Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses.

To probe the genetic basis of disease specificity of nondefective murine type C viruses, we are constructing recombinants in vitro between molecular clones of Friend murine leukemia virus (Fr-MuLV) and Moloney murine leukemia virus (Mo-MuLV). Fr-MuLV induces erythroleukemias when injected into newborn NFS mice, whereas Mo-MuLV almost invariably induces T-cell lymphomas. We find that a recombinant whose genome is derived primarily from Fr-MuLV but which has 621 nucleotides of Mo-MuLV information at its 3' end induces almost exclusively thymic lymphomas.

The reaction kinetics of four sheep haemoglobins with identical alpha-chains.

Sheep haemoglobins A, B, C and F are known to have identical alpha-chains but differing beta-chains. Rate constants were determined for the combination of CO with these four deoxy haemoglobins (l') and for the dissociation of O2 from the fully saturated tetramers (k4) from 15 to 38 degrees C at physiological pH in the presence of CO2, and at pH 9.1 in the absence of CO2.

Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates.

Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation.

Studies of the extracellular proteolytic activity produced by Propionibacterium acnes.

Of several commercial media tested, trypticase soya both containing 0.4% (w/v) D-sorbitol was superior as a growth medium for the production of extracellular proteinase by Propionibacterium acnes (strain P-37). Extracellular proteinase, production of which was shown to be growth-associated by both batch and continuous culture studies, was partially purified by 70% (NH4)2SO4 saturation.

Phase I study of L-alanosine (NSC 15353).

L-alanosine (NSC 15353) is a newly developed antitumor antibiotic which acts as an inhibitor of purine intermediary metabolism. Experimental antitumor activity was demonstrated in a variety of murine neoplasms. A Phase I trial was undertaken on a daily x 5 (d x 5) schedule in 22 evaluable patients.

Enzymes of de novo pyrimidine biosynthesis in Babesia rodhaini.

The pathway of de novo pyrimidine biosynthesis in the rodent parasitic protozoa Babesia rodhaini has been investigated. Specific activities of five of the six enzymes of the pathway were determined: aspartate transcarbamylase (ATCase: E.C.

Effects of harringtonine in combination with acivicin, adriamycin, L-asparaginase, cytosine arabinoside, dexamethasone, fluorouracil or methotrexate on human acute myelogenous leukemia cell line KG-1.

Harringtonine (HT) is a new antitumor agent reported to be active in patients with leukemia and lymphoma. The interaction of HT with various antitumor agents was studied in vitro using a human acute myelogenous leukemia cell line KG-1. For the analysis of the drug - drug interaction at the cellular level, Steel proposed the concept of an envelope of additivity.

Dosimetry of PAH skin carcinogenesis: covalent binding of benzo[a]pyrene to mouse epidermal DNA.

Benzo[a]pyrene (BaP) is metabolized to the chemically reactive anti and syn isomers of the 7,8-diol-9,10-epoxides of BaP (BPDE) which bind covalently to DNA to form DNA/BPDE complexes. Tetrols liberated from the DNA/BPDE complex by acid hydrolysis are easily quantified by h.p.

Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial.

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement.

Analysis of viral and defective-interfering nucleocapsids in acute and persistent infection by rhabdoviruses.

We have isolated and characterized the RNA of intracellular virus nucleocapsids recovered from a number of cell cultures persistently infected with rabies virus or vesicular stomatitis virus (VSV). VSV persistent infections in BHK21, L cells and Aedes albopictus (mosquito) cells generally showed the presence of large amounts of defective-interfering (DI) nucleocapsid RNA and much smaller amounts of standard (B) nucleocapsid RNA. Persistent infections of BHK21 cells by two rabies virus strains, challenge virus standard (CVS-11) or HEP-Flury, were followed for several months during which time the ratio of DI to B nucleocapsid RNA cycled dramatically.

Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins (l).

High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.

Donor transaminase and recipient hepatitis. Impact on blood transfusion services.

To assess the relationship of donor alanine aminotransferase (ALT) level to recipient hepatitis, 283 transfused patients were prospectively followed up after open heart surgery; hepatitis developed in 12.7%, of which 97% was non-A, non-B. The ALT tests of 3,359 donors to these patients indicated that risk of hepatitis was significantly associated with the level of donor ALT; 29% of 52 patients receiving at least 1 unit of blood with an ALT level greater than 53 IU/L had hepatitis develop (20.

Non-myelinated nerve fibres and their terminals in the sub-odontoblastic plexus of the feline dental pulp.

Serial thin sections of the coronal dental pulp of the cat's canine tooth were cut. Parts of the sub-odontoblastic neural plexus were photographed from 100 of the sections. The plexus consists of many slender, predominantly unmyelinated nerve fibres.

Initial clinical study with N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with advanced cancer.

