were more obese, and were 2.5-times more likely to have a parental history of hypertension. Among 34 patients with masked hypertension (median follow-up 37 months), 18 became normotensive, 13 had persistent masked hypertension, and 3 had sustained hypertension. Patients with persistent masked hypertension (n=17) or who progressed from masked to sustained hypertension (n=3) had a higher left ventricular mass index (34.9 versus 29.6 g/m2.7; P=0.023) and a higher percentage with left ventricular mass index above the 95th percentile (30% versus 0%; P=0.014) than normotensive controls. In children and adolescents, masked hypertension is a precursor of sustained hypertension and left ventricular hypertrophy. This condition warrants follow-up and, once it becomes persistent, is an indication for blood pressure-lowering treatment.

Adolescent↗
PubMed1997

Tumor recurrence and hypertension persistence after successful pheochromocytoma operation.

Pheochromocytoma is a catecholamine-secreting tumor and a rare cause of hypertension that is usually curable. However, pheochromocytoma may recur as a benign or malignant tumor, and hypertension may persist after successful surgical intervention. The frequency of and risk indicators for tumor recurrence and hypertension persistence after successful surgical intervention have not been adequately studied. We determined tumoral and blood pressure outcome in 129 patients followed-up from initial pheochromocytoma resection to death or to 1994 (796 patient-years). We assessed several candidate indicators for their predictive value for the risk of tumor recurrence or hypertension persistence. Recurrence was defined as the reappearance of disease after normalization of biochemical tests. Pheochromocytoma caused death or persistent or recurrent disease in 28 patients. Of the 114 with benign tumors at initial operation, pheochromocytoma recurred as a benign or malignant tumor 17 to 194 months after initial operation in 16 cases. Kaplan-Meier estimates of pheochromocytoma-free survival were 92% and 80% at 5 and 10 years, respectively. In the 98 living patients without recurrence, Kaplan-Meier estimates of hypertension-free survival were 74% and 45% at 5 and 10 years. In the Cox model, familial pheochromocytoma and a low ratio of plasma epinephrine to total catecholamines were independently associated with recurrence. Familial hypertension and age were similarly associated with hypertension persistence. After surgery for pheochromocytoma, patients should be followed-up indefinitely, especially those with familial tumors or a low epinephrine secretion. Pheochromocytoma should not unreservedly be considered a surgically remediable cause of hypertension.

Adult↗
PubMed1999

Uncoupling of oxygen and glucose metabolism in persistent crossed cerebellar diaschisis.

BACKGROUND AND PURPOSE: The pathophysiology of deafferentation-induced changes after stroke remains unclear. Some supratentorial strokes cause persistent decreases in blood flow and metabolism in the contralateral cerebellum (persistent crossed cerebellar diaschisis[CCD]). Our previous study showed uncoupling of oxygen consumption and blood flow in this condition, which may reflect a characteristic change in brain metabolism caused by deafferentation. This uncoupling might be related to oxidation of some substrates other than blood-borne glucose, which could also lead to the uncoupling of oxygen consumption and glucose utilization. The purpose of this study was to investigate whether oxygen consumption is uncoupled from glucose utilization in persistent CCD. METHODS: Using positron emission tomography in 10 unilateral supratentorial stroke patients, we evaluated regional blood flow, oxygen consumption, and glucose utilization in the cerebellar cortex in the chronic stage. Eight patients with a significant cerebellar blood flow asymmetry, defined as outside the 95% confidence limits predefined in 9 normal subjects, were selected as patients with persistent CCD. RESULTS: In patients with CCD, the cerebellar cortex contralateral to the stroke showed significant decreases in both oxygen consumption and glucose utilization compared with the ipsilateral cerebellar cortex. The decrease in oxygen consumption was less than the decrease in glucose utilization, resulting in a significant increase in the oxygen consumption/glucose utilization ratio. CONCLUSIONS: Persistent CCD caused by stroke may induce uncoupling of oxygen consumption and glucose utilization, which may reflect a characteristic change in brain metabolism caused by deafferentation.

Aged↗
PubMed2005

Mechanism of persistent ischemic mitral regurgitation after annuloplasty: importance of augmented posterior mitral leaflet tethering.

BACKGROUND: We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated. METHODS AND RESULTS: In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001). CONCLUSIONS: Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.

Aged↗
PubMed2007

Mean-driven and fluctuation-driven persistent activity in recurrent networks.

