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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 37 records · Page 2Linked to original sources

The effects of a 0.12% chlorhexidine gluconate mouthrinse on orthodontic patients aged 11 through 17 with established gingivitis.

The purpose of this study was to assess the effectiveness of a 0.12% chlorhexidine gluconate (CH) mouthrinse, Peridex, on orthodontic patients 11 through 17 years of age with established gingivitis. Thirty-four subjects were divided into two groups (CH and placebo) of 17 subjects each on the basis of gender, and they were evaluated at baseline, at 6 weeks, and at 12 weeks in a double-blinded manner. The gingival index (GI) of Löe and Silness, the plaque index (PI) of Silness and Löe, the Eastman Interproximal Bleeding Index, and the CWRU staining index were recorded for each subject. The subjects in the CH group, as compared with the placebo group, had statistically significant reductions, expressed as percent reductions against baseline, at the conclusion of this 3-month period: PI = 64.9%, GI = 60.0%, and gingival bleeding = 77.2%. Staining was in the moderate range, and it was concentrated on the mandibular lingual surfaces. Peridex, in combination with mechanical plaque removal, proved to be an important therapeutic agent in controlling gingival inflammation, bleeding, and plaque accumulation in orthodontic patients 11 through 17 years of age with established gingivitis.

Adolescent

The systemic and genetic significance of congenital optic disc anomalies.

Optic disc anomalies have great significance as a clue to associated systemic problems and as a marker of inherited disease. Optic nerve hypoplasia and colobomas of the optic disc are the main visually significant disorders; however, the Morning Glory disc anomaly and Aicardi's syndrome may also be associated with visual impairment.

Coloboma

Laparoscopic cholecystectomy in acute cholecystitis.

The experience of laparoscopic cholecystectomy in 79 patients with acute cholecystitis is described. This group is subdivided into acute and severe acute cholecystitis. These categories are defined. Six percent of our patients with acute disease and 30% of our patients with severe acute disease were converted to open cholecystectomy. Those patients who were converted to open cholecystectomy are discussed. The four port technique and decompression of the gallbladder is described. We conclude that acute cholecystitis should not be a contra-indication to the well-trained laparoscopic surgeon.

Acute Disease

Laparoscopic choledocholithotomy.

Common duct stones present a special problem to the surgeon when he performs a laparoscopic cholecystectomy. We describe a method of exploring the common duct and extracting stones. The procedures for opening of the common duct, removal of stones, and the placement of a T-tube are carefully outlined.

Catheterization

Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae.

Isolates of serotype 23F Streptococcus pneumoniae with high levels of resistance of penicillin have been commonly recovered in Spain for more than a decade. Recently penicillin-resistant serotype 23F S. pneumoniae strains were also isolated from children attending a day-care center in Cleveland. A number of Spanish and Cleveland isolates were compared by electrophoretic analysis of penicillin-binding protein (PBP) profiles and DNA restriction endonuclease cleavage profiles of the PBP 2X and 2B genes amplified with the polymerase chain reaction and by multilocus enzyme electrophoresis. All strains were identical by these criteria. The findings demonstrate that the Spanish and Cleveland isolates are clonally related and suggest that this antibiotic resistant clone of serotype 23F S. pneumoniae has spread intercontinentally from Spain to the United States.

Bacterial Proteins

HLA class II specificities and haplotypes in South Africa detected using polymerase chain reaction and sequence-specific oligonucleotide typing.

DNA sequencing of HLA class II alleles has revealed a degree of polymorphism much greater than was expected on the basis of the standard serological typing methods. Amplification of the polymorphic second exon of the class II genes using the polymerase chain reaction, followed by hybridization with sequence-specific oligonucleotide probes, allows the unambiguous identification of alleles which could not be detected previously. Using the protocols of the Eleventh International Histocompatibility Workshop, we have applied this procedure for the typing of several individuals and their families with suspected alleles that had been observed using serology, cellular typing and restriction fragment length polymorphism (RFLPs). These included an allele related to DRw8 and DRw14, which has only been observed in the mixed ancestral South African population. In addition, unusual combinations of class II genes forming unique haplotypic associations were seen.

Alleles

Minimally invasive colon resection (laparoscopic colectomy).

