Expression and characterization of SPARC in human lens and in the aqueous and vitreous humors

SPARC (secreted protein, acidic and rich in cysteine) is a matricellular glycoprotein that regulates morphogenesis, cellular proliferation, and differentiation. SPARC is a critical factor in the development and maintenance of lens transparency in mice. SPARC-null mice develop lenticular opacity at an early age that progresses gradually to mature cataract. Despite the high level of homology between the mouse and human genes, little is known about SPARC in the human lens. We have studied the expression of SPARC protein in human lens and surrounding ocular tissues from normal human donors (60-70 years old). Immunohistochemical and immunoblot analyses were conducted on lens, aqueous humor, vitreous, ciliary epithelium, pigment epithelium, cornea and retina. The epithelia and capsule of the lens contained SPARC, whereas the cortical and nuclear fibers did not. In contrast, the aqueous humor and vitreous, which provide nutrients to the lens and regulate its development and function, contained significant amounts of SPARC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts of various ocular tissues revealed bands of 43 and 29 kD after disulfide bond reduction that were reactive with anti-SPARC IgG. Despite the presence of protease inhibitors during sample preparation, we observed cleavage of intact SPARC to a 29 kD fragment, a peptide reported in other tissues and attributed to endogenous proteolysis. In addition, bands of molecular mass 150 and 200 kD were present that appeared to be disulfide-bonded complexes of SPARC monomers. Human cornea, ciliary epithelium, pigment epithelium and retina also contained SPARC. The presence of SPARC in the aqueous humor and vitreous, as well as in the lens, indicates a functional importance of SPARC in adult human eye as well as in lens development.     

Isolation and characterization of a novel gene induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in rat liver

The differential display technique was used to identify geneswhose expression was regulated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD). Expression of a novel sequence was up-regulated in adose-dependent fashion in liver of Sprague-Dawley male ratsexposed to both chronic and acute treatment with TCDD, as measuredby densito-metry of Northern blot analyses (P < 0.01). Arapid amplification of cDNA ends (RACE) procedure was used toisolate a 1.8 kb cDNA from a rat liver cDNA preparation. Thiscloned cDNA, called 25-Dx, was sequenced and found to encodea peptide of 223 amino acids. In control rats, the 25-Dx genewas expressed at high levels in lung and liver. A hydrophobicdomain of 14 residues followed by a proline-rich domain, bothlocated in the N-terminal region, showed 71% homology with thetransmembrane domain of the precursor for the interleukin-6receptor and a conserved consensus sequence found in the cytokine/growthfactor/prolactin receptor superfamily respectively.     

A low sperm concentration does not preclude fertility in men with isolated hypogonadotropic hypogonadism after gonadotropin therapy

In order to define the minimal number of sperm needed for conception, we studied semen characteristics of men with isolated hypogonadotropic hypogonadism (IHH) who became sperm-positive during gonadotropin therapy. Twenty-two of 24 men (92%) proved fertile, initiating a total of 40 pregnancies. The mean (+/- standard error of the mean) sperm concentration at the time of conception was 16.7 +/- 4.0 X 10(6)/ml. However, 71% of pregnancies were conceived when the mean sperm concentration was less than 20 X 10(6)/ml; in 16%, the mean sperm concentration was less than 1 X 10(6)/ml. Mean total sperm count correlated highly with sperm concentration (r = 0.67, P less than 0.001). We conclude that men with IHH can initiate conception even when their sperm concentration is well below the conventional lower limit of 20 X 10(6)/ml.     

Septic shock during pregnancy

A multiinstitutional review of 10 pregnancies complicated by septic shock was undertaken to identify the clinical characteristics and hemodynamic alterations associated with this condition. Prolonged rupture of membranes with the subsequent development of chorioamnionitis or postpartum endometritis were risk factors that commonly preceded the diagnosis of septic shock. The majority of septic shock cases occurred during the puerperium. There were two maternal deaths in this selected series. Associated complications included pulmonary edema, adult respiratory distress syndrome, disseminated intravascular coagulation, pulmonary emboli, and cardiac arrest. The primary hemodynamic derangements were reduced systemic vascular resistance with depressed myocardial function. The mean initial systemic vascular resistance index in eight surviving women was 885 +/- 253 dyne.sec/cm5.m2. Despite an overall presenting cardiac index of 4.20 +/- 2.01 L/min/m2, five patients (50%) had evidence of myocardial depression based on analysis of their left ventricular function curves. Mean arterial pressure, systemic vascular resistance, and left ventricular stroke work index all showed significant improvement after therapy. A hemodynamic algorithm based on volume therapy, inotropic agents, and peripheral vasoconstrictors is offered. This therapeutic approach is designed to optimize cardiac performance and maintenance of organ perfusion in the critically ill patient with septic hypotension during pregnancy.     

