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Biomedical subjects

P Russell

Publications and source records attributed to P Russell.

At least 307 records · Page 17Linked to original sources

Differential synthesis of rat lens proteins during development.

Developmental regulation of crystallin protein synthesis was observed in rat lenses between embryonic day 19 and postnatal day 21. Studies on lenses incubated in [35S]-methionine and on lens messenger RNAs translated in a reticulocyte lysate showed that several new polypeptides were synthesized in the lens beginning approximately 1 week after birth. One new polypeptide which had a molecular weight of 27 000 comigrated with the beta crystallins on SDS-PAGE and became a predominant component in older lenses. By crossed rocket immunoelectrophoresis and isoelectric focusing, synthesis of several native beta crystallins and one gamma crystallin was detected only in the postnatal lens. Many crystallin proteins were synthesized in the embryonic and the postnatal lens and did not change during the time period studied. These data suggest a differential regulation of the crystallin proteins during development. It appears that the lens undergoes a transition from embryonic to adult crystallin expression during the first weeks after birth. Factors such as maturation of the retina may be necessary for this transition.

Aging↗

Comparison of the lens crystallin proteins from normal, rd, and rds mutant mice utilizing specific monoclonal antibodies.

The lens proteins from three lines of congenic mice which are homozygous for the gene retinal degeneration (rd) or retinal degeneration slow (rds) or carrying the normal alleles (normal) were analyzed by SDS-PAGE and by immunological reactivity to specific monoclonal antibodies. The lens proteins of normal, rd, and rds mice showed a similar developmental pattern between postnatal day 0 and postnatal day 30. The expression of the 25000 molecular weight (MW) beta-crystallin polypeptide which appears postnatally in the normal lens was not affected by retinal abnormalities in the mutant mice. It is concluded that the regulation of the 25000 MW beta-crystallin polypeptide is not dependent upon differentiation or maintenance of the photoreceptor outer segments or continued presence of the photoreceptor cells.

Animals↗

Analysis of the proteins in the rhesus monkey lens.

The proteins of the Rhesus monkey (Macaca mulatta) lens were studied and characterized. In general, there is a similarity of the monkey lens to the human lens particularly in the alpha- and beta-crystallins and the membrane proteins, although the amount of beta 1-crystallin may be greater in the monkey. There is immunological cross-reactivity in the crystallins between monkey and human lenses including the monkey low molecular weight proteins and the human low molecular weight proteins. The monkey lens low molecular weight material showed three differently sized proteins by gel exclusion chromatography. In this respect, the monkey lens proteins are similar to the human. However, the monkey lens low molecular weight proteins differ from the human low molecular weight proteins in charge as well as molecular weight determined by SDS-PAGE. One of the monkey low molecular weight proteins is more prevalent in the nucleus than in the cortex suggesting that this protein may be more important to the embryonic lens that to the adult lens.

Adolescent↗

Metastasizing placental site trophoblastic tumor: a case study.

The clinicopathologic features of placental site trophoblastic tumor (PSTT), a rare form of trophoblastic disease, were systematically described only relatively recently. Previously, in endometrial curettage and hysterectomy specimens, PSTT was not distinguished from choriocarcinoma or sarcoma, although in most cases the natural history had been benign. A case of biopsy-proved metastasis to para-aortic lymph nodes with radiologic evidence of lung metastasis is reported. Histologically, the tumor appeared similar to the tumors in other reported cases of PSTT. The mitotic rate was variable, being very high in a few small fragments obtained by curettage. Flow cytometric analysis of the tumor showed cells with diploid DNA content and a relatively low proliferative fraction. The tumor maintained its morphologic and functional characteristics following xenotransplantation into Balb/c nu/nu mice. In spite of a treatment regimen that included hysterectomy and multiagent chemotherapy, the patient continued to have evidence of persistent trophoblastic disease 15 months after presentation.

Adult↗

Ovarian tumour xenografts in the study of the biology of human epithelial ovarian cancer.

Human epithelial ovarian tumours were successfully established as xenografts in nude mice in 54% of cases. An evaluation of the biological characteristics of tumours propagated in nude mice was carried out and the functions investigated included morphology, growth kinetics, cellular DNA content, cell surface antigen expression and sensitivity to chemotherapy. To allow a more detailed study of the influence of ploidy on biological behaviour, xenografted tumour with varying degrees of aneuploidy and tumours with a common ancestry but different ploidies were also established. Although this is a highly selective model system favouring the growth of biologically aggressive tumours the xenografts, in general, reflect many of the characteristics of the tumours from which they were derived and are likely to provide a useful model for investigating the biology of ovarian cancer.

Animals↗

Phosphorylation of lens fiber cell membrane proteins.