The successful application of laparoscopic surgery to gallbladder disease and acute appendicitis has encouraged clinical investigators to develop this technology further in an attempt to manage other pathologic disorders of the gastrointestinal (GI) tract. After gaining experience with various laparoscopic skills while performing clinical biliary tract surgery, appendectomy and then in a controlled animal laboratory, a pilot program for laparoscopic colonic surgery was initiated. Twenty patients with ages ranging from 43 to 88 years (mean age of 57 years) underwent laparoscope-assisted colon resection. In nine patients, a right hemicolectomy was performed and a sigmoid colectomy in eight. A low anterior resection, Hartman's procedure, and abdominal perineal resection were each performed in one patient. Indications for surgery were large villous adenomas or adenocarcinoma in 12, diverticular disease in 5, sigmoid endometrioma in 1, cecal volvulus in 1, and inflammatory bowel disease in 1. Eighty percent of patients were able to tolerate a liquid diet on the first postoperative day and 70% were discharged within 96 h eating a regular diet and having normal bowel movements. There were three operative complications: a 3 unit postoperative bleed managed without surgery, one patient developed marked edema of the rectosigmoid anastomosis requiring decompression with a rectal tube, and one individual with metastatic colon cancer was operated on for a mechanical small bowel obstruction 7 days after the initial laparoscopic surgery. Although laparoscope-assisted colonic surgery may still be considered a procedure in evolution, we feel that in time it has the potential to be as popular as laparoscopic cholecystectomy.

Adult

Contamination during in vitro processing of bone marrow for transplantation: clinical significance.

We determined the prevalence and clinical significance of positive microbiologic cultures obtained from 194 consecutive bone marrow harvests intended for infusion in 188 consecutive adult bone marrow transplant patients. Microbiologic cultures were obtained at harvest, after manipulation in vitro (for ABO imcompatibility or purging procedures), and at the time of thawing and infusion (after earlier cryopreservation). Only one of 194 marrow harvests was culture-positive intra-operatively (from an ABO-compatible allogeneic marrow that was infused without manipulation). None of 39 other allogeneic marrows (including 21 ABO-incompatible marrows which were manipulated in vitro) and none of 154 autologous marrows (including 40 which were purged in vitro) grew bacteria or fungi. On the other hand, 12 of 153 (8%) bone marrow samples were positive for micro-organisms after thawing at the time of infusion. The predominant organisms cultured were gram negative bacilli (including five Pseudomonas sp.), probably introduced during the thawing process in a water bath. In only one of 13 contaminated marrows was the same organism(s) (Pseudomonas picketti and Pseudomonas paucimobilis) recovered in vivo during the transplant course. This patient experienced a bacteremia which was eradicated without sequelae. Contamination of marrow can occur during the procurement and in vitro handling processes. With proper sterile technique bone marrow infusion does not pose a significant infectious risk for the immunocompromised transplant patient.

Adolescent

[Dialysis quantity and dietary protein during continuous ambulatory peritoneal dialysis].

Calculation of a dialysis index (Teehan; Perit Dial Bull 1985, 3:152-156) and estimations of the protein catabolic rate (PCR) (reflecting protein intake under steady state conditions) were performed in 20 CAPD patients instructed to eat 1.2-1.5 g/kg BW protein per day and treated with 8-101 dialysate exchange per day. Dialysis indices were 1.20 +/- 0.44, greater than 1.0 reflecting adequate treatment. PCR was based on nitrogen loss by dialysis and urine as well as by losses assumed to be constant in stools and through skin; dialysis loss was obtained either by collection of the 24 h dialysate volume or by estimating the equilibration ratio between blood and dialysate for calculation of nitrogen removal from serum urea nitrogen and 24 h dialysate volume. Values obtained were 0.90 +/- 0.23 and 0.89 +/- 0.23 g/kg BW, respectively (r = 0.97, P = 0.0001). These low PCR values were found to correlate with data from dietary surveys (r = 0.77). Total serum protein, albumin content and transferrin concentration were all within the normal range and there was no correlation between these parameters and protein intake. It is concluded that protein intake and dialysis adequacy must be monitored individually. Whereas generally recommended CAPD schedules provide effective treatment, a mean protein intake greater than 0.9 g/kg BW seems to be adequate.

Adult

Identification of amino acids in the gamma-carboxylation recognition site on the propeptide of prothrombin.

A gamma-carboxylation recognition site on the propeptide of the vitamin K-dependent blood coagulation proteins directs the carboxylation of glutamic acid residues by binding to the vitamin K-dependent carboxylase. To determine residues that define this site, we evaluated the effect of mutation of certain residues in the prothrombin propeptide on the extent of carboxylation. The prothrombin cDNA modified by site-specific mutagenesis was expressed in Chinese hamster ovary cells using a system that yields functional fully carboxylated prothrombin. The cell supernatants containing recombinant prothrombin were evaluated for the extent of gamma-carboxylation by immunoassay. Conformation-specific anti-prothrombin:Ca(II)-specific antibodies measure native completely carboxylated prothrombin; anti-prothrombin:total antibodies measure all forms of prothrombin, regardless of gamma-carboxyglutamic acid content. Mutation of His-18 to Gly, Val-17 to Ser, Leu-15 to Gly or Asp, or Ala-10 to Asp was associated with a partial (30-65%) inhibition of gamma-carboxylation. Mutation of Ala-14 to Ser or Ser-8 to Val did not inhibit gamma-carboxylation. From this and earlier work, residues whose mutation leads to a significant impairment of carboxylation include His-18, Val-17, Phe-16, Leu-15, and Ala-10. Residues whose mutation does not alter the carboxylation recognition site include Ala-14, Ser-8, Arg-4, and Arg-1. To determine the size of the recognition site, the in vitro carboxylation of propeptide-containing synthetic peptides was compared. A 28-residue peptide, based upon residues -18 to +10 of prothrombin, and a 54-residue peptide, based upon residues -18 to +36 of prothrombin, were carboxylated by partially purified bovine carboxylase with similar Km values of 2-5 microM. These results indicate that the gamma-carboxyglutamic acid-rich region of prothrombin makes a minimal contribution to carboxylase binding. A molecular surface of about five amino acids located within the propeptide appears to define the carboxylation recognition site on the precursor forms of the vitamin K-dependent proteins.