Eating self-efficacy and weight cycling: a prospective clinical study

Previous retrospective studies have not identified global psychosocial consequences of weight cycling. These lack of findings may be due to limitations associated with retrospective research or with using general psychological measures rather than weight-specific measures. This prospective study examined changes in a weight-specific measure, eating self-efficacy, using an obese clinical population who returned to a multidisciplinary weight management program subsequent to weight regain. Subjects did not demonstrate any change in eating self-efficacy despite experiencing weight loss and then weight regain. Individuals returning for treatment may be a select population, thus suggesting that there may not be negative psychological effects of weight cycling for all individuals. Implications for further research are discussed.     

Rotavirus serotype-specific neutralizing activity in human milk

A plaque reduction neutralization assay was used to determine rotavirus serotype-specific neutralizing activity in human breast milk from 25 mothers of upper socioeconomic background and 20 mothers of a lower socioeconomic status. Levels of neutralizing activity, as well as those of rotavirus-specific antibodies detected by enzyme-linked immunosorbent assay (ELISA), were comparable for each socioeconomic group. Overall, neutralizing activity in human milk was detected in the majority of samples and can be increased many months postpartum. The prevalence of neutralization antibodies (titers, greater than or equal to 1:10) was 77% against Wa (serotype 1), 86% against SA-11 (serotype 3), and 75% against NCDV (bovine) rotavirus. Rotavirus-specific IgA and IgG antibodies detected by ELISA (titers, greater than or equal to 1:10) were present in 35% and 55% of breast milks, respectively. Sequential analysis of repeated breast milk samples from five individual mothers revealed that rotavirus neutralizing activity fluctuated over time, with high activity observed in one mother's milk at 18 months postpartum. Mothers who breast-fed for six months or more tended to have higher milk neutralizing titers against rotavirus.     

Speech perception using a two-formant 22-electrode cochlear prosthesis in quiet and in noise

A new speech-processing strategy has been developed for the Cochlear Pty. Ltd. 22-electrode cochlear prosthesis which codes an estimate of the first formant frequency in addition to the amplitude, voice pitch and second formant frequencies. Two groups of cochlear implant patients were tested 3 months after implant surgery, one group (n = 13) having used the old (F0F2) processing strategy and the other (n = 9) having used the new (F0F1F2) strategy. All patients underwent similar postoperative training programs. Results indicated significantly improved speech recognition for the F0F1F2 group, particularly on open set tests with audition alone. Additional testing with a smaller group of patients was carried out with competing noise (speech babble). Results for a closed set spondee test showed that patient performance was significantly degraded at a signal-to-noise ratio of 10 dB when using the F0F2 strategy, but was not significantly affected with the F0F1F2 strategy.     

Nasopharyngeal carcinoma: the Dana-Farber Cancer Institute experience with 24 patients treated with induction chemotherapy and radiotherapy

Nasopharyngeal carcinoma traditionally has been treated with radiotherapy alone. Although the probability of cure for patients with stage I and II nasopharyngeal carcinoma is high, the probability of cure for patients with stage III and IV disease is poor because of a higher rate of local-regional and distant failure. Between February 1981 and August 1986, 24 patients with previously untreated, stage IV nasopharyngeal carcinoma were treated with two to four monthly courses of cisplatin-based combination chemotherapy prior to radiotherapy. A response to induction chemotherapy was recorded in 75% of patients (29% complete response and 46% partial) prior to radiotherapy. By actuarial estimate with a median follow-up of 42 months, the 2-year failure-free survival for all patients was 57%. In conclusion, induction chemotherapy has significant activity in nasopharyngeal carcinoma. The toxicity of this approach, as well as the influence of initial histopathology and response to chemotherapy on survival, will be discussed.