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Biomedical subjects

J Anthony

Publications and source records attributed to J Anthony.

At least 19 recordsLinked to original sources

Sequential 1H and 15N NMR assignments and secondary structure of a recombinant anti-digoxin antibody VL domain.

A uniformly 15N-labeled recombinant light-chain variable (VL) domain from the anti-digoxin antibody 26-10 has been investigated by heteronuclear two-dimensional (2D) and three-dimensional (3D) NMR spectroscopy. Complementary homonuclear 2D NMR studies of the unlabeled VL domain were also performed. Sequence-specific assignments for 97% of the main-chain and 70% of the side-chain proton resonances have been obtained. Patterns of nuclear Overhauser effects observed in 2D NOESY, 3D NOESY-HSQC, and 3D NOESY-TOCSY-HSQC spectra afford a detailed characterization of the VL domain secondary structure in solution. The observed secondary structure--a nine-stranded antiparallel beta-barrel--corresponds to that observed crystallographically for VL domains involved in quaternary associations. The locations of slowly exchanging amide protons have been discerned from a 2D TOCSY spectrum recorded after dissolving the protein in 2H2O. Strands B, C, E, and F are found to be particularly stable. The possible consequences of these results for domain-domain interactions are discussed.

Amino Acid Sequence

Fibromyalgia syndrome in patients infected with human immunodeficiency virus. The Boston City Hospital Clinical AIDS Team.

PURPOSE: To prospectively assess rheumatic manifestations of human immunodeficiency virus (HIV) disease in a municipal hospital clinic population in which intravenous drug use was the most common risk factor for HIV infection. PATIENTS AND METHODS: Patients with documented HIV infection were evaluated for rheumatic disease using a standardized questionnaire and examination. Patients with fibromyalgia were compared with HIV-infected patients without fibromyalgia and with fibromyalgia patients without known risk factors for HIV infection. RESULTS: Thirty-seven of 140 patients with HIV infection had muskuloskeletal symptoms. Three of these 37 patients had arthritis, but none had Reiter's syndrome or psoriatic arthritis. Thirty (81%) of 37 patients had chronic musculoskeletal symptoms (for 3 months or longer). Twenty of 30 patients with chronic musculoskeletal symptoms had polyarthralgia, and of those, 15 (75%) were found to have either definite or probable fibromyalgia syndrome. Therefore, fibromyalgia syndrome was found in 41% of HIV-infected patients with musculoskeletal symptoms and in approximately 11% of all HIV-infected patients. Fibromyalgia patients with HIV infection had a longer duration of HIV infection (p = 0.01) and more frequently reported past depressed mood (p = 0.001) than HIV-infected patients without fibromyalgia. Compared with 301 patients with fibromyalgia syndrome and no known risk behavior for HIV, known HIV-infected patients with fibromyalgia were more commonly male (p = 0.001) and reported current depressed mood more frequently (p = 0.0001). CONCLUSION: Few patients with arthritis were noted among HIV-infected patients who had intravenous drug use as risk behavior. By comparison, fibromyalgia syndrome appeared to be a common cause of musculoskeletal symptoms in this patient population.

Acute Disease

Production of stable anti-digoxin Fv in Escherichia coli.

We have created a bacterial expression-export system and have used it to express (14 mg l-1) the variable region fragment (Fv) of an anti-digoxin antibody (26-10) in Escherichia coli. The expression-export plasmid contains a T7 promoter and the E. coli signal sequences ompA [Movva et al., J. biol. Chem. 255, 27-29 (1980)] and phoA [Inouye et al., J. Bacteriol. 149, 434-439 (1982)] fused to heavy chain (VH) and light chain (VL) variable region sequences to generate an artificial cistron. The 26-10 Fv protein made using this system was soluble, unlike many other expression systems which produce insoluble proteins in the form of inclusion bodies. The 26-10 VH and VL proteins were cleaved at their mature N-termini and exported into the bacterial periplasm where they could be easily extracted and affinity purified on ouabain-Sepharose. 26-10 Fv bound to digoxin with similar affinity and specificity as the whole 26-10 antibody (Ka for Fv, 1.3 x 10(9) M-1, Ka for IgG, 7 x 10(9) M-1). 26-10 Fv appears to be remarkably stable in comparison with other Fv fragments. The half-life for chain dissociation of 26-10 Fv was 48 hr compared to the reported 1.5 hr half-life of McPC603 Fv. We present the proton NMR spectra of the 26-10 Fv as preliminary evidence that this expression-export system can be used to facilitate the analysis of the solution structure of 26-10 Fv by NMR.

