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Biomedical subjects

J Mills

Publications and source records attributed to J Mills.

At least 235 records · Page 13Linked to original sources

Topoisomerase I phosphorylation in vitro and in rapidly growing Novikoff hepatoma cells.

Changes in phosphorylation modulate the activity of topoisomerase I in vitro. Specifically, enzymatic activity is stimulated by phosphorylation with a purified protein kinase (casein kinase type II). The purpose of this study was to compare the sites that are phosphorylated in vitro by casein kinase type II with the site(s) phosphorylated in vivo in rapidly growing Novikoff hepatoma cells. Topoisomerase I labeled in vitro was characterized by three major tryptic phosphopeptides (I-III). Separation of these peptides by a C18-reverse phase h.p.l.c. column resulted in their elution at fractions 18 (I), 27 (II) and 44 (III) with 17%, 22.5% and 33% acetonitrile, respectively. In contrast, only one major phosphopeptide was identified by h.p.l.c. in topoisomerase I labeled in vivo. This phosphopeptide eluted at fraction 18 corresponding to the elution properties of phosphopeptide I labeled in vitro. It also co-migrated with tryptic phosphopeptide I when subjected to high-voltage electrophoresis on thin-layer cellulose plates. Preliminary experiments suggest that phosphorylation occurs at a serine residue six amino acids from the N-terminus of the peptide. These data indicate that topoisomerase I is phosphorylated in vivo and in vitro within the same tryptic peptide and suggest that topoisomerase I is phosphorylated in vivo by casein kinase II.

Amino Acid Sequence↗

Acute and latent herpes simplex virus neurological disease in mice immunized with purified virus-specific glycoproteins gB or gD.

Groups of 5-week-old BALB/c mice were immunized intraperitoneally with approximately 10 micrograms of purified alum-precipitated glycoprotein gB or gD of either herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) origin. Control mice received injections of alum-precipitated 1% bovine serum albumin (BSA). Following a second immunization 4 weeks later, seroconversion was confirmed by demonstrating the presence of glycoprotein-specific antibody by immune precipitation. All animals were challenged with lethal doses of either HSV-1 or HSV-2 by footpad inoculation and assessed for acute virus-induced neurological disease and the development of ganglionic latency. Whereas 70% of control (BSA-immunized) HSV-1-infected animals developed ascending myelitis and died, 100% of mice immunized with either gB-1, gB-2, gD-1, or gD-2 antigens remained free of clinical illness and survived HSV-1 challenge. In contrast, gB-1-or gB-2-immunized mice were not protected against acute HSV-2-induced neurological disease and showed a mortality rate of 60-90% (equivalent to that seen in controls), although mean survival times were prolonged. However, significant protection against HSV-2 challenge was observed with gD-1 or gD-2 immunization. When sacral ganglia were removed from surviving mice 9-12 months after virus challenge, latent virus was detected in all gB- or gD-immunized animals, although the extent of latent infection was restricted. These results provide evidence that glycoprotein gD might be superior to glycoprotein gB as an immunogen for the control of acute HSV-1 and HSV-2 neurological disease in mice. However, neither glycoprotein prevents ganglionic latency, the source of virus for recurrent herpesvirus infections.

Animals↗

Effects of exopolysaccharide production by viridans streptococci on penicillin therapy of experimental endocarditis.

The influence of exopolysaccharide production by viridans streptococci on penicillin therapy of endocarditis was studied in rabbits with experimental aortic-valve endocarditis. Animals were first infected with penicillin-susceptible streptococci known to produce varying amounts of exopolysaccharide in cardiac vegetations. Treatment with procaine penicillin, 300,000 U every 12 hr, was begun one to two days after infection. After five days of therapy, animals infected with Streptococcus sanguis II and Streptococcus morbillorum, both vigorous exopolysaccharide producers, continued to have infected vegetations, while animals infected with Streptococcus salivarius and a different Streptococcus sanguis II, both deficient in exopolysaccharide production, had sterile vegetations. These findings indicate that failure to eradicate streptococci from vegetations correlates with exopolysaccharide production and that this property may be important in determining outcome of therapy.

Animals↗

Aircraft noise annoyance at three joint air carrier and general aviation airports.