Spike trains from cortical neurons show a high degree of irregularity, with coefficients of variation (CV) of their interspike interval (ISI) distribution close to or higher than one. It has been suggested that this irregularity might be a reflection of a particular dynamical state of the local cortical circuit in which excitation and inhibition balance each other. In this "balanced" state, the mean current to the neurons is below threshold, and firing is driven by current fluctuations, resulting in irregular Poisson-like spike trains. Recent data show that the degree of irregularity in neuronal spike trains recorded during the delay period of working memory experiments is the same for both low-activity states of a few Hz and for elevated, persistent activity states of a few tens of Hz. Since the difference between these persistent activity states cannot be due to external factors coming from sensory inputs, this suggests that the underlying network dynamics might support coexisting balanced states at different firing rates. We use mean field techniques to study the possible existence of multiple balanced steady states in recurrent networks of current-based leaky integrate-and-fire (LIF) neurons. To assess the degree of balance of a steady state, we extend existing mean-field theories so that not only the firing rate, but also the coefficient of variation of the interspike interval distribution of the neurons, are determined self-consistently. Depending on the connectivity parameters of the network, we find bistable solutions of different types. If the local recurrent connectivity is mainly excitatory, the two stable steady states differ mainly in the mean current to the neurons. In this case, the mean drive in the elevated persistent activity state is suprathreshold and typically characterized by low spiking irregularity. If the local recurrent excitatory and inhibitory drives are both large and nearly balanced, or even dominated by inhibition, two stable states coexist, both with subthreshold current drive. In this case, the spiking variability in both the resting state and the mnemonic persistent state is large, but the balance condition implies parameter fine-tuning. Since the degree of required fine-tuning increases with network size and, on the other hand, the size of the fluctuations in the afferent current to the cells increases for small networks, overall we find that fluctuation-driven persistent activity in the very simplified type of models we analyze is not a robust phenomenon. Possible implications of considering more realistic models are discussed.

Action Potentials↗
PubMed1980

Persistent wheeze. Its relation to respiratory illness, cigarette smoking, and level of pulmonary function in a population sample of children.

In a study of early-life risk factors for the development of adult obstructive airway disease, respiratory symptoms, disease and smoking histories, and spirometry were obtained for 650 children 5 to 9 yr of age and their families in East Boston, Massachusetts. Persistent wheezing was the most frequently reported chronic symptom, occurring in 9.2% (60/650) of the population. Children with persistent wheezing were more likely to report cough and phlegm (p < 0.001), a history of asthma (p < 0.001), hay fever (p < 0.02), or past hospitalization with a respiratory illness (p < 0.001) than their asymptomatic peers. Prospective evaluation of a subsample of the 650 children confirmed a greater occurrence of acute lower respiratory illness in those children with persistent wheeze. Parental cigarette smoking was linearly related to the occurrence of persistent wheezing (p = 0.012) and lower degrees of mean normalized forced expiratory flow during the middle half of the forced vital capacity (FEF-Z score). A multiple linear regression identified the mother's current smoking status and current persistent wheeze as significant predictors of the children's mean FEF-Z score. Other variables, such as the father's smoking, children's personal smoking, a doctor's diagnosis of asthma, and a past history of lower respiratory illness were not significant predictors of the FEF-Z score.

Child↗
PubMed1970

Nature of fetal hemoglobin in the Greek type of hereditary persistence of fetal hemoglobin with and without concurrent beta-thalassemia.

The fetal hemoglobin in the affected members of three Greek families with the hereditary persistence of fetal hemoglobin has only gamma-chains of the type with alanine in position 136. Although certain Negro families had been considered to have only this type of gamma-chains in their fetal hemoglobin, further studies required that they be reclassified. Consequently, the Greek cases are the sole examples of this class among the heterozygotes for the hereditary persistence of fetal hemoglobin. In Greek double heterozygotes for beta-thalassemia and the hereditary persistence of fetal hemoglobin, fetal hemoglobin is increased above the level of hemoglobin F in simple heterozygotes and gamma-chains with glycine in position 136 become apparent. In these individuals, gamma-chains with alanine in position 136 apparently derive from the chromosome for the hereditary persistence of fetal hemoglobin and are present in the hemoglobin F with gamma-chains of both types from the chromosome for beta-thalassemia. When these data are correlated with earlier knowledge of the genetic state of the Greek individuals, modifications of our previous ideas about deletions as the genetic basis of the hereditary persistence of fetal hemoglobin must be considered.

Alanine↗