The case of medium-dependent dual mechanisms for photoisomerization: one-bond-flip and hula-twist

This paper critically reviews examples in the literature of photochemical cis-trans isomerization paying particular attention to the medium effect and accompanied conformational changes. A case is made that the Hula-Twist mechanism, postulated in 1985 as a photochemical reaction pathway for a polyene chromophore imbedded in a protein binding cavity such as those of rhodopsin and bacteriorhodopsin, is also a dominant reaction pathway for a diene, or a longer polyene confined in a rigid (relative to isomerization rate) medium. The conventional one-bond-flip process is the preferred reaction pathway in a fluid medium. While defining experiments are proposed, this dual mechanistic approach successfully accounts for all examples in the literature on photoisomerization reactions whether involving conformational changes or not.     

In vitro transformation of bioactive glass granules into Ca-P shells

Bioactive glass (BG) granules of narrow size are excavated when implanted in mandibular bone of beagles. Bone tissue forms within these internally hollowed particles without a connection to the bone at the margins of the defect. In this study the internal excavation of BG granules was simulated by in vitro immersion experiments. Postimmersion solutions were analyzed for changes in Si, Ca, and P concentrations. Using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and Fourier Transform Infrared (FTIR) spectroscopy, granules were analyzed for compositional, morphologic, and structural changes resulting from immersion. Only when the solution was continuously replenished and only if this solution was composed of electrolyte- and protein-containing serum was excavation achieved. Without solution replenishment, that is, under so-called integral immersion conditions, the solution quickly became saturated in silicon, and the silicon no longer dissolved. When the glass was immersed in a solution with serum, a porous surface structure with fine precipitates was formed, in contrast to a dense surface reaction layer with closely packed globular precipitates that was formed in a solution without serum. The combined effect of continuous solution replenishment and the use of a solution containing serum proteins led to the formation of a surface reaction layer that did not impede continued corrosion. As such, all Si was released, and eventually a hollow Ca-P shell was formed. Thus this study supports the hypothesis that there is a physico-chemical mechanism of Si transport through the Ca-P-rich layer followed by Si dissolution. This mechanism may be operative in vivo and thereby may contribute to the observed in vivo excavation.     

Fertility rates in men with normal semen characteristics: spermatozoal testing by induction of the acrosome reaction and Wright-Giemsa staining for subtle abnormal forms

Little is known about the fertility potential of semen from men who fulfill the accepted criteria of normal semen quality. We examined retrospectively the fertility rates of semen donors with normal semen quality. Donor performance was evaluated in women who had no known infertility factors or had only ovulatory dysfunction corrected by clomiphene. Cycles of therapeutic donor insemination were monitored for ovulation, and pregnancy outcome was followed up. Pregnancy resulted from therapeutic donor insemination with 21 donors and did not result in pregnancy with five (the range of the percentage of cycles in which pregnancy occurred was zero to 31). The comparison of donor semen analysis characteristics with pregnancy rates indicated that the total number of motile spermatozoa per ejaculate correlated with pregnancy rate (P = .04). Cox proportional hazard regression analysis showed that when the value for percentage of abnormal forms was combined with the total number of motile spermatozoa, a significant negative association was found between abnormal forms and conception (P = .04). Experiments comparing semen from high-fertility donors (top quartile of pregnancy rate) and low-fertility donors (lowest quartile) demonstrated a greater proportion of spermatozoa with inducible acrosome reactions in the high-fertility group (P less than .05). A Wright-Giemsa stain used to detect subtle abnormal forms in spermatozoa did not discriminate between the groups. These data suggest that differences in fertility potential exist among donors, even though all may exceed the accepted criteria for normal semen quality. Differences in the ability of spermatozoa to capacitate or undergo the acrosome reaction may be a mechanism for diminished fertility in donors with normal semen characteristics.     

Estrogen replacement therapy: What the future holds

Although hormonal replacement therapy has proved beneficial for many postmenopausal women, several issues remain to be resolved through future research. Improved combination therapy, better delivery systems, and optimal dosing may enhance compliance, which is essential for maximum benefit from therapy. Epidemiologic studies are necessary to clarify the role of estrogen in osteoporosis and cardiovascular disease. Additionally, the contribution of hormonal replacement therapy to the development of breast and endometrial cancers needs to be clarified.     

Expression of myeloid differentiation antigens in acute nonlymphocytic leukemia: increased concentration of CD33 antigen predicts poor outcome--a report from the Childrens Cancer Study Group.

