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J Baird

Publications and source records attributed to J Baird.

At least 19 recordsLinked to original sources
PubMed1992

Which comes first, Kt/V or PCR--chicken or egg?

We previously hypothesized that PCR is dependent on Kt/V (urea). To test the hypothesis, 30 patients from two hemodialysis (HD) units with PCR values consistently less than 1 regardless of the Kt/V (urea) without an obvious cause (such as malignancy, peptic ulceration, etc.) were identified. These patients were randomized into an experimental group where an increase in the Kt/V (urea) was made or into a control group where a Kt/V (urea) remained unchanged. In the experimental group the minimal increment in Kt/V (urea) was 0.3 plus a minimum requirement of a Kt/V (urea) greater than or equal to 1. The control group were to maintain the existing Kt/V (urea) within +/- 0.2. Urea kinetic modeling was monitored monthly and the patients followed for three months. Of 30 patients, 18 fulfilled the criteria (9 experimental; 9 controls). In the experimental group, the initial Kt/V (urea) was 0.82 +/- 0.19 (means +/- SD); the final Kt/V (urea) was 1.32 +/- 0.21 (P = 0.000). These patients had an initial PCR of 0.81 +/- 0.08. This increased to 1.02 +/- 0.15 (P = 0.005). The control group had an initial Kt/V (urea) of 0.82 +/- 0.16. The final Kt/V (urea) was 0.87 +/- 0.15. Their initial PCR was 0.87 +/- 0.14 and the final PCR was 0.86 +/- 0.087 (P = NS). In the experimental group, the mean increments in Kt/V (urea) and PCR were 0.49 +/- 0.17 and 0.21 +/- 0.16 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance.

We have analyzed the inheritance of maturity-onset diabetes of the young (MODY) on chromosome 20 in a large multigeneration family, the R.-W. family, and in two other MODY families. Of the four branches of the R.-W. pedigree which have been studied, two have documented early onset of non-insulin-dependent diabetes mellitus (NIDDM), while there is no evidence of early onset in the other two branches. The early-onset branches have apparently inherited the same D20S16 allele from the affected parent, while another D20S16 allele was inherited in the two branches without evidence of early onset. A test for homogeneity, the M-test, using the results of two-point linkage analysis with D20S16 indicates heterogeneity between early- and late-onset branches of the R.-W. family (P less than or equal to .014). In addition, analysis strongly suggests that MODY as expressed in the EDI and WIS families is unlinked to loci on chromosome 20 (P less than or equal to .018-.004). Comparable results are seen when the data are analyzed by the HOMOG program. Three polymorphic loci-D20S16, D20S17, and ADA--show no recombination with the MODY locus when two-point linkage analysis is used in the early-onset branches of the family. The multipoint lod score in the early-onset branches of the R.-W. family is 10.16, with the most likely location being between D20S4 and D20S17. Multipoint linkage analysis using the CHROMPICS option of the program CRI-MAP has been used to follow inheritance of the MODY disease locus. This analysis has identified two cases of possible nonpenetrance in the early-onset branches of the family (odds of at least 156:1), as determined by the appearance of apparent isolated double crossovers at the MODY locus in these unaffected individuals.

Adolescent↗
PubMed1991

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression.

Insulin-dependent diabetes mellitus can be transferred into young irradiated non-obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly-2+) enter the pancreas 2 weeks following transfer. They are present initially at peri-islet locations but progressively infiltrate the islet with accompanying beta cell destruction. The infiltrate is heterogeneous with respect to V beta usage. Inflammatory macrophages (Mac-1+, F4/80+) can be detected at peri-islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of intra-islet infiltration. MHC class II and ICAM-1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on beta cells implying that presentation of autoantigen by the beta cell itself does not play a role in the beta cell destruction in NOD mice.

Animals↗
PubMed1990

In vitro properties of human melanoma cells metastatic in nude mice.

We have developed a human melanoma metastasis model in nude mice. In this model, a human variant cell line (451-LU) was obtained that spontaneously metastasized in nude mice. This variant cell line was selected from the lung of a nude mouse after several in vivo passages of human melanoma WM164 cells previously isolated from a melanoma metastasis of a patient. The WM164 cells were not competent for metastasis in nude mice prior to this selection. We compared the phenotypes of the parental nonmetastatic cell line and the metastatic variant with respect to growth at clonal seeding densities in protein-free medium (growth factor independence), in vitro invasion through reconstructed basement membranes, secretion of proteolytic enzymes, expression of tumor-associated antigens, and chromosomal abnormalities. Metastatic 451-LU cells showed significantly increased growth factor independence when grown at clonal seeding densities as compared to the parental cells. In in vitro chemoinvasion assays, metastatic 451-LU cells were significantly more invasive than the parental cells. The metastatic variant secreted collagenase and tissue type plasminogen activator at levels 10- and 3-fold higher than the parental WM164 cells, respectively. Polyclonal antibodies to tissue type plasminogen activator significantly inhibited invasion through reconstructed basement membranes. In metastatic 451-LU cells, expression of nerve growth factor receptor was elevated, both at the protein and transcriptional level. Metastatic cells were aneuploid with a mode of 97 chromosomes, whereas the parental nonmetastatic cells had a mode of 52 chromosomes. Our studies suggest that metastatic melanoma cell variants selected in vivo show increased independence of exogenous growth factors when grown at clonal cell densities, enhanced invasiveness in vitro, greater secretion of proteolytic enzymes, and increased chromosome mode as compared to the nonmetastatic parental cells. The data further suggest that melanoma cells isolated from metastatic lesions and maintained in vitro have an unstable invasive phenotype but that metastatic variant cells can readily be selected.

