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Biomedical subjects

M Kirk

Publications and source records attributed to M Kirk.

At least 91 records · Page 5Linked to original sources

Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system.

Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested.

Amoxicillin↗

Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report.

Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.

Chromium↗

Sensorineural hearing loss and mumps.

Out of 360 children with hearing loss seen during 1 year in the Haringey Audiology Unit, 21 had unilateral, sensorineural hearing loss. Sixteen had previously been checked to have no loss. It is strongly suspected that the hearing loss resulted from mumps, and therefore the disability in such children could be prevented by introducing mumps vaccination into the immunisation programme.

Child↗

Genetic tests for autosomal non-disjunction and chromosome loss in mice.

Two new genetic methods for detecting autosomal non-disjunction and chromosome loss in mice are described. Both methods involve the use of marker genes and Robertsonian translocations, the latter present only in tester parents, to detect events in chromosomally normal mice. With the Rb method, the tester parent carries one or more Robertsonian translocations heterozygously; with the MBH method the tester parent carries two Robertsonian translocations showing monobrachial homology. The high rates of meiotic non-disjunction in the tester mice provide gametes with specific extra or missing chromosomes which, at fertilization, can allow the survival of a proportion of the zygotes lacking or carrying an extra specific chromosome from tested chromosomally normal parents. The Rb method has been assessed for X-ray-induced chromosome 1 loss and non-disjunction in mature oocytes and also for such chromosome 1 loss from the maternal pronuclei of 1-cell zygotes. The MBH method has been assessed for X-ray-induced chromosome 1 loss in male postmeiotic cells and for non-disjunction in spermatocytes. Both methods proved effective in detecting chromosome 1 loss. A single case of the much rarer non-disjunctional event was also found. As applied, both methods compared favourably with the numerical sex chromosome anomaly (NSA) method and have considerable potential for further development.

Animals↗

Osler's nodes, pseudoaneurysm formation, and sepsis complicating percutaneous radial artery cannulation.

Percutaneous arterial cannulation is useful for hemodynamic monitoring and frequent arterial blood gas determinations in selected intensive care patients. However, this procedure is not without risk. We report a case of localized Osler node formation, distal to a radial artery catheter, associated with sepsis, pseudoaneurysm formation, and thrombosis at the site of catheterization. Complications of this technique require aggressive medical and, in selected cases, surgical intervention.

Adult↗

Two new X-autosome translocations in the mouse.

The reciprocal translocations T(X;4)37H and T(X;11)38H were induced by acute X-irradiation of spermatozoa. Male heterozygotes are completely aspermic with a spermatogenic block at pachytene and testis masses about one third of normal, though metaphase I is very occasionally reached in T37H. For both translocations the X chromosome breakpoints are in band XA2, and the autosomal breakpoints are in 4D3 for T37H and 11E1 for T38H, leading to long and short marker chromosomes. Chain quadrivalents predominated in oocytes at MI, with no rings; there were 32% trivalent + univalent configurations in T37H and 40% in T38H. These generated (1) XO mice, (2) tertiary trisomics carrying 20 bivalents and the small X4 (T37H) or X11 (T38H) markers. These trisomics were apparently lethal in T37H but sub-viable in T38H and sometimes fertile as XX11 and trisomic XXX11 females, though sterile as XX11Y males. However, many developed exencephaly in utero, probably because of the distal duplication on chromosome 11. No tertiary monosomics were found in 12 to 14 day embryos. Seven percent of all female progeny were XO, with a higher than expected frequency in T37H and a lower than expected one in T38H. T37H is about two units and T38H about five units from the spf locus on the X chromosome with evidence for some crossover suppression between the T38H breakpoint and Ta. Autosomal linkages found were T37H-m-b (R.F. of 16 +/- 4% between T37H and m) and T38H-Rewc (R.F. of 5 +/- 3%). T37H/+ females weighed about 10% less than normal females at birth and about 30% less at weaning; there was little if any effect in T38H/+ females or in males carrying either translocation. Neither translocation had any marked effect on viability. T37H/+ females showed variegation when heterozygous for b with the wild type allele in the long 4X marker. On average, about 20% of the coat was brown rather than black. However, no clear evidence for m variegation was found.

