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Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 307 records · Page 17Linked to original sources
PubMed1983

Expression of pp60c-src protein kinase in adult and fetal human tissue: high activities in some sarcomas and mammary carcinomas.

An endogenous protein of human cells pp60c-src, which is closely related to the product of the transforming gene of Rous sarcoma virus, pp60v-src, has been quantitated by measuring its enzymatic activity in an immunoglobulin G protein kinase assay. The influence of normal developmental processes on pp60c-src expression was assessed by comparative analysis of various adult and fetal human tissues. The maximal difference detected was a 2- to 3-fold-enhanced activity in fetal muscle compared with adult muscle. Organ-specific variations in the enzyme level were observed. Highest activity was found in brain, followed by kidney, lung, muscle, and connective tissue. Since overexpression of the cellular counterparts of viral-transforming genes may play a role in carcinogenesis, pp60c-src kinase was measured in nine spontaneous human sarcomas and 21 mammary carcinomas. Compared with the respective normal tissues and human diploid fibroblasts, 4- to 20-fold-enhanced activities were observed in one-third of the sarcomas and carcinomas. The remainder showed no or insignificantly elevated activity. The enzymes from normal and malignant tissues were indistinguishable from the virus-coded enzyme with respect to specificity for divalent cations and a predominance of phosphorylation in tyrosine. Patients carrying tumors with high pp60c-src protein kinase activity did not develop kinase-reactive antibodies against pp60c-src or pp60v-src.

Animals↗
PubMed1983

Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity.

Renal dysfunction is the dose-limiting toxic effect for many patients receiving cisplatin (CP). Despite hydration and/or forced diuresis, some patients develop nephrotoxicity, and patients at risk cannot be easily identified. We studied 77 patients with several types of carcinoma who received 115 cycles of CP, by 24-hour infusion, at doses of 40-100 mg/m2. Blood samples for platinum (Pt) analysis were obtained during and after CP infusion; plasma Pt levels were dose- and time-dependent. A significant rise in serum creatinine was seen after the first cycle and cumulatively over subsequent CP cycles. The largest subgroup of patients, those who received 80 mg/m2, was analyzed for predictors of nephrotoxicity. Twenty-five percent of patients exhibited nephrotoxicity (greater than 30% rise in serum creatinine or greater than 30% fall in creatinine clearance). These nephrotoxic patients had significantly higher plasma Pt levels during CP infusion than did nonnephrotoxic patients. Age, sex, cycle number, and pretreatment creatinine did not predict nephrotoxicity. Patients predisposed to nephrotoxicity with CP chemotherapy may be identifiable, on the basis of elevated plasma Pt, early in the course of CP infusion.

Cisplatin↗
PubMed1983

Mechanism of cisplatin nephrotoxicity.

cis-Diamminedichloroplatinum II (cisplatin) is widely used in cancer treatments. Renal dysfunction is the major toxic effect of this drug. Micropuncture studies suggest that cisplatin reduces single-nephron glomerular filtration rate (GFR) and causes a significant backleak of inulin across the renal tubule. Pathological alterations are localized to the S3 segment of the proximal tubule situated in the outer stripe of the outer medulla. Renal clearance studies in humans demonstrate that the free platinum clearance exceeds the GFR, which suggests that cisplatin or a platinum metabolite is actively secreted by the kidney. Studies with renal cortex slices indicate that platinum is accumulated by renal tissue against a concentration gradient. This uptake is blocked by metabolic inhibitors and the organic base triethanolamine. Heavy metals are thought to produce renal damage because of interaction with renal sulfhydryl (SH) groups. After cisplatin administration to rats, total renal SH groups decreased by 14% owing to a decrease of protein-bound SH groups. The greatest decline of SH groups occurred in the mitochondrial and cytosolic fractions. These fractions also had the highest platinum concentrations. These results suggest that the nephrotoxic effects of cisplatin may be related to depletion of SH groups, but a cause and effect relationship has not been definitively established.

Animals↗
PubMed1983

Phase I trial of intravenous L-phenylalanine mustard plus the sensitizer misonidazole.

Misonidazole (MISO), a hypoxic cell radiosensitizer, has been shown in vivo to enhance tumor cell killing by melphalan (LPAM) with little or no enhancement of normal tissue injury. A Phase I trial was conducted using MISO p.o. 2 hr before i.v. LPAM. The highest doses used were the single maximum tolerated doses of MISO, 4 g/sq m, and LPAM, 0.6 mg/kg. Thirty-five patients were entered; 30 were evaluable for assessment of hematological toxicity, which was predicted to be the dose-limiting toxicity. The median age was 60 years (range, 28 to 72 years). Mild to moderate nausea and vomiting occurred in 80% of patients. Five developed serious hematological toxicity defined as nadir white blood cell count less than 1000/cu mm, platelets less than 20,000/cu mm or 4-week posttreatment white blood cell count less than 2000/cu mm, platelets less than 50,000/cu mm. Four of the toxicities occurred at the LPAM dose of 0.6 mg/kg but were independent of MISO dose. One patient died of infection. Two patients whose tumor demonstrated an objective response to therapy and 10 others with disease stabilization received additional courses. Four patients developed mild MISO neuropathy. Pharmacokinetic studies demonstrated that MISO did not appear to affect the pharmacokinetics of LPAM in plasma. Both LPAM and MISO can be given safely at their individual maximum tolerated dose. This combination will proceed to Phase II trials.

