Crystallization patterns in anterior vaginal fluid from bitches in oestrus

Bitches exhibited a characteristic arborization pattern of the fluid from the anterior vagina during pro-oestrus and oestrus. These changes were monitored together with conventional vaginal cytology and plasma oestrogen and progestagen concentrations. A classical ferning pattern, similar to that seen in bovine cervical mucus at oestrus, occurred after the peak in plasma oestrogen concentrations. Ferning was most intense after the second peak of cornification of vaginal epithelial cells. It is suggested that a 'Ferning Index', when combined with conventional vaginal cytology, can be of use in determining the optimum mating time in the bitch.     

Genetic galactocerebrosidase deficiency (globoid cell leukodystrophy, Krabbe disease) in rhesus monkeys (Macaca mulatta)

Globoid cell leukodystrophy, or Krabbe disease, is a severe disorder of the peripheral and central nervous system myelin caused by deficient galactocerebrosidase (GALC) activity. This autosomal recessive disease affects humans and animals including dogs, mice, and rhesus monkeys. Cloning of the human and animal GALC genes opened opportunities for therapeutic trials using animal models. We describe the clinical, pathologic, and biochemical features of the affected rhesus monkey. Affected monkeys had very low GALC activity and a two base pair deletion in both copies of the GALC gene. Clinical signs of tremors, hypertonia, and incoordination led to humane euthanasia by 5 months of age. At necropsy, peripheral nerves were enlarged. Microscopically, the cerebral, cerebellar, and spinal cord white matter was infiltrated with periodic acid-Schiff-positive multinucleated globoid cells, and there was a striking lack of myelin. Peripheral nerve fibers were decreased in number and separated by Alcian blue- and safranin O-positive material. Myelin sheaths were greatly diminished. Lipid analysis of brains of 12-day-old and 158-day-old affected monkeys revealed a great excess of psychosine in white matter. The rhesus monkey model will be especially useful for exploring treatment options, including prenatal bone marrow transplantation and various approaches to gene therapy.     

Distinct domains of the voltage-gated K+ channel Kvbeta 1.3 beta -subunit affect voltage-dependent gating

The Kv1.3 subunit confers a voltage-dependent, partialinactivation (time constant = 5.76 ± 0.14 ms at +50 mV), anenhanced slow inactivation, a hyperpolarizing shift in the activationmidpoint, and an increase in the deactivation time constant of theKv1.5 delayed rectifier. Removal of the first 10 amino acids fromKv1.3 eliminated the effects on fast and slow inactivation but notthe voltage shift in activation. Addition of the first 87 amino acids of Kv1.3 to the amino terminus of Kv1.5 reconstituted fast and slowinactivation without altering the midpoint of activation. Although aninternal pore mutation that alters quinidine block (V512A) did notaffect Kv1.3-mediated inactivation, a mutation of the external mouthof the pore (R485Y) increased the extent of fast inactivation whilepreventing the enhancement of slow inactivation. These data suggestthat 1) Kv1.3-mediated effects involve at least two distinct domains of this -subunit,2) inactivation involves openchannel block that is allosterically linked to the external pore, and3) the Kv1.3-induced shift in theactivation midpoint is functionally distinct from inactivation.

     

Toxicity of Trimethoprim-Sulphamethoxazole in Patients with Megaloblastic Haemopoiesis

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.     

Expression of the mitochondrial genome in HeLa cells. XXI. Mitochondrial protein synthesis during the cell cycle

Chloramphenicol sensitive [³H]leucine incorporation into protein (due to mitochondrial protein synthesis) in synchronized HeLa cells has been found to continue throughout interphase, its rate per cell approximately doubling from the G₁ to the G₂ phase. This increase in the rate of [³H]leucine incorporation during the cycle does not seem to parallel closely the increase in cell mass. In fact, the observations made on cultures incubated at 34.5 °C, where the G₁ and S phases are better resolved than at 37 °C, indicate that the rate remains constant during the G₁ phase, and starts to accelerate with the onset of nuclear DNA synthesis. Correspondingly, on a per unit mass basis, there appears to be a slight decline in the rate of [³H]leucine incorporation into protein during the G₁ phase, which is compensated by an increase in the early S phase. No significant variations were observed in the mitochondrial leucine pool labeling during the cell cycle; therefore, the observed pattern of [³H]leucine incorporation into protein should reflect fairly accurately the behavior of mitochondrial protein synthesis. Evidence has been obtained indicating a depression in the rate of incorporation of [³H]leucine into protein in mitochondria of mitotic cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the products of mitochondrial protein synthesis has not revealed any differences in the size distribution of the proteins synthesized in the various portions of the cell cycle.