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Biomedical subjects

C A Williams

Publications and source records attributed to C A Williams.

At least 19 recordsLinked to original sources
PubMed1992

Two forms of ribulose-1,5-bisphosphate carboxylase/oxygenase from Thiobacillus denitrificans.

The autotrophic, sulfur-oxidizing bacterium Thiobacillus denitrificans possesses two forms of the Calvin cycle enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). The form I and form II genes were isolated from a cosmid library using heterologous DNA probes. Restriction enzyme analysis indicated that the genes are within 17 kbp of each other. Other Calvin cycle enzyme genes are not present. Analysis of T. denitrificans RNA indicated that the form I genes for the large and small subunits are co-transcribed with a length of 2800 nucleotides. The transcript for the form II gene is 1900 nucleotides in length.

DNA Probes↗
PubMed1992

Release of immunoreactive enkephalinergic substances in the periaqueductal grey of the cat during fatiguing isometric contractions.

Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with alpha-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 +/- 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey.

Animals↗
PubMed1992

A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes.

The Angelman (AS) and Prader-Willi (PWS) syndromes are two clinically distinct disorders that are caused by a differential parental origin of chromosome 15q11-q13 deletions. Both also can result from uniparental disomy (the inheritance of both copies of chromosome 15 from only one parent). Loss of the paternal copy of 15q11-q13, whether by deletion or maternal uniparental disomy, leads to PWS, whereas a maternal deletion or paternal uniparental disomy leads to AS. The differential modification in expression of certain mammalian genes dependent upon parental origin is known as genomic imprinting, and AS and PWS represent the best examples of this phenomenon in humans. Although the molecular mechanisms of genomic imprinting are unknown, DNA methylation has been postulated to play a role in the imprinting process. Using restriction digests with the methyl-sensitive enzymes HpaII and HhaI and probing Southern blots with several genomic and cDNA probes, we have systematically scanned segments of 15q11-q13 for DNA methylation differences between patients with PWS (20 deletion, 20 uniparental disomy) and those with AS (26 deletion, 1 uniparental disomy). The highly evolutionarily conserved cDNA, DN34, identifies distinct differences in DNA methylation of the parental alleles at the D15S9 locus. Thus, DNA methylation may be used as a reliable, postnatal diagnostic tool in these syndromes. Furthermore, our findings demonstrate the first known epigenetic event, dependent on the sex of the parent, for a locus within 15q11-q13. We propose that expression of the gene detected by DN34 is regulated by genomic imprinting and, therefore, that it is a candidate gene for PWS and/or AS.

Blotting, Southern↗
PubMed1992

Gingivitis/stomatitis in cats.

Any alteration in the balance of bacterial challenge versus the host's ability to resist and repair will result in oral lesions that are similar in appearance. The bacterial cause of gingivitis and periodontitis in humans and in all other animals in which it has been studied is firmly established, and specific species of predominantly gram-negative anaerobes have been implicated. Naturally occurring or acquired immunopathologies are likely to result in premature dental disease. When oral disease is associated with the accumulation of plaque, a positive response can be achieved by reducing the bacterial challenge to the host through the maintenance of oral hygiene by timely professional dental prophylaxis and home care. Disease that is the result of atypical immune responses, however, can be much more difficult to manage. Such oral disease can occur with either immune deficiencies or exaggerated immune responses, and it is likely that multiple mechanisms are active concurrently. In any case, gram-negative anaerobes present in plaque are likely to be a major contributing factor. Therefore patients with chronic refractory gingivitis-stomatitis must be considered to be plaque intolerant. Only with a frequent regimen of aggressive and thorough professional dental treatment plus meticulous oral home care on a daily basis can one expect to keep these cases in remission. Because this is often unrealistic, the only other way to keep these patients free of disease is by total dental extraction. The tissues that are colonized by the causative organisms must be eliminated. All root tips and bony sequestra must be removed and healing with intact epithelium accomplished before these cases will go into remission. Edentulous feline patients that continue to have signs of gingivostomatitis have been found to have an area of nonhealed bony sequestrum and chronic osteomyelitis. Once effective debridement has been accomplished and epithelial healing completed, nonresponsive cases can be expected to go into remission (Color Plate 2, Figure 7). It is hoped that as more is learned about this frustrating problem, the many factors influencing feline oral disease will be scientifically documented. In the future, actual diagnoses can be systematically made early on in disease, and treatment will be more than just symptomatic.

Animals↗
PubMed1992

Angelman syndrome: clinical profile.