Adult↗
PubMed1982

Changing role of chemotherapy in treatment of head and neck cancer.

The role of chemotherapy in the management of head and neck cancer includes treatment for recurrent disease and as an adjunct to conventional therapy with radiation and/or surgery in the primary treatment program. The best single agents, methotrexate and cisplatin, used for recurrent disease give response rates of 20 to 50 percent but of short duration. Results may be improved with combination chemotherapy, but often with increased toxicity. Prognostic factors that influence response are discussed. A newer role of chemotherapy in this disease is in the initial treatment program. Pretreatment chemotherapy can debulk these lesions prior to surgery and/or irradiation in up to 80 percent of patients. Controlled trials are in progress to determine the effect on cure rates. Chemotherapy utilized during radiotherapy has resulted in survival benefit in several studies. Post-treatment adjuvant chemotherapy still needs to be evaluated. The potential advantages and disadvantages of chemotherapy used in the initial treatment are discussed. Major strides have been made in the last decade in the treatment of head and neck cancer, and chemotherapy is assuming an increasingly important role.

Antineoplastic Agents↗
PubMed1982

Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study.

A survival analysis was applied to 1,453 patients treated between 1972 and 1978 in 33 French dialysis centers and prospectively followed up in the computerized Diaphane Dialysis Registry. 198 deaths (overall mortality = OM) were registered, of which 87 (43%) were secondary to cardiovascular complications (cardiovascular mortality = CVM). Risk factors for OM and CVM (p values less than 0.05) were age, male sex, nephroangiosclerosis or diabetic nephropathy as the primary renal disease, elevated systolic and diastolic blood pressure and two weekly dialysis rather then three. In contrast with the results observed for the general population, a high body mass index and elevated cholesterol, triglycerides and uric acid were not found to be associated with significantly increased CVM or OM. On the contrary, low body mass index (less than 20 kg/m2), low cholesterol (less than 4.5 mmol/l) and low mean predialysis blood urea (less than 4.6 mmol/l) were associated with increased OM and CVM, and more especially with high stroke mortality. Results for urea but not for cholesterol remain significant after adjustment for age, sex, weekly dialysis schedule and body mass index. They suggest that, in addition to elevated blood pressure, a poor nutritional state and/or low protein intake may be important factors for explaining the high cardiovascular mortality, particularly for strokes, observed in dialyzed patients.

Adolescent↗
PubMed1982

Use of methotrexate and 5-FU for recurrent head and neck cancer.

Thirty patients with recurrent squamous cell carcinoma of the head and neck were treated with methotrexate (250 mg/m2) followed 1 hour later by 5-FU (600 mg/m2). One patient had a complete response and four had partial responses, for an overall response rate of 16%. The response rate in patients with no prior chemotherapy was 21%. Toxic effects included neutrophenia in ten patients, with one associated death from infection; severe mucositis in three patients; and severe diarrhea in seven patients. Three patients had acute abdominal pain requiring hospitalization, with one associated death. The combination of methotrexate and 5-FU as given in our study was not superior to methotrexate alone and had substantial toxicity.

Adult↗
PubMed1982

Dialysis treatment and psoriasis in Europe.

One hundred and fifty out of 944 European dialysis centers reported experience with patients suffering from psoriasis. Ninety-three centers returned special questionnaires on 97 patients with end stage renal failure (ESRF patients) and on 49 patients dialyzed for psoriasis but who had normal renal function (NRF patients). Improvement of skin disease was reported in 17 out of 27 NRF patients according to both "objective criteria" and the patients' personal opinions. However, most of these patients had been on dialysis for less than one year (9.9 +/- 11.1 months) which is too short to allow for the spontaneous recurrence of psoriasis. In contrast, 60% of ESRF patients had been on dialysis for 45 +/- 3.1 months. Skin disease definitely improved in 20% of these patients after commencement of dialysis. This proportion is greater than the expected spontaneous long-term remission of psoriasis.

Adult↗
PubMed1981

[Results of one year (1978) of kidney transplantation (author's transl)].

Kidney transplantation in France is not as common as both patients and health authorities would wish. While at least 1 000 transplantations would be required each year, only 550 were done in 1978. The authors report on the experience of a team which for the first time was able to perform 75 transplantations in one year, and bring to the pull of transplantation 74 cadaver kidneys. The 75 patients will be followed up by the same group which operated upon them not only during the post-operative period, but also for many years to come. As far as possible, the team endeavours to transplant kidneys from local donors or sent directly to the surgeons. Such a "regionalisation" of kidney transplantations suffers from the drawback of lesser compatibility, but makes it possible to obtain the expected results.

Adolescent↗