Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

Circulating hormones in patients with tongue cancer

Serum FSH, LH, prolactin and plasma estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were estimated by RIA method in male patients with tongue cancer (N=110) and in healthy age-matched male controls (N=25). In this retrospective study, there was a trend towards higher levels of FSH (P<0.01), LH (P<0.01), prolactin (P<0.001), estradiol (P<0.0001), progesterone (P<0.0001) and DHEA (P<0.01) with concomitant lower levels of testosterone (P<0.001) and DHEA-S (P<0.02) in patients with tongue cancer compared to controls. We did not find significant difference in hormone levels when grouped according to the site of the tumor and stage of the disease. Patients below 40 years of age had significantly higher levels of DHEA and DHEA-S and lower levels of FSH than their counterparts. We observed a decreased ratio of testosterone: estradiol and increased levels of FSH, LH and prolactin in tongue cancer patients. These hormonal abnormalities clearly suggest a disturbance in the pituitary-adrenal-testicular axis. Based on our previous work and from these results, we suggest that prolactin might be playing an important role in the development and progression of tongue cancer.     

Hormones in male-patients with advanced esophageal-carcinoma

Hormones are believed to play a dominant role as promoters in the growth and development of hormone-dependent cancers. Much less is known about the circulating hormones in male patients with oesophageal cancer. This lack of attention led us to evaluate the role of peptide and steroid hormones (by RIA) in male patients with oesophageal cancer (n=49). Blood samples of patients were collected pretherapeutically and data was compared with age matched controls (n=25). In this retrospective study, significantly high levels of FSH (P<0.02), LH (P<0.001) and prolactin (P<0.001) were observed with concomitant low levels of estradiol (P<0.001), DHEA-S (P<0.02) and testosterone (P<0.001) in patients when compared with respective controls. The patients when grouped according to anatomical site and histological type of the tumor, intergroup variation was not observed in these hormones. From our, study, it seems that hormonal imbalance or altered ratio of peptide and steroid hormones might be playing a significant role in the development and/or progression of oesophageal carcinoma in men.     

The effects of long-term psychotherapy on patients' self-perception.

A review of the literature regarding the effects of long-term psychotherapy indicates that it has rarely been examined purely from the standpoint of the patient. This study attempts to determine how the patients perceive attitudinal change in themselves and their therapists during the treatment process. Twenty patients who received dynamically oriented psychotherapy in excess of one year in a typical outpatient clinic participated. These patients were randomly assigned a therapist who was either a Clinic staff member or senior resident in psychiatry. Slightly more than half the patients included in the study had a diagnosis of psychoneurosis, while the remainder were viewed as possessing characterological or psychotic disturbances. Evaluation of patient attitudes was achieved through the use of a modified version of Osgood's Semantic Differential Scale. It was determined that patients perceived themselves as becoming significantly more like their therapists after one year of psychotherapy. They saw themselves as more active, independent, dominant, outgoing, realistic and happy. This "psychic shift" is discussed in terms of identification, transference and counter-transference phenomena.     

The influence of reported paternal attitudes on the decision to breast-feed

Objective: To identify factors that influence a woman's decision to breast-feed.
Methodology: Five hundred and fifty-six women were recruited from the maternity wards of two Perth hospitals. Data were collected from a self-administered questionnaire completed by participants prior to discharge. Logistic regression analysis was used to determine factors influencing the initiation of breast-feeding.
Results: At discharge from hospital 83.8% of women were breast-feeding, including 6% who were giving complementary formula feeds. After controlling for potentially confounding demographic and biomedical factors, the father's reported preference for breast-feeding was found to be the most important factor influencing a woman's decision to breast-feed (OR 10.18).
Conclusion: Fathers participate in and influence the choice of infant feeding method and should be included in breast-feeding discussions.     

Margin of safety for discharge after apnea in preterm infants

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at 相似文献