Two intrinsic membrane proteins of calf lens fiber cells can be phosphorylated by a soluble bovine lens cAMP-dependent protein kinase and rabbit muscle cAMP-dependent protein kinase. After electrophoresis of the phosphorylated membranes, 32P comigrates with the lens main intrinsic protein at 26-27 kDa and with a minor band of protein that migrates at 19-20 kDa. 32P is also found with proteins that, based on the molecular sizes, are likely multimers of the 19-kDa and 26-kDa proteins. Upon boiling in NaDodSO4, all the radioactivity is found at the top of the gel, suggesting that both phosphoproteins are intrinsic membrane proteins. Serine is the only phospho amino acid detected in both proteins regardless of the source of protein kinase. The phosphorylation sites of both proteins are lost upon cleavage with trypsin and chymotrypsin. The smaller phosphoprotein is likely not a crystallin, because antibodies directed against alpha-, beta-, or gamma-crystallins do not cross-react with the 19-kDa protein. The 19-kDa 32P-labeled protein does not migrate coincident with calf alpha-crystallin.

Animals↗

Multifocal tumorigenesis in the upper female genital tract--implications for staging and management.

A review of 128 cases of "primary" ovarian müllerian carcinoma treated at the King George V Memorial Hospital was undertaken to determine the relative frequency with which such tumors were associated with evidence of multifocal primary neoplasia. Of the 128 cases studied, 115 were invasive carcinomas and 13 were noninvasive or borderline ovarian tumors ("tumors of low malignant potential"). Eight of 10 borderline serous ovarian tumors (80%) and 37 of 75 invasive serous carcinomas (49%) exhibited evidence of independent primary neoplasia at more than one anatomical site in the biopsy material available for review. Many of these cases represented bilateral primary ovarian tumors, but autochthonous extraovarian neoplasia was also commonly encountered. A single borderline endometrioid ovarian tumor and six of 15 endometrioid carcinomas (40%) were associated with biopsy-proven multifocal primary tumorigenesis. These were predominantly neoplasms in one or both ovaries plus adenocarcinoma in the uterine corpus. Other histological types of malignant common epithelial tumors of the ovaries did not demonstrate any such tendency, highlighting major differences in pathogenesis between members of this loosely associated group of ovarian cancers. Our study suggests that gynecological endometrioid and serous malignancies are commonly multifocal and we feel this has significant implications for the way these neoplasms are staged and therefore treated.

Biopsy↗

Isolation and characterization of the DNA region encoding nodulation functions in Bradyrhizobium japonicum.

The DNA region encoding early nodulation functions of Bradyrhizobium japonicum 3I1b110 (I110) was isolated by its homology to the functionally similar region from Rhizobium meliloti. Isolation of a number of overlapping recombinant clones from this region allowed the construction of a restriction map of the region. The identified nodulation region of B. japonicum shows homology exclusively to those regions of R. meliloti and Rhizobium leguminosarum DNA known to encode early nodulation functions. The region of homology with these two fast-growing Rhizobium species was narrowed to an 11.7-kilobase segment. A nodulation-defective mutant of Rhizobium fredii USDA 201, strain A05B-2, was isolated and found to be defective in the ability to curl soybean root hairs. Some of the isolated recombinant DNA clones of B. japonicum were found to restore wild-type nodulation function to this mutant. Analysis of the complementation results allows the identification of a 1.8-kilobase region as essential for restoration of Hac function.

DNA Restriction Enzymes↗

Combined renal and pancreatic dysplasia in the newborn.

A term female infant with early onset respiratory distress and pneumothorax died on day 20 with renal failure. Autopsy revealed dysplastic kidneys with occasional cortical cysts. The pancreas showed focal dysplasia with cysts and dilated ducts lying in primitive mesenchyme. A mild chronic inflammatory infiltrate was present in the dysplastic areas of kidneys and pancreas. The abnormalities in the affected organs were similar to those in two siblings described by Ivemark et al. in 1959 and designated "familial dysplasia of kidneys, liver and pancreas". Relationships to subsequently reported cases, including some with major congenital malformations, and the validity of this dysplastic triad as a disease entity are examined.

Female↗

The comparison of human lens crystallins using three monoclonal antibodies.

Three monoclonal antibodies against lens crystallin have been used to study the accumulation of specific polypeptides during development of the human lens. One antibody which recognizes an antigen common to three polypeptides with molecular weights close to 31,000 reacted equally well to the human lens cortex and nucleus and had a similar binding activity to proteins isolated from embryonic and older human lenses. This suggests that the antigen accumulates to the same degree in human lenses during development. The second monoclonal antibody to the 24,000 molecular weight gamma-crystallin showed increased binding at the older ages indicating the increased accumulation of this protein during lens development. The third monoclonal antibody to a beta-crystallin of 27,000 molecular weight showed little if any reactivity at the embryonic age and revealed a clear difference between the binding with cortical and nuclear protein at older ages. It appears that the 27,000 molecular weight beta-crystallin may not be synthesized in the embryonic human lens.