Ninety-eight cryopreserved specimens of acute nonlymphocytic leukemia (ANLL) cells obtained at initial diagnosis of children enrolled on the Childrens Cancer Study Group 251 protocol (CCG 251) were examined by indirect immunofluorescence using four monoclonal antibodies to myeloid differentiation antigens. The relationship between the level of differentiation of ANLL cells as determined by their antigen phenotype and the clinical outcome of treatment, including complete remission (CR) rate, survival, and event-free survival, was evaluated. Most leukemic specimens were determined to express the CD33 antigen (L4F3), a 67-kD protein. Because the level of differentiation of normal myeloid cells is reflected by the concentration of the CD33 antigen expressed, samples were categorized as CD33-bright (immature) versus CD33-dull (mature). Patients with CD33-bright leukemic blasts had a marginally inferior CR rate to those with CD33-dull blasts (P = 0.08). With respect to survival and event-free survival, there was a significantly inferior outcome in the CD33-bright patients (P = 0.04 and P = 0.06, respectively). Reactions of ANLL with anti-CD15 antibody (1G10), anti-CD36 antibody (5F1), or anti-CD17 antibody (T5A7) did not predict clinical outcome. This study indicates that patients whose ANLL blasts displayed the CD33 antigen in an amount associated with immature myeloid cells experienced a worse outcome than patients with ANLL blasts that expressed a phenotype associated with more mature cells.     

The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world

The age-specific immunity to human parvovirus infection was estimated in Victoria, Australia using prospectively collected samples from the Royal Children's Hospital, the Royal Women's Hospital and the Australian Red Cross Blood Service and from sera stored at the Victorian Infectious Diseases Reference Laboratory (VIDRL). All testing was performed at VIDRL using a commercial enzyme-linked immunosorbent assay (Biotrin). Of the 824 sera tested, 28% of those drawn from people aged 0-9 years contained protective antibodies to human parvovirus. This rose to 51% in the next decade of life. There was then a slow rise to about 78% immunity over 50 years of age. An analysis of all requests for parvovirus serology at VIDRL from 1992 to 1998 suggested that parvovirus tended to occur in 4-year cycles, with 2 epidemic years followed by 2 endemic years. A review of published reports of parvovirus immunity suggested that parvovirus infection may be more common, with a correspondingly higher proportion of the community immune, in temperate as opposed to tropical countries.     

Comparison of stage IV and IV-S neuroblastoma in the first year of life

Clinical staging and factors related to survival were evaluated in 44 stage IV-S and 44 stage IV patients with neuroblastoma, ages 0 to 12 months, seen at Children's Cancer Study Group (CCSG) institutions from 1972 to 1979. In 73 patients with complete surgical staging, the life-table projected survival at 3 years was 91% for stage IV-S and 44% for stage IV. The only deaths in stage IV-S disease occurred in three patients less than 2 months old at diagnosis. In stage IV-S, 3 to 12 months old at diagnosis, the disease-free survival was 97%. Chemotherapy or radiation therapy did not appear to improve the survival rate in stage IV-S. These studies further document a significant clinical and biologic difference between patients with stage IV and stage IV-S neuroblastoma and suggest that they require different therapeutic management.     

Factors affecting pregnancy rates in a donor insemination program using frozen semen

The results of therapy of 226 women receiving frozen and fresh donor semen are reported. Overall, 45.6% of patients conceived with a monthly fecundability of 0.102. The effect of a variety of factors on fertility rates was analyzed in life-table analysis of 1000 cycles. Optimal pregnancy rates were obtained in couples with azoospermia (0.17) or no female infertility factors (0.2). Patients with ovulatory dysfunction treated with clomiphene also had optimal pregnancy rates (0.17 per cycle). Endometriosis reduced fecundability significantly (0.04 per cycle). There was no significant difference in pregnancy rates per cycle between fresh (0.12) and frozen (0.09) semen. Acceptable pregnancy rates were obtained with frozen semen therapy and in patients with treated ovulatory dysfunction.     

Exogenous gonadotropin requirements are increased in leuprolide suppressed women undergoing ovarian stimulation

We used a subcutaneously administered GnRHa for 21 to 26 days prior to menotropin stimulation, to suppress endogenous LH surges in four patients participating in IVF. GnRHa-pretreated cycles were compared with previous menotropin treatment cycles. Endogenous LH surges were successfully suppressed in all patients. Peak E2 levels and ultrasonographic parameters of follicular development were comparable in the two treatment groups. Exogenous gonadotropin requirements were increased 2- to 4-fold in GnRHa pretreated cycles (P less than 0.05). Ovum recovery rates were not improved by adjuvant LA. These studies indicate that there was an increased ovarian requirement for exogenous gonadotropins as a result of GnRHa therapy. It has to be considered that this may be a direct effect of GnRHa upon the ovary. Alternatively, the absence of endogenous pituitary support in GnRHa-treated patients may account for the increased gonadotropin requirement. Finally, it is possible that this effect is indigenous to this select patient population of poor responders to menotropin stimulation, or to a specific effect of subcutaneously (as opposed to intranasally) administered GnRHa on the ovary. Further studies are needed to clarify the extent to which any or all of these postulated mechanisms may be influencing ovarian response to exogenous gonadotropins after subcutaneous GnRHa pretreatment.     

Treatment of Pneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer: report from the Children's Cancer Study Group

Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.