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L A Phillips

Publications and source records attributed to L A Phillips.

At least 19 recordsLinked to original sources

Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3.

Experiments using recombinant vaccinia viruses expressing rat proinsulin I coinfected into COS-7 cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that in this system both Kex2 and furin produce mature insulin, whereas PC2 selectively cleaves proinsulin at the C-peptide-A-chain junction. This is a property consistent with its probable identity with the rat insulinoma granule type II proinsulin processing activity as described by Davidson et al. [Davidson, H. W., Rhodes, C. J. & Hutton, J. C. (1988) Nature (London) 333, 93-96]. PC3 generates mature insulin but cleaves preferentially at the proinsulin B-chain-C-peptide junction. This pattern of cleavage by PC3 is similar, but not identical, to that of the highly B-chain-C-peptide junction-selective type I activity as described by Davidson et al., perhaps due to the presence of a P4 arginine residue near the C-peptide-A-chain junction unique to the rat proinsulins. These results along with data presented on the expression of both PC2 and PC3 in islet beta cells strongly support the conclusion that these proteases are involved in the conversion of proinsulin to insulin in vivo.

Amino Acid Sequence

Intrafamilial phenotypic expression of autosomal dominant polycystic kidney disease.

It has been suggested that the clinical expression of autosomal dominant polycystic kidney disease (ADPKD) is uniform among individuals of a given family. To test this hypothesis, intrafamilial variations in ages at onset of first symptoms, types of first symptoms, serum creatinine concentrations, and renal sizes were evaluated in 131 patients with ADPKD from 36 unrelated families. These parameters were compared in younger and older affected relatives in the same family at a single time, due to difficulties of following them longitudinally. Because the natural course of the disease is to progress with age, it was presumed that disease progression in a given family was nonuniform if older individuals had lower serum creatinine concentrations, and/or smaller kidneys than their affected younger relatives, or if relatives of similar ages had different serum creatinine concentrations and/or kidney sizes. Nonuniform progression was suggested in 38% of affected relatives by serum creatinine concentrations and in 53% by kidney sizes. Ages at onset of first symptoms and types of first symptoms were also different in patients from the same families. These data indicate that phenotypic expression of ADPKD may differ considerably among patients who belong to the same families.

Adolescent

Clinical manifestations of autosomal dominant polycystic kidney disease in patients older than 50 years.

The purpose of this study was to define manifestations of autosomal dominant polycystic kidney disease (ADPKD) in older patients with the disease. Fifty-seven subjects age 50 years or more, who were at risk for having inherited the gene for ADPKD, were evaluated for renal size, hypertension, back and abdominal pain, symptoms consistent with urinary tract infection (UTI), hematuria, end-stage renal failure, and liver cysts. The diagnosis of ADPKD was made in 32 of the 57 at-risk subjects (56%). At the time of study, only one patient with the disease was asymptomatic and normotensive and denied any previous symptoms suggestive of the disease. Clinical manifestations of ADPKD in the 31 symptomatic patients were hypertension (69%), a history of back and abdominal pain (47%), symptoms consistent with UTI (41%), hematuria (31%), and end-stage renal failure (47%). Liver cysts were found in 44% of patients. No statistically significant differences in the frequency of any manifestations of ADPKD between men and women were found, although the frequency of symptoms consistent with UTI tended to be higher in women (53%) than in men (27%). Most patients developed symptoms after the age of 40 years. Notably, 31% of the older patients with ADPKD had normal serum creatinine levels. Thus, older subjects with kidney cysts who are at risk to have inherited the gene for ADPKD, should be considered to have the disease even in the presence of well-preserved kidney function. This observation may play an important role in assessing the prognosis of older subjects at risk who have bilateral renal cysts and in genetic counseling of their relatives.

Abdominal Pain

Autosomal dominant polycystic kidney disease: symptoms and clinical findings.

