PubMed HealthSearch

Biomedical subjects

D J Weaver

Publications and source records attributed to D J Weaver.

15 recordsLinked to original sources

A crustacean neuronal cytoskeletal protein with characteristics of neurofilaments and microtubule-associated proteins.

The purpose of this study was to characterize further a unique protein that is a component of the cytoskeleton of crayfish neurons. This protein, referred to as P600, is unique because it is unusually large (Mr greater than 600 kD), and because it has characteristics in common with both mammalian microtubule-associated proteins and neurofilaments. Immunohistochemical techniques have shown that P600 colocalizes with microtubules and is a component of the fibrous side-arms that extend from microtubules (Weaver and Viancour, Brain Res. 544:49, 1991). We have developed a method for obtaining purified P600 by using gel filtration techniques. When viewed by negative staining electron microscopy, P600 obtained by that method produced 11 nm-wide beaded filaments. The number of filaments was strictly related to the P600 concentration in a column fraction. A small amount of P600 consistently copurified with taxol-stabilized microtubules. The proportion copurifying with microtubules was increased by using apyrase to deplete ATP, or by using a nonhydrolyzable ATP analogue to compete with ATP. Immunogold labeling localized P600 near the ends of a subset of the fibrous side-arms extending from endogenous axonal microtubules. Several polyclonal antibodies against mammalian microtubule-associated proteins were tested for P600 labeling on immunoblots, and positive labeling was obtained with an antiserum directed against a region of microtubule-associated protein 1B that has microtubule binding activity. Epitope homology between P600, mammalian microtubule-associated protein 1B, and the mammalian mid-molecular weight neurofilament subunit is discussed in the context of possible evolutionary relationships among these cytoskeletal proteins.

Animals

The crayfish neuronal cytoskeleton: an investigation of proteins having neurofilament-like immunoreactivity.

We have evaluated the possibility that proteins similar to mammalian neurofilament proteins (NFPs) are present in crustacean neurons. A panel of monoclonal antibodies (mAbs), raised against mammalian NFP, was used to identify candidate proteins. The degree to which these proteins are similar to mammalian NFPs was further evaluated using the following criteria: tissue specificity, recognition by the neurofilament-specific Bodian silver strain, recognition by the intermediate filament-specific Pruss mAb, and insolubility following detergent-extraction. Three candidate polypeptides were identified by mAb screening: a very high molecular weight polypeptide (Mr greater than 300 kDa), a 40 kDa polypeptide, and a group of 4 bands at Mr = 66-84 kDa. Although all of these polypeptides were recognized by one or more anti-NFP mAb, not one of them was found exclusively in neuronal tissue, not one was stained by the NFP-specific Bodian method, and all were soluble under conditions in which mammalian NFPs are insoluble. As a result of this thorough evaluation, we conclude that crayfish neurons do not contain neurofilament-like proteins. Although not closely related to mammalian neurofilaments, the very high molecular weight crayfish polypeptide which was strongly labeled by a commercially available anti-NF-M mAb (clone NN18) during the mAb screening, may be a novel cytoskeletal protein. The evidence for this conclusion comes from immunocytochemical labeling experiments. Indirect immunofluorescence labeling of this protein differentially labeled axons, such that labeling intensity of specific axons was proportional to the relative concentration of cytoskeletal organelles in those axons. Labeling of neuronal cell bodies delineated a fibrous network throughout the cytoplasm, and intensely labeled microtubule-rich regions of cytoplasm which are characteristic of larger neuronal somata. Immunogold labeling and electron microscopic analysis of the distribution of this protein revealed that the NN18-clone antibody bound to an antigen located on microtubule side-arms.

Animals

Late results of combined iodine-125 and external beam radiotherapy in carcinoma of prostate.

A total of 96 patients were treated for localized carcinoma of the prostate using combined Iodine-125 (125I) implantation and external beam radiotherapy. The implant was tailored to deliver 10,000 rad to the periphery of the prostate. A significant incidence of serious late rectal complications was observed. Positive pelvic nodes were found in 28 percent of the patients. Disease-free survival at seven years was 76 percent for those with negative nodes and 46 percent for patients with positive nodes.

