A newly established human acute lymphoblastic leukemia cell line with characteristics of the earliest B-cell maturation

A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was established from the bone marrow of a patient with non-T-ALL. The HBL-3 cell line expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface immunoglobulin (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked the common acute lymphoblastic leukemia antigen (CALLA) and antigenic markers characteristic of T-cell and myeloid cell lineages. The HBL-3 cells had structural rearrangements of both the homologous chromosome 9s, including a translocation with chromosome 1 which has been reported in a patient with common ALL. The cell line had rearranged immunoglobulin heavy chain genes but retained germ-line κ light chain genes and germ-line T-cell receptorβ- and γ-chain genes. The HBL-3 cell line was strongly positive for terminal deoxynucleotidyl transferase (TdT). These findings indicate that the HBL-3 cell line is derived from the earliest B-cell committed to B-cell lineage.     

Purification and characterization of a heat-stable enterotoxin of Vibrio mimicus

A heat-stable enterotoxin produced by Vibrio mimicus (VM-ST) was studied. VM-ST was purified from a culture supernatant of V. mimicus strain AQ-0915 by ammonium sulfate fractionation, hydroxyapatite treatment, ethanol extraction, column chromatography on both SP-Sephadex C-50 and DEAE-Sephadex A-25, and HPLC, and the recovery rate was about 15%. Purified VM-ST was heat-stable. VM-ST activity was cross-neutralized by anti-STh antiserum. The amino acid composition of the purified VM-ST was determined 17 amino acid residues in the following sequence: Ile-Asp-Cys-Cys-Glu-Ile-Cys-Cys-Asn-Pro-Ala-Cys-Phe-Gly-Cys-Leu-Asn. This composition and sequence were identical to those of V. cholerae non-O1-ST. These results clearly demonstrate the production of a characteristic VM-ST by V. mimicus.     

Cutaneous vascular responses to heat simulated at a high altitude of 5,600 m

Six healthy young men were studied in a high-altitude chamber during a 60-min heat exposure at a simulated altitude of 5,600 m or 0.5 atmosphere absolute (ATA). The heat load was provided by increasing the chamber temperature to 38 degrees C at the rate of 1 degree C/min after a 60-min equilibrium period at thermoneutrality (28 degrees C). Our question was whether or not hypoxia causes differential changes in regional cutaneous circulation during heat exposure. Skin blood flow in the forearm (FBF) and the finger (FiBF), temperatures of the esophagus (Tes) and of the skin, and cardiac output (CO) were measured during the heat exposure at 0.5 ATA and at the sea level (1 ATA). During the equilibrium period, hypoxia increased the mean skin temperature and mean heat transfer coefficient, as well as FBF and forearm vascular conductance. The increased blood flow in the cutaneous circulation during the hypoxic exposure may reflect cutaneous vasodilation and vasoconstriction in other regions of the body, since there was no alteration in CO and total peripheral resistance. During heat exposure, Tes rose faster at high altitude than at sea level. However, at the end of the 60-min heat exposure, all thermal as well as circulatory parameters showed no difference between the two altitudes, except for the FiBF. An attenuated vasodilation in the fingers during heat exposure at high altitude suggests differential vascular controls and possible impairment of thermoregulation when additional stress, such as heat, is imposed. The data suggest that cutaneous blood flow during heat exposure is not uniform throughout the entire skin in a hypoxic environment.     

Primary structure of heat-stable enterotoxin produced by Yersinia enterocolitica

A heat-stable enterotoxin was isolated and purified from the culture supernatant of $\text{Yersinia enterocolitica}$ by reversed-phase high-performance liquid chromatography. The amino acid sequence of the purified toxin was determined to be as follows: Gln-Ala-Cys(X)-Asp-Pro-Pro-Ser-Pro-Pro-Ala-Glu-Val-Ser-Ser-Asp-Trp-Asp-Cys-Cys-Asp-Val-Cys-Cys-Asn-Pro-Ala-Cys-Ala-Gly-Cys (X: not determined). The C-terminal sequence containing 6 half-cystine residues was highly homologous to that of heat-stable enterotoxin of enterotoxigenic $\text{Escherichia coli.}$     

The effects of short-chain fatty acids on the neuronal membrane functions ofHelix pomatia. I. electrical properties