In 259 subjects at risk to have inherited autosomal dominant polycystic kidney disease (PKD), the frequency of symptoms consistent with urinary tract infection, haematuria, back and abdominal pain, hypertension, renal stones, and end-stage renal failure was evaluated. The diagnosis of PKD was made in 140 of these subjects (54 per cent). At the time of the study, 36 per cent of males and 7 per cent of females with PKD were asymptomatic, normotensive, and denied any previous problems. In patients younger than 30 years, 66 per cent of males but only 11 per cent of females were asymptomatic. In female patients, urinary tract infection (69 per cent) and hypertension (61 per cent) were the most frequent clinical manifestations. In contrast, in males with PKD, these problems were present in only 19 per cent and 42 per cent, respectively. Frequency of other clinical manifestations was similar in women and men with PKD. End-stage renal failure was present in 5 per cent of the 81 patients younger than age of 40, in 33 per cent of the 27 patients 40-49 years old, and in 47 per cent of the 32 patients aged 50 years or more. Physical examination was unreliable in estimating kidney size in most patients, particularly in early stages of the disease. Hypertension and symptoms such as haematuria and back pain, but not urinary tract infections, correlated well with renal size measured by radiograms.

Adolescent

Radiologic assessment of head trauma.

We have endeavored through the use of an actual clinical scenario to emphasize that reliance on skull radiographs for assessing the acutely traumatized patient is both unwarranted and unwise. Not only are these films fundamentally useless, but they have the potential to lull us into a false sense of security. A negative skull examination cannot and does not imply that the brain substance is normal. If there is a legitimate indication for any examination, that examination should be computed tomography. To reinforce this notion, we offer for your consideration the following algorithm for the management of head trauma (Table 1: see text).

Adolescent

Fertility and pregnancy complications in women with autosomal dominant polycystic kidney disease.

Fertility and pregnancy complications were assessed in 137 women at risk of having inherited the gene for autosomal dominant polycystic kidney disease. Seventy-six (55%) of these subjects were found to have polycystic kidney disease (multiple renal cysts). The remaining 61 women served as controls. The prevalence of fertility, spontaneous abortion, stillbirth, and symptoms consistent with urinary tract infection were not different in the two groups. However, the frequency of hypertension first diagnosed during pregnancy (with or without preeclampsia or eclampsia) and the frequency of pregnancy-unrelated hypertension were higher in women with polycystic kidney disease. No evidence was found that pregnancy had an adverse effect on the natural course of polycystic kidney disease. The incidence of renal failure was not higher in women with polycystic kidney disease who had three or more pregnancies than in women of similar ages who had two, one, or no pregnancies.

Abortion, Spontaneous

Complementary DNA copies of leukemia and sarcoma virus RNA contain sequences of deoxycytidylate and deoxyguanylate.

Single-stranded complementary DNA (cDNA) of the RNA of Gazdar murine sarcoma virus, Gz-MSV/MuLV; Moloney murine leukemia virus, M-MuLV; mouse mammary tumor virus, MMTV; and simian sarcoma virus, SSV-1, were synthesized in endogenous reverse transcriptase reaction. Gz-MSV/MuLV cDNA was also synthesized in exogenous in vitro reverse transcriptase reactions. In the endogenous reaction, 30-35S, or 6.0- to 7.9-kilobase-length cDNA transcripts were synthesized in high yield. In comparison, transcripts synthesized in exogenous reactions were 6.7S, or 0.39 kilobases. The complementarity of the transcripts was verified by both RNA/DNA hybridization and protection studies. dG and dC sequences were detected in 50-77% of the cDNA molecules by affinity chromatography, by annealing and masking studies, and by resistance to S1 nuclease. dT and dA sequences were not detected in the transcripts. These findings are discussed in relation to the possible selective blocking of transcription of retrovirus genes without interfering significantly with the transcription of cellular genes.

Base Sequence

Autosomal dominant polycystic kidney disease: early diagnosis and data for genetic counselling.

Because of the onset of symptoms in patients with autosomal dominant polycystic kidney disease is generally delayed until adulthood, genetic counseling is imprecise. In an attempt to identify patients early, 261 offspring of subjects with the gene for polycystic disease were tested. Agreement between the results of excretory urography with nephrotomography and radionuclide imaging was excellent. In the 15-19 year age group, polycystic kidney disease was diagnosed in only 30% of 33 subjects at risk, whereas the expected figure was 50%. The disease was diagnosed in 57% of 228 subjects at risk who were aged over 19. When the probands were excluded, this figure was 43% and did not differ significantly from the expected 50%. These data suggest that persons at risk aged over 19 years who have normal urograms and radionuclide images have less than a 5% chance of having inherited the gene for polycystic kidney disease.

