The role of smell, taste, flavour and texture cues in the identification of vegetables.

It has been shown that the identification of many foods including vegetables based on flavour cues is often difficult. The effect of providing texture cues in addition to flavour cues on the identification of foods and the effect of providing taste cues only on the identification of foods have not been studied. The aim of this study was to assess the role of smell, taste, flavour and texture cues in the identification of ten vegetables commonly consumed in The Netherlands (broccoli, cauliflower, French bean, leek, bell pepper, carrot, cucumber, iceberg lettuce, onion and tomato). Subjects (n = 194) were randomly assigned to one of four test conditions which differed in the sensory cues available for vegetable identification: taste, smell (orthonasal), flavour (taste and smell) and flavour-texture (taste, smell and texture). Blindfolded subjects were asked to identify the vegetable from a list of 24 vegetables. Identification was the highest in the flavour-texture condition (87.5%). Identification was significantly lower in the flavour condition (62.8%). Identification was the lowest when only taste cues (38.3%) or only smell cues (39.4%) were provided. For four raw vegetables (carrot, cucumber, onion and tomato) providing texture cues in addition to flavour cues did not significantly change identification suggesting that flavour cues were sufficient to identify these vegetables. Identification frequency increased for all vegetables when perceived intensity of the smell, taste or flavour cue increased. We conclude that providing flavour cues (taste and smell) increases identification compared to only taste or only smell cues, combined flavour and texture cues are needed for the identification of many vegetables commonly consumed in The Netherlands.

Conserved proline residues prevent dimerization and aggregation in the ß-lactamase BlaC.

Evolution leads to conservation of amino acid residues in protein families. Conserved proline residues are usually considered to ensure the correct folding and to stabilize the three-dimensional structure. Surprisingly, proline residues that are highly conserved in class A ß-lactamases were found to tolerate various substitutions without large losses in enzyme activity. We investigated the roles of three conserved prolines at positions 107, 226, and 258 in the ß-lactamase BlaC from Mycobacterium tuberculosis and found that mutations can lead to dimerization of the enzyme and an overall less stable protein that is prone to aggregate over time. For the variant Pro107Thr, the crystal structure shows dimer formation resembling domain swapping. It is concluded that the proline substitutions loosen the structure, enhancing multimerization. Even though the enzyme does not lose its properties without the conserved proline residues, the prolines ensure the long-term structural integrity of the enzyme.

[Acute abdomen caused by a large vesical cystine calculus]. / Acute buik veroorzaakt door een grote cystineblaassteen.

A 73-year-old man underwent an emergency laparotomy because of acute abdominal pain and a palpable mass in the lower abdomen. A giant vesical calculus was found which had perforated the bladder, small intestine and sigmoid colon due to pressure necrosis. The stone had a length of 11.5 cm and weighed 1280 g. Further analysis revealed benign prostate hyperplasia, bladder diverticula and cystinuria as underlying causes. Initial therapy consisted of stone removal, partial bladder resection, a Hartmann procedure and partial resection of the small intestine. Secondarily, lifestyle advice was given and transurethral resection of the prostate followed later.

Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.

The effect of hematoporphyrin derivative photoradiation on tumor and normal tissue microcirculation was studied microscopically in vivo on rats with mammary carcinomas transplanted into subcutis in transparent observation chambers. One day after i.p. injection of hematoporphyrin derivative (15 mg/kg), chambers were exposed to red light (632 +/- 2 nm, eight light dose values, 0 to 270 J/cm2). After an initial blanching (ischemia) of the tumor accompanied by apparent vasoconstriction, reperfusion was observed with a slowing down of the tumor circulation, vasodilatation, and eventually a complete stasis, together with diffuse hemorrhages and subsequent necrosis. Besides, in large normal tissue vessels, platelet aggregates were observed, but no hemorrhage. Tumor regrowth occurred unless the tumor circulation and the adjacent normal tissue circulation were both destroyed. Tumor cell viability after treatment was assessed by transplanting the tumor from the chamber into the flank of the same animal. Even after a combined porphyrin and light dose 4 times the lethal dose for all tissues in the chamber, five of five transplanted tumors did regrow. This leads to the conclusion that, in our model system, tumor cell death after photoradiation occurs secondary to destruction of the microcirculation. In order to obtain additional information on normal tissue damage, rat ears were also irradiated. For the same light dose, the biological effect was only slightly larger than that of the normal tissue in the observation chambers, even though the measured ratio of porphyrin concentrations in ears and normal tissue in the chambers (subcutis) was about six.

[Disorders of concentration and memory in young adults and middle-aged persons]. / Concentratie- en geheugenstoornissen op jongvolwassen en middelbare leeftijd.