Thirty-seven patients with inoperable malignancies were given 75 courses of N-(phosphonaceteyl)-L-aspartic acid (PALA). Twenty-seven of these patients received PALA as a continuous iv infusion over 24 hours at dose levels ranging from 500 to 10,500 mg/m2 of estimated body surface area. In addition, ten patients were given PALA by continuous iv infusion over 120 hours at total doses ranging from 4000 t0 8700 mg/m2.

Characterization of herpes simplex virus type 1 RNA present in the absence of de novo protein synthesis.

We used herpes simplex virus type 1 (HSV-1) DNA and restriction fragments of HSV-1 DNA covalently coupled to cellulose as a reagent to isolate for further characterization the major and minor HSV-1 immediate-early mRNA species in HeLa cells infected and maintained in the absence of de novo protein synthesis. Five major and several minor immediate-early mRNA species were characterized. One major species was a 4.

Regulation of prolactin and growth hormone secretion. Site and mechanism of action of thyrotropin-releasing hormone, L-dopa and L-5-hydroxytryptophan in unanesthetized dogs.

A heterologous radioimmunoassay for canine prolactin was developed and used to study the role of catecholamines and indoleamines in the regulation of prolactin secretion in dogs. Females dogs were found to have a higher plasma prolactin concentration than male dogs. Thyrotropin-releasing hormone (TRH) increased plasma prolactin in male and female trained conscious dogs.

Antihypertensive comparison of furosemide with hydrochlorothiazide for black patients.

Furosemide and hydrochlorothiazide were compared for treatment of black patients with mild to moderate hypertension in a randomized, open-label, crossover study design. Hydrochlorothiazide produced a significantly greater fall in mean arterial (24.7 vs 16.

Lessons from the study of induced alterations in amino acids in patients with cancer.

The sensitivity of the neoplastic cell to amino acid deprivation shows considerable variation. The responsiveness of human leukemic cell cultures to L-asparaginase indicates that those of T cell origin are much more sensitive to the action of this L-asparagine-depleting enzyme than those of B cell origin. A cautionary note is raised concerning amino acid analogs.

The concentrations of free L-carnitine and L-O-acetylcarnitine in spermatozoa and seminal plasma of normal, fresh, and frozen human semen.

Free-L-carnitine and L-O-acetylcarnitine concentrations have been determined in spermatozoa and seminal plasma of normal, fresh, and frozen human semen. Results show that in fresh semen most of the free L-carnitine (0.213 +/- 0.

Rhabdoviridae. Report of the Rhabdovirus Study Group, International Committee on Taxonomy of Viruses.

The family Rhabdoviridae comprises approximately 75 viruses infecting vertebrates, invertebrates and plants. The main characteristics of the member viruses are: (i) the viruses infecting vertebrates and invertebrates are bullet-shaped and the viruses infecting plants are usually bacilliform; (ii) the viruses have particle lengths varying from 130 to 380 nm and widths varying from 60 to 95 nm; (iii) the viruses possess unit-membrane envelopes from which protrude spikes 5 to 10 nm long; (iv) the viruses have precisely coiled helical nuecleocapsids with a diameter of approx. 50 nm; (v) most of the viruses which have been studied contain 5 proteins; the prototype, vesicular stomatitis virus, contains proteins designated L (large), G (glycoprotein), N (nucleoprotein), NS (nonstructural) and M (matrix); N or NS is phosphorylated in most members which have been studied; (vi) the viruses contain single-stranded RNA which is transcribed into several messenger RNA species with sizes corresponding to the structural proteins; (vii) the nucleocapsid contains the RNA-dependent RNA polymerase and is infectious; and (viii) many of the viruses produce morphologically distinct defective-interfering (T) particles.

Hemolytic activity of Fusobacterium necrophorum culture supernatants due to presence of phospholipase A and lysophospholipase.

Culture supernatants of Fusobacterium necrophorum demonstrated hemolytic activity. The hemolysin(s), which was partially purified by ammonium sulfate precipitation, was temperature-dependent and heat labile. The spectrum of hemolytic activity against various erythrocytes included rabbit, human, and dog erythrocytes.

The effect of insulin and hydrocortisone on the isolated rat liver.

Isolated rat livers were perfused at 35 degrees C with bovine serum albumin (40 g/l) in Krebs Ringer bicarbonate buffer, or with the same solution containing insulin (0.22 x 10(-6) mol/l), hydrocortisone (0.068 x 10(-3) mol/l), or both hormones together.

Biosynthesis of plasma-membrane proteins during myogenesis of skeletal muscle in vitro.

1. Surface labelling of plasma-membrane proteins with 125I, catalysed by lactoperoxidase, and radioactive l-fucose incorporation into glycoprotein were used as plasma-membrane markers for skeletal-muscle cells in culture. 2.