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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 163 records · Page 9Linked to original sources

Simultaneous treatment with single-agent chemotherapy and radiation for locally advanced cancer of the head and neck.

A substantial proportion of patients with squamous cell carcinoma of the head and neck have extensive locoregional disease at presentation. While extensive surgical procedures may completely eradicate local disease with acceptable morbidity for smaller tumors, in patients with stage III and IV disease, high local relapse rates and relatively short survival times still characterize the course of the majority of such patients. For patients with locally unresectable disease, the combined use of chemotherapy and radiation has resulted in encouraging data both in terms of local control and survival. Combined-modality programs frequently employ platinum coordination complexes, and standard or hyperfractionated radio-therapy toxicity data suggest that the overall tolerance of such programs is acceptable and, more important, long-term follow-up has shown that function can be largely preserved. In this review we illustrate the experience with combined single-agent chemotherapy and radiotherapy, and discuss the methodologic difficulties of clinical trials in this setting. We describe our experience with combined carboplatin and simultaneous conventional radiation in patients with extensive unresectable locoregional disease. Encouraging results and modest toxicity clearly support further testing with this approach, especially in patients with less advanced and bulky disease.

Aged↗

[Selenium poisoning in fattening swine].

A case of selenium toxicosis was observed in fattening pigs. Intoxication was caused by high levels of selenium in a commercial mineral premix. Instead of the recommended dose of 16 ppm Se, the mineral feed contained selenium at concentrations of 657 and 1059 ppm. The ration in use was found to contain more than 14 ppm selenium. Clinical symptoms were observed 5 to 6 weeks after the pigs began consuming the contaminated feed mixture. Feed intake was markedly reduced and animals showed severe lameness due to separation and necrosis of the hoof wall at the coronary band. Some pigs were reluctant to stand. In some cases alopecia was detected. At histopathological examination one animal with paralysis of the hind limbs revealed a focal bilaterally symmetric poliomyelomalacia in the lumbar segment of the spinal cord. Diagnosis was confirmed by high selenium contents of liver, kidneys and blood. After removing the incriminated feed no further pigs developed signs of intoxication. New horn growth was present and lame animals recovered slowly.

Alopecia↗

Plant protoplasts as genetic tool: selectable markers for developmental studies.

Protoplasts have usually been presented as a methodological tool. Even as such, they make possible an impressive array of applications in plant biology. Here we report on the use of protoplast-derived selectable markers in the study of several disturbed genetic systems with obvious effects on plant development: (1) auxotrophic mutants and the control of amino acid biosynthesis and transport in vegetative and reproductive tissues; (2) introgression of alien genetic information across phylogenetic boundaries by protoplast fusion, a consequence of controlled dedifferentiation-redifferentiation processes and attenuated incompatibility reactions in cultured cells; (3) expression (in)stability of foreign genes in transgenic plants during successive meiotic generations and in crosses between independent transformants.

Cells, Cultured↗

The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide.

This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferryl myoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferryl myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferryl myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide.

Erythrocyte Membrane↗

Highly bioluminescent Bacillus subtilis obtained through high-level expression of a luxAB fusion gene.

Bioluminescence levels comparable to those achievable in Escherichia coli have yet to be obtained from luxAB expression in gram-positive bacteria. In this communication we describe the gene engineering required to generate a highly bioluminescent derivative of Bacillus subtilis. The combination of a powerful promoter, Pxyn, a fusion derivative of luxAB from Vibrio harveyi and translational coupling have overcome the previously reported limitations in luxAB expression. The implications for highly bioluminescent gram-positive organisms are discussed.

Bacillus subtilis↗

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↗