Morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures.

A morphologically differentiated strain of rat pheochromocytoma (PC-12H) metabolically labeled with [35S]methionine and incubated with a phorbol ester displayed reduced 140-kDa and increased 15 kDa bands relative to cells incubated without phorbol ester after immunoprecipitation with antisera elicited by the C-terminal peptide of the Alzheimer amyloid precursor protein (APP). These bands correspond to glycosylated full length APP and a C-terminal fragment previously reported by Anderson et al. (Neurosci. Lett. 120:126-128, 1991) to result from a cleavage within the amyloidotic A4 region of APP, which releases a 120 kDa extracellular fragment. The 15 kDa fragment, not immunoprecipitated with an antisera elicited by the N-terminal portion of A4 amyloid, is nonamyloidogenic. Incubation of these cells with p-nitrophenylxyloside, known to inhibit proteoglycan formation, also increased this nonamyloidogenic cleavage of APP. In contrast to these results, an undifferentiated low passage PC-12-L strain constitutively displayed rapid nonamyloidogenic APP cleavage. Incubation of PC-12-L with phorbol ester did not affect the relative abundance of 140 or 15 kDa bands. Growth of PC-12-L with 7 S NGF or dibutyryl cAMP resulted in increased morphological differentiation and decreased APP cleavage which was now phorbol-inducible. Similar analyses of dividing and senescent human astrocytes and normal and F-AD fibroblasts indicate 5-fold lower rates of mid-A4 APP cleavage. Phorbol esters decreased the 140 kDa APP band without affecting the intensity of the 15 kDa band in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cyanide loss from tissue baths in the presence and absence of tissue

Loss of cyanide from Krebs-Henseleit solution (KHS) was studied in aerated tissue baths at 38°C in the presence and in the absence of tissue. The rate of cyanide loss was greater from 300-μM than from 30-μM solutions and still greater from 300-μM solutions in the presence of vascular tissue. Initial cyanide loss was much greater from the tissue-containing bath, and the half-time was shorter in the presence of tissue (54 min) than in its absence (98 min) in baths containing the same initial cyanide concentration (300 μM).     

Transsphenoidal treatment of non-neoplastic intrasellar cysts. A report of 38 cases

Thirty-eight patients underwent transsphenoidal microsurgical treatment of non-neoplastic intrasellar cysts: 36 had cyst drainage and biopsy of the cyst wall, and in two the cyst was totally removed. Surgical morbidity was 8%. The mean follow-up time was 46.3 months; 100% patient follow-up evaluation was achieved. Sixteen female patients (mean age 24.6 years) had pars intermedia cysts: 88% had menstrual irregularities, 63% had galactorrhea, 31% had headache, and 56% had hyperprolactinemia. Within these groups, menstrual cycles returned in 86%, galactorrhea ceased in 90%, headaches resolved in 80%, and serum prolactin levels were restored to normal in 66%. Eight females and three males had Rathke's cleft cysts (mean age 34.0 years): of these 11 patients, 91% had headaches and 18% had hyperprolactinemia; of the eight females, 63% had amenorrhea and 63% had galactorrhea. Within these groups, serum prolactin levels normalized in 50%, and 80% noted reduced headache. Of the females, 80% had return of menses and 50% noted cessation of galactorrhea. Six males and two females had arachnoid cysts (mean age 42.2 years): 50% had headaches; 50% were asymptomatic. Preoperatively, 50% of these patients had hypothyroidism and 25% had adrenal hypofunction. Postoperatively, 75% of patients with headache noted improvement, and 33% of patients with abnormal thyroid function had normal function. Adrenal function did not improve. Three patients had an intrasellar cysticercosis cyst, epidermoid cyst, and postoperative cyst, respectively. All had evidence of partial hypopituitarism; none improved postoperatively. The results indicate that different types of pituitary cysts produce different clinical syndromes, and suggest that simple transsphenoidal drainage and partial removal of the cyst wall can provide safe and effective therapy.     

Application of image-guided surface coil P-31 MR spectroscopy to human liver, heart, and kidney

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.     

Effectiveness of individualized neurodevelopmental care in the newborn intensive care unit (NICU)

The individual infant's neurodevelopmental process provides an integrative framework for the delivery of medical care needed to assure the infant's survival and quality of outcome. The infant's neurobehavioral functioning and expression provides an opportunity for caregivers to estimate the individual infant's current strengths, vulnerabilities and threshold to disorganization, as well as to identify the infant's strategies in collaborating in his or her best progression. This perspective supports caregivers in seeing themselves in a relationship with the infant, and in considering opportunities to enhance the infant's strengths and reduce apparent stressors in collaboration with the infant and the family. The results of several randomized studies supporting the effectiveness of such a neuro developmental approach to NICU care will be presented, and suggest implications for staff education and nursery-wide implementation.     