Animals↗

A male-sterile insertion in the mouse.

Is(7;1)40H was found in the daughter of a male mouse given spermatozoal X-irradiation. It is a non-inverted insertion of about half of chromosome 7 into chromosome 1, generating a long somatic marker chromosome. Breakpoints are in bands 1B, 7B1, and 7F1; linkage tests show that these breakpoints are about midway between fz and In on the 1, and 0.2 units distal to ru-2 and 12 units proximal to fr on the 7. Female carriers had litters of about one-third normal size and showed some decline in length of reproductive life. Males were sterile, with testis weights only 30% of normal and with abrupt cessation of spermatogenesis in pachytene at stage IV of the seminiferous epithelial cycle. Positive sex-vesicle contact with the insertional configuration was found in only 40% of pachytene spermatocytes, which suggested that other factors may be involved in the spermatogonial breakdown. In oocytes at metaphase I 76% of insertion configurations were multivalent, because of one or more chiasmata in the inserted segment, as were 79% of synaptonemal complex configurations in male pachytenes. Karyotyping at 12.5 to 14.5 days of gestation showed that all embryos with duplications of the inserted segment were exencephalic, and the only example of a corresponding deficiency was retarded. Analysis of the consequences of heterozygosity for the insertion shows that the insertion length should be correlated with the frequency of unbalanced offspring and thus with the amount of F1 lethality. The genetic length of 36 cM estimated in this way from data on liveborn offspring is in reasonable agreement with estimates from cytological measurements and meiotic configurations but rather higher than that from linkage tests.

Animals↗

Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays.

Female mice were exposed to varying absorbed doses (108-504 rad) of X-rays and mated at different intervals after irradiation (1-7, 8-14, 15-21 and 22-28 days). Uterine contents were examined at late pregnancy in order to detect early fetal deaths (dominant lethality) and malformations in the live fetuses. Two trends were apparent from data on abnormal fetuses. At each weekly interval, the incidence of abnormalities tended to rise with increase in dose, and, at any given dose, the incidence tended to increase with time after irradiation. Dwarfism and exencephaly were the two most common malformations found. The changes in incidence of dominant lethality and of abnormal fetuses with time and with dose follow each other closely, the highest incidence for both being reached in week 3 (59 +/- 4.7% for dominant lethals and 12.5 +/- 3.1% for abnormal fetuses, after 504 rad) indicating increased radiosensitivity of less mature oocytes. These results parallel those obtained from known genetic effects reported by other workers and suggest that testing for incidence of congenital malformations among offspring of treated animals may prove a useful means of assessing genetic hazards of radiation or chemicals.

Abnormalities, Radiation-Induced↗

Interneurons of the crayfish brain: the relationship between dendrite location and afferent input.

This study was undertaken to examine the relationship between the structure and function of the descending interneurons of the crayfish brain. In particular, the dendritic fields were examined to ascertain if the location of an interneuronal dendrite in any of the six cerebral hemineuromeres (which subserve specific sensory modalities) is a necessary or sufficient condition to determine the functional and/or synaptic input to the interneuron. If a neuron projects a dendrite to a hemineuromere of the deutocerebrum or tritocerebrum, the neuron derives sensory input from the corresponding afferent root in 95% of our observations. Most of these inputs (86%) contain at the least a monosynaptic component. Conversely, if a cell derives monosynaptic input from any one of three of the four deutocerebral and tritocerebral roots tested, it has a corresponding dendrite (in 98% of our observations) in the appropriate hemineuromere. Input from the contralateral antennal nerve is an exception to this rule. The presence of a dendrite in the protocerebrum is not sufficient for predicting detectable visual input, but every instance of detectable visual input is associated with a protocerebral dendrite. Polysynaptic inputs are frequently (42%) not associated with corresponding dendrites. In neurons that were repeatedly dye filled in different animals, we observed significant variation only in the number and precise location of the smaller secondary and tertiary neurites. This variation rarely influenced the subset of sensory lobes innervated by the neuron.

