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I Kogan

Publications and source records attributed to I Kogan.

At least 19 recordsLinked to original sources

A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions as a phosphorylation-regulated chloride channel on the apical surface of epithelial cells, and lack of this function is the primary cause for the fatal disease cystic fibrosis (CF). Previous studies showed that purified, reconstituted CFTR can function as a chloride channel and, further, that its intrinsic ATPase activity is required to regulate opening and closing of the channel gate. However, these previous studies did not identify the quaternary structure required to mediate conduction and catalysis. Our present studies show that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes close to the predicted size of CFTR dimers can be captured by chemical cross-linking reagents and detected using nondissociative PAGE. However, CFTR function does not require a multimeric complex for function as we determined that purified, reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity.

Adenosine Triphosphatases↗

Perturbation of the pore of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits its atpase activity.

Mutations in the cystic fibrosis gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) lead to altered chloride (Cl(-)) flux in affected epithelial tissues. CFTR is a Cl(-) channel that is regulated by phosphorylation, nucleotide binding, and hydrolysis. However, the molecular basis for the functional regulation of wild type and mutant CFTR remains poorly understood. CFTR possesses two nucleotide binding domains, a phosphorylation-dependent regulatory domain, and two transmembrane domains that comprise the pore through which Cl(-) permeates. Mutations of residues lining the channel pore (e.g. R347D) are typically thought to cause disease by altering the interaction of Cl(-) with the pore. However, in the present study we show that the R347D mutation and diphenylamine-2-carboxylate (an open pore inhibitor) also inhibit CFTR ATPase activity, revealing a novel mechanism for cross-talk from the pore to the catalytic domains. In both cases, the reduction in ATPase correlates with a decrease in nucleotide turnover rather than affinity. Finally, we demonstrate that glutathione (GSH) inhibits CFTR ATPase and that this inhibition is altered in the CFTR-R347D variant. These findings suggest that cross-talk between the pore and nucleotide binding domains of CFTR may be important in the in vivo regulation of CFTR in health and disease.

Adenosine Triphosphatases↗

Obstructive sleep apnea and acute myocardial infarction: clinical implications of the association.

It is not known whether patients with acute myocardial infarction (MI) with coexistent obstructive sleep apnea (OSA) have a poor clinical course during the acute phase of MI. Therefore, we investigated the impact of OSA on in-hospital morbidity and mortality during an acute MI. Patients admitted to the intensive cardiac unit (ICU) with acute MI underwent Holter monitoring and night pulse oximetry (SpO2). During the first complete day at the ICU, both recordings (ECG and SpO2) were matched in time to determine association between cardiac arrhythmias and hypoxemia episodes. We identified and compared 55 heavy snorers with daytime sleepiness who showed more than 10 episodes of desaturation per hour on pulse oximetry (OSA group), and 196 nonOSA patients. There was an increase in the incidence of premature ventricular contraction (PVC, p < 0.05) and couplets PVC (p < 0.05) in OSA patients; the proportion of those arrhythmias increased in parallel with desaturation episodes in the OSA group. There were no differences between OSA and nonOSA groups for major MI complications (38.2% vs 34.2%, p > 0.05), ICU/hospital stay (3.6 +/- 1.2 vs 2.7 +/- 0.9 days, p > 0.05), or mortality within 30 days (14.5% vs 12.2%, p > 0.05). In conclusion, despite the greater incidence of some types of cardiac arrhythmias during an acute MI in OSA, these patients have the same clinical course in hospital and mortality rate as nonOSA patients.

Acute Disease↗

Prostate-specific antigen induction by a steroid hormone in T47D cells growing in SCID mice.

Previous studies revealed that prostate-specific antigen (PSA) is present in > 30% of human breast tumor cytosols. Survival analysis showed that patients with PSA-producing tumors have a reduced risk for relapse, suggesting PSA to be an independent favorable prognostic marker for a large subset of breast cancer patients. The present investigation established an in vivo model for the induction of PSA in human breast cancer tumors growing as xenografts in severe combined immunodeficient (SCID) mice. The human mammary cancer cell-line T47D was grown i.m. in female mice. When the tumor and leg diameter reached 10 mm, the mice were stimulated daily with norgestrel for either 5 or 7 days to produce PSA, and sacrificed on day 8. The prostate cancer cell-line LNCaP was grown in male mice and functioned as a positive control for PSA production. After T47D and LNCaP mice were sacrificed, a highly sensitive immunofluorometric assay was used to analyze the PSA concentration in the tumor, muscle, liver, and kidney cytosols. Norgestrel-stimulated T47D mice showed significantly more PSA in the tumors compared to tumors of the control mice. However, PSA levels in tumors of the stimulated mice were significantly lower than those in the LNCaP xenografts. No PSA levels above background were present in the blood and normal tissue of the norgestrel-stimulated or control T47D xenografts. This mouse model will be a valuable tool for investigating and screening new therapies for a subgroup of breast cancer patients who have significant PSA concentrations in their tumors.

