Surface organization of orientation and direction selectivity in cat area 18

Two-dimensional maps of orientation and direction preference were made in area 18 of the cat's visual cortex using multiple electrode penetrations 150-300 micron apart. The maps were then analyzed by autocorrelation and Fourier transformation. The power spectrum of the orientation map was sharply peaked below the theoretical cutoff frequency for the sampling function (the pattern of electrode penetrations) used to obtain the map. This suggested that it would be possible to interpolate orientation values between the sample points in the cortex. This was done and the resulting fine-grain maps of orientation preference were studied. Empirical testing showed that the interpolated orientation values were accurate to within +/- 30 degrees. Study of the fine-grain maps showed that iso-orientation domains for broad orientation ranges (0 degrees-90 degrees) were branching bands running from an anterolateral to a posteromedial direction across the surface of the cortex with a periodicity of 1.25 +/- 0.13 mm. Domains for smaller orientation ranges (0 degrees-30 degrees) were periodically spaced, but somewhat irregularly shaped patches. The orientation maps contained numerous point singularities where orientation changed discontinuously. These were spaced about 750 micron apart and most were surrounded by a single 180 degrees cycle of orientations. Autocorrelation analysis of the maps of preferred direction revealed local clustering that extended over a distance of 250-300 micron, but spectral analysis failed to reveal any evidence of periodicity. The absence of periodicity was probably due to a relatively large number of 180 degrees reversals in the map of direction preference, which do not affect the continuity of the orientation map and are not sufficiently numerous to destroy local continuity in the direction map. It is shown that the direction map, if it is to be as continuous as possible, must nevertheless contain lines across which direction preference reverses by 180 degrees. These lines run from one orientation singularity to another. Evidence that the direction map approaches this degree of continuity is presented.     

Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Regulation of the acid-labile subunit of the insulin-like growth factor ternary complex in patients with insulin-dependent diabetes mellitus and severe burns

OBJECTIVE Little information is available regarding the regulation of serum acid-labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin-like growth factor (IGF) ternary complex in children with untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients. DESIGN Serum samples were obtained from children with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtained from adult patients with severe burns who were on a continuous infusion of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under basal conditions, after a 1-week period of continuous insulin infusion, and after an additional week of insulin plus recombinant GH. PATIENTS Twenty children and adolescents with untreated IDDM, aged 1.2–16 years, and 6 young adult patients with severe burns aged 17–28 years were studied longitudinally. Control sera were obtained from age, sex and pubertal status matched subjects (for children with IDDM) and from fed healthy adults. MEASUREMENTS Serum insulin, GH, cortisol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment periods. RESULTS Serum ALS levels were lower in untreated children with IDDM (69 ± 6% of control children). Insulin therapy significantly increased serum ALS (79 ± 5%, P<0.05) in these children. Patients with severe burns also had lower serum ALS levels (79 ± 10% of control adults). After one week of insulin therapy serum ALS levels increased to 90 ± 15% of control values (P<0.05). Addition of GH to insulin therapy for another week did not significantly further increase serum ALS levels (95 ± 27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects and fourfold in burn subjects at the end of the study periods. There were no proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera. CONCLUSION Serum ALS levels were diminished in children with untreated IDDM and were partially restored after the initiation of insulin therapy. Serum ALS levels were also diminished in patients with severe burn injury and restored by insulin treatment. Addition of GH to insulin therapy did not significantly increase serum ALS levels over levels obtained during insulin therapy alone. These decreases in serum ALS were smaller than the decrease in serum IGF-I concentrations in both conditions, suggesting that IGF-I is the limiting factor for the ternary complex formation in the catabolic states. Insulin may regulate circulating ALS levels in catabolic states and helps to restore the IGF system.     

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m², using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm³ in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.     

Expression of the glutathione S-transferase placental form in human lung carcinomas

Expression of glutathione S-transferase placental form (GST-)in human lung carcinoma tissue taken at autopsy or biopsy wasinvestigated immunohistochemically. All of 34 cases of squamouscell carcinomas, including poorly, moderatelyand well-differentiatedexamples were shown to stain positively for GST-. Poorly differentiatedadenocarcinomas were, however, negatively stained (0/5 cases),while moderately and well differentiated adenocarcinomas werefound tostain with GST- at rates of 69% (9/13 cases) and 71%(5/7 cases), respectively. Six cases of small cell carcinomasexamined were all negative. The results indicate that GST- maybe a useful marker fornon-small cell type lung cancer, especiallysquamous cell carcinoma which is in agreement with findingsfor rat lung neoplastic lesions reported previously.     

