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Biomedical subjects

C A Harris

Publications and source records attributed to C A Harris.

At least 55 records · Page 3Linked to original sources

Three distinct human thymopoietins are derived from alternatively spliced mRNAs.

Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine thymus in studies of the effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T-cell differentiation and function. We now report the isolation of cDNA clones for three alternatively spliced mRNAs that encode three distinct human T-cell TPs. Proteins encoded by these mRNAs, which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa), contain identical N-terminal regions, including sequences nearly identical to that of the originally isolated 49-aa protein, but divergent C-terminal regions. TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal liver of the tissues so far examined. Distinct structural domains and functional motifs in TPs alpha, beta, and gamma suggest that the proteins have unique functions and may be directed to distinct subcellular compartments.

Alternative Splicing↗

Molecular analysis of the recA gene of Agrobacterium tumefaciens C58.

The complete nucleotide sequence of the Agrobacterium tumefaciens recA gene was determined. A comparison of the translated open reading frame of the gene with other known recA sequences revealed significant sequence conservation. However, unlike its Escherichia coli equivalent, A. tumefaciens recA lacks the upstream 'SOS box', suggesting a different mechanism of regulation for this gene.

Agrobacterium tumefaciens↗

Induction of leucine aminopeptidase by interferon-gamma. Identification by protein microsequencing after purification by preparative two-dimensional gel electrophoresis.

The protein previously called "Mr approximately 50/pI approximately 6.9," which we observed to be induced by the immunoregulatory cytokine interferon (IFN)-gamma in human fibroblasts, was purified from a total cell lysate by preparative two-dimensional gel electrophoresis and identified by partial amino-terminal sequencing as leucine aminopeptidase (LAP), a 53-kDa cytosolic exopeptidase. Induction of LAP protein by IFN-gamma, confirmed by immunoblotting with an antiserum raised against bovine lens LAP, is a consequence of induction of LAP mRNA and occurs in all four human cell lines examined: HS153 fibroblasts, ACHN renal carcinoma, A549 lung carcinoma, and A375 melanoma. Induction of LAP mRNA is a secondary response to IFN-gamma, blocked by inhibition of protein synthesis with cycloheximide.

Amino Acid Sequence↗

Manganese superoxide dismutase is induced by IFN-gamma in multiple cell types. Synergistic induction by IFN-gamma and tumor necrosis factor or IL-1.

We have previously characterized more than 20 proteins induced by the immunoregulatory lymphokine IFN-gamma in human fibroblasts by their m.w. and isoelectric points determined in two-dimensional gels. Some of these proteins are induced uniquely by IFN-gamma, whereas others are also induced by IFN-alpha, TNF, or IL-1. Recent technologic advances have allowed us to begin to rapidly identify proteins induced by IFN-gamma and other cytokines by sequencing the induced proteins from blots of preparative two-dimensional gels of total cell lysates. In this study, we show that the approximately 21 kDa, isoelectric point greater than 7 protein induced by IFN-gamma is manganese superoxide dismutase (Mn-SOD), a mitochondrial protective enzyme encoded by a nuclear gene. Mn-SOD is induced by IFN-gamma and also by TNF in all four human cell lines examined: HS153 fibroblasts, ACHN renal carcinoma, A549 lung carcinoma, and A375 melanoma. Induction of Mn-SOD mRNA is a primary, rapid, and dose-dependent response to IFN-gamma. In ACHN renal carcinoma cells, Mn-SOD mRNA and protein are induced synergistically by IFN-gamma in combination with either TNF or IL-1, and the induced protein is enzymatically active. IFN-gamma and TNF together induce Mn-SOD mRNA by more than 100-fold relative to its level in untreated ACHN cells. The induction of Mn-SOD by IFN-gamma and its synergistic induction by IFN-gamma in combination with TNF and IL-1 should protect healthy cells from the toxicity of O2- during an immune response, and may provide a mechanism for selective killing of infected cells.

Amino Acid Sequence↗

Sternocostoclavicular hyperostosis: two cases with differing dermatologic syndromes.

Sternocostoclavicular hyperostosis is a rare rheumatic condition characterized by ossification and erosion of the clavicle and the first rib, that has been shown to be associated with pustular skin lesions. We present 2 cases, one of which had features of pustulosis palmaris et plantaris and the other dissecting cellulitis of the scalp. Although the dermatologic manifestations differ, both cases have rheumatologic and roentgenographic features diagnostic of sternocostoclavicular hyperostosis.

Adult↗

Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections.

