Human mini-chromosomes in mouse embryonal stem cells

We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size into mouse embryonal stem cells. Although these human mini- chromosomes are stable in hamster and chicken cells, they re-arrange or segregate aberrantly in the embryonal stem cells and are rapidly lost in the absence of selection. However, one of the mini-chromosomes re- arranged, acquired mouse centromeric sequences and was then stably maintained for at least 60 population doublings in culture. This mini- chromosome, which is 4 Mb in size, is a candidate for a mouse germ line chromosome vector.      

Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection

Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy.      

Case-control study of late onset "probable Alzheimer's disease"

A case-control study was conducted on 64 cases of "probable Alzheimer's disease" with late onset of illness (after age 70 years) and 64 controls matched by age (+/- 3 years), race, and sex. Information was obtained on birth order, lifetime medical and surgical history, personal characteristics, exposure to toxins and animals, and a family history of various illnesses. None of the variables studied, including family history of dementia, reached statistical significance. An antecedent history of head trauma with loss of consciousness, though not statistically significant, was more frequently found in cases than in controls.     

Motor neuron disease in the United States, 1971 and 1973-1978: patterns of mortality and associated conditions at the time of death

Mortality rates for deaths "due to" and "with" motor neuron disease are presented for the first time. Age-specific mortality rates increase with age until 70 to 74 years and then decline. There appear to be no major differences by race in the age-adjusted mortality rates, but these rates are higher for males both white and nonwhite. A case-control study of all deaths with amyotrophic lateral sclerosis (ALS) was conducted for deaths due to ALS in the year 1971. Conditions associated with ALS at the time of death include pneumonia and bronchopneumonia, symptoms referable to respiratory system, superficial injury to shoulder and upper arm, essential benign hypertension, chronic skin ulcer, and malnutrition. No association was found between ALS and malignancies, Parkinson's disease, or dementia.     

Age-dependent variation of T1 and T2 relaxation times of adenocarcinoma in mice

The T1 and T2 values of adenocarcinoma EO 771 inoculated into the hind leg of mice are characterized and correlated with the histopathologic state of the tumor. Growth-dependent changes (indicated by a T1 of 630-910 msec and a T2 of 68-185 msec) can be separated into four characteristic phases. The increase in relaxation times in the early phases (A and B) is due to an increasing amount of viable tumor tissue relative to normal muscle tissue. In the later phases (C and D), a decline of the relaxation parameters is observed that is parallel to an increase in the fraction of necrotic tissue. By multiexponential analysis, two relaxation components (indicated by and, respectively) for T1 and T2 and the corresponding fractions alpha 1 and alpha 2 can be observed for both tumor and surrounding muscle tissue. A tissue criterion ("magnetic resonance fingerprint") is defined by a combination of these multiple parameters. This criterion allows separation of not only muscle and tumor tissue but also viable (early state) and necrotic (late state) tumor tissue.     

Giving a voice to patient experiences through the insights of pragmatism

As a philosophical position, pragmatism can be critiqued to distinguish truth only with methods that bring about desired results, predominantly with scientific enquiry. The article hopes to dismiss this oversimplification and propose that within mental health nursing, enquiry enlightened by pragmatism can be anchored to methods helping to tackle genuine human problems. Whilst pragmatists suggest one reality exists, fluctuating experiences and shifting beliefs about the world can inhabit within; hence, pragmatists propose reality has the potential to change. Moreover, pragmatism includes being cognisant of what works to whom reality concerns, making reality context-driven, with a view to understand how actions shape experiences so what is generated has usefulness. Hence, it somewhat follows pragmatism can inform mental health nursing, after all, nursing is a discipline of action, and awareness is needed in how actions produce experiences that patients find helpful. Given the principles of recovery are preferably adopted in mental health care, the paper will explore how pragmatism can help nurses move towards that goal; specifically, with patients voicing their experiences. This is because like pragmatism, recovery subscribes to hope that reality can progress, and through meaningful experiences and beliefs, patients have expertise about personal difficulties alongside how life may flourish, despite mental illness.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Detection of adenocarcinoma by urinary microsatellite analysis after augmentation cystoplasty

Augmentation cystoplasty is associated with an increased risk of bladder cancer development between 10 and 20 years after augmentation. Using microsatellite analysis, we analyzed urine obtained before surgical resection of the malignant lesion from a patient who developed invasive adenocarcinoma after augmentation cystoplasty. Loss of heterozygosity was identified in both urine and tumor samples from this patient. This observation suggests that microsatellite urine analysis may be useful as a monitoring tool for patients after augmentation cystoplasty.