To further delineate the clinical and developmental features of Angelman syndrome, we collected data through three sources of information: (1) physical examinations; (2) laboratory data and family questionnaire data of affected individuals; and (3) literature review. The questionnaire data describes a generally normal prenatal and birth history. Feeding difficulties, developmental delay, or seizures were the presenting problems in all infants. The diagnosis of Angelman syndrome, however, was not made in any infant prior to 1 year of age. Except for seizures, no medical or surgical complication was common, although a variety of visual complaints or findings were common. Sixty percent of Angelman syndrome children had a cytogenetically demonstrated deletion of chromosome 15q11-q13. The individuals with and without a deletion could not be differentiated clinically. Diagnosis in early childhood is therefore difficult, and a high index of suspicion is recommended.

Adolescent↗
PubMed1992

Improvement in intergenerational health.

Differences in health status between subjects, their parents, and their children were analyzed in 2206 subjects who had attended the University of Pennsylvania during the 1939 to 1940 school year. Subjects compared their overall health status at the average age of 70 with that of their same-sex parent at the same age and with that of their same-sex child at the approximate average age of 45, providing reasons for reported differences. Thus, health status in family members of the same sex at the same age in 1988 was compared with that in approximately 1963. Subject health was strikingly improved compared with that of their parents a generation earlier, with 58% reporting their health to be better or much better, and only 9% reporting it to be worse or much worse (P less than .001). The major reasons for the difference were decreased prevalence of chronic conditions and healthier life-styles. The same results were observed in a community-based population of 317 subjects and, even more strikingly, in a group of 422 aging long-distance runners. These observations suggest substantial improvement in senior health status over the past quarter century in selected populations, and they contrast with equivocal changes that have been noted with traditional serial survey techniques.

Age Factors↗
PubMed1991

Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat.

Antibody microprobes were used to study release of immunoreactive neurokinins in the dorsal horn of the anaesthetized spinal cat following sustained isometric contraction of ipsilateral hindlimb muscles. Microprobes had immobilized antibodies to neurokinin A (NKA) on their outer surfaces and bound a proportion of released molecules when inserted in the central nervous system. Bound molecules were detected in autoradiographs as zones of reduced binding of 125I-NKA in which microprobes were incubated after withdrawal from the spinal cord. The left hindlimb was immobilized using an epoxy bandage splint and isometric contraction of muscles induced by intermittent tetanic stimulation of a ventral root. A basal presence of immunoreactive neurokinins was detected and this was increased by sustained isometric muscle contraction. It is probable that ergoreceptors contain and release neurokinins.

Anesthesia, General↗
PubMed1991

The relative toxicity of nonsteroidal antiinflammatory drugs.

Toxicity Index scores were computed from symptoms, laboratory abnormalities, and hospitalizations attributed to nonsteroidal antiinflammatory drug (NSAID) therapy in 2,747 patients with rheumatoid arthritis receiving 5,642 courses of 11 NSAIDs over 8,481 patient-years. Substantial differences in overall toxicity were found, the differences between drugs often being clinically significant (2-3 times as toxic) and highly statistically significant. The results strengthened after adjustment for differing patient characteristics, held generally across multiple ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) data bank centers, and persisted after use of different techniques for the weighting of side effects. The most toxic side effects were experienced by patients taking indomethacin (mean +/- SEM score 3.99 +/- 0.58), tolmetin sodium (3.96 +/- 0.74), and meclofenamate sodium (3.86 +/- 0.66). Least toxic were coated or buffered aspirin (1.19 +/- 0.10), salsalate (1.28 +/- 0.34), and ibuprofen (1.94 +/- 0.43). The most toxic drugs were generally taken in the lowest relative doses. There are statistical differences in overall toxicity between different NSAIDs as used in rheumatoid arthritis, and these differences are both clinically and statistically significant.

Adverse Drug Reaction Reporting Systems↗
PubMed1991

Radiographic features of craniometadiaphyseal dysplasia, wormian bone type.

We describe the radiographic findings in two siblings with a previously unrecognized craniotubular bone dysplasia. We call this condition craniometadiaphyseal dysplasia, wormian bone type. Because the parents of the siblings are consanguineous, this is probably a genetically determined condition with an autosomal recessive type of transmission. The findings in the siblings are compared with those of a woman with the same condition, previously reported as an example of craniometaphyseal dysplasia. The combination of findings in these patients seems diagnostic: characteristic skull changes including multiple wormian bones; wide long tubular bones without normal metaphyseal flaring; wide short tubular bones without normal diaphyseal constriction and sometimes actual diaphyseal expansion; and wide ribs and clavicles.

Bone Diseases, Developmental↗
PubMed1991

Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models.