Antigens of human (HIV) or simian immunodeficiency viruses (SIV) were identified with polyclonal or monoclonal antibodies and avidin-biotin complex (ABC) immunohistochemistry in fixed surgical pathology and autopsy specimens of humans or monkeys with the acquired immunodeficiency syndrome. With B-5 fixative, viral antigens were readily detected in lymph nodes of 8 of 13 patients with follicular hyperplasia, but in only 1 of 12 patients with follicular atrophy. Antigen was detected in follicular dendritic reticular cells and rare blastlike cells, extracellularly, and in postcapillary venules, medullary lymphocytes, sinus histiocytes, and macrophages in some lymph nodes. In the brain at autopsy, antigen could be found in gliomesenchymal-cell nodules, astrocytes, vascular endothelial cells, multinucleated cells, and astrocytes and macrophages associated with demyelination. In contrast, 4 rhesus monkeys with experimental SIV infection had abundant antigen in sinus histiocytes, macrophages, and multinucleated giant cells of lymph nodes and spleen and in thymic epithelial cells. Brain lesions of monkeys resembled those of humans, with antigen found in macrophages and multinucleated giant cells. Antibodies to HIV also were immunoreactive in formalin-fixed tissue sections of monkeys containing SIV antigens. The ABC technique provided a fast and efficient method for localizing HIV and SIV antigens in fixed surgical and autopsy specimens. These findings are consistent with those found with in situ hybridization, ultrastructural studies, frozen sections of lymph nodes, and permanent sections of brain.

Acquired Immunodeficiency Syndrome↗

Effects of vitamin D on renal handling of calcium, magnesium and phosphate in the hamster.

The effects of 1,25(OH)2D3 on the renal handling of calcium (Ca), magnesium (Mg), and phosphate (Pi) in the thyroparathyroidectomized (TPTX) hamster were studied in the presence of exogenous PTH. Clearance experiments were performed in the following groups: acutely TPTX animals (group 1), acute TPTX plus continuous infusion of PTH in low or high doses sufficient to (1) reduce or (2) abolish the hypocalcemic effect of TPTX (groups 2 and 3, respectively), and acute TPTX plus Ca (group 4) or Pi (group 5) infusion. Each group was subdivided into control and experimental subgroups. In all animals an initial control phase was followed by a second phase in which experimental animals received an infusion of 1,25(OH)2D3 (1 U prime + 0.5 U/hr) while control animals received only the ethanol vehicle. GFR and urine flow rate, were not altered significantly in any of the groups. PCa and PMg increased significantly in group 3 only. Group 2 showed an increase in FECa (5.2 +/- 1.4 to 13.2 +/ 2.2%, P less than 0.001) and FEMg (7.3 +/- 1.3 to 17.3 +/- 2.2%, P less than 0.001) in response to 1,25(OH)2D3. Group 3 showed a significant increase in FEMg only (2.2 +/- 0.4 to 5.5 +/- 1.0%, P less than 0.01). The changes in the control groups were not significant. The administration of 1,25(OH)2D3 reduced phosphate excretion only in the presence of PTH. The FEPi decreased from 11.9 +/- 2.1 to 3.6 +/- 0.9% (P less than 0.001) in group 2 and 29.2 +/- 4.0 to 16.5 +/- 2.5% (P less than 0.02) in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

Forty-four episodes of Pneumocystis carinii pneumonia (PCP) occurred in 36 of 70 patients with the acquired immunodeficiency syndrome. Thirty-four patients with 40 episodes of PCP were treated with trimethoprim-sulfamethoxazole. Therapy was successful in 18 episodes (45%), but was unsuccessful in 15 episodes (37.5%). In the latter cases, two patients died within 72 hours; 13, of whom nine died, had therapy changed to pentamidine. In seven additional episodes (17.5%), trimethoprim-sulfamethoxazole was changed to pentamidine due to adverse reactions; all patients survived. Seven patients (26% of survivors) developed recurrent PCP. Twenty-two patients (65%) developed adverse reactions to trimethoprim-sulfamethoxazole, including leukopenia (20), hepatotoxicity (12), fever (eight), rash (six), and immediate reactions (two). Reactions were most common during the second week of therapy. Patients with the acquired immunodeficiency syndrome who have PCP have a high trimethoprim-sulfamethoxazole failure rate, due either to adverse reactions or unresponsive infection. Late recurrence is common.

Acquired Immunodeficiency Syndrome↗

Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome.

