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D Weissman

Publications and source records attributed to D Weissman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lack of connectivity between the induced and autoimmune repertoires of lpr/lpr mice.

It has been proposed that the autoantibody-secreting cells active during autoimmune diseases are derived from B cells initially responding to environmental antigens. In order to test the relationship between the antigen-induced and autoimmune repertoires, we monitored the fate of antigen-activated idiotypically defined B cells present in mice that developed the systemic lupus erythematosus (SLE)-like syndrome associated with the lpr mutation. Mice homozygous for both the A/J-derived Igh and Ig kappa region haplotypes and the lpr mutation were bred. Immunization of these mice with p-azophenylarsonate (Ars)-protein conjugates elicited the idiotypic components (IdCR) characteristic of the A/J anti-Ars response and did not interfere with the spontaneous development of the lpr-mediated autoimmune disease. These Id/lpr mice provided an ideal system for studying the relationship between the exogenously and endogenously induced responses because: (1) VHIdCR antibodies have been shown to bind autoantigens in vitro; and (2) serological and molecular reagents exist which can identify and monitor VHIdCR antibody production as disease progresses. Serum samples and hybridoma cell lines derived from non-immune as well as Ars-keyhole limpet haemocyanin (KLH)-immunized Id/lpr mice were monitored for idiotype expression as well as Ars and ssDNA reactivity at various stages of disease progression. We found that antibodies utilizing the VHIdCR gene segment did not preferentially contribute to the autoantibody pool. Moreover, even when IdCR B-cell clones were expanded by deliberate immunization with Ars-KLH, Ars non-binding variants were only rarely detected among the activated B-cell populations of diseased mice. These results indicate that there is only minimal overlap between the VHIdCR conventional and autoimmune repertoires.

Animals↗
PubMed1991

Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders.

Some patients with hypoplastic marrow disorders, including aplastic anemia (AA), are at risk for clonal evolution to myelodysplastic syndromes (MDS) and leukemia. Magnetic resonance imaging (MRI) of marrow of the spine, pelvis, and femurs was performed in 24 patients with hypoplastic marrow disorders. In 12 patients (three AA, nine MDS) MRI was compatible with the clinical and biopsy diagnoses and served to define the spectrum of marrow patterns in these disorders. In eight patients with hypocellular marrow biopsies and a clinical diagnosis of AA, MRI showed an unexpected inhomogeneous or diffuse cellular pattern. Concurrent or subsequent marrow or cytogenetic studies have led to diagnoses of hypoplastic MDS in seven of these patients. In four patients with prolonged hypoplasia after bone marrow transplantation for lymphoma, a speckled pattern superimposed on a fatty background appeared in serial MRI studies. One case evolved to AML, two developed megaloblastic foci, and one remains hypoplastic at 19 months. This study suggests that MRI is able to detect early clonal disease in patients with AA, and can distinguish AA from hypoplastic MDS.

Adult↗
PubMed1991

Lipase/amylase ratio. A new index that distinguishes acute episodes of alcoholic from nonalcoholic acute pancreatitis.

Because of observations that patients with acute episodes of alcoholic pancreatitis had high serum lipase levels whereas patients with gall stone pancreatitis had high serum amylase levels, a prospective study was undertaken to determine whether the ratio of serum lipase to serum amylase, a newly computed ratio, would discriminate between acute episodes of alcoholic and nonalcoholic pancreatitis. In phase one, 30 consecutive patients with acute pancreatitis were entered into the study and divided into groups A and B. Patients with renal failure were excluded from the study. Group A consisted of 20 patients in whom the etiology of pancreatitis was alcohol. Group B consisted of 10 patients whose pancreatitis was nonalcoholic in etiology (predominantly gallstones). Serum lipase values in group A ranged 492 to 25,706 U/L (median, 3433 U/L) and in group B from 711 to 31,153 U/L (median, 1260 U/L). These differences were not significant statistically. Serum amylase values in group A ranged from 104 to 2985 U/L (median, 331 U/L) and in group B from 423 to 13,000 (median, 1187 U/L). Although these figures were statistically different (P less than 0.005), there was a considerable degree of overlap in the values between the two groups. The lipase/amylase ratio calculated from the blood sample obtained at presentation appeared to be a promising discriminatory index. The lipase/amylase ratio was calculated by using the amylase and lipase levels expressed as multiples of the upper limit of normal in each case. The lipase/amylase ratios in the alcoholic group ranged from 2.2 to 14.8, whereas the lipase/amylase ratio in nonalcoholic pancreatitis ranged from 0.31 to 1.93. These differences were statistically significant (P less than 0.005). A lipase/amylase ratio of greater than 2 was indicative of an alcoholic etiology, and a ratio of less than 2 suggested that the pancreatitis was nonalcoholic in nature. In phase two, this lipase/amylase ratio of 2 was applied prospectively to an unselected population of 21 consecutive patients with acute pancreatitis. Thirteen patients had a lipase/amylase ratio of greater than 2; in 11 of them, the etiology of the pancreatitis was alcohol. Eight patients had a lipase/amylase ratio of less than 2; of them, only 1 patient had an alcoholic etiology for the pancreatitis. These differences were statistically significant (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1990

Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus after p-chlorophenylalanine administration. I. A model to study the turnover of the enzymatic protein.