Growth and Production of Steroid Saponin in Solanum aculeatissimum During One Vegetation Period

SOLANUM ACULEATISSIMUM (Solanaceae) plants, which were cultivated in the open field, were harvested once a month from June 1985 to January 1986. The growth matter and content of steroid saponins, aculeatiside A and B which are precursors of steroid hormones in root, were then measured in order to examine their seasonal variations during one vegetation period. The aerial parts of the plants died of chill and frost in January. In November the dry weight of root reached the maximum, and the content of steroid saponins was more than 10% and showed a maximum. The yield of steroid saponins per plant was greatest in November. These results suggest that November is the appropriate time for harvest, and that S. ACULEATISSIMUM can be more useful than the DIOSCOREA species which is now used as a source plant of steroid hormones.     

A cysteine-activated protease isolated from Todarodes pacificus squid degrades collagen below its denaturation temperature

Collagen purified from the mantle muscle of the Japanese common squid, Todarodes pacificus, showed autodegradation during incubation under acidic conditions at 25 degrees C, without the addition of exogenous enzymes. This suggests that the collagenolytic proteases bind to collagen tightly through the steps of collagen preparation. Collagenolytic activity also was detected in a crude extract of mantle muscle, and leupeptin and E-64 were observed to inhibit collagenolytic activity within the collagen fraction and muscle extract. We purified these collagenolytic cysteine proteases by leupeptin column chromatography and cellulose acetate membrane electrophoresis. Optimal enzymatic activity was observed at pH 3.5, and collagenolytic activity was completely suppressed at neutral or alkaline pH. The purified enzymes were 28 kDa and 25 kDa in size, and both had gelatinolytic activity, as detected by gelatin zymography, and cut the specific site of denatured collagen alpha chain. The purified enzymes degraded squid collagen at 25 degrees C, which is 2.5 degrees lower than the temperature at which squid collagen normally denatures; however, the proteases were ineffective at 20 degrees C. Interestingly, the isolated proteases were capable of digesting both squid and bovine gelatin. In this article, we describe collagenolytic cysteine proteases that bind to the collagen of Todarodes pacificus, thereby digesting it by attacking microunfolding regions generated by incubation 2-3 degrees C below the denaturation temperature.     

Distant metastases in differentiated thyroid carcinomas: a clinical and pathologic study

Of 514 patients with differentiated thyroid carcinoma treated between 1970 and 1987, 34 (6.6%) had distant metastases. Twelve patients died of their distant metastases; eight of these patients died within 5 years from the time of initial diagnosis. Death from cancer was most frequent in the seventh decade. The metastases were most often found in the lungs and bones. In the fatal group, pleural, brain, and pericardial metastases were noted. Local recurrences were found only in 24% of these 34 patients. Histologic types of primary thyroid tumors and metastatic tumors were reexamined and classified using our criteria, which were mainly based on the World Health Organization nomenclature and currently obtained pathologic observations of thyroid tumors. In 31 thyroid tumors, the surgical specimens were available for review. Twenty-four tumors were papillary and seven were follicular. Of the 24 papillary carcinomas, nine were follicular, eight were well-differentiated, and seven were trabecular. On the other hand, the seven follicular carcinomas consisted of four well-differentiated, two solid, and one oxyphilic. The majority of the thyroid tumors showed an extrathyroidal extension; however, two were intrathyroidal carcinomas and two were encapsulated carcinomas, larger than 5 cm in diameter. Distant metastases were confirmed morphologically in 18 patients (11 by surgical or biopsy material, five by autopsy, and two by cytology). The histologic types of metastatic tumors were consistent with those of primary thyroid tumors. Diagnostic 131I uptake was examined in 32 patients and absorption of diagnostic 131I in metastatic tumors was demonstrated in 21 patients. The 10-year survival rate of patients with 131I accumulating metastases (70%) was significantly better than that of patients with metastases lacking such uptake (40%). Immunoreactivity for thyroglobulin in metastatic tumors was correlated with the 131I absorption. This finding indicated that immunostaining of thyroglobulin in metastatic tumors might be useful in the prediction of the effectiveness of 131I therapy.     

Neonate blood IgE levels on filter paper as indicators of atopic disease

Measurements of IgE levels in the blood of neonates were investigated using filter paper for blood collection in mass screening of congenital metabolic disorders. Time-resolved fluoroimmunometric assay system for the measurement of filter paper blood IgE levels was also studied. In an analysis of the present results, IgE values of at least 0.015U/ml, the measurement limit, were considered as high. High IgE levels in filter paper blood were seen in 28 (7.2%) of the 389 cases. When the relation with serum IgE levels at 18 months of age was investigated in 134 of 389 subjects, high serum IgE levels were also found in about 86.7% of the subjects with high IgE levels in filter paper blood. In addition, when the relation between family history of atopic disease and presence of atopic disease in the first 18 months of age was investigated in 203 of the 389 subjects, about 90% of the subjects with a family history of atopic disease and high IgE levels in filter paper blood developed atopic disease. Since filter paper blood is routinely collected in Japan, IgE levels in this blood should be widely checked for the prediction of onset of atopic disease in infants.