We studied the frequency with which unexplained oral candidiasis led to unequivocal acquired immunodeficiency syndrome (AIDS) in patients at risk. Twenty-two previously healthy adults with unexplained oral candidiasis, of whom the 19 tested had a reversed T4/T8 ratio and 20 had generalized lymphadenopathy, were compared with 20 similar patients with a reversed T4/T8 ratio and generalized lymphadenopathy who did not have oral candidiasis. All were intravenous-drug abusers, homosexual or bisexual men, or both. Thirteen of the 22 patients with oral candidiasis (59 per cent) acquired a major opportunistic infection or Kaposi's sarcoma at a median of three months (range, 1 to 23) as compared with none of 20 patients with generalized lymphadenopathy and immunodeficiency but without candidiasis who were followed for a median of 12 months (range, 5 to 21) (P less than 0.001). AIDS developed in 12 of 15 patients with candidiasis and T4/T8 ratios less than or equal to 0.51, as compared with none of four with ratios equal to or greater than 0.60 (P less than 0.01). We conclude that in patients at high risk for AIDS, the presence of unexplained oral candidiasis predicts the development of serious opportunistic infections more than 50 per cent of the time. Whether the remainder will have AIDS is not yet known.

Acquired Immunodeficiency Syndrome↗

Acquired immunodeficiency syndrome. Ophthalmic manifestations in ambulatory patients.

Twenty-five ambulatory patients with acquired immunodeficiency syndrome (AIDS) were studied over a 6-month period. Fourteen (56%) of the patients were heterosexuals with a history of intravenous drug abuse. Ocular involvement was seen in 40% of patients, cotton-wool spots being the major manifestation. Findings consistent with cytomegalovirus retinitis were seen in only one patient. Ophthalmologists should be aware of the ocular findings and epidemiology of AIDS.

Acquired Immunodeficiency Syndrome↗

Effects of parathyroid hormone on electrolyte transport in the hamster nephron.

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.

Animals↗

Resistance to the phosphaturic effect of parathyroid hormone in the hamster.

The renal effects of parathyroid hormone (PTH) and dibutyryl 3'5'-cyclic AMP (DBcAMP) were studied in thyroparathyroidectomized hamsters. The hamsters were permitted free access to food and water or fasted for 16 h. PTH caused a phosphaturia in the fed hamster (fractional excretion of phosphate (FEPO4) increased from 5.8 +/- 1.3 to 27.4 +/- 4.6%, P less than 0.001) but not in the fasted hamster (from 9.9 +/- 2.5 to 12.4 +/- 2.5%, NS), whereas calcium excretion decreased significantly in both groups. There was no significant difference in blood acid-base or phosphate levels between the two groups. Insulin did not restore the phosphaturic response to PTH (FEPO4 from 7.7 +/- 2.6 to 5.3 +/- 1.7%), whereas phosphate or NH4Cl infusion did, FEPO4 increasing from 20.9 +/- 3.1 to 38.1 +/- 5.4% (P less than 0.02) and from 19.5 +/- 3.8 to 39.0 +/- 7.5%, respectively. DBcAMP caused a phosphaturia both in the fasted (from 9.6 +/- 2.7 to 20.1 +/- 4.5%, P less than 0.01) and fed (from 2.5 +/- 0.5 to 10.7 +/- 1.5%, P less than 0.02) hamster. A fasting state of up to 64 h did not produce resistance to PTH in the rat. It is concluded that fasting produces resistance to the phosphaturic but not the calcium-retaining effects of PTH in the hamster. The resistance may occur, at least partly, prior to the production of cAMP within the renal tubular cell.

Animals↗

Potentiation of d-tubocurarine (d-Tc) neuromuscular blockade in cats by lithium chloride.

I.v. infusion of LiCl at 1.0 mEq/0.25 ml/min produced significant decrease in plasma Na+ from 158 +/- 4.5 mEq/l (p less than 0.025) and in Ca2+ from 7.8 +/- 0.34 to 6.8 +/- 0.24 mg% (p less than 0.01) with insignificant increase in K+. No significant changes in plasma electrolytes were observed on infusion of NaCl. The d-Tc induced neuromuscular blockade in Li Cl infused animals was significantly greater than that in Na Cl infused ones.

Animals↗

Strike-through of moist contamination by woven and nonwoven surgical materials.

A test is described which correlates the stress of stretching surgical gown and drape material with moist bacterial strike-through. By application of this test to a number of woven and nonwoven surgical gown and drape materials, it was found that not all of these materials, either woven or nonwoven, are impermeable to moist contamination for equal periods of time. Nonwoven disposable materials now in use range from those which remain impermeable to moist bacterial permeation through all tests while some remain impermeable for limited periods of time, and others almost immediately permeable to moist bacterial penetration. The same situation holds for woven materials. Under conditions of our test, Quarpel treated Pima tight-woven cotton cloth was impermeable to moist bacterial strike-through, through up to 75 washing and sterilizing cyclings, while ordinary linen and untreated Pima cloth permitted bacterial permeation almost immediately. These results have significance in lengthy wet surgical operations.

Bacteria↗