The results of social surveys conducted near three airports that support both general aviation and scheduled air carrier operations are presented and discussed. Inferences supported by these data include: The nature of noise exposure and community reaction at smaller airports may differ from that at larger airports; survey techniques are capable of identifying changes in annoyance associated with numerically small changes in noise exposure; changes in the prevalence of annoyance are causally produced by changes in noise exposure; and changes in annoyance associated with changes in exposure vary with time.

Adult↗

Effectiveness of aztreonam for the treatment of gonorrhea.

Aztreonam, 1 g intramuscularly, was compared with spectinomycin, 2 g intramuscularly, for uncomplicated gonorrhea. There were no failures with either drug. For aztreonam, there were 26 urethral, 3 rectal, and 3 endocervical sites that were infected. Aztreonam in a single dose of 1 g intramuscularly is satisfactory therapy for uncomplicated urethral gonorrhea in men and may be effective for rectal and endocervical infection as well.

Adolescent↗

Once-daily ceftriaxone for skin and soft tissue infections.

We prospectively compared once-daily administration of ceftriaxone with cefazolin given every 8 h for the treatment of skin and soft tissue infections. Thirty-one patients received cefazolin for a mean of 4.5 days, and 26 patients received ceftriaxone for a mean of 4.0 days. All patients had a satisfactory response. Adverse reactions were few and reversible. Ceftriaxone given as a single daily intramuscular injection is effective therapy for skin and soft tissue infections.

Adult↗

Cytomegalovirus infection and abnormal T-lymphocyte subset ratios in homosexual men.

T-helper:T-suppressor cell ratios of 1 or less were found in 2 of 42 homosexual men without antibodies to cytomegalovirus but in 33 of 67 homosexual men with antibodies (p less than 0.001). Of 34 men without antibody who were followed prospectively, 12 became seropositive for cytomegalovirus and all 12 developed helper: suppressor ratios of less than 1.0. These ratios remained at 1 or less for an average of 9.6 months but persisted for 15 months or more in 3 men. None of the men in the prospective study developed antibodies to the acquired-immunodeficiency-syndrome-associated retrovirus. These results indicate that in the homosexual men studied, abnormally low T-lymphocyte helper: suppressor ratios occurred almost exclusively in those who were infected with cytomegalovirus, and in those prospectively followed low ratios did not reflect contact with the syndrome-associated retrovirus. Abnormal ratios were rarely seen in men who had never been exposed to cytomegalovirus. Thus, cytomegalovirus infection may be an important cofactor in the immunologic disorders leading to the acquired immunodeficiency syndrome.

Antibodies, Viral↗

Risk of infection after penetrating abdominal trauma.

To identify the risk factors for the development of postoperative septic complications in patients with intestinal perforation after abdominal trauma, and to compare the efficacies of single-drug and dual-drug prophylactic antibiotic therapy, we studied 145 patients who presented with abdominal trauma and intestinal perforation at two hospitals between July 1979 and June 1982. Logistic-regression analysis showed that a higher risk of infection (P less than 0.05) was associated with increased age, injury to the left colon necessitating colostomy, a larger number of units of blood or blood products administered at surgery, and a larger number of injured organs. The presence of shock on arrival, which was found to increase the risk of infection when this factor was analyzed individually, did not add predictive power. Patients with postoperative sepsis were hospitalized significantly longer than were patients without infection (13.8 vs. 7.7 days, P less than 0.0001). Both treatment regimens--cefoxitin given alone and clindamycin and gentamicin given together--resulted in similar infection rates, drug toxicity, duration of hospitalization, and costs.

Abdominal Injuries↗

The acquired immune deficiency syndrome: an international health problem of increasing importance.

The Acquired Immune Deficiency Syndrome (AIDS) is a new disease which first appeared in human populations about 1979. The disease is defined by the development of unusual types of cancer (e.g. Kaposi's sarcoma), or severe cellular immunodeficiency manifested by opportunistic infections (e.g. Pneumocystis carinii infection), or both. Although the etiology of AIDS is unknown, the epidemiologic evidence is consistent with an infectious agent transmitted by blood (e.g. transfusion, needle sharing) or sexual intercourse. Over three-quarters of the cases have been in homosexual or bisexual males and in intravenous drug abusers; about 5% of cases do not have recognized risk factors. A small number of cases have resulted from transfusion of blood or blood products. The early clinical manifestations are non-specific, and may include asymptomatic skin lesions, dyspnea and dry cough, weight loss, chronic diarrhea, and focal and non-focal central nervous system findings. Treatment for the associated cancers and opportunistic infections may be successful in individual instances, but the underlying immunosuppression of AIDS appears to progress inexorably and the fatality rate approaches 100% within a few years from diagnosis. Although nosocomial transmission has not been documented, infection control guidelines have been developed by analogy with hepatitis B infection.