PURPOSE: The most prevalent serious drug toxicity in the United States is increasingly recognized as gastrointestinal (GI) pathology associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The incidence of serious GI events (hospitalization or death) associated with NSAID use was therefore prospectively analyzed in patients with rheumatoid arthritis (RA) and patients with osteoarthritis. PATIENTS, METHODS, AND RESULTS: The study consisted of 2,747 patients with RA and 1,091 patients with osteoarthritis. The yearly hospitalization incidence during NSAID treatment was 1.58% in RA patients and was similar in all five populations studied. The hazard ratio of patients taking NSAIDs to those not taking NSAIDs was 5.2. The incidence in osteoarthritis may be less. The risk of GI-related death in RA patients was 0.19% per year with NSAIDs. Multivariate analyses assessing risk factors for serious GI events were performed in the 1,694 (98 with an event) RA patients taking NSAIDs at the predictive visit. The main risk factors were higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, level of disability, and NSAID dose. A rule is presented that allows estimation of the risk for the individual patient with RA. CONCLUSION: Knowledge of the risk factors for NSAID-associated gastropathy and their inter-relationships provides a tool for identification of the patient at high risk and for initiation of appropriate therapeutic action.

Adult↗
PubMed1991

Effect of muscle mass on the pressor response in man during isometric contractions.

1. Changes in blood pressure and heart rate were measured in six healthy male subjects during voluntary isometric contractions of the forearm and quadriceps muscles. Arterial pressure was measured directly via a catheter inserted into the radial artery of the non-contracting arm. Each subject exerted two types of contractions: (a) sustained contractions at 70% of the maximum voluntary contraction (MVC) until fatigue occurred and (b) sustained contractions starting at maximum tension (100% MVC), held for a total duration of 1 min. 2. During fatiguing contractions at 70% MVC, there was a progressive increase in blood pressure, reaching a peak level at fatigue. The same level of mean arterial pressure was achieved during contractions of the same relative tension, regardless of the muscle mass. The same trend was observed for the changes in heart rate. 3. During contractions which started with the maximum tension, where tension fell continuously during the 60 s of maximal effort, mean arterial pressure rapidly increased to high levels within a few seconds, and then increased further by 20-30 mmHg during the sustained maximal effort. There was no difference in the initial rapid increases in mean arterial pressure, nor in the final mean arterial pressures reached between contractions of the forearm or quadriceps muscles. There were no differences in the heart rates achieved during these contractions either. 4. There was no significant difference between the mean arterial pressures observed at fatigue of a 70% MVC contraction or at the end of the 60 s maximum effort during handgrip contractions, or during contractions with the quadriceps muscles. 5. These results support the view that muscle mass is not a determinant of the magnitude of the cardiovascular reflexes during fatiguing isometric contractions in man.

Adult↗
PubMed1991

Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis.

The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is an X-linked neurologic disorder characterized by dysmyelination in the central nervous system. Proteolipid protein (PLP), a major structural protein of myelin, is coded on the X chromosome. It has been postulated that a defect in the PLP gene is responsible for PMD. Different single-nucleotide substitutions have been found in conserved regions of the PLP gene of four unrelated PMD patients. Novel Southern blot patterns suggested a complex rearrangement in a fifth family. Linkage to PLP has been shown in others. We evaluated the PLP locus in a four-generation family with two living males affected with X-linked PMD. Analysis of DNA from the affected males revealed complete absence of a band, with PLP probes encompassing the promoter region, the entire coding region, and the 3' untranslated region and spanning at least 29 kb of genomic DNA. DNA from unaffected relatives gave the expected band pattern. Two obligate and one probable carrier women were hemizygous for the PLP locus by dosage analysis. Although it is unlikely, the previously described point mutations in PLP could represent polymorphisms. The finding of complete deletion of the PLP gene in our family is a stronger argument that mutations in PLP are responsible for X-linked PMD.

Adult↗
PubMed1990

Transforming growth factor-beta 1 stimulates fibronectin production in bovine adrenocortical cells in culture.

Transforming growth factor-beta (TGF-beta 1) suppresses cortisol production when added to cultured bovine adrenocortical (BAC) cells while concomitantly increasing fibronectin synthesis and assembly into extracellular fibrils. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of gelatin-Sepharose-treated media from BAC cells demonstrated a 2-fold stimulation of fibronectin production by TGF-beta 1 in both the presence and absence of serum. Indirect immunofluorescence studies revealed that TGF-beta 1 caused a striking increase in the fibronectin content of BAC extracellular matrix. TGF-beta 1 caused a 4-fold increase in deoxycholate-insoluble fibronectin after 12 h and a 7-fold increase after 24 h over that of control BAC cultures. Northern hybridization analyses indicated that TGF-beta 1 stimulated levels of fibronectin poly(A)+ RNA 2.3-fold. We found that cultured BAC cells express TGF-beta 1 mRNA, suggesting a possible autocrine role for TGF-beta 1 in the adrenal.

Adrenal Cortex↗