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Biomedical subjects

C Grant

Publications and source records attributed to C Grant.

At least 145 records · Page 8Linked to original sources
PubMed1985

Reconstitution of nude mouse T cell function in vivo: IL 2-independent effect of human T cells.

The i.p. injection of 1 to 5 X 10(6) heavily irradiated human T lymphocytes resulted in the lasting reconstitution of T cell functions in young mice bearing the nu/nu mutation. IgM and IgG responses to immunization with sheep red cells or ovalbumin, splenic lectin responses, and the expression of easily detectable Thy-1 determinants on up to 20% of spleen cells could be documented for several months after the injection of human cells. Only a narrow cell dose range was effective. Injection of larger cell numbers not only failed to induce immune reconstitution but also resulted in the development of resistance to subsequent treatments. Only mature T cells, but not thymocytes, could induce nude mouse T cell development. Lymphoblasts from one patient with acute T cell leukemia consistently immune-reconstituted nude recipients. These cells were completely unable to produce IL 2 in vitro. In contrast, the IL 2-producing T cell line Jurkat was ineffective, indicating that the abilities to produce IL 2 and to induce nude mouse T cell development are independent. In an extension of earlier models of the nude mouse immune defect, two distinct T precursor cell pools are proposed as the major components of an extrathymic differentiation pathway. As an adequate trigger of differentiation, interaction with thymus-processed T cells guides the development of precursors in the first cell pool towards populating the second IL 2-responsive pool of T precursor cells.

Animals↗
PubMed1984

The prognostic significance of endodermal sinus tumor histology among patients treated for stage III nonseminomatous germ cell tumors of the testes.

A retrospective study was undertaken to determine the prognostic significance of endodermal sinus tumor (EST) elements in 56 patients with Stage III nonseminatous germ cell tumors of the testes (NSGCTT). The study patients were treated with conventional vinblastine, bleomycin and cisplatinum chemotherapy prior to our recognition of EST as a distinct entity. Twenty-one (37.5%) of the patients had EST elements in their tumors. Nineteen patients had EST in their primary testis tumor, whereas two had EST in metastatic sites only. Prognostic criteria (tumor volume, Dixon-Moore classification and chemotherapy vinblastin and bleomycin [VB] and VB plus cisplatin [VB + P] ) were similar in EST and non-EST patients. Long-term disease-free survival was significantly poorer for patients with Stage III NSGCTT containing EST (38%) compared with those not containing EST (71%) (P = 0.04). All 12 patients with small volume disease (III-B1-III-B2), independent of the presence of EST, are alive and free of disease for more than 2 years. Only 6 of 18 patients (33%) with advanced disease and EST are alive and free of disease, whereas 17 of 26 (65%) of patients with advanced disease not containing EST are alive and free of disease (P = 0.074). The addition of single agent bolus cisplatin to the treatment of patients with advanced disease achieved no improvement in survival. Endodermal sinus tumor must be included in future studies of advanced Stage III NSGCTT as an important prognostic variable.

Abdominal Neoplasms↗
PubMed1984

The symptomatology of the climacteric in relation to hormonal and cytological factors.

Climacteric symptomatology was investigated in a group of non-selected women aged between 54 and 56 years of age, Vasomotor complaints and dyspareunia, in particular, were noted and related to plasma hormone levels and vaginal cytology. Only 33% of those women who were within 5 years of the menopause had symptoms of a magnitude that might require hormone replacement therapy. Neither the vasomotor complaints nor dyspareunia correlated with the hormone levels or cytology findings to such an extent as to be helpful in planning treatment. Apparently only a minority of women in their middle 50s demonstrate a symptomatic need for hormone replacement therapy and laboratory investigations are of little use in their identification.

Cervix Uteri↗
PubMed1984

Use of the fluorescent probe 1-N-phenylnaphthylamine to study the interactions of aminoglycoside antibiotics with the outer membrane of Pseudomonas aeruginosa.

The mode of interaction of the polycationic aminoglycoside antibiotics with the surface of Pseudomonas aeruginosa cells was studied with the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN). The addition of the aminoglycoside gentamicin to intact cells in the presence of NPN led to a shift in the fluorescence emission maximum from 460 to 420 nm. At the same time the NPN fluorescence intensity increased fourfold. Gentamicin caused no such effects when added to outer membrane vesicles, suggesting that the increased fluorescence resulted from the interaction of gentamicin with intact cells. Gentamicin-promoted NPN uptake was inhibited by the divalent cations Mg2+ and Ca2+, but occurred in the absence of gentamicin transport across the inner membrane. Low concentrations of gentamicin (2 micrograms/ml) caused NPN fluorescence to increase over a period of 4 min in a sigmoidal fashion. At higher concentrations (50 micrograms/ml) the increase occurred within a few seconds. The final fluorescence intensity was almost independent of the gentamicin concentration. A centrifugation technique was used to demonstrate that gentamicin caused actual uptake of NPN from the supernatant. The initial rate of NPN uptake varied according to the gentamicin concentration in a sigmoidal fashion. Similar data were obtained for seven other aminoglycoside antibiotics. The data, when reanalyzed as a Hill plot, gave a series of lines with a mean slope (the Hill number) of 2.26 +/- 0.26, suggesting that the interaction of aminoglycosides with the cell surface to permeabilize it to NPN involved at least three sites and demonstrated positive cooperativity. There was a statistically significant relationship between the pseudoassociation constant K, from the Hill plots and the minimal inhibitory concentrations for the eight antibiotics. These results are consistent with the concept that aminoglycosides interact as a divalent cation binding site on the P. aeruginosa outer membrane and permeabilize it to the hydrophobic prove NPN.