Animals↗

Variation in the branching of the axillary artery. A description of a rare case.

A case is described in which a rare variation of a branch arising from the axillary artery is defined as a thoracoepigastric artery. This variation was observed in the cadaver of a 72-year-old man. This artery branched from the axillary artery, passing as a common trunk between the roots of the median nerve, and divided into two branches. The lateral one gave rise to muscular branches supplying the shoulder and fasciae, while the medial one descended on the anterior aspect of the axillary fossa, reaching the hypogastric region, and anastomosed with the superficial epigastric artery, which is a branch of the femoral artery. To our best knowledge, no variation similar to this one has been described. We suggest naming this artery the thoracoepigastric artery.

Aged↗

Termination and the problem of analytic goals: patient and analyst, different perspectives.

The author of this paper explores the different perspectives through which patient and analyst view termination and the problem of analytic goals. These differences become clear through a case study, in which the patient offered resistance to many of the treatment goals, which did not fit her life goals and, at the same time, threatened her defences and her precarious well-being. In order to achieve the main treatment goal, that of maturity and growth (which in analysis was expressed through sub-goals like separation from her mother, understanding of her symptoms, acceptance of her feminine identity, acceptance of limitations of age and the terminability of life), the patient and the analyst had to confront an intense psychic pain connected to what they perceived as irretrievable losses. The fear of growth and growing old affected both partners of the analytic couple and had an impact on the extent to which analytic goals were met. The author explores the satisfactory aspects of termination, as well as what the analyst viewed as the incomplete results of analysis, when analysis was terminated and ten years later.

Adult↗

[Ultrasound evaluation of acute abdominal pain in the emergency department].

In a retrospective study the value of sonography in the diagnosis of acute traumatic and nontraumatic conditions was evaluated. Records of patients who underwent emergency sonography during 1989 (group A, 159 patients) and 1991 (group B, 415 patients) were reviewed. In nontraumatic cases sonography confirmed the preliminary diagnosis in 43% and 50% of patients in groups A and B, respectively. In cases of acute abdominal pain with fever or leukocytosis, but without initial specific diagnosis, biliary disease was diagnosed in 3 group B patients; in a group A patient an abdominal aortic aneurysm was detected. There were positive sonographic findings in 42% and 17% of cases of blunt abdominal trauma in groups A and B, respectively. Sonographic evaluation of suspected splenic trauma confirmed the diagnosis in only 2 out of 9 patients in group B. Both studies show that sonography is a very effective, complementary, noninvasive method for evaluating patients with suspected acute surgical conditions. Sonography significantly reduced misdiagnosed biliary disease in cases of abdominal pain with fever or leukocytosis. In trauma, sonography obviated invasive diagnostic and surgical interventions in a significant number of cases. We recommend routine sonography in evaluating suspected, acute surgical conditions of traumatic or nontraumatic nature and in cases of undiagnosed abdominal pain with fever or leukocytosis.

Abdominal Injuries↗

Love and the heritage of the past.

In this paper, the author explores the difficulties in developing the capacity to fall and remain in love, as shown in a case study of a Holocaust survivor's daughter whose mother lived through the Holocaust as a child. These difficulties arose from the inability of the daughter to go through the mourning processes necessary for the separation from her bereaved mother, as well as from the daughter's fixation on the mother's interminable, unresolved mourning. The daughter exploited her relationships with the love objects in her life to play the role of the victim/persecutor. She thus enacted the drama of facing death and being rescued through flight or promiscuity, elements which were dominant in her fantasies relating to her mother's past. The working through of the transference relationship helped her become aware of the unconscious meaning embedded in her actions and eventually lessened her need to live her mother's past in her own life.

Adult↗

Curative factors in the psychoanalyses of Holocaust survivors' offspring before and during the Gulf War.