Animals↗
PubMed1990

Urokinase and tissue type plasminogen activators in human keratinocyte culture.

Using immunocytochemical and biochemical techniques, we have demonstrated that cultured human epidermal keratinocytes contain both urokinase and tissue type plasminogen activators. In subconfluent colonies the distribution of the two enzymes differed. Tissue type plasminogen activator (tPA) was distributed evenly throughout the colony, while, as we have demonstrated previously, urokinase type plasminogen activator (uPA) was preferentially localized at the migrating edges of the colony. Using zymographic analyses, both tPA and uPA activities were detected in cell extracts. Depending on the procedure used to prepare cell extracts, tPA was detected either as free enzyme or in complex with PA inhibitor type 1. PA inhibitor type 1 was deposited onto the extracellular matrix of the keratinocyte cultures and formed a complex with cell-associated tPA when cells and matrix were extracted together. The most differentiated keratinocytes in the culture, which were spontaneously shed from the culture surface, also contained both tPA and uPA. However, these spontaneously shed cells had a higher ratio of tPA:uPA than did the less differentiated cells from the same culture. In conjunction with our previous studies, these results demonstrate the complex nature of the plasminogen activator system, including enzymes and inhibitors, that is present in human keratinocytes. In addition, our data suggest that the relative amounts of uPA and tPA in epidermal cells vary with differentiation state.

Cell Adhesion↗
PubMed1990

mRNA for tissue-type plasminogen activator is present in lesional epidermis from patients with psoriasis, pemphigus, or bullous pemphigoid, but is not detected in normal epidermis.

Plasminogen activator (PA), which catalyzes the conversion of plasminogen to the proteinase plasmin, has been implicated in a variety of cutaneous disorders. Lesional epidermis from patients with psoriasis, pemphigus, bullous pemphigoid, and Hailey-Hailey disease contains elevated levels of tissue-type PA (tPA) activity compared to non-lesional epidermis or to epidermis from normal individuals. In the present study, we have used Northern blot analysis to demonstrate that mRNA for tPA is detectable in lesions from patients with psoriasis, pemphigus, and bullous pemphigoid, but is not detectable in normal epidermis. These data strongly suggest that the tPA enzymatic activity present in lesional epidermis results from enhanced synthesis of the enzyme in situ, secondary to elevated steady-state levels of tPA mRNA. Cultured keratinocytes likewise are shown to contain tPA mRNA. Previous investigators have suggested that the phenotypes of keratinocytes in culture, psoriatic epidermis, and epidermis in the process of wound reepithelialization are comparable. Our findings, combined with those of other investigators, suggest that elevated tPA expression may be another common feature of epidermis under these circumstances.

Biopsy↗
PubMed1989

Characterization of keratinocyte plasminogen activator inhibitors and demonstration of the prevention of pemphigus IgG-induced acantholysis by a purified plasminogen activator inhibitor.

To investigate the mechanisms by which cutaneous plasminogen activator (PA) may be regulated, we have tested cultured keratinocytes for the presence of PA inhibitors. Using biosynthetic labeling experiments with 35S-methionine in conjunction with specific antibody precipitation, we have shown that human keratinocytes in culture synthesized and secreted both PA inhibitor 1 and PA inhibitor 2. PA inhibitor 1 was present in conditioned media in the inactive form, but it could be detected with reverse phase autography. PA inhibitor 2 was detected by its ability to form complexes with 125I-uPA. Potential therapeutic relevance for cutaneous PA inhibitor 2 was suggested in skin organ culture experiments which demonstrated that purified PA inhibitor 2 from human placenta was able to prevent the acantholytic changes induced by pemphigus IgG.

Acantholysis↗
PubMed1989

Vasopressin secretion in the DIDMOAD (Wolfram) syndrome.