1-Naphthylamine↗
PubMed1984

Tumor seeding associated with bone marrow aspiration and biopsy.

A 53-year-old man with small-cell lung carcinoma underwent bone marrow aspirations and biopsies for tumor staging and harvest for autologous bone marrow infusion. Fourteen months after bone marrow aspiration and biopsy, a subcutaneous lesion grew over the posterior iliac crest, and a biopsy specimen disclosed small-cell carcinoma. To our knowledge, this is the first case report of tumor seeding associated with bone marrow aspirate and biopsy.

Biopsy, Needle↗
PubMed1983

Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer.

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.

Adenocarcinoma↗
PubMed1982

Management of pelvic complications of malignant urothelial tumors with combined intra-arterial and iv chemotherapy.

Twenty-nine patients with local-regional pelvic recurrences of malignant urothelial tumors were treated with combined intra-arterial and iv chemotherapy. 5-FU (1 g/m2) was infused daily for 5 days via bilateral percutaneously placed hypogastric catheters. Doxorubicin (25 mg/m2) was infused iv on Days 1 and 2 and mitomycin (5 mg/m2) was infused iv on Days 3 and 4 of each course. Seventeen patients (58%) demonstrated an objective decrease in the size of the pelvic mass. All four patients with one of the adenocarcinoma variants of malignant urothelial tumors responded to therapy, while the three patients with squamous transformation of a transitional cell carcinoma failed to respond. The median survival of the responding patients was significantly longer (52 weeks) than that of nonresponding patients (28 weeks) (P = 0.002). Patients with initial low-volume pelvic disease demonstrated durable control of local residual tumors, with four of six patients having negative repeat cystoscopic examinations.

Adenocarcinoma↗
PubMed1979

Dopamine beta-hydroxylase and plasma renin activity in patients with low-, normal-, and high-renin essential hypertension.

The relationship of serum dopamine-beta-hydroxylase (DBH), plasma renin activity (PRA) and urinary catecholamines (IU catechols) in various forms of essential hypertension (EHT) (low, normal and high renin) was evaluated. Eighty-four predominantly white, young (37 +/ 8 years (SD)), mildly hypertensive patients (diastolic pressure 93 +/- 4 mm Hg (SD)) continued their regular diet and received no medications. Thirteen patients had low-renin, 64 had normal-renin, and seven had high-renin EHT. DBH, total IU catechols and urinary norepinephrine were not different between these renin subgroups. DBH was significantly lower in all hypertensives (55.6 +/- 36 IU) and in the low-renin subgroup (46 +/- 30 IU) compared with normal subjects (68 +/- 35 IU) (p less than 0.01). However, the DBH range was so broad that an individual DBH value did not distinguish EHT from normals. After a baseline period, patients were randomly assigned to receive chlorthali done 50 mg q.a.m. or placebo in a double-blind study. In the chlorthalidone group 1 month after therapy, the diastolic pressure decreased, PRA increased, and total IU catechols and urinary norepinephrine increased. Serum DBH did not change during diuretic therapy. A significant correlation could not be shown between pretreatment DBH and the changes in PRA and IU catechols before and after diuretics for all treated EHT patients. However, within the normal PRA EHT subgroup receiving chlorthalidone, the one-third of patients with lowest pretreatment DBH levels (n = 10) were compared with the one-third of patients with the highest pretreatment DBH values (n = 10). The lower DBH patients showed significantly less change in PRA (delta PRA = 2.9 +/- 1.8 ng/ml/hr) compared with the higher DBH patients (delta PRA = 8.2 +/- 1.6; P less than 0.05). In some EHT patients, DBH levels may be related to PRA response to diuretic therapy.

Adult↗
PubMed1978

Lapine rotavirus: preliminary studies on epizoology and transmission.

Antibody to rotavirus was found in sera of domestic rabbits, wild cottontail rabbits and Snowshoe hares. Eight out of 187 stools from a rabbitry contained rotavirus, though no clinical symptoms were apparent. The virus extracted from one such stool infected a five week old seronegative rabbit and led to distention and congestion of the colon, excretion of virus in the stool and a serological response to virus. Human and Simian rotaviruses did not replicate in the rabbits.

Animals↗