Search PubMed⌕ Search

Biomedical subjects

N Hillman

Publications and source records attributed to N Hillman.

At least 37 records · Page 2Linked to original sources

Paroxysmal nocturnal hemoglobinuria associated with the acquired immunodeficiency syndrome.

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.

Acquired Immunodeficiency Syndrome↗

Prolymphocytic leukemia: postmortem findings after long-term survival.

A patient had prolymphocytic leukemia and survived for 44 months. A partial remission for more than 11 months and a short complete remission were induced by agents commonly used for the treatment of acute myelocytic leukemia. However, surface markers identified the disease as of B-cell origin.

Antineoplastic Agents↗

The effects of dehydration on the dynamics of transcapillary refill.

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.

Animals↗

The phenotypic expression of a t6/t6/t6 genotype.

In vivo, embryos which are homozygous for the t6 mutation die during egg cylinder development (gestation days 5.5--6.5). In vitro, these mutant embryos can be distinguished from their wild-type littermates by their developmental arrest and by the failure of their trophoblast cells to transform to giant cells. We have investigated the nature of this lethality by constructing triploid embryos with varying combinations of the t6 mutant chromosome. The phenotypes of outgrowths from these triploid embryos were examined and compared with the phenotypes of outgrowths from +/+, +/t6, and t6/t6 embryos. The data show 1) that +/t6/t6 embryos are phenotypically wild-type, while t6/t6/t6 embryos are phenotypically mutant and 2) that t6/t6/t6 and t6/t6 embryos are developmentally arrested at the same stage of outgrowth.

Animals↗

The effect of delay on the expression of the t6/t6 genotype.

In vivo, t6/t6 embryos are developmentally arrested between gestation days 5.5 (short-egg-cylinder stage) and 6.75 (long-egg-cylinder stage). In the present series of studies we used both in vivo and in vitro blastocyst delay followed by in vitro outgrowth to determine whether the t6/t6 lethality is time- or stage-specific. The results show that the t6/t6 genome is expressed differently in vivo and in vitro and that the in vitro expression of the homozygous t6 genome differs with different methods of effecting developmental delay. Although delay increases the life span of t6/t6 embryos it does not alter the stage of lethality. One method used to effect delay (ovariectomy) causes the t6/t6 embryos to remain as blastocysts for a significantly longer period of time than their wild-type littermates when placed into outgrowth medium. This distinction provides a unique method for obtaining a sample composed entirely of t6/t6 embryos at a stage prior to the lethal period.

Animals↗

Sterility in mutant (tLx/tLy) male mice. III. In vitro fertilization.

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.

Animals↗

Sterility in mutant (tLx/tLy) male mice. I. A morphological study of spermiogenesis.

The results from a comparative ultrastructural study of spermiogenesis in 6-, 10-, 14- and 17-month-old sterile t6/tw32, and fertile T/t6, T/tw32 and BALB/c, mice are reported. The studies show that all of the males contained the same types of defective spermatids and that defects were not limited to specific spermatid stages. Younger males had fewer abnormal spermatids than older males of the same genotype and at each age the BALB/c and t6/tw32 males appeared to contain more abnormal spermatids than the other males. No unique spermatid defect or increased frequency of a specific defect was found which can be correlated with infertility of the t6/tw32 males.

Acrosome↗

Sterility in mutant (tLx/tLy) male mice. II. A morphological study of spermatozoa.

A comparative light and electron microscopy study was done on cauda epididymal spermatozoa obtained from correspondingly-aged sterile t6/tw32, and fertile T/tw32, T/t6 and BALB/c, mice. The results show that all of the males, regardless of age, contained defective gametes and that all contained the same types of aberrant gametes. The oldest males of each genotype contained more abnormal gametes than the younger males of the same genotype. No unique spermatozoan defect and no increased frequency of a specific spermatozoan defect was noted which could be correlated with the sterility of the t6/tw32 animals.

Age Factors↗

The in vitro transmission frequency of the t12 mutation in the mouse.

Male mice which are heterozygous for a recessive lethal mutation (+/tL) transmit the tL mutation in non-Mendelian ratios. In the present studies, spermatozoa obtained from +/t12 males were used to fertilize ova from +/t12 females in vitro. The frequency of transmission of the t12 mutation determined from these in vitro studies was compared with the frequency of transmission of this mutation in normal and delayed matings. The data show that the transmission frequency of the t12 mutation, in vitro, is Mendelian and is the same as the transmission frequency of the t12 mutation in vivo when matings are delayed until the time of ovulation.

Animals↗

The metabolism of exogenous fatty acids by preimplantation mouse embryos developing in vitro.

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.

Animals↗

Ultrastructural studies of lethal c25H/C25H mouse embryos.

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.

Animals↗

A comparative study of spermiogenesis in wild-type and T:t-bearing mice.

The results of a comparative ultrastructural study of spermiogenesis in T/tx, +/tx, +/T, C57BL/LJ, BALB/c and randomly breeding Swiss Albino mice are reported. The observations show that aberrant spermiogenesis occurs in males of all strains and genotypes and that the same specific types of abnormal spermatids are found in all of the males examined. No unique morphological defect which could be correlated with the increased transmission frequency of tx-bearing gametes can be found in males heterozygous for the tx allele.

Alleles↗