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Biomedical subjects

J Howard

Publications and source records attributed to J Howard.

335 records · Page 19Linked to original sources

cis-Dichlorodiammineplatinum(II)-based chemotherapy as initial treatment of advanced head and neck cancer.

During the past 2--3 years, a total of 73 patients with advanced head and neck cancer (mostly stage IV) were treated with cis-dichlorodiammineplatinum(II) (cis-platinum) as initial therapy, either alone or in combination with other agents. After chemotherapy, the patients received surgery and/or radiation therapy in standard fashion. Major degrees of tumor regression were seen in 40%--71% of the patients. cis-Platinum and bleomycin given by infusion gave the highest response rate (71%). The addition of high-dose methotrexate to cis-platinum plus bleomycin produced an unacceptable level of toxicity. Similarly, a four-drug regimen in which low-dose methotrexate and vinblastine were added to cis-platinum and bleomycin resulted in increased toxicity without additional therapeutic effect. Initial chemotherapy does not compromise subsequent surgery or increase either the immediate complications of surgery or the acute toxicity of radiation therapy. It seems unlikely that initial chemotherapy has altered the grim prognosis of an advanced, inoperable presentation. The effect of initial chemotherapy on advanced, operable disease will have to be assessed by suitable controlled trials.

Antineoplastic Agents↗

Parental visiting in foster care: law and practice.

Parental visiting of children in foster care is a key element in both reunification of families and termination of parental rights. The authors contend that these two uses of visiting must be balanced. To this end, they recommend that state statutes allow termination based on failure to visit but require agencies to promote visiting, and they suggest that agencies review their practices to determine if they discourage meaningful visits.

Adoption↗

Zona pellucida piercing enhances zona penetration by spermatozoa from normospermic and teratospermic domestic cats.

Poor quality ejaculates appear associated with reduced zona penetration and poor fertilization in vitro in some felid species or populations. Even morphologically normal sperm from these teratospermic ejaculates are compromised in ability to penetrate the zona pellucida and fertilize oocytes. A domestic cat model and zona piercing were used to study the function of normal and malformed sperm. Male cats naturally producing different proportions of morphologically normal sperm (group I, > 60%; group II, 45-55%; group III, < 40%) were identified. Electroejaculates were subjected to sperm washing (WS) and half of these to swim-up (SU) processing following WS, and all samples were assessed for a sperm motility index (SMI) over time. Zonae of salt-stored (SS), domestic cat oocytes were mechanically pierced (ZnPd) three times each. Control (nonmanipulated) SS oocytes (n = 430) and ZnPd-SS oocytes (n = 430) were coincubated with sperm in vitro. The proportion of morphologically normal sperm/ejaculate differed (P < 0.05) among groups averaging 68.8% for group I, 53.5% for group II, and 34.7% for group III. After SU processing, the percent normal sperm among groups was similar (P > 0.05; range, 70.8-80.2%). Average SMI for all groups was high (> 70) at 0 hour and decreased over time, but the descent of slope was greater (P < 0.05) for group III than groups I and II. The proportion of oocytes penetrated was not influenced (P > 0.05) by sperm-processing treatment. For all groups, inner zona penetration was greater (P < 0.05) in ZnPd-SS than SS oocytes (group I, 52.3% vs. 34.9%; group II, 37.9% vs. 20.3%; group III, 32.0% vs. 17.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A balancing act: the tension between case-finding and primary prevention strategies in New York State's voluntary HIV counseling and testing program in women's health care settings.

This study sought (1) to identify factors that influence women's willingness to accept voluntary HIV counseling and testing at New York State Family Planning Programs (FPPs) and Prenatal Care Assistance Programs (PCAPs) and (2) to evaluate the effectiveness of such a voluntary counseling and testing program. Telephone interviews elicited organizational-level data from 136 agencies; a combination of telephone and face-to-face interviews was used to gather provider data from 98 HIV counselors; and client data were gathered from 354 women in face-to-face interviews at counseling sites. Slightly fewer than 60% of women agreed to be counseled, and, of those, under half consented to an HIV test at the counseling site. Approximately two thirds of the women who were tested returned for their results and posttest counseling. Clients' recall of pretest counseling content was relatively poor. Bivariate and regression analyses suggest that client, provider, and organizational factors are all associated with rates of pretest counseling and testing. The current voluntary counseling and testing program is achieving only moderate success. Although a substantial number of clients accept HIV counseling, many women remain reluctant to consent to HIV testing, and many who accept testing do not return for their results. Moreover, among those who receive pretest counseling, many do not recall important informational content, which suggests variation may exist in the quality of counseling or that one-time HIV counseling interventions are insufficient to communicate complex information. Medical Subject Headings (MeSH): AIDS, HIV serodiagnosis, women's health, patient education.

