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Biomedical subjects

W Kohler

Publications and source records attributed to W Kohler.

At least 19 recordsLinked to original sources
PubMed2000

Thermal diffusion and soret feedback of gold-doped polyorganosiloxane nanospheres in toluene

We have investigated diffusion and thermal diffusion properties of light-absorbing colloidal polyorganosiloxane microgels containing tiny nanometer-sized gold clusters dispersed in toluene. Transient holographic gratings allow for very subtle perturbations in the linear regime where Soret feedback is negligible. Gold-doped colloids of different size and crosslink ratios show different Soret coefficients but identical thermal diffusion coefficients D(T). Undoped colloids tend to aggregate, but a consistent interpretation is obtained if an identical D(T) is assumed for the doped, the undoped, and the aggregated particles. Previously reported Soret feedback measurements on similar systems incidentally yielded comparable Soret coefficients. We show, however, that they suffer from strong convective perturbations.

Journal Article↗
PubMed1997

LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes.

N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl ]-benzoyl]-L-glutamic acid (LY231514) is a novel pyrrolo[2,3-d]pyrimidine-based antifolate currently undergoing extensive Phase II clinical trials. Previous studies have established that LY231514 and its synthetic gamma-polyglutamates (glu3 and glu5) exert potent inhibition against thymidylate synthase (TS). We now report that LY231514 and its polyglutamates also markedly inhibit other key folate-requiring enzymes, including dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). For example, the Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibition against TS, DHFR, and GARFT, respectively. In contrast, although a similar high level of inhibitory potency was observed for the parent monoglutamate against DHFR (7.0 nM), the inhibition constants (Ki) for the parent monoglutamate are significantly weaker for TS (109 nM) and GARFT (9,300 nM). The effects of LY231514 and its polyglutamates on aminoimidazole carboxamide ribonucleotide formyltransferase, 5,10-methylenetetrahydrofolate dehydrogenase, and 10-formyltetrahydrofolate synthetase were also evaluated. The end product reversal studies conducted in human cell lines further support the concept that multiple enzyme-inhibitory mechanisms are involved in cytotoxicity. The reversal pattern of LY231514 suggests that although TS may be a major site of action for LY231514 at concentrations near the IC50, higher concentrations can lead to inhibition of DHFR and/or other enzymes along the purine de novo pathway. Studies with mutant cell lines demonstrated that LY231514 requires polyglutamation and transport via the reduced folate carrier for cytotoxic potency. Therefore, our data suggest that LY231514 is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multiple inhibition of several key folate-requiring enzymes via its polyglutamated metabolites.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1997

[Fornix reconstruction in ocular pemphigoid with Goretex surgical membrane].

UNLABELLED: After separation of symblepharons in ocular pemphigoid, transplantation of nasal or bucal mucosa is recommended to prevent recurrent lid fusion; however, it is not always successful. BACKGROUND: An 86-year-old patient was referred to our eye clinic because of trichiasis in ocular pemphigoid. In the right eye, the only functional eye, fusion of the lower lid and the globe was present. There was severe trichiasis with multiple lesions of the cornea and beginning neovascularization. The left eye showed complete fusion of the lid fissure and neovascularization of the cornea. To prevent the right eye from suffering the fate of the left, we tried to find a simple surgical method that could easily be performed on the multimorbid patient. METHOD: Under parabulbar anesthesia we separated the lower lid from the globe until free passive motility of the lower lid was achieved. A cut-to-size piece of Gore-Tex surgical membrane was prepared and fixated with resorbable u-sutures on the inner lid. The membrane was left in place for 4 weeks until suture lysis. A silicone tube, which was transitorily fixed to the outer lower lid, had an additional ectropionizing effect. Three months later, lower-lid ectropion surgery was performed, combined with tarsectomy to obtain a long-term effect. RESULT: Six months later the lower-lid fornix had stabilized, and the lid and globe had good motility. The corneal lesions had healed. CONCLUSION: The use of 0.1 mm membrane prevents penetration of cell because of the microstructure. Similar to the "bare sclera" technique, which is used in selected cases in strabismus or pterygium surgery, the inner lid and sclera were epithelialized separately from the remaining conjunctiva. The surgical membrane prevented recurrence of the symblepharon. We think the presented technique is an easy, quick method of preventing recurrence of lid fusion after separation of symblepharons.

Aged↗
PubMed1996

bli-4, a gene that is rapidly induced by blue light, encodes a novel mitochondrial, short-chain alcohol dehydrogenase-like protein in Neurospora crassa.