Fistula

Scrotal temperature and semen quality in men with and without varicocele.

The exact role of varicocele in human male infertility remains controversial. Fifty-five male partners of infertile couples randomly selected and 17 fertile semen donors were evaluated for semen quality, scrotal temperature, and presence of varicocele using clinical palpation and Doppler ultrasound. The incidence of varicocele was 42% in male partners of infertile couples and 41% in fertile semen donors. Left scrotal temperature was significantly (p less than .001) higher in infertile males with varicocele as compared to all groups. No significant differences were observed in the percentage of morphologically normal sperm in semen of males with and without varicocele. However, the incidence of tapered, elongated, and immature sperm was significantly higher in the infertile patient population with a varicocele. Measurement of scrotal temperature and assessment of sperm morphology may be used as predictors of the presence and deleterious effect of varicocele.

Body Temperature

Nonpalpable occult testis tumor.

We present a case study of a patient with seminoma who had normal testicles on palpation. Testicular ultrasound is the technique of choice to locate occult nonpalpable testis lesions. We recommend its use in the search for the source of any retroperitoneal mass of undetermined origin.

Adult

Cytogenetics of bilateral renal cell carcinoma.

We analyzed cytogenetically 6 tumors from 4 patients with bilateral renal cell carcinoma. Comparison among findings in these patients with bilateral disease and previously reported cases of unilateral tumor demonstrates that bilaterality is associated with a more frequent loss of a sex chromosome, and gain of chromosomes 7 and 3, whereas unilateral tumors often are associated with loss of chromosome 3 material. It is proposed that bilateral tumors are distinct genetically from unilateral tumors and that most bilateral tumors have a genetic propensity to either enhanced metastatic spread to other renal tissue or spontaneous degeneration.

Adult

Cytogenetic analysis in renal cell carcinoma: correlation with tumor aggressiveness.

Twenty-eight tissue specimens from 26 patients with renal cell carcinoma were subjected to cytogenetic analysis using a newly developed combined method of enzymatic technique and short term tissue culture. Of the 28 tumor samples studied, 21 were chromosomally abnormal. Four (including two oncocytomas) were normal, and three did not grow in tissue culture. Of the 21 tumors with abnormal chromosomes, the most frequent abnormality was either trisomy or tetrasomy of chromosome 7 (18 of 21 tumors). In four of these tumors, trisomy 7 was the only visible abnormality. Ten tumors contained abnormalities of chromosome 3. Three showed a previously reported chromosome 3 interstitial deletion, five were hyperdiploid, and two revealed a monosomy 3. Of these 10 patients, six have had disease progression, compared to one of the 16 remaining patients without an abnormal chromosome 3. These data suggest that abnormalities of chromosome 7 represent a primary abnormality, and that when these abnormalities are present in association with abnormalities involving chromosome 3, they may correlate with a more aggressive clinical course and a corresponding higher stage of disease at diagnosis.

Carcinoma, Renal Cell

Genomic defects in nonfamilial renal cell carcinoma. Possible specific chromosome change.

Using a newly developed combined method of enzymatic technique and short-term tissue culture, 30 tumor specimens from 26 patients with nonfamilial renal cell carcinoma were subjected to cytogenetic analysis. Of the 26 patients, 19 had chromosomally abnormal tumors, four (including two oncocytomas) were normal, and three did not grow. The modal chromosome numbers ranged from 44 to 98 (including two pseudotetraploids). Banding analysis revealed 38 clonal aberrations and ten nonclonal aberrations. Abnormalities were of structure and number. The most consistent clonal abnormality was a trisomy or tetrasomy chromosome 7 occurring in tumors from 15 of the 19 patients with cytogenetically abnormal tumors. In four cases, trisomy 7 was the only visible abnormality observed, and in an additional five it was the only abnormality in two or more cells. An abnormal chromosome 3 was found in ten (38%) of the cases. Two were trisomic for #3, two were monosomic, three were hyperdiploid, and three had interstitial deletions with breakpoints clustered from p11 to p25. In only one case was a deleted #3 the only abnormality observed in a clone of cells. Loss of the sex chromosome was seen in eight (35%) of the 23 chromosomally abnormal cases including all four (100%) patients with bilateral disease. One of the patients with bilateral disease had an abnormal clone with monosomy X as the only abnormality. These data suggest that trisomy or tetrasomy 7 more often represents the specific primary abnormality than abnormalities of either chromosome 3 or the sex chromosomes. From this, a model of chromosomal progression may be constructed for nonfamilial renal cell carcinoma, which could assist in pathologic classification and prognostic and therapeutic considerations.