Amino Acid Sequence

Aeromonas hydrophila infections following use of medicinal leeches in replantation and flap surgery.

Aeromonas hydrophila infections are a recognized complication of postoperative leech application, and can occur with measurable frequency in populations of patients treated with leeches. We review 11 previously reported leech-related Aeromonas infections and analyze seven unreported cases. These infections range from minor wound complications to extensive tissue loss and sepsis. Often, these infections followed leech application to tissue with questionable arterial perfusion. Onset of clinical infection in these patients ranged from within 24 hours of leech application to 10 days or more after leech application. Late infections may represent bacterial invasion from colonized necrotic tissue. Based on these observations, we recommend that leech applications be restricted to tissue with arterial perfusion to minimize contamination of necrotic tissue. We also recommend that patients treated with leeches receive antibiotics effective against Aeromonas hydrophila before leech application. Patients treated with leeches and discharged with eschars or open wounds might benefit from oral antibiotic therapy until wound closure. These precautions may minimize or eliminate this complication of leech use.

Adolescent

Platelet count and liver function tests in proteinuric and chronic hypertension in pregnancy.

Platelet counts and plasma enzyme estimations were performed in 207 pregnant patients with proteinuric hypertension and in 60 patients with chronic hypertension. Patients with abruptio placentae were excluded. In the proteinuric hypertensive patients a low platelet count (less than 150,000/mm3) was found in 63 (30%) and elevated transaminase levels in 50 (24%) and both abnormalities were present in 47 patients (23%). The serum lactate dehydrogenase (LDH) value was mildly elevated in most proteinuric hypertensive women, but a markedly elevated LDH level (greater than 400 IU/l) was usually associated with other evidence of liver necrosis. Raised plasma alkaline phosphatase and gamma-glutamyltransferase levels were not related to the occurrence or severity of liver necrosis. In proteinuric hypertensive patients a low platelet count or elevated transaminase level was associated with deteriorating renal function, increased maternal morbidity, increased incidence of low-birth-weight babies and a raised perinatal mortality rate (149/1,000). In patients with chronic hypertension, 1 had a low platelet count but none had elevated transaminase, LDH or other enzyme levels and there was no recorded perinatal mortality.

Adolescent

Placental bed spiral arteries in the hypertensive disorders of pregnancy.

OBJECTIVE: The investigation of the histology of the placental bed spiral arteries in normal pregnancy and in pregnancies complicated by hypertension, with or without proteinura. DESIGN: An observational study, based on women having caesarean sections for clinical reasons. SUBJECTS: 17 normal pregnant women, 43 with gestational hypertension, of whom 39 had proteinuria, 17 with chronic hypertension, of whom 6 had proteinuria, and 5 with unclassified hypertension. INTERVENTIONS: Placental bed biopsies obtained during caesarean section. MAIN OUTCOME MEASURES: Histological appearance of sections stained with haematoxylin and eosin PAS and Lendrum's MSB. RESULTS: Biopsies containing spiral arteries were obtained from 6 normotensive and 44 hypertensive women. Trophoblastic invasion was present in 5 of the 6 normotensive biopsies but absent in the majority of those with hypertension. Subintimal proliferation was seen in all the normotensive biopsies but in only 8 of 28 from those with gestational hypertension and proteinuria. Other features seen predominantly or only in the hypertensive biopsies, in order of frequency, were medial hyperplasia, fibrin deposits, acute atherosis, endothelial vacuolation and thrombosis. CONCLUSION: Absence of physiological changes may not be peculiar to preeclampsia but may be associated or even a result of various forms of hypertension in pregnancy. Spiral arteries show a spectrum of changes in hypertensive pregnancies that do not appear to bear a clear-cut relation to the clinical signs.