Afferent Pathways↗

SOS induction and autoregulation of the himA gene for site-specific recombination in Escherichia coli.

The himA gene of EScherichia coli controls the lysogenization of bacteriophage lambda at the level of catalysis of site-specific recombination and expression of the lambda int and cI genes required for lysogenic development. We have analyzed the regulation of himA by two methods: (i) beta-galactosidase synthesis from a lacZ gene inserted into the himA gene and (ii) detection of radioactive HimA protein after fractionation by two-dimensional gel electrophoresis. We find that himA- mutations produce enhanced expression of the himA gene, indicating that HimA protein controls its own synthesis. The himA gene is also induced by treatment of cells with UV or mitomycin C, suggesting control by the inducible DNA repair (SOS) system regulated by the LexA and RecA proteins. Regulation of himA follows the pattern expected for a typical SOS gene: constitutive high expression in mutants that have inactive LexA or the altered RecA conferred by the recA441 (tif1) mutation and low noninducible expression in a mutant that has a deleted recA gene. We conclude that the himA gene is a component of the inducible SoS response, repressed by LexA and induced by the capacity of activated RecA to cleave LexA. We suggest that HimA may be subject to SOS induction because it functions as an "acquisitionase" for new genetic material and thus is of special utility under conditions of impaired capacity for growth of the bacterial population.

Coliphages↗

Reduction of oxygen by the electron transport chain of chloroplasts during assimilation of carbon dioxide.

In photosynthetically competent chloroplasts from spinach the quantum requirements for oxygen evolution during CO2 reduction were higher, by a factor often close to 1.5, than for oxygen evolution during reduction of phosphoglycerate. Mass spectrometer experiments performed under rate-limiting light indicated that an oxygen-reducing photoreaction was responsible for the consumption of extra quanta during carbon dioxide assimilation. Uptake of 18O2 during reduction of CO2 was considerably higher than could be accounted for by oxygen consumption during glycolate formation and by the Mehler reaction of broken chloroplasts which were present in the preparations of intact chloroplasts. The oxygen reducing reaction occurring during CO2 assimilation resulted in the formation of H2O2. This was indicated by a large stimulation of CO2 reduction by catalase, but not of phosphoglycerate reduction. Catalase could be replaced as a stimulant of photosynthesis by dithiothreitol or ascorbate, compounds known to react with superoxide radicals. There was no effect of dithiothreitol and ascorbate on phosphoglycerate reduction. A main effect of superoxide radicals and/or H2O2 was shown to be at the level of phosphoglycerate formation. Evidence for electron transport of oxygen was also obtained from 14CO2 experiments. The oxidation of dihydroxyacetonephosphate during a dark period or after addition of carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone in the light was studied. The results indicated a link between the chloroplast pyridine nucleotide system and oxygen. Oxygen reduction during photosynthesis under conditions where light is rate limiting is seen as important in supplying the ATP which is needed for CO2 reduction but is not provided during electron transport to NADP. A mechanism is discussed which would permit proper distribution of electrons between CO2 and oxygen during photosynthesis.

Carbon Dioxide↗

Sequence of Formation of Phosphoglycolate and Glycolate in Photosynthesizing Chlorella pyrenoidosa.

In Chlorella pyrenoidosa which have been photosynthesizing in either 1.5% (14)CO(2) or 0.05% (14)CO(2) in air, gassing with 100% O(2) results in rapid formation of phosphoglycolate which is apparently converted to glycolate. However, only about one-third to one-half of the rate of glycolate formation can be accounted for by this route. The remaining glycolate formation may be the result of the oxidation of sugar monophosphates. The rates of formation of both glycolate and phosphoglycolate are about four times greater with algae that have been photosynthesizing in 1.5% (14)CO(2) than with algae which have been photosynthesizing with air, when the algae are then gassed with 100% O(2).

Journal Article↗