Four patients, two women aged 29 and 52 and two men aged 46 and 25, respectively, consulted a neurologist for attention and memory disorders. Further investigation revealed that the symptoms were caused by metachromatic leucodystrophy, Graves' disease, Huntington's disease, and a psychological background, respectively. The first patient became dependent in 1.5 years, the second recovered after treatment, the third was independent with slowly progressive symptoms after 1 year, and the fourth was advised to consult a psychologist. Disorders of attention and memory in relatively young people deserve a detailed evaluation at the very first visit, involving the elaboration of an initially extensive differential diagnosis. Too early a separation between a psychic and an organic pathogenesis should be avoided. Indications for the presence of a neurological condition include: consultation at the initiative of others, a relatively brief duration of symptoms without a clear provoking factor, the absence of a psychiatric history or life event, cognitive dysfunction in several areas, abnormal behaviour and an incriminating family history.

Dose-effect relationships for glucose-induced tumour acidification and its erythrocyte flux.

Preclinical investigations were performed with glucose administration in WAG/Rij rats carrying the rhabdomyosarcoma BA1112 in two sites per animal: one in the subcutis of the flank (for pH measurements in the tumour tissue) and one in the transparent "sandwich" chamber for measuring the erythrocyte flux in the tumour tissue as an indication for changes in tumour blood flow. A glucose solution (20%) was slowly infused intravenously in a range of dose levels, similar to those reported for inducing long-term hyperglycaemia in man. The eventual aim of such investigations is to sensitise tumours for hyperthermic treatment. This approach is not new, but the present experiments were performed with the aim to explore the level of the minimal amount of glucose which would nonetheless yield a likely therapeutic effect. Endpoints in this study were the blood glucose level and pH and the relative erythrocyte flux in the tumour tissue. Obviously, as one would expect, many significant changes in the various parameters were found as a response to administration of glucose. However, the changes in the blood glucose level, the induced decrease in tumour pH and the influence of the tumour volume did not show a well-defined relationship which was reliable enough to predict the exact influence of the various parameters on the magnitude of the desired changes in individual animals and/or tumours. This was probably caused by interfering differences in physiological feedback mechanisms. Nonetheless, the data indicate that the optimal effect was not obtained with the highest treatment level, but with moderate doses of glucose, i.e. 2.4-3 g.kg/h which induced a satisfactory tumour acidification of 0.25 pH units. This may turn out to a clinically useful pH drop for enhancing the cytotoxic effect of hyperthermia. The erythrocyte flux through the tumour tissue does not appear to be influenced to a sizeable extent by such a treatment.

A moderate elevation of blood glucose level increases the effectiveness of thermoradiotherapy in a rat tumor model. I. Relative contributions of glucose and heating to tumor acidification.

PURPOSE: To establish dose-effect relationships for tumor acidification induced by heat and glucose as a basis for testing the value of adding glucose administration to combined heat and x-ray treatment at clinically achievable glucose and temperature levels. METHODS AND MATERIALS: Rhabdomyosarcoma BA1112 was grown s.c. in the upper leg of 16-20-week-old Wag/Rij rats. Animals were given 2 consecutive 100-min periods of saline (S) or glucose (G) infusion, while keeping tumor temperature at 37 degrees, 42 degrees, or 43 degrees C for 1 or 2 periods, in various combinations, each involving 6 animals. Glucose was infused i.v. as a 20% solution at 2.4-3 g/kg/h. Tumors were heated using 2,450-MHz electromagnetic radiation, and tumor pH was measured using a 0.7 mm fiberoptic probe. RESULTS: Mean overall baseline pH was 7.00 (SD 0.10). The change induced by G37G43 (i.e., glucose infusion for a full 200 min, first 100 min at 37 degrees C, final 100 min at 43 degrees C) was -0.48 +/- 0.03 (SEM) pH units, and -0.17 +/- 0.03 for S37S43. The effect of G37G42 was -0.37 +/- 0.03 pH units, compared with -0.08 +/- 0.02 for S37S42 and -0.28 +/- 0.04 for glucose alone (G37G37). Glucose was less effective when given after or fully parallel to heating: -0.21 +/- 0.02 pH units for S43G37 and -0.37 +/- 0.02 for G43G43. CONCLUSION: The glucose-induced tumor pH drop is much more pronounced than that induced by heat, both of which are dose dependent. The effects of glucose and heat seem additive if heating is started when glucose-induced acidification has reached its plateau level, but the overall effect is diminished if administration is fully simultaneous or in reversed order. Schedule G37G43 is optimal with respect to tumor acidification. Its predicted superiority in thermoradiotherapy as compared with S37S42, S37S43, and G37G42 treatment regimens was confirmed in a subsequent experimental tumor control study.

A moderate elevation of blood glucose level increases the effectiveness of thermoradiotherapy in a rat tumor model II. Improved tumor control at clinically achievable temperatures.