Adolescent

Liver cysts in patients with autosomal dominant polycystic kidney disease.

Liver cysts were found in 46 (29 per cent) of 158 patients over 10 years of age with documented autosomal dominant-type polycystic kidney disease (PKD) from 62 unrelated families. Hepatic cysts were not found in any patient at risk for PKD in whom renal cysts were not detected. The prevalence of liver cysts increased with advancing age and with declining rate of glomerular filtration. Results of clinical and laboratory studies indicate that polycystic liver disease in patients with autosomal dominant-type PKD is a benign condition, rarely, if ever, causing impaired liver function or portal hypertension.

Adolescent

Poly(U)-agarose affinity chromatography: specific, sensitivity selectivity, and affinity of binding.

These studies were done to determine four basic intrinsic properties of poly(U)-agarose affinity columns. Specificity of binding studies demonstrated that binding to these columns is highly specific with greater than 90% complementary binding and less than or equal to 3% noncomplementary binding. Sensitivity of binding studies indicated that a minimum sequence of 10 adenylates is required for detectable complementary binding. Selectivity of binding studies revealed that nonsequential adenylates in native RNAs and randomly distributed adenylates in synthetic poly(A)-poly(C) co-polymers did not bind to poly(U)-agarose affinity columns. Whereas, affinity of binding studies demonstrated that A=U complementary base pairing is independent of chain-lengths of greater than or equal to 25 adenylates and dependent of chain-lengths of less than 25 adenylates. Thus the data demonstrates that poly(U)-agarose affinity chromatography is scientifically sound and expedient for the detection and isolation of poly(A)-containing cellular and viral RNAs.

Chromatography, Affinity

Labetalol ('trandate') in hypertension: a multicentre study in general practice.

A study was carried out in 1286 hypertensive patients seen in general practice to evaluate the effectiveness of labetalol given for periods of up to 24 months. Initial dosage was 300 mg per day. The results showed that blood pressure was readily controlled and maintained by labetalol alone in the majority of patients. Pulse rate, vision and fundi were unchanged. There was little difference between the supine and upright blood pressures, confirming the clinical finding that postural hypotension was not a problem. The incidence of side-effects leading to withdrawal was small (7.2%), most side-effects being minor and transient. No drug interactions with concomitant therapy were apparent and the incidence of bronchospasm was very low. The incidence of myocardial infarction and cerebrovascular accident in the population studied was lower than expected.

Adult

Comparative evaluation of the effect of a high yield criteria list upon skull radiography.

Based on results of studies using high yield criteria to determine the need for skull radiography, the Utilization Review Committee of the University Hospital (UH), University of Washington, Seattle implemented a policy encouraging use of the criteria in ordering skull radiology. The Bureau of Radiologic Health of the FDA supported a project comparing skull radiology use patterns at UH, with the high yield criteria policy, and Harborview Medical Center (HMC), without a policy. Results showed an increase of around 60% at HMC since the 1972--73 academic year. At UH, there was a decrease of 40% since the 1972--73 academic year. At HMC a medical record review showed only 51 positive reports that significantly contributed to patient care, about the same rate observed in 1967. At the UH, only nine positive reports significantly contributed to patient care, with 62% compliance with the high yield criteria. A current demonstration project under the auspices of the Washington State Professional Standards Review Organization and Bureau of Radiologic Health involves implementing the high yield criteria list at both HMC and UH. After three months, out of 6,003 patient visits, skull radiography was deemed necessary in 518 cases. Of this total 181 had high yield criteria checked. There were 37 positive reports out of these and 23 examinations that made a documented significant contribution to patient care. In the group without high yield criteria, 434 cases, there were 22 positive reports but no significant contribution to patient care documented after four weeks.

Craniocerebral Trauma

The normal 99mTc-DMSA renal image.

Renal images of 194 normal subjects given 99mTc-dimer captosuccinic acid (DMSA) were reviewed to establish normal values an optimal imaging techniques for this new renal agent. Images were consistently of high quality. Normal renal size (posterior length) averaged 11.5 +/- 1 cm, and renal radioactivity (functioning tubular mass) was equally divided between the left and right kidney. 99mTc-DMSA appears to be an excellent renal parenchymal imaging agent.

Adolescent