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The phenocritical period of the t6/t6 genome extends from the late blastocyst substages through the elongated egg-cylinder stage. Most of the homozygous mouse embryos die during the short egg-cylinder stage. The viable egg-cylinder staged t6/t6 embryos can be distinguished from their phenotypically wild-type litter-mates at both the light and electron microscopic levels. The distinguishing characteristics of these embryos are aberrantly arranged entodermal cells, excessive cytoplasmic lipid and crystal-containing mitochondria. These same features are also characteristic of those mutant embryos which are developmentally arrested at both the short and elongated egg-cylinder stages. Over 50% of the t6/t6 embryos can be identified as early as the late blastocyst substages by the presence of large, electron-dense cytoplasmic lipid droplets.

Mouse embryos which are homozygous for the c25H deletion at the albino locus are developmentally arrested at the 2- to 6-cell cleavage stages. This study reveals that the mutant embryos cease development before they can be distinguished ultrastructurally from their normal litter-mates. After prolonged developmental delay (24--48 h), the nuclei of the mutant embryos become extremely aberrant in shape, whereas other subcellular organelles remain normal and there are no signs of pyknosis. Eventually, the mutant embryos do become pyknotic and begin to degenerate. The striking effects of this deletion on nuclear ultrastructure of cleavage-stage embryos are discussed in relation to biochemical and ultrastructural defects caused by other lethal deletions at the albino locus.

The utilization of fatty acids from the culture medium has been examined in preimplantation mouse embryos developing in vitro. Incorporation of exogenous fatty acid into embryo lipids was examined by culturing 8-cell mouse embryos for 2h in a medium containing 0.1 mM [9, 10-3H]palmitic acid (900 mCi/mmol). Lipids were extracted from the embryos, and the total lipid extract was fractionated into various neutral lipid and polar lipid classes by thin-layer chromatography. Most of the radioactivity, over 93%, was recovered in neutral glycerides (mono- di-, and triacylglycerols). About 2% of the total radioactivity was recovered in other neutral lipid species including fatty acids, fatty alcohols, and sterol esters. The remainder of the radioactivity was recovered in polar lipids. Seventy-four per cent of the polar lipid radioactivity was present in the amine phosphatides, inositol and/or serine phosphatides, sphingomyelin, choline lysophosphatides, sulfatides, cerebrosides, and monoglycosylglycerides. Chemical degradation studies of labelled embryo lipids indicated that the tritium lable was entering into embryo lipids as the fatty acid and not via metabolic recycling. The oxidation of exogenous fatty acids by mouse embryos was assessed by incubating variously staged embryos for 4h in medium containing 0.1 mM [U-14C]palmitic acid (50 mCi/mmol) and quantitating the production of 14CO2. The rate of fatty acid oxidation was found to be relatively constant from the unfertilized egg up to the 8-cell stage and then increase significantly between the 8-cell and late blastocyst stages. The results suggest that preimplantation mouse embryos developing in vitro can utilize fatty acids from the medium both for incorporation into embryo lipids and for energy production via oxidation.

Mice which are heterozygous for two complementary lethal t mutations (t6/tw32) exhibit complete male sterility. Experiments have been conducted to determine if spermatozoa from these heterozygous males can fertilize oviducal ova in vitro. The experiments have been designed so that specific barriers which are present during in vivo fertilization can be sequentially removed and the fertilizing ability of the spermatozoa tested after each barrier is eliminated. Our results show that spermatozoa from t6/tw32 males are unable to effect fertilization even after all of the barriers normally imposed by the female reproductive tract have been removed.

Pancytopenia is a well-recognized manifestation of clinical illness related to human immunodeficiency virus infection. The mechanism of this has been debated, but has been thought to relate either to a nonspecific marrow suppressive effect of opportunistic infections, or to direct involvement of bone marrow hematopoietic precursors as a target of human Immunodeficiency virus. We report the unique temporal association of the acquired immunodeficiency syndrome and paroxysmal nocturnal hemogloblnuria.

Since the water reserve of the interstitium plays a major role in circulatory homeostasis, its reduction by dehydration may produce severe changes in the organism's response to hemorrhage but this has not been measured experimentally. Twelve immature pigs (22 +/= 2 Kg) were divided into two groups of six each. Control animals had free access to food and water prior to bleeding. Dehydrated animals had water withheld for 48 hours preceding the bleeding. All animals were bled 30 per cent of their calculated blood volumes while awake. No resuscitation was performed. No mortality was observed in the control group of animals, while four of the six dehydrated animals died (66%). All deaths occurred between one and four hours posthemorrhage. Plasma refill reached 33 per cent by 0.5 hours in the control group compared to only 17 per cent by 0.5 hours in the dehydrated group (p less than or equal to .05). Refill in the control group reached 50 per cent by three hours, whereas dehydrated animals surviving to three hours demonstrated no further refill (p less than or equal to .05). BUN, calcium, sodium, and osmolality were consistently higher in dehydrated than control animals (p less than or equal to .05). It is concluded that a reduction in the interstitial water reserve significantly impairs ability to recover from hemorrhage.

Spermatozoa from sterile t6/tw32 and control fertile +/+, T/tw32, T/t6 mice were compared for their abilities to hydrolyse protein matrices and for their levels of acrosin activity. The data show that the immature and mature gametes from both the experimental and control males hydrolyse protein matrices. The quantitative acrosin assays show, however, that the mature gametes from the intercomplement males have significantly less total acrosin activity than any of the control groups of gametes. These findings suggest that this reduced acrosin activity is an additional phenotypic expression of the intercomplement genotype which results in male sterility.