Amino Acid Sequence

Randomized prospective trial comparing the native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant therapy.

The dosage of the anticoagulant warfarin sodium is based upon the prolongation of the prothrombin time into an optimal therapeutic range. We have developed a new assay for the native prothrombin antigen that measures the fully gamma-carboxylated prothrombin using a radioimmunoassay. Based on preliminary data that indicated that the native prothrombin antigen predicted both bleeding and thrombotic complications more accurately than the prothrombin time in patients anticoagulated with warfarin sodium, we have performed a randomized prospective trial comparing the complication rate in warfarin-treated patients monitored with the native prothrombin antigen or the prothrombin time. Patients with indications for anticoagulation were randomized to be monitored by the native prothrombin antigen (therapeutic range, 12 to 24 micrograms/mL) or the prothrombin time index (therapeutic range, 1.5 to 2.0). Of the prothrombin time group (N = 80), seven (8.8%) had bleeding or thrombotic complications, with a complication rate of 9.5%/patient-year. In the native prothrombin antigen group (N = 76), one subject (1.3%) had a bleeding complication. The complication rate per patient-year was 1.5%. These results indicate an 85% reduction in the complication rate of the native prothrombin antigen group compared with the complication rate of the prothrombin time group. This difference is statistically significant by the Fisher exact test (P = .037) and by Kaplan Meier survival analysis (P = .040). This study suggests that the use of the native prothrombin antigen assay has the potential to decrease the complications associated with anticoagulation therapy with warfarin sodium.

Humans

Yeast RAS2 affects cell viability, mitotic division and transient gene expression in Nicotiana species.

Overexpression of the budding yeast RAS2 gene in Nicotiana plumbaginifolia cells revealed that RAS2 acted as 'suicide' gene in freshly isolated protoplasts from leaves and blocked cell proliferation in cell suspension-derived protoplasts. Among a series of genes tested (such as npt II, CDC35, PDE2), RAS2 was the only one to block the expression of the cat gene, as measured in a transient gene expression assay. Another ras gene, v-Ha-ras, had similar effects. Furthermore, the RAS2 effect was species-specific and depended on the modulation of hormonal metabolism in the transfected cells, while no differences were noticed between the normal and the activated val19 gene. Transfected plant cells are shown to synthesize a RAS2 protein of the same electrophoretic mobility as the yeast RAS2 product. The results are discussed in the broader context of the evolutionarily conserved ras genes involved in vital cellular functions.

Cell Differentiation

Hybrid genes in the analysis of transformation conditions. 3. Temporal/spatial fate of NPTII gene integration, its inheritance and factors affecting these processes in Nicotiana plumbaginifolia.

Freshly isolated haploid mesophyll protoplasts of Nicotiana plumbaginifolia were transformed for kanamycin resistance. In 38% of the 224 transformants analysed, transmission of the NPTII gene occurred as a homozygous trait, while 62% of the transformants were heterozygous for the trait. In the first case, the foreign DNA integration predominantly (95%) resulted in monogenic inheritance. The second group was characterized by a significant (46%) proportion of multiple insertions. However, there was no clear-cut difference in the integration pattern between the two groups. Furthermore, transformation rates were increased by 4- to 10-fold when transformed diploid protoplasts were treated with UV light or with 3-aminobenzamide. The number of insertion sites was also increased by these treatments. These results shed further light on the fate of the foreign DNA in transformed plants and on means to control or manipulate the integration event(s).

Benzamides

Sequence analysis of two null-mutant alleles of the single Arabidopsis Adh locus.

Data presented in this paper deal with a further molecular characterization of 2 out of 32 EMS-induced Arabidopsis ADH null mutants that we isolated previously. In order to localize and characterize each mutation at the molecular level, we have cloned and completely sequenced the R002 and R006 null mutant alleles. For mutant R002, which does not contain any detectable levels of ADH protein and mRNA, we have found that the mutation is due to a single C to T base pair substitution in the reading frame; this leads to the incorporation of a TAG stop codon (amber nonsense mutation). For mutant R006, which contains normal levels of inactive protein and mRNA levels, we found a G to A base pair transition. This gives rise to a Cys to Tyr amino acid substitution in the active site of the ADH enzyme.

Alcohol Dehydrogenase