Thyroid gland in dwarf mice: a stereological study

Stereological methods were used to compare thyroids of dwarf mice and of their heterozygote littermates. In the thyroid of dwarf mice unorganized cellular masses, adipous tissue and ultimobranchial cysts are abundant. Follicles are small and their distribution function is unimodal. The number of cells per follicle is considerably lowered if compared with the normal. In control mice the distribution function of thyroid follicles is bimodal. These data show that origin of the thyroid anomaly in dwarf mice is due to a drastic diminution of cell divisions, probably resulting from the lack of growth hormone.     

Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.     

Diamines and polyamines in DMBA-induced breast carcinoma containing mast cells resistant to compound 48/80

Obstetric factors were studied in an unselected series of mothers of LBW-children and compared with those in a corresponding control series. Both groups consisted of 161 women with single pregnancies and 16 with twin pregnancies. Of the 188 LBW-children, 14% were twins. Of the single infants, 42% were appropriate for gestational age (AGA), i.e. within the 10th to 90th percentile according to Swedish curves for intrauterine growth, and 58% small for gestational age (SGA). The commonest causes of low birthweight (LBW) in the AGA-group were bleeding (34%) and premature rupture of the membranes (28%). In the SGA-group toxaemia was found in 15%, but in 50% of the SGA-group no cause of LBW was demonstrable. In this latter group the average placental weight was low. The mortality was noted and 89% of the living children were examined neurologically at 5 years of age. The prognosis of the child depended on the duration of pregnancy. Bleeding during pregnancy was a prognostically unfavourable sign, but even serious bleeding complications did not exclude a normal development of the child. The prognosis was best for those infants in whom no cause of LBW was demonstrable.     

Terminal nitrogen rise

Eighteen-breath nitrogen washouts were performed on eight subjects. Each washout could be simulated by a four-compartment model, each compartment with a different ventilation-to-volume ratio and a variable contribution to expiratory flow. In large breaths initiated near residual volume, a terminal nitrogen rise (TNR) was seen. To account for the TNR with this model, there were relatively small changes in flow from compartments with markedly different nitrogen concentration. Reasons are given for believing these compartments could not be the upper and lower lung. Three of these subjects were studied in the supine, seated, and head-down positions. The TNR was seen at the same lung volume in all positions. At routine bronchospirometry in a second group of subjects, sampling with small catheters during a nitrogen washout showed a TNR in the expirate of lungs, lobes, segments, and subsegments in the upright and supine positions. Apparently a large vertical hydrostatic gradient is unnecessary to produce a TNR. Finally, the TNR was shown to occur at that lung volume where transpulmonary pressure is very small and changing rapidly with volume. This TNR was often followed by a terminal nitrogen fall while the lung was continuing to empty. The TNR occurs when flow from a large poorly ventilated compartment increases relative to the flow from other compartments. A model of lung in which the poorly ventilated compartment develops high specific compliance at low lung volume explains these data.     

Confusions in recognizing phonemes spoken by esophageal speakers: II. Vowels and diphthongs

A methodology was developed to determine the patterns of phonemic errors that listeners would make in receiving the vowels and dipthongs of monosyllables spoken by esophageal speakers. Analyses of the features preserved in the errors were performed. The identified phonemic error patterns and the features found to be poorly preserved in the errors were used to structure multiple-choice intelligibility practice materials for esophageal speakers.     

Adrenal mitochondrial and serum corticosteroid studies in rats resistant to adrenal-regeneration hypertension (ARH)

Female rats of the Wistar-Furth (W/Fu) strain appear to be resistant to the development of adrenal regeneration hypertension. At a time period, after adrenal enucleation, when Holtzman female rats had elevated serum 11-deoxycorticosterone levels and were hypertensive, none of the W/Fu rats became hypertensive. In vitro adrenal studies after quiescent kills of W/Fu rats indicated that cholesterol side chain cleavage activity was greater in mitochondria from regenerating adrenals than from controls. Both serum deoxycorticosterone and corticosterone levels were significantly greater in the adrenal-enucleated group. These studies were repeated in animals which were given a standard ether anesthetic stress. Ether stress increased cholesterol side chain cleavage activity comparably in control and adrenal-enucleated rats and also increased their serum deoxycorticosterone and corticosterone levels. Adrenal-enucleated Wistar-Furth rats had higher serum deoxycorticosterone levels than controls, whereas controls had higher serum corticosterone levels than the adrenal-enucleated group after the ether stress. These results indicate that although the adrenal-enucleated W/Fu rats have increased serum deoxycorticosterone levels, none of these rats develop frank hypertension. This suggests a resistance to deoxycorticosterone-induced hypertension in this strain of rat.     

Retinal vascular changes in congenital hypertrophy of the retinal pigment epithelium

The overlying retinal blood vessels were abnormal in five cases of congenital hypertrophy of the retinal pigment epithelium. This illustrated the well-recognized association between outer retinal degeneration and obliteration of the overlying retinal vasculature. The proposed pathophysiological mechanisms, however, seem inadequate to explain completely the morphological changes of the retinal blood vessels in the presence of atrophy of the outer retina.     

Macromolecules of the central nervous system and acoustic priming in C57BL/6Bg mice

Short-term cultures of androgen-responsive Shionogi 115 (S115) cells exhibited density-dependent regulation of proliferation rate in the presence or absence of testosterone. The average surface area per cell exposed to the growth medium was inversely proportional to population density. By contrast, long-term cultures (serially passaged in testosterone-containing medium for several months) did not exhibit density-dependent regulation of proliferation rate when grown in testosterone-containing medium. In this medium, cells became elongated and no longer exhibited any obvious decrease in exposed surface area with increasing density. Nevertheless, when subcultured into testosterone-free medium, these cells reverted to an epithelial morphology and exhibited density-dependent regulation of proliferation rate. These relationships suggested that the proliferation rate of cells decreased with density in proportion to the decrease in exposed surface area...     

Ca2+ differentially regulates conventional protein kinase Cs' membrane interaction and activation

The regulation of conventional protein kinase Cs by Ca2+ was examined by determining how this cation affects the enzyme's 1) membrane binding and catalytic function and 2) conformation. In the first part, we show that significantly lower concentrations of Ca2+ are required to effect half-maximal membrane binding than to half-maximally activate the enzyme. The disparity between binding and activation kinetics is most striking for protein kinase C betaII, where the concentration of Ca2+ promoting half-maximal membrane binding is approximately 40-fold higher than the apparent Km for Ca2+ for activation. In addition, the Ca2+ requirement for activation of protein kinase C betaII is an order of magnitude greater than that for the alternatively spliced protein kinase C betaI; these isozymes differ only in 50 amino acids at the carboxyl terminus, revealing that residues in the carboxyl terminus influence the enzyme's Ca2+ regulation. In the second part, we use proteases as conformational probes to show that Ca2+dependent membrane binding and Ca2+-dependent activation involve two distinct sets of structural changes in protein kinase C betaII. Three separate domains spanning the entire protein participate in these conformational changes, suggesting significant interdomain interactions. A highly localized hinge motion between the regulatory and catalytic halves of the protein accompanies membrane binding; release of the carboxyl terminus accompanies the low affinity membrane binding mediated by concentrations of Ca2+ too low to promote catalysis; and exposure of the amino-terminal pseudosubstrate and masking of the carboxyl terminus accompany catalysis. In summary, these data reveal that structural determinants unique to each isozyme of protein kinase C dictate the enzyme's Ca2+-dependent affinity for acidic membranes and show that, surprisingly, some of these determinants are in the carboxyl terminus of the enzyme, distal from the Ca2+-binding site in the amino-terminal regulatory domain.