An immunoblot procedure was developed to quantify the amount of tryptophan hydroxylase (TpOH), the rate limiting enzyme in the synthesis of serotonin, in the rat raphe dorsalis nucleus (NRD). Using this method we have studied the time course variations in TpOH protein level after a single p-chlorophenylalanine (PCPA) i.p. injection (300 mg/kg). PCPA provoked a rapid and large decrease of TpOH in the NRD, without affecting neuron-specific enolase in the NRD or TpOH in the locus coeruleus. The decrease in TpOH was maximum (-60% of the control value) 2 days after the drug administration and followed a monoexponential law which allowed us to estimate the half-life of this enzymatic protein as 1.43 days and to postulate that, during these 2 days, TpOH synthesis was inhibited. The neosynthesis of TpOH molecules from 2 to 7 days was estimated to be 57.8 U TpOH/NRD/day which was comparable to the initial steady state of synthesis (48.44 U TpOH/NRD/day). In vivo administration of 6-fluorotryptophan or in vitro incubation of raphe homogenates with either halogenated derivative had no effect on TpOH protein levels. PCPA should be an interesting tool to study the turnover rate of TpOH protein.

Animals↗
PubMed1990

A new method for selective left main bronchus intubation in premature infants.

Unilateral massive pulmonary atelectasis, and pulmonary interstitial emphysema (PIE) are problems that frequently occur in ventilated premature infants. Selective main bronchus intubation (SBI) of the atelectatic lung, or the contralateral lung in unilateral PIE, is an accepted procedure. However, whereas right SBI is usually easily performed, left SBI is frequently difficult. We have developed a method for left SBI using a regular portex endotracheal tube in which an elliptical hole 1 cm in length has been cut through half the circumference 0.5 cm above the tip of the oblique distal end. With the elliptical side hole directed to the left lung, left SBI can easily, and repeatedly be accomplished. This method may prove life saving in certain cases of unilateral atelectasis or PIE.

Bronchi↗
PubMed1990

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Adult↗
PubMed1990

Bleeding from a tuberculous gastric ulcer.

A 26-yr-old male of Ecuadorian descent developed epigastric pain and bleeding per rectum, necessitating hospitalization. Upper endoscopy revealed an irregularly shaped gastric ulcer which was biopsied. Because of persistent bleeding and hemodynamic compromise, the patient underwent an exploratory laparotomy. Findings included peritoneal and visceral surfaces studded with small, round yellow lesions. Frozen section examination revealed granulomas with giant cells. Gastric biopsies from the endoscopy showed AFB. Although gastric involvement is seen in association with tuberculosis, the occurrence of upper gastrointestinal bleeding is unusual.

Adult↗
PubMed1985

A rapid method for comparing monoclonal antibodies by limited proteolysis and electrophoresis.

A rapid and sensitive method for comparing the primary structure of proteins has been adapted to the study of monoclonal antibodies. Samples were digested with alpha-chymotrypsin in the presence of sodium dodecyl sulfate after which peptide fragments were separated into distinctive banding patterns by polyacrylamide gel electrophoresis. This method could easily detect differences in the primary structure of antibodies with related as well as unrelated binding specificities. In addition, antibody molecules derived by somatic diversification from the same germ line gene segments could be distinguished from one another.

Amino Acid Sequence↗
PubMed1982

Sodium butyrate induced structural changes in HeLa cell chromatin.

Postsynthetic modifications of core histones by treatment of HeLa S3 cells with 5mM sodium butyrate lead to alterations in the structure of high molecular weight chromatin. Whole chromatin from butyrate-treated cells, which results in highly acetylated core histones, has an ellipticity [theta]282.5 of 3700 deg cm2 dmol-1 (0.2 mM EDTA, pH 7.4) that is 1200 deg c m2 dmol-1 less than chromatin from untreated HeLa cells, suggesting a more condensed structure. No difference in the circular dichroism spectra was observed in H1-stripped, high molecular weight chromatin obtained from control and butyrate-treated cells at low (0.2 mM EDTA, pH 7.4) ionic strength. Thermal denaturation profiles of high molecular weight chromatin were resolved into three transitions and exhibited a shifting of hyperchromicity from transition I to transitions III, at a higher Tm, with butyrate treatment of HeLa cells, further indicating a more compact structure. Thermal denaturation profiles of H1-stripped chromatin were not affected by butyrate treatment. Ionic strength studies in the range of 0-5 mM NaH2PO4, 0.2 mM EDTA, pH 7.4, of high molecular weight chromatin exhibited a decrease in [theta]282.5 and a shifting of hyperchromicity from transition I to transition III with increasing ionic strength. Control high molecular weight chromatin was more sensitive to changes in ionic strength than its highly acetylated counterpart. These results suggest that acetylation of histones alone does not result in a change in histone-DNA interactions but other changes associated with butyrate treatment most probably cause a more condensed structure, of the fraction studied herein, which is mediated by H1 or other materials removed during stripping in 0.35 M NaCl.

Acetylation↗
PubMed1978

[Effect of propyl-2-pentene-2-oic acid on GABA levels in different regions of mouse brain].

An elevation in cerebral GABA level (65%) is observed after administration of an anticonvulsant, sodium propyl 2-pentene-2 oate, a branched chain fatty acid, comformationally restricted GABA analogue, competitive inhibitor of GABA-T in regard to GABA. The concentration of GABA increases in some regions i.e. substantia nigra, frontal and temporal cortex, cerebellum and olfactory bulbs. The GABA level remains unchanged in caudate nucleus, hippocampus and occipital cortex. Results are discussed comparatively to the effect of sodium n-dipropylacetate.

Animals↗