The diabetes insipidus which accompanies the DIDMOAD (Wolfram) syndrome is thought to be hypothalamic in origin, though no formal study of vasopressin secretion in the syndrome has been published, and some data in the literature suggest a renal tubular defect. We have studied vasopressin secretion in seven patients with the Wolfram/DIDMOAD syndrome during three dynamic stimuli: an osmotic stimulus (hypertonic saline infusion), hypoglycaemia (insulin tolerance test) and a baroregulatory stimulus (trimetaphan infusion). Hypertonic saline infusion demonstrated three patients to have complete and four to have partial hypothalamic diabetes insipidus; administration of (per nasal) desmopressin excluded nephrogenic diabetes insipidus in all seven patients. Insulin hypoglycaemia failed to stimulate vasopressin release, but trimetaphan-induced hypotension produced significant though subnormal rises in plasma vasopressin in three patients with partial diabetes insipidus, though it produced a negligible rise and no rise in plasma vasopressin in two patients with complete diabetes insipidus. The data suggest a much greater frequency of hypothalamic diabetes insipidus in the Wolfram/DIDMOAD syndrome than is reported, but did not identify nephrogenic diabetes insipidus. The absence of vasopressin responses to non-osmotic stimuli in patients with complete diabetes insipidus suggests global lack of vasopressin secreting neurones, rather than an isolated osmoreceptor defect or selective vasopressin secreting neuronal loss, as the lesion producing diabetes insipidus in the DIDMOAD syndrome.

Adult↗
PubMed1988

Epidermal plasminogen activator is abnormal in cutaneous lesions.

To investigate the role of plasminogen activator (PA) in cutaneous disease, we have used biochemical and immunocytochemical techniques to examine PA in normal and lesional skin. In normal human dermis, tissue PA is the predominant PA activity; however, in normal epidermis, urokinase type PA is the predominant PA activity. In contrast, PA activity in epidermis from lesions of patients with a variety of cutaneous diseases was predominantly tissue type enzyme with a much smaller contribution from urokinase. Our patient population included individuals with benign chronic pemphigus, pemphigus vulgaris, pemphigus foliaceous, bullous pemphigoid, or psoriasis. Using rabbit antibody specific for tissue type PA, we have immunocytochemically localized this enzyme in lesions from individuals with the above disorders. Our results indicate that tissue PA is consistently elevated in cutaneous lesions with diverse etiology, pathology, and clinical presentation.

Adult↗
PubMed1988

Keratinocyte urokinase-type plasminogen activator is secreted as a single chain precursor.

Urokinase-type plasminogen activator (uPA) is produced and secreted by cultured human keratinocytes as a single chain precursor. UPA in keratinocyte conditioned medium is not susceptible to inhibition with diisopropylfluorophosphate (DFP), and it has an apparent molecular weight of 55 kD under both reducing and nonreducing conditions. Cleavage of keratinocyte uPA by plasmin results in the formation of a 96 kD complex comprised of activated uPA and PA inhibitor 2. PA extracted from normal human epidermis is only partially inhibited by DFP, suggesting that precursor uPA is also present in vivo. The synthesis of uPA as a precursor with reduced enzymatic activity as well as decreased affinity for inhibitors is likely to be a mechanism by which normal epidermis regulates plasminogen activation in vivo.

Cells, Cultured↗
PubMed1985

Late results of valve replacement and factors influencing survival in patients with severe chronic mitral regurgitation.

Between July 1967 and September 1981 50 patients with isolated severe mitral regurgitation underwent mitral valve replacement. There were 29 males and 21 females (mean age 52 years). The aetiology of the valve lesion was rheumatic in 14 patients (mean age 42 years) and non-rheumatic in 36 patients (mean age 56 years). At the time of operation 36 patients (72%) were in class 3 or 4 of the New York Heart Association classification (mean duration of symptoms 20 months). Pre-operative ejection fraction was normal in only four patients (8%) and was below 0.50 in 27 patients (54%). There were two early deaths (4%) within one month of operation, and 17 late deaths (34%) during a follow-up period of four months to 10 years (mean 43 months). Actuarial analysis showed a 71% survival at five years and a 62% survival at 10 years after valve replacement. Of the 31 current survivors, 22 (71%) are in class 1 of the New York Heart Association classification, and all but two patients showed significant improvement in symptoms. Significant morbidity after operation occurred in 10 patients (20%) and was largely related to problems with anticoagulant control. Analysis of factors which may influence survival, showed that age greater than 55 years and parameters of left ventricular geometry, demonstrated by angiography, were the major determinants of survival.

Adult↗
PubMed1978

A technique for the direct observation of the unanesthetized fetal sheep.

A method is described for the chronic implantation of a lucite window in the uterus of a pregnant ewe which allows direct access to the amniotic fluid compartment in the unanesthetized state. The window can be directly connected to an extrauterine viewing compartment allowing repeated observations and measurements of physiologic function. The compartment also provides an easy method of changing the fetal environment.

Animals↗
PubMed1977

Plasma insulin and glucose levels in maturity onset diabetics treated with chlorpropamide.

19 diabetic patients taking various doses of chlorpropamide were studied throughout a normal day. Plasma chlorpropamide levels were related to the daily dose of the drug and were relatively constant throughout the day. Blood glucose concentration was highest and the plasma insulin concentration lowest in patients taking the largest dose of chlorpropamide. Patients on a small daily dose of chlorpropamide were well controlled and had higher than normal insulin levels. --12 patients were restudied 10 days after stopping chlorpropamide. Although diabetic control deteriorated in all patients, plasma insulin concentration did not change significantly. This suggests that the long-term hypoglycaemic action of chlorpropamide is not dependent on an effect on the concentration of insulin in peripheral venous blood.

Aged↗