The effects of short-chain fatty acids on the membrane excitability, current-voltage (I-V) characteristics, and cell volume of Helix pomatia neurons were studied. 2-Decenoic acid (DA), having 10 carbon atoms in the hydrocarbon chain, suppressed the excitability of bursting neurons RPa1 (Sakharov and Salanki, 1969) for 30-60 min, while valeric acid (VA), having 5 carbon atoms, had no significant effect on excitability. DA had three different effects on the excitability of beating neurons: in some neurons DA suppressed excitability as in bursting neurons; in a second type of neuron DA had a negligible effect on excitability; and in the neuron located near RPa1 DA had a pentylentetrazol (PTZ)-like effect, i.e., it converted the discharge of the neuron from beating to bursting. DA decreased the peak value of the current, inducing a negative-resistance region in the I-V curve of the bursting neuron without any change in the level of the voltage at which the current reaches its maximal value. DA inhibited the hyperpolarization induced by activation of the Na+ pump, tested after preliminary enrichment of neurons with Na+ ions by incubation in a potassium-free solution for 20 min. DA caused a swelling of the neuron by about 10% which was independent of the Na+ pump. In all the above-mentioned cases VA had no significant effect.     

The growth pattern of chimpanzees: Somatic growth and reproductive maturation inPan troglodytes

Growth of chimpanzees reared at the Kumamoto Primates Park of Sanwa Kagaku Kenkyusho Co. Ltd. was studied cross-sectionally from the viewpoints of somatic growth and reproductive maturation. Distance and velocity curves were expressed using spline function method. Males showed adolescent growth acceleration in body weight, with a peak at 7.86 yrs of age, but not in trunk length. Females showed continuous rapid growth from mid-juvenile to adolescent phase in both body weight and trunk length, but no isolated adolescent spurt. The Sanwa chimpanzees matured at about 12.5 yrs of age for females and 15.0 yrs for males. The mean adult weights and trunk lengths were 53.2 kg and 507.8 mm for males and 42.7 kg and 481.6 mm for females. The Sanwa chimpanzees had similar growth patterns to those of the Yerkes chimpanzees, although they showed a slight delay in infancy, and a higher growth rate from the early juvenile phase onwards. Growth patterns in these two laboratories may be regarded as “normative” for laboratory-reared chimpanzees. They matured earlier than wild chimpanzees by more than two years. The major reason for the retarded maturation in wild chimpanzees is the delay of growth from infant to the early juvenile phases (0–4 yrs of age), probably owing to a limited nutritional supply from the mother. Development of the testes comprised three phases: slow growth from infant to juvenile (until 6.4 yrs); rapid growth around adolescence (until 9.2 yrs); and adult (mean testicular volume, 187 cm³). Setting the nutritional standard at 2,000–2,600 Cal/day (= Kcal/day) per adult, calories were considered for captive chimpanzees in each age class.     

Construction of a novel bifunctional biogenic amine receptor by two point mutations of the H2-histamine receptor.

BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously cloned the H2-histamine receptor gene and noted that only three amino acids on the receptor were sufficient to define its specificity and selectivity. Despite only modest overall amino acid homology (34% amino acid identity and 57.5% similarity) between the H2-histamine receptor and the receptor for another monoamine, the beta 2-adrenergic receptor, there is remarkable similarity at their critical ligand binding sites. We hypothesized that, if the specificity and selectivity of both receptors are invested in just three amino acids, it should be possible to convert one of the receptors into one that recognizes the ligand of the other by simple mutations at only one or two sites. MATERIAL AND METHODS: We explored the effect of two single mutations in the fifth transmembrane domain of the H2-histamine receptor, which encompasses the sites that determine H2 selectivity. The canine H2 receptor gene was mutated at Asp186 and Gly187 (Asp186 to Ala186 and Gly187 to Ser187) by oligonuceotide directed mutagenesis. The coding region of both the wild-type and mutated H2 receptors was subcloned into the eukaryotic expression vector, CMVneo, and stably transfected into Hepa cells and L cells. The biological activity of histamine and epinephrine on the expressed receptor was examined by measurement of cellular cAMP production and inositol trisphosphate formation. RESULTS: Hepa cells transfected with the Ala186-Ser187 mutant H2 receptor demonstrated a biphasic rise in cAMP in response to epinephrine with an early phase (ED50 approximately 10(-11) M) that could be inhibited by both propranolol and cimetidine. Epinephrine also induced IP3 generation in the same cells, a biological response that is characteristic of activation of the wild-type H2 but not of the beta-adrenergic receptor. L cells transfected with the Ala186-Ser187 mutant H2 receptor also responded to epinephrine in a cimetidine and propranolol inhibitable manner. CONCLUSIONS: We converted the H2-histamine receptor into a bifunctional one that has characteristics of both histamine and adrenergic receptors by two simple mutations. These results support the hypothesis that ligand specificity is determined by only a few key points on a receptor regardless of the structure of the remainder of the molecule. Our studies have important implications on the design of pharmacological agents targeted for action at physiological receptors.