PURPOSE: To assess the therapeutic gain (at the TCD(50) level) that can be obtained by boosting thermoradiotherapy with intravenous glucose infusion at different temperatures. This completes our series of studies to determine the optimal conditions and the effectiveness of glucose administration at clinically achievable glucose levels and treatment temperatures. METHODS AND MATERIALS: Subcutaneous rat rhabdomyosarcoma BA1112 was irradiated with graded single doses of 300-kV X-rays (dose range 0-60 Gy). Fifteen minutes after irradiation, a 100-min intravenous infusion was started, consisting of either glucose (20% solution, 2.4-3 g/kg/h) or saline as a control. Then heat was applied to the tumors at 42 degrees C or 43 degrees C (water bath) during a subsequent 100-min period of infusion. Tumor control was scored as the absence of palpable growth at 100 days after treatment. RESULTS: Glucose infusion enhanced tumor control independent of temperature in the range 42-43 degrees C. At 42 degrees C, the TCD(50) for X-irradiation decreased by 5.9 Gy (SEM 1.8 Gy), from 41.6 (1.6) to 35.7 (1.5) Gy, and at 43 degrees C from 33.3 (1.6) to 27.3 (1.5) Gy, representing a glucose enhancement ratio of approximately 1.2. At doses corresponding to the TCD(50) at either 42 or 43 degrees C, the addition of glucose increased tumor control from 50% to 70%. An enhancement ratio of 2.1 was found for the combination of irradiation, glucose infusion, and heating at 43 degrees C, with respect to irradiation alone (TCD(50) 56.3 Gy, reanalyzed earlier data). The contribution of combined heat and glucose to tumor control represented an additive effect, probably on the hypoxic cell population. CONCLUSION: Moderate glucose administration (blood concentration 300 mg/100 mL) sizably improves experimental tumor control after combined X-irradiation and hyperthermia under clinically feasible conditions. Clinical treatment should benefit from this additional modality, in particular if unsatisfactory local control rates are due to insufficient heating. The therapeutic gain has to be evaluated further in clinical studies.

The efferent connections of the nuclei of the descending trigeminal tract in the mallard (Anas platyrhynchos L.).

The efferent and intranuclear connections of the nuclei of the descending trigeminal tract of the mallard have been studied with lesion methods, and by axonal transport techniques following injections of tritiated leucine, and of horseradish peroxidase. The large subnucleus oralis neurons, including those belonging to the nucleus of the ascending glossopharyngeal tract, have proven to be the sole origin of trigeminocerebellar connections. The cerebellar afferents are of the mossy fiber type, and terminate predominantly in lobules V, VI and VII, and possibly, lobule IV. Trigeminocerebellar projections are ipsilateral except for the vermal area. Subnucleus interpolaris is the main source of intratrigeminal fibers that terminate in subnucleus oralis and the ventral part of the main sensory nucleus. These intranuclear connections are bilateral, but the medium-celled caudal part of subnucleus interpolaris in particular contains the majority of bi- and/or contralaterally projecting neurons. Additionally, the small cells in the rostral part of subnucleus interpolaris project ipsilaterally upon the parabrachial region, and upon the lateral reticular formation. Projections upon the parabrachial region furthermore emanate bilaterally from layer I of the rostral subnucleus caudalis. A minor part of layer I neurons sends its axons contralaterally along with those of the dorsal column nuclei toward the thalamic nucleus dorsolateralis posterior. Associated with the medial lemniscus, contralateral termination is also present in the lateral part of the ventral lamella of oliva caudalis, in the marginal zone of nucleus mesencephalicus lateralis, pars dorsalis and immediately surrounding intercollicular grey and, finally, in the nucleus intercalatus thalami. Furthermore, a bilaterally descending projection from subnucleus caudalis upon layers I and II of the rostral cervical cord was observed. Close to their origin subnucleus caudalis neurons project upon the adjoining caudal part of the lateral reticular formation.

Characteristics of IgA deposits in liver and skin of patients with liver disease.

The presence of IgA deposits in a continuous pattern along hepatic sinusoids is a specific entity for alcoholic liver disease. In superficial skin blood vessels of patients with liver disease, IgA deposits can occur. The authors characterized the deposits for IgA-subclass epitope expression and for macromolecular configuration (assessment of [hidden] J-chain determinants and of secretory component-binding capacity). A variety of monoclonal anti-IgA-subclass reagents were applied, which proved to be specific in control experiments on blastoid cells generated by pokeweed mitogen stimulation of blood mononuclear cells and frozen tissue sections of normal jejunum. IgA1 is the major component in IgA deposits in liver (n = 83) and skin (n = 31) of patients with liver disease. Macromolecular IgA is detectable in only one-fifth of the cases. The authors' data do not indicate that hepatic IgA deposits in liver disease are of gastrointestinal origin. Out of the circulating IgA pool, IgA1 appears to be most capable of being deposited in tissue.