Arteries

Respiratory function in severe gestational proteinuric hypertension: the effects of rapid volume expansion and subsequent vasodilatation with verapamil.

OBJECTIVES: (1) To define the baseline respiratory function in untreated severe gestational proteinuric hypertension (GPH) and (2) to assess the effects of volume expansion with dextran (MW = 70,000 Dalton) and subsequent vasodilatation with the calcium antagonist verapamil on the baseline respiratory function in severe GPH. DESIGN: Prospective descriptive study. SETTING: Reproductive Research Unit, Groote Schuur Hospital, Cape Town, South Africa. SUBJECTS: Six women with severe GPH undergoing stabilization and delivery. INTERVENTIONS: Baseline haemodynamic and respiratory function was assessed using invasive monitoring. Patients then underwent volume expansion to a pulmonary capillary wedge pressure of 16 mmHg with dextran-70, followed by vasodilatation with the calcium antagonist verapamil. Haemodynamic and respiratory variables were measured, before and after both the fluid load and the reduction (20%) in the mean arterial pressure. MAIN OUTCOME MEASURES: Mean arterial pressure, heart rate, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance, pulmonary vascular resistance, respiratory rate, blood gases, alveolar arterial oxygen difference, oxygen availability, oxygen consumption, pulmonary shunt fraction. RESULTS: Baseline oxygen availability/delivery and oxygen consumption indices were consistent with severe tissue ischaemia. Volume loading with 400 +/- 114 ml dextran-70 normalized these variables, and subsequent vasodilatation with verapamil did not reduce these indices below the normal limits for pregnancy. CONCLUSIONS: These data support the theory that some of the complications of severe GPH may follow organ damage due to prolonged tissue ischaemia. They also support the appropriateness of controlled volume expansion in the management of this condition. We suggest, from these data, that the combination of volume expansion and verapamil vasodilatation lowers the blood pressure without compromising the maternal respiratory function.

Blood Volume

Topical tretinoin decreases healing times of electroepilation-induced wounds.

There is evidence that topical tretinoin promotes wound healing, especially when the wound area is pretreated. In our study, 5 patients were pretreated for 2 weeks with 0.05% tretinoin cream to one groin or axilla, followed by electroepilation to both sides. Electroepilation created small, superficial wounds. Healing was defined as complete re-epithelialization. In all patients the pretreated side showed a significantly decreased healing time as compared to the nonpretreated side. Pretreatment of skin with topical tretinoin may be useful in reducing healing times of patients undergoing electroepilation.

Administration, Topical

Psychologic aspects of exercise.

Physicians are well aware of the health benefits of exercise, but probably less cognizant of the many psychologic benefits of regular exercise. In recent years more attention has been paid to the psychologic effects of exercise, and much evidence can be found in the literature to support these beneficial effects. Psychologic states such as anxiety, distress, depression, and coronary-prone behavior have been found to be reduced by regular aerobic exercise. Exercise has also been shown to elevate mood, increase intellectual functioning, and improve self-concept. In encouraging their patients to exercise, physicians can more effectively motivate them by following certain psychologic principles, thereby ensuring greater compliance and adherence to the exercise program. Doing an objective fitness assessment establishes a baseline and creates a stimulus for awareness for the patient. The resulting exercise prescription will more likely be followed if the physician helps the patient establish realistic goals, and understand the minimums of exercise that can still lead to improvement, the exercise physiology behind the prescription, and the physical and psychologic gains to be made from exercise. It can also be extremely helpful if the physician individualizes the program to make it convenient and fun, provides supervision and ample positive reinforcement, and teaches by example, that is, not only be a proponent of exercise, but a participant. In spite of the many benefits of exercise, there are certain psychologic liabilities as a result of excessive exercise. Negative states such as exercise addiction, overtraining, and burnout can be attributed to excess exercise, but they are also often a result or symptom of other psychologic problems. By being aware and knowledgeable, the physician can intervene in this system to help the individual confront the real problems and maintain his or her participation in the sport or exercise program.