In this paper, I have attempted to explore the curative effect of insight and relational factors in the analyses of Holocaust survivors' offspring before and during the Gulf War. A particular characteristic of children of survivors is their tendency to recreate their parents' experiences in their own life through concretization. An important analytic goal is to help these patients become aware of the unconscious meaning embedded in their acting out through increased insight, so they will be able to extricate themselves from the need to concretize and verbalize instead. The impact of the Gulf War on the children of Holocaust survivors was particularly strong. These patients reacted to the existential threat with feelings of impotence and terror, perceiving it as a repetition of the past. Thus, strengthening the ego forces became the focus of treatment during the war period, and this was facilitated by relational factors. Only near the end of the war was it possible to begin working through the regressive transferences evoked by the traumatic situation through increased insight, or to attempt to disentangle the present from the past through interpretation.

Adaptation, Psychological↗

From acting out to words and meaning.

This paper presents an explanation and illustration of the behavioural phenomenon of concretization through acting out. The phenomenon refers to the realization of fantasies and psychic conflicts pertaining to the traumatic past of Holocaust survivor parents, which might have been transmitted to the next generation narratively or beyond words. I have illustrated this phenomenon by material taken from the first stages of the analysis of a young man who shot and wounded his father during the latter's attempt to save him from suicide. The analytic experience facilitated the stabilization of ego boundaries and the emergence of a more secure sense of self.

Acting Out↗

A journey to pain.

This paper explored the restoration of the capacity to feel pain and guilt as a result of the emotional experience in analysis. This was illustrated by the first part of an analysis of a woman who lost her four-month-old baby in a car accident. Analysis revealed in this case a fragmented self unable to deal with unbearable feelings of pain and guilt which threatened to annihilate it. She connected the accident to a series of events which appeared to her to be the realization of her aggressive wishes towards primary objects throughout her life. The perception of the impairment and loss of loved objects as due to her destructiveness led to the inability to differentiate self from object, the impairment in the work of mourning, and aggression turned against the self. The analyst's survival of the destructive attack without retaliation enabled the differentiation, a better adaptation to reality and the restoration of the capacity to feel pain and guilt.

Accidents, Traffic↗

[Facilitated and real trauma in the psychoanalysis of children of Holocaust survivors].

The author investigates the effect of retraumatization on the children of Holocaust survivors who have appropriated their parents' trauma through unconscious identification. The author proposes that the working through of the real trauma results in a mitigation of the transmitted trauma in the psychic reality and mobilizes the work of mourning that facilitates the mastery of the real as well as the transmitted trauma. Two case examples are cited as illustration.

Adult↗

The search for the self.

In this paper, I attempted to illustrate the process of separation and growth in the third analysis of a Holocaust survivor's daughter. The first phase of analysis began by working through her externalization of the past by means of acting out. Her encounter with death allowed a re-activation and re-working of sadomasochistic fantasies, making her aware of an additional facet of the Holocaust, namely its defensive aspect. The working through of feelings of mourning and guilt facilitated differentiation from the burden of her father's past. The second part of the analysis dealt with furthering the process of growth by working through separation from her mother. Differentiation from primary objects' representations, which enabled her to marry and become a mother herself, was made possible through the analytic experience. An 'interminable' analysis thus came to an end.

Adult↗

Identification processes and denial in the shadow of Nazism.

This paper presents an analysis of the vicissitudes of individual and group identification processes during and after the Holocaust. We also examine denial as a defence mechanism when confronted with massive traumatization, and in the period of readaptation and reintegration to life. Identification with (idealized) lost objects and with group myths, in fantasy as well as in action, and denial sustained by fantasy, words and acts, were connected to mourning processes which helped to initiate the re-individuation process developing in face of danger. We consider some of the basic problems of survivors of the Holocaust such as avoidance of mourning and rebuilding of self-structure with reemergence of superego, in connexion to various processes of identification and denial. We focus on the 'Mythos of Survival' which reveals a special way of coping with life and death problems, and attempt to show how processes of identification connected with it, influence the survivors' way of mourning up to the second and third generation. The aim of therapy with children of survivors is to aid the process of mourning for lost objects, to free them from the burden of the past, by differentiating between their own experiences and that of their parents, thus helping them in the process of re-individuation.

Adult↗

Primary squamous cell carcinoma of the pilonidal area.

Two patients with primary squamous cell carcinoma of the pilonidal area are presented. No chronic infection or any other lesion predisposing to malignant transformation was present in either patient. Physicians and surgeons should be aware of the possibility of skin cancer appearing in this area in elderly patients. Biopsy of the lesion, leading to an early diagnosis, may prompt surgical treatment. Complete excision of the lesion is a prerequisite for cure.

Aged↗