Acquired Immunodeficiency Syndrome↗

A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo.

Patient-initiated treatment of recurrent genital herpes with topical acyclovir was compared with placebo treatment in a multicenter collaborative trial involving 309 patients. No differences were found between the group using acyclovir and that using placebo except that herpes simplex virus was excreted for a shorter period by women using acyclovir. This difference was partially accounted for by the fact that some patients whose viral culture results subsequently proved positive began to use their medication before lesions formed. One hundred patients initially applied ointment within 6 hr of onset of the prodrome and before actual lesion formation. Separate analysis of this group showed a diminished duration of viral excretion by women using acyclovir and a reduced interval between lesion formation and total crusting in men using acyclovir, but both differences were of only borderline significance (.05 less than P less than .10). The results indicate that patient-initiated therapy with topical acyclovir in polyethylene glycol exerts no clinically significant effect on recurrent genital herpes.

Acyclovir↗

Exopolysaccharide production by viridans streptococci in experimental endocarditis.

Light and electron microscopy with histochemical staining were used to estimate exopolysaccharide production by strains of viridans streptococci recovered from patients with endocarditis. Six strains were selected for study because they represented a wide range of in vitro polysaccharide production. By light microscopy, there was good agreement between three polysaccharide stains (ruthenium red, periodic acid-Schiff and calcifluor white) in the amount of glycocalyx produced, which ranged from minimal (0 to 1+) to maximal amounts (4+). Two strains selected for minimal (strain 1) and maximal (strain 6) in vitro exopolysaccharide production were studied after we used them to experimentally infect cardiac vegetations. Glycocalyx could be demonstrated surrounding organisms in cardiac vegetations, and the relative amounts produced were similar to those seen in vitro. Vegetations formed by glycocalyx-producing strains were also larger than those formed by glycocalyx-deficient strains. Viridans group streptococci which produce exopolysaccharide in vitro also do so within cardiac vegetations. The relationship of exopolysaccharide production to maintenance of endocardial infection is discussed.

Animals↗

Large-scale serological screening for cytomegalovirus antibodies in homosexual males by enzyme-linked immunosorbent assay.

We compared an enzyme-linked immunosorbent assay (ELISA) with complement fixation and radioimmunoassay in determining the presence of immunoglobulin antibodies to cytomegalovirus. Of an initial 93 serum samples tested, the correlation between ELISA and radioimmunoassay was 98.9% and that between ELISA and complement fixation was 96.1%. ELISA was used to screen 1,123 homosexual men in San Francisco. Of 479 men attending a homosexual health fair, 35 (7%) lacked cytomegalovirus antibodies by ELISA. Only 15 (2%) of 644 homosexual men attending a municipal sexually transmitted disease clinic were found to be seronegative. All but one of the seronegatives detected by ELISA were also seronegative by radioimmunoassay and complement fixation. We conclude that ELISA can be used to reliably perform large-scale screening for the presence of immunoglobulin G antibodies to cytomegalovirus.

Antibodies, Viral↗

Adverse reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome.

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotemia, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p less than 0.005).

Acquired Immunodeficiency Syndrome↗

Insulin release pattern after blockade of catecholamine synthesis with alpha-methyl tyrosine in vivo.

Insulin release pattern in vivo was studied using 30 control rats and 30 rats treated with alpha-methyl tyrosine to block catecholamine synthesis in vivo four days before the time of investigation. The drug treated animals exhibited significantly higher fasting insulin levels, and also the first phase insulin release after the B cell was challenged with a glucose load was significantly higher in these animals than occurred in the controls. This observation implies that the B cell is modulated by the sympathetic nervous system in its function and the insulin release would vary according to the emotional state of the individual.

Animals↗