Tissue-localizing properties of some photosensitizers studied by in vivo fluorescence imaging.

Using fluorescence imaging, the tissue-localizing properties of five photosensitizers were studied in vivo in tumours in 'sandwich' observation chambers and in tumours growing on thigh muscle. The preliminary results indicate that of the three photodynamically active dyes tested (haematoporphyrin derivative, Photofrin II and aluminium phthalocyanine tetrasulphonate), the phthalocyanine possesses the best tumour-localizing properties. This makes it possible to combine tumour fluorescence detection and photodynamic therapy with reduced skin photosensitivity. The two photodynamically inactive dyes tested (uroporphyrin I and acridine red) may be useful for application in fluorescence imaging to localize superficial tumours without inducing skin photosensitivity. In particular, acridine red has remarkable tumour-localizing properties, but is rather toxic.

Use of cytomorphometry and cytology in the diagnosis of transitional-cell carcinoma of the upper urinary tract.

Because of the rise in incidence of upper urinary tract tumors, there is a need for a simple and reliable method for diagnosing these tumors, especially in people in a "high-risk" group. This retrospective study showed the usefulness of cytology and cytomorphometry in making the diagnosis of transitional-cell carcinoma of the upper urinary tract. The study also emphasized that the methods of collection and processing are of the utmost importance: the cytologic evaluation of ureteral catheterized urine specimens gave 100% accuracy as compared with a 40% false-negative rate in the cytologic diagnosis of voided urine specimens. A higher accuracy of urinary cytology for the diagnosis of upper urinary tract lesions clearly requires selective catheterization of the ureter. Objective cytomorphologic grading of the urinary cytology specimens was shown to compare favorably with histologic grading. Cytomorphologic grading not only can offer important information in determining the prognosis and in planning treatment but can also assist in quality control of other diagnostic methods and can help to resolve apparent diagnostic discrepancies.

Factors influencing the neovascularization of experimental tumours.

When experimental tumours are inoculated into a host animal, the tumour growth depends, among other things, on its vascular supply. This vascular supply has been shown to be initiated by substances released by the tumour tissue, and vascular sprouting towards implanted tumour substances has been extensively demonstrated in nonvascular tissue. Most tissues, however, already contain a vascular supply sufficient for their own needs. In such conditions, the host vascular system is probably incorporated into the tumour without much vascular sprouting. It is well known that, as a tumour grows larger, the center tends to become ischaemic and necrotic. It is not clear why the tumour vascularity does not respond to this development with reactive vascular proliferation, but increased interstitial tissue pressure and impaired fluid transport may be implicated.

Renal dysplasia in three young adult Dutch kooiker dogs.

Chronic renal failure as consequence of renal dysplasia was diagnosed in three young adult Dutch kooiker dogs (Dutch decoy dogs). Two animals were anorectic from an early age and were thinner than healthy dogs of the same breed. All three were presented because of apathy and weakness. Laboratory examination revealed anaemia and uraemia. One dog was presented with severe dehydration and died during emergency treatment. One dog was euthanatised because of a poor prognosis, and one was given a low-protein diet. This dog survived for 7 months after the diagnosis of chronic renal failure. At necropsy all three animals had shrunken, pale, and firm kidneys that showed microscopical lesions characteristic of canine renal dysplasia, such as asynchronous differentiation of nephrons, persistent immature mesenchyme, persistent metanephric ducts, and adenomatoid proliferation of the tubular epithelium. Secondary degenerative and inflammatory changes consisted of interstitial fibrosis and predominantly lymphocytic/plasmacytic inflammation. This is the first report of renal dysplasia in the Dutch kooiker dog. The disease should be included in the differential diagnosis in young Dutch kooiker dogs with signs of chronic renal failure. The presentation of three cases of this rare disease in this breed, which is based on a rather small gene pool, suggests that it is a familial or hereditary nephropathy.

[The immunological aspects of primary chronic septic endocarditis in acquired heart defects. The treatment approaches]. / Immunologicheskie aspekty pervychnogo khronicheskogo septicheskogo éndokardita na fone priobretennykh porokov serdtsa. Podkhody k lecheniiu.

A total of 266 patients with degree I primary chronic septic endocarditis concurrent with acquired heart disease and 101 apparently healthy subjects were examined. The patients were found to have scarce T helper cells and higher levels of T suppressors (quite the reverse in some patients), decreased proliferative responses of T and B cells and normal levels of circulating immune complexes. It was conceived that there was a block in the synthesis of specific antibodies and a decrease in their affinity. It was proposed that cytokine (enzyme) genes (initiators or repressors) should be exposed at intervals as immunomodulating therapy of immune diseases, as well as in some hereditary diseases.