Incestuous experiences within homosexual populations: A preliminary study

The incidence, frequency rates, and effects of both homosexual and heterosexual incestuous experiences within lesbian and male homosexual populations are examined. Twenty-nine female homosexuals and 54 male homosexuals from diverse demographic backgrounds were administered a 16-page anonymous questionnaire designed to capture a wide range of demographic, personality, life history, and attitudinal information. Differences in family characteristics that exist between individuals who have experienced nuclear family incest, extended family incest, and those who have never experienced incest are investigated. Differences that exist between the two populations, incest and nonincest, were also studied.Albert Einstein College of Medicine     

Hemizentralarterienverschluss bei Moyamoya-Syndrom

Moyamoya syndrome is a rare cerebrovascular disorder characterized by bilateral progressive supraclinoidal stenosis or occlusion of the internal carotid artery and development of collateral vessels in the lenticulostriate region. The syndrome manifests itself in association with another disease or other clinical symptoms. We present the case of a 12-year-old girl with hemicentral retinal artery occlusion due to moyamoya syndrome associated with clinical and laboratory findings of presumed systemic lupus erythematosus.     

Methamphetamine use among young adults: health and social consequences

The current research analyzed the relationship between methamphetamine use and health and social outcomes. Interviews were conducted with a sample of 106 respondents. Virtually all of the respondents experienced negative consequences of methamphetamine use. The most serious, but least prevalent, methamphetamine-related health problem was seizures and convulsions. The most prevalent health effect was weight lose. A substantial number of respondents experienced severe psychological symptoms: depression, hallucinations, and paranoia. Of the 106 respondents, 34.9% had committed violence while under the influence of methamphetamine. The data suggest that methamphetamine-based violence was more likely to occur within private domestic contexts, both family and acquaintance relationships. It is apparent from the findings that methamphetamine use heightens the risk for negative health, psychological, and social outcomes. Having said this, it is crucial to acknowledge that there was no evidence of a single, uniform career path that all chronic methamphetamine users follow. Furthermore, a significant number of sample members experienced limited or no serious social, psychological, or physical dysfunction as a result of their methamphetamine use.     

The clinical and laboratory response to recombinant factor VIIA in trauma and surgical patients with acquired coagulopathy

OBJECTIVE: In bleeding patients who are coagulopathic, the clinical response to administration of recombinant factor VIIa (rFVIIa) relates to the changes in prothrombin time (PT). DESIGN: Retrospective review of all surgical and trauma patients who were coagulopathic and received factor VIIa at the authors' institution over the past 27 months. SETTING: Academic tertiary referral facility and level I trauma center. PARTICIPANTS: Eighteen patients met inclusion criteria, 10 trauma and 8 surgical. Mean age 50 years (range, 17-84). RESULTS: Overall mortality was 39%. All but 1 patient (17/18) had resolution of coagulopathic bleeding with rFVIIa, and all clinical responders (n = 17) (defined as clinical cessation of bleeding within 24 hours determined by either attending surgeon or chief resident progress note) had a decrease in PT to normal range. In contrast, the single clinical nonresponder had an insignificant PT decrease (19 to 18 seconds). Prothrombin time decreased from 20 +/- 4 seconds to 12 +/- 2 seconds, p < 0.05 (n = 17). International Normalized Ratio (INR) decreased from 1.59 to 0.86, p < 0.05 (n = 17). Fibrinogen before administration was 299.73 (range, 105-564) (n = 15). pH before administration was 7.25 (+/-0.18) (n = 10). Patient temperature was 98.64 (+/-2.06). Effect in partial thromboplastin time (PTT) was inconsistent (50 +/- 49 seconds to 34 +/- 6 seconds, p > 0.05). Transfusion requirements for red blood cells (14 to 3 units) and plasma (12 to 3 units) were significantly reduced after rFVIIa. There were no significant differences in percentage PT decrease between dose > or =100 mcg/kg vs <100 mcg/kg, surgical vs trauma patients, survivors vs nonsurvivors, and those with pretreatment platelet count > or =100 K vs <100 K. CONCLUSIONS: The administration of rFVIIa caused a decrease in the PT in nearly all patients. There were an insufficient number of patients to support the use of PT as a clinical predictor of response; however, the data are suggestive of such utility. If the PT does not correct, then it is likely that there is a deficiency of other factors of the coagulation cascade.