Exercise

Indoramin in the treatment of pregnancy hypertension. A placebo-controlled trial comparing the efficacy of indoramin with alpha-methyldopa.

A placebo-controlled trial was used to assess the antihypertensive efficacy of indoramin in the management of pregnancy hypertension. Sixty patients were recruited into the study and only 17 attained satisfactory blood pressure control. In the doses of drugs administered indoramin was not shown to be more effective than alpha-methyldopa.

Drug Therapy, Combination

Tolerance for rectosigmoid distention in irritable bowel syndrome.

Two hypotheses were tested: (a) lowered tolerance for balloon distention of the rectosigmoid in patients with irritable bowel syndrome is caused by a psychological tendency to exaggerate the painfulness of any aversive stimulus, and (b) contractions elicited by balloon distention are responsible for pain reports. Tolerance for stepwise distention of a balloon in the rectosigmoid was compared with tolerance for holding one hand in ice water in 16 irritable bowel patients, 10 patients with functional bowel disorder who did not satisfy restrictive criteria for irritable bowel, 25 lactose malabsorbers, and 18 asymptomatic controls. Contractile activity was measured 5 cm above and 5 cm below the distending balloon. Psychometric tests were used to assess neuroticism, anxiety, and depression, and a standardized psychiatric interview was administered. Patients with irritable bowel syndrome had significantly lower tolerance for balloon distention but not ice water, and balloon tolerance was not correlated with neuroticism or other psychological traits measured. Rectosigmoid and rectal motility were also not related to tolerance for balloon distention. Both hypotheses were rejected. A peripheral mechanism such as altered receptor sensitivity may be the cause of distention pain in irritable bowel syndrome.

Colon, Sigmoid

Hemodynamic changes associated with intravenous infusion of the calcium antagonist verapamil in the treatment of severe gestational proteinuric hypertension.

The calcium antagonist verapamil was intravenously infused after plasma volume expansion with dextran-70 in nine patients with severe gestational proteinuric hypertension. The hemodynamic response of these patients was monitored using a flow-directed pulmonary artery catheter. Verapamil produced a statistically significant reduction in mean arterial pressure and systemic vascular resistance without adversely affecting the cardiac output. The decrease in blood pressure was smooth and controlled and was associated with an insignificant increase in heart rate. There were no adverse fetal effects as evidenced by cardiotocographic monitoring. The apparent efficacy of verapamil in this study justifies further investigation.

Adult

Histologic study of the regeneration of axillary hair after removal with subcutaneous tissue shaver.

It was observed that after subcutaneous tissue shaving for the radical therapy of hircismus and hyperhidrosis axillary hair often regrew. Histologic study of this phenomenon showed that hair bulb and most of the follicle up to a level near the sebaceous duct opening had been removed. Hair regrows from remnant outer root sheath, but only when sebaceous glands are preserved, that is when the upper portion of the follicular isthmus is intact. One or several solid epithelial pegs grow downward from the cut end of the trichilemma, and inner root sheath and new young hair are formed in its center. In hair peg stage, the lower tip of the hair follicle descends while new hair is growing in its center through the mitotic activity is growing in its center through the mitotic activity of hair germ cells and is prevented from pushing toward the skin surface by interlocking fusion between hair cuticula and sheath cuticula. Eventually, the epithelial cells wrap around a mass of mesenchymal cells and form a new bulb from which the terminal hair grows upward. The new matrix acquires a new complement of functioning melanocytes.

Adult

Ultrastructure of nerve in erythema nodosum leprosum (ENL).

Gross changes of myelinated fibres and Schwann cells at different degenerative stages were present in all five ENL nerve lesions. Besides these changes, infiltrating cells mainly macrophages, deposition of excessive collagen and perineurial vessel damage were also observed.

Blood Cells

Radical operation to stop axillary odor and hyperhidrosis.

We have developed a subcutaneous tissue shaver for the radical treatment of hircismus and hyperhidrosis. With this shaver the sweat glands can be removed from the undersurface of the axillary skin through a small incision. We report 3,000 cases of hircismus and hyperhidrosis treated by our method. The postoperative scar has been minimal, healing has been quick, and good results were achieved by this method.

Axilla