AIDS Serodiagnosis↗

Compromised sperm protein phosphorylation after capacitation, swim-up, and zona pellucida exposure in teratospermic domestic cats.

Tyrosine phosphorylated proteins recently have been found in mouse and human spermatozoa. Our objectives were to (1) determine if domestic cat spermatozoa also express tyrosine phosphorylated proteins, and (2) examine the changes in protein phosphorylation between normospermic and teratospermic domestic cats following sperm capacitation, swim-up separation and exposure to zona pellucida (ZP). Membranes from cat spermatozoa contained two phosphorylated proteins of molecular weights 160 kDa and 95 kDa (designated as p160 and p95) that immunoreacted with monoclonal antibodies to tyrosine phosphate. The p95 protein was distinct from sperm-specific hexokinase. Following capacitation, the extent of phosphorylation of p95 was increased (P < 0.05) 3-fold in normospermic cats compared to only 1.75-fold in teratospermic cats. Similarly, phosphorylation of p160 also increased (P < 0.05) 2.4-fold in normospermic compared to 1.84-fold in teratospermic cats. Although swim-up separation increased the percentage of normal spermatozoa in teratospermic ejaculates, phosphorylation of p95 in swim-up, aliquots was increased (P < 0.05) only 1.95-fold in teratospermic cats compared to 2.9-fold in normospermic counterparts. Likewise, phosphorylation of p160 was lower (P < 0.05) in teratospermic (1.5-fold) compared to normospermic cats (2.0-fold) cats. Phosphorylation also was influenced by exposure to cat ZP proteins (P < 0.05). Solubilized cat ZP bound to the sperm proteins of apparent molecular mass 120, 95, 50, 42, 30, 27, 23 and 20 kDa, suggesting a direct binding interaction between p95 and the ZP. Overall, these findings (1) indicate the presence of tyrosine phosphorylated proteins in the domestic cat spermatozoon that directly interact with homologous ZP glycoproteins; (2) demonstrate that cat sperm hexokinase is not phosphorylated on tyrosine residues; and (3) suggest that the diminished phosphorylation efficiency of sperm from teratospermic cats may result in a compromise in capacitation and the acrosome reaction.

Animals↗

Regulation of sperm function by protein tyrosine phosphorylation in diverse wild felid species.

Protein tyrosine phosphorylation is associated with sperm capacitation and the acrosome reaction in several mammalian species. Changes in phosphorylation of a 95-kDa protein in human, mouse, and domestic cat spermatozoa are known to be influenced by capacitation and exposure to zona pellucida (ZP) proteins. We previously reported diminished phosphorylation of 95- and 160-kDa proteins in spermatozoa from teratospermic cats, compared with normospermic domestic cats. To determine if these proteins and mechanisms are present in other species in the phenotypically diverse Felidae family, we examined the relationship between tyrosine-phosphorylated sperm proteins and sperm morphology in the leopard cat (approximately 65% normal sperm/ejaculate), tiger (approximately 65%), clouded leopard (approximately 15%), and cheetah (approximately 30%). Furthermore, we investigated the involvement of cyclic adenosine monophosphate (cAMP) in the regulation of sperm protein tyrosine phosphorylation. Specifically, we assessed the following: 1) presence of tyrosine-phosphorylated proteins in sperm extracts; 2) changes in protein tyrosine phosphorylation after sperm capacitation and swim-up separation; 3) impact of tyrosine kinase inhibition on leopard cat sperm protein phosphorylation and ZP penetration; and 4) involvement of a cAMP-dependent pathway in the regulation of protein tyrosine phosphorylation. Immunoblotting analysis with anti-phosphotyrosine antibody (PY20) indicated that a 95-kDa protein was present in all four species. Additional phosphorylated proteins were detected in the leopard cat (145- and 175-kDa proteins), tiger (185-kDa protein), clouded leopard (160- and 190-kDa proteins), and cheetah (115- and 155-kDa proteins). Sperm capacitation in vitro increased phosphorylation of one or more proteins in the leopard cat, tiger and clouded leopard, but not in the cheetah. Although swim-up separation increased the proportion of morphologically normal spermatozoa in the clouded leopard and cheetah, no changes were observed in phosphorylation of the 95-kDa sperm protein. Thus, phosphorylation of the 95-kDa protein appeared to be related to the condition of teratospermia. Exposing leopard cat spermatozoa to the tyrosine kinase inhibitor, tyrphostin, reduced (P < 0.05) phosphorylation of the 95- and 145-kDa proteins, as well as ZP penetration, without affecting sperm motility. Similarly, when spermatozoa were incubated in the presence of cAMP analogs or active and inactive stereoisomers of cAMP, phosphorylation of sperm proteins was either stimulated or inhibited. Together, these data suggest that protein tyrosine kinase mechanisms appear conserved within the family Felidae and are regulated by a cAMP/protein kinase A pathway.

Animals↗