Blue light plays an important role in developmental control throughout nature. The bli-4 gene of Neurospora crassa, together with bli-3, al-1 and al-2, is rapidly inducible by blue light. Induction leads to a ninety-fold increase in transcription rate over the dark control level, and the gene therefore appears to be of prime importance in the blue-light induction pathway of N. crassa. We describe the sequencing and analysis of bli-4 and the 38 kDa protein it encodes. We show that the protein is very rapidly imported into the mitochondria and exhibits high homology with the family of short-chain alcohol dehydrogenases.

Alcohol Dehydrogenase↗
PubMed1996

Purification and some properties of streptococcal NAD-glycohydrolase.

NAD-glycohydrolase (NADase) was purified from culture supernatant fluids of group C streptococci by adsorption on silica gel, chromatography on hydroxyapatite and ion exchange on Mono S column. After inactivation of a chymotrypsin-like protease, a homogeneous enzyme was isolated with an N-terminal sequence of VSGKEGKKSDVKYEMTKVMEANATSSKEDKHVMHTLDKVM. According to serological methods, the purified enzyme of group C streptococci was identical to the group A enzyme showing a specific activity of 10 000 000 U mg-1. It did not attack NADH, NADP or NADPH. In addition, a streptodornase was isolated having an N-terminal sequence of KTVSVNQTYGE.

Amino Acid Sequence↗
PubMed1996

Cognitive and brain magnetic resonance imaging findings in adrenomyeloneuropathy.

Neuropsychological functioning and brain magnetic resonance imaging (MRI) were evaluated in 84 men with adrenomyeloneuropathy (AMN). MRI was normal in 61%, the "pure AMN" group, while 39%, the "cerebral AMN" group, showed brain white matter abnormalities. Except for mild deficits in psychomotor speed and visual memory, neuropsychological function was normal in pure AMN. Most patients with cerebral AMN had normal IQ and language but evidenced impaired psychomotor speed, spatial cognition, memory, and executive functions. Patients with MRI evidence of very severe cerebral disease had global and language impairment as well, and deficits in all patients were highly correlated with degree of brain MRI involvement.

Adrenoleukodystrophy↗
PubMed1996

Kinetics and regulation of erythrogenic toxins type A and C during growth of Streptococcus pyogenes.

The production of erythrogenic toxins type A (ETA) and C (ETC) is described as a function of growth kinetics. Group A streptococcal strains C 203 S and NY 5 were cultivated in yeast-peptone extract, Todd-Hewitt medium and a synthetic medium. Two main growth phases occurred during growth: a first logarithmic phase and a second linear phase. These phases were separated by a short stationary interphase caused by limitation of the amino acids L-serine and L-leucine. Maximum production of ETC was observed during the logarithmic phase, it was correlated to a high level of viable cells. ETA was produced mainly during the short stationary interphase. The production of ETC is regulated by L-isoleucine. A stagnation or reduction of the concentration of viable cells was observed during the interphase. The phosphate limitation caused during streptococcal growth induced expression of the extracellular protein phosphatase and surprisingly, of a serine proteinase activity. The association between these results and the pathogenicity of streptococci is discussed.

Acid Phosphatase↗
PubMed1993

Prothymosin alpha gene expression correlates with proliferation, not differentiation, of HL-60 cells.

Accumulating evidence suggests that prothymosin alpha has an as yet undefined intracellular, perhaps intranuclear, function related to cell proliferation. Prothymosin alpha mRNA and/or peptide levels increase when cells are stimulated to proliferate. Because proliferation and differentiation events are often inversely correlated, we examined prothymosin alpha gene expression during proliferation and differentiation of HL-60 myeloid leukemia cells. Steady-state levels of prothymosin alpha mRNA, which are high in exponentially growing HL-60, decrease within hours after induction of HL-60 to differentiate along the neutrophil pathway with dimethylsulfoxide (DMSO) or along the macrophage lineage with either tetradecanoylphorbol acetate (TPA) or bryostatin 1. The decline in prothymosin alpha mRNA in response to these differentiation signals parallels that of c-myc mRNA under the same conditions. We then determined whether the downregulation of prothymosin alpha and c-myc mRNA were due to differentiation or cessation or proliferation. Recombinant human gamma-interferon induces monocytic differentiation of HL-60, but permits continued proliferation, and, under these conditions, expression of prothymosin alpha, as well as of c-myc, mRNA remains elevated. We conclude that prothymosin alpha and c-myc expression are coregulated in differentiating HL-60 and that their expression correlates with the proliferative state of HL-60 cells, rather than with the differentiated state.

Cell Differentiation↗
PubMed1992

Light and the recovery from heat shock induce the synthesis of 38 kDa mitochondrial proteins in Neurospora crassa.