Carcinoma, Renal Cell

Cytomorphological lesions induced by chemotherapeutic agents in transitional cell carcinoma in vitro.

Transitional cell carcinoma from 20 patients and two human cell lines were maintained in short-term tissue culture. Each was studied ultrastructurally before and after incubation with cisplatinum, adriamycin, or mitomycin C. Sequential ultrastructural changes were noted and were found to be specific for each agent tested. Ultrastructural changes in the nucleoli were produced by exposure to cisplatinum or mitomycin C; alterations in the heterochromatin of the nuclei were characteristic of treatment with adriamycin. The changes in the nucleoli seen with cisplatinum have not been described previously and support an alkylating property as a mechanism of action. Intravesical chemotherapeutic agents are now commonly used in clinical treatments. The morphological changes produced by these agents are specific and may be seen in the clinical setting.

Antineoplastic Agents

Transitional explant reduction assay--a new in vitro testing system for intravesical chemotherapy.

Eighty-five tumors from 49 patients with transitional cell carcinoma were examined in a model for in vitro sensitivity using tumor explant reduction assay. Individual sensitivity patterns were obtained for each tumor tested. Explants were most frequently found to be sensitive to cis-platinum (49 per cent) and least frequently sensitive to thiotepa (20 per cent). Thirteen patients were studied on multiple sequential intervals, with resistance to specific agents noted to develop in 53 per cent of the patients. To date, a prospective cross-over study has been conducted on seven patients with 15 correlates. Overall, clinical correlation of this assay for both resistance and sensitivity is 93 per cent. We report a new assay for transitional cell carcinoma of the bladder that is adaptable to small specimen samples and provides adequate material for testing 73 per cent of the time.

Carcinoma, Transitional Cell

Impotence in scleroderma.

Hormonal, neurologic, and vascular factors affecting potency were evaluated in 10 men with scleroderma and in 10 age-matched men with rheumatoid arthritis. Impotence was reported by 6 of the patients with scleroderma and none with rheumatoid arthritis. Studies of serum testosterone, free testosterone index, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, thyroxine, and thyrotropin did not show a hormonal basis for impotence in any patient. Neurologic causes were not found on physical examination. Penile blood pressures were markedly abnormal in 4 impotent patients, intermediate in 2 impotent and 3 potent patients, and normal in 11 potent patients. A history of claudication and diminished ankle blood pressures indicated large vessel disease in 2 impotent patients; the remaining 4 impotent men had normal ankle pressures, suggesting that their poor penile blood pressures and impotence were due to small vessel disease, perhaps the small artery lesions of scleroderma.

Adult

Opiates, endorphins and the developing organism: a comprehensive bibliography.

A comprehensive bibliography of the literature concerned with opiates, endorphins, and the developing organism is presented. A total of 1378 clinical and laboratory references, with citations beginning in 1875, are recorded. A series of indexed accompanies the citations in order to make the literature more accessible. These indexes are divided into clinical and laboratory topics. The clinical section is subdivided into: age of subject examined; maternal aspects; effects on the fetus; pharmacology, physiology, and the withdrawal syndrome; and "other" effects on the offspring. The laboratory section is subdivided into: type of opiate/endorphin studied; species utilized; and major subject areas explored.

Aging