In vivo targets of recombinant human tumour necrosis factor-alpha: blood flow, oxygen consumption and growth of isotransplanted rat tumours

The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.     

Differentiation of cardiac murmurs by dynamic auscultation

The techniques described in this monograph will aid in the accurate identification of the origin of a cardiac murmur or abnormal heart sound. They do not necessarily reveal the presence or severity of cardiac disease. No maneuver is 100% accurate in elucidation of cardiac abnormalities, and a given maneuver's effectiveness varies in its application. The systematic application of a combination of maneuvers improves the accuracy of diagnosis. Auscultatory findings must be interpreted with consideration of the total clinical examination including history, other physical findings, ECG, chest x-ray, and possibly an echocardiogram. Thus, the careful physiological approach to the physical examination represents a powerful noninvasive tool that can be used in combination with other information to accurately diagnose cardiac disease in many patients and efficiently direct further evaluation when necessary.     

Dietary Tryptophan Reverses Alcohol-induced Impairment of Facial Recognition But Not Verbal Recall

The present study demonstrates that alcohol-induced memory impairment can be attenuated by pretreatment with an oral tryptophan supplementation. These results provide support for the role of a brain serotonin deficit in this impairment and highlight the impact a dietary manipulation can have on a complex behavioral process.     

Impaired Lymphocyte Proliferative Response to Mitogen in Alcoholic Patients. Absence of a Relation to Liver Disease Activity

Concanavalin A-induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose-response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.     

Tissue-specific regulation of pyroglutamate aminopeptidase II activity by thyroid hormones

Among the enzymes capable of degrading thyrotropin-releasing hormone (TRH) in vitro, two pyroglutamate aminopeptidases (PGA) are specific for TRH: thyroliberinase, a seric enzyme and PGAII, a membrane-bound peptidase. The effect of thyroid hormone status on the activity of these enzymes was evaluated in serum and various tissues. Only in adenohypophysis, triiodothyronine treatment increased PGAII to 376% of control; hypothyroidism produced the reverse effect (decrease to 23% of control). As previously reported, similar changes were observed for thyroliberinase. TRH degradation at the adenohypophysis level may participate in the negative feedback control of thyroid hormones.     

A novel hybridoma antibody (PASE/4LJ) to human prostatic acid phosphatase suitable for immunohistochemistry

A murine monoclonal antibody PASE/4LJ to prostatic acid phosphatase (PAP) was used to immunostain a wide variety of sections of benign and malignant tissues (654 blocks). Non-neoplastic adult and fetal prostatic glands, primary and metastatic prostatic carcinomas, and scattered cells in prostatic and penile urethra were positive. Rat, dog and rabbit prostates were negative. Nine of 400 tumours of non-prostatic origin showed some positivity: 6/36 carcinoids, 1/9 islet cell tumours, 1/55 ovarian adenocarcinomas (serous) and one carcinosarcoma of the lung (epithelial portion). Positive staining was seen in islet cells in 4/5 specimens of normal pancreas, and in 4/9 blocks of normal pancreas surrounding a pancreatic tumour. Loops of Henle, maculae densae, and distal tubules in 10/10 fetal and 2/9 adult kidneys were also positive, with proximal tubules and collecting ducts negative. All other 159 blocks of non-neoplastic adult and fetal tissues were negative. The antibody was also affinity purified from ascitic fluid, and shown not to inhibit the enzyme activity of prostatic acid phosphatase.     

Adjuvant systemic treatment of resectable breast cancer: eleven years results of a monoinstitutional chemo-hormone-immunotherapy trial

131 patients with resectable, node-positive breast cancer were treated at the National Institute for Cancer Research of Genoa, Italy with a systemic adjuvant regimen based on 14 cycles of chemotherapy, immunostimulation with levamisole, and--for postmenopausal patients--hormone therapy with tamoxifen. The present evaluation is performed eleven years after the admission of the first patient: so far, 75 patients (57.3%) have relapsed and 52 (39.7%) have died. An analysis of prognostic factors for relapse and death shows that the number of positive axillary lymph nodes and the dimension of the primary tumor are significantly associated with survival and relapse-free survival, while age and menopausal status are not.