The effect of light on the protein synthesis pattern in the mitochondria of Neurospora crassa was examined by in vivo labelling with [35S]-methionine and two-dimensional gel electrophoresis. A brief 5-min illumination induced the rapid and transient synthesis of a 38-kDa protein. White collar-mutants were not stimulated to synthesize this protein by light. A protein of a similar molecular weight and isoelectrical point was synthesized during recovery from heat shock.

Autoradiography↗
PubMed1992

Streptococcal toxic shock syndrome in children.

Two children with toxic shock-like syndrome due to streptococcal infection are reported. In both cases (one fatal) the site of infection was in the soft tissues. Both strains of group A hemolytic streptococci isolated from blood culture produced large amounts of erythrogenic toxin B (ET B) small amounts of ET C but no ET A. This report confirms the implication of Streptococcus pyogenes in toxic shock like syndromes. When ET A seems to be responsible for most cases observed in the USA, our cases and others observed in Europe could be related to strains producing large amounts of ET B.

Child↗
PubMed1992

[Scapula fractures--classification and differential therapy].

The classification of fractures of the scapula (type A: body and process fractures; type B: neck fractures; type C: glenoid fractures) is shown, and the indications for conservative and operative treatment are described, as are the surgical approaches and operative techniques. In our hospital, 93 patients with 153 fractures of the scapula type A, B or C (ratio 1.6:1) were treated. This ratio was 1.7:1 in patients treated by operation. The indication for operation was usually glenoid fractures with accessory process fractures.

Adolescent↗
PubMed1991

[Diseases and causes of death in native wild birds--a literature review].

Little attention was dedicated to diseases and causes of death of indigenous wild birds compared to poultry until recent decades. The interest of veterinary medicine in the spectrum of causes of morbidity and mortality of wild birds increased with the understanding of the importance of these birds as vectors in the epidemiology of zoonoses and as a biological indicator for the occurrence of substances noxious for the environment. The climate as a natural factor and the influences of civilization as traffic, high voltage lines and oil contamination of the sea lead to a reduction of bird species by starvation, traumata, intoxication and degenerative or proliferative and inflammatory or non inflammatory processes. Many parasitological, bacteriological, mycotic and viral diseases are wide spread among free living birds and make difficulties in keeping and breeding endangered birds.

Animals↗
PubMed1990

On the role of Ca2(+)-calmodulin-dependent and cAMP-dependent protein phosphorylation in the circadian rhythm of Neurospora crassa.

Pulses of some Ca2+ channel blockers (dantrolene, Co2+, nifedipine) and calmodulin inhibitors (chlorpromazine) lead to medium (maximally 5-9 h) phase shifts of the circadian conidiation rhythm of Neurospora crassa. Pulses of high Ca2+, or of low Ca2+, a Ca2+ ionophore (A23187) together with Ca2+, and other Ca2+ channel blockers (La3+, diltiazem), however, caused only minor phase shifts. The effect of these substances (A 23187) and of different temperatures on the Ca2+ release from isolated vacuoles was analyzed by using the fluorescent dye Fura-2. A 23187 and higher temperatures increased the release drastically, whereas dantrolene decreased the permeation of Ca2+ (Cornelius et al., 1989). Pulses of 8-PCTP-cAMP, IBMX and of the cAMP antagonist RP-cAMPS, also caused medium (maximally 6-9 h) phase shifts of the conidiation rhythm. The phase response curve of the agonist was almost 180 degrees out of phase with the antagonist PRC. In spite of some variability in the PRCs of these series of experiments all showed maximal shifts during ct 0-12. The variability of the response may be due to circadian changes in the activity of phosphodiesterases: After adding cAMP to mycelial extracts HPLC analysis of cAMP metabolites showed significant differences during a circadian period with a maximum at ct 0. Protein phosphorylation was tested mainly in an in vitro phosphorylation system (with 35S-thio gamma-ATP). The results showed circadian rhythmic changes predominantly in proteins of 47/48 kDa. Substances and treatments causing phase-shifts of the conidiation rhythm also caused changes in the phosphorylation of these proteins: an increase was observed when Ca2+ or cAMP were added, whereas a decrease occurred upon addition of a calmodulin inhibitor (TFP) or pretreatment of the mycelia with higher (42 degrees C) temperatures. Altogether, the results indicate that Ca2(+)-calmodulin-dependent and cAMP-dependent processes play an important, but perhaps not essential, role in the clock mechanism of Neurospora. Ca2+ calmodulin and the phosphorylation state of the 47/48-kDa proteins may have controlling or essential functions for this mechanism.

Calcium↗
PubMed1990

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation.

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

Adolescent↗