Adult↗

Partial characterization of three distinct populations of human gamma-crystallins.

Certain low molecular weight crystallins may be involved preferentially in the process of human cataractogenesis. Three distinct populations of monomeric crystallins with molecular weights ranging from 19,000 to 24,000 have been demonstrated previously by electrophoresis in the presence of sodium dodecyl sulfate (SDS). The authors now report the chromatographic separation of these three components from young human lenses. Each of the three species has unique profiles on isoelectric focusing and native polyacrylamide gels as well as on SDS gels. All three species show similar patterns of age-related modification in their charge characteristics. These three populations of polypeptides all appear to be gamma-crystallins. The relative amounts of the three vary with age, which accounts for the greater ease of their separation in extracts from young lenses as compared with adult lenses.

Aged↗

Cytostatic and cytolytic activities of macrophages regulation by prostaglandins.

Murine peritoneal macrophages (M phi), activated in vivo or in vitro, remarkably inhibited the uptake of thymidine by a lens epithelial cell line, while resident M phi, or M phi induced by thioglycollate, exhibited much lower or no cytostatic capacity. The target cells were partially protected from the cytostatic activity by the anti-inflammatory agents indomethacin, aspirin, and dexamethasone, but not by lipoxygenase inhibitors. The protective activity of indomethacin and aspirin, but not of dexamethasone, was completely counteracted by prostaglandin E2 (PGE2). Yet, PGE2 alone has no effect on the uptake of [3H]thymidine by lens epithelial cells. PGE1 resembled PGE2 in its effect on this system, whereas PGA2, PGB2, or PGF2 alpha had no detectable activity. The counteracting effect of PGE2 was mimicked by dibutyryl cAMP or by cholera toxin, an agent which increases cAMP levels. These findings suggest that PGEs are not direct cytostatic agents, but rather, are essential mediators for the development of the cytostasis. Activated M phi did not lyse cells of the original lens epithelial cell line, but caused substantial cytolysis of cells of a subline derived from it. In contrast to its aforementioned effect on the cytostasis, PGE2 inhibited the cytolytic activity of M phi. Thus, this study provides a first demonstration in a single system of the opposite effects of PGEs on M phi activity on target cells, i.e., mediating the cytostasis and inhibiting the cytolysis.

Animals↗

The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study.

Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗

Cellular DNA content--a stable feature in epithelial ovarian cancer.

Detailed flow cytometric analysis of cellular DNA content was performed on neoplastic tissue from 33 patients with malignant common epithelial ovarian tumours in order to investigate the intratumoral stability of ploidy and proliferative fraction. There was a remarkable stability, both spatial and temporal, in the DNA pattern for any particular tumour. Of 24 tumours that were analysed in multiple areas tumour ploidy was found to be a stable marker in all but 3 cases where regional variations were evident. In 9 patients serial analyses were performed on tumour obtained either at initial diagnosis (6 patients) or second look laparotomy (3 patients) and then some time later (7-17 months) at relapse or death and in all cases the tumour ploidy remained unchanged. In addition, 10 ovarian carcinomas established in nude mice have maintained a DNA content during serial passage similar to that of the original implanted tumour. In contrast in 50% of tumours that were evaluable for S-phase analysis we demonstrated a considerable intratumoral variability in the S-phase fraction. We conclude that cellular DNA content is a stable feature of ovarian carcinoma while S-phase fraction is commonly subject to intratumoral variation.

Animals↗

Long-term follow-up of newborns with persistent pulmonary hypertension.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome associated with high morbidity and mortality. Mechanical ventilation attempts to maintain a PaCO2 less than 30 torr and a pH greater than 7.5 until pulmonary hypertension resolves. To assess whether the disease or its therapy adversely affects neurodevelopmental or cardiorespiratory outcome, 11 infants diagnosed and treated for PPHN were evaluated at a mean age of 31 months. Nine had normal developmental quotients (DQs) and 2 had mildly delayed DQs. Eight children were entirely normal neurologically, 2 had slightly increased lower-extremity tone, and 1 had unilateral hypertonia. All cardiac exams, echocardiograms, and ECGs were normal. Four children had chronic lung disease requiring either daily or intermittent bronchodilator therapy; however, their activity levels were unaffected. These results suggest that subsequent normal development with little significant medical compromise may be expected in this group of critically ill infants.

Child Development↗