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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 523 records · Page 29Linked to original sources

Correction for tissue attenuation in radionuclide gastric emptying studies: a comparison of a lateral image method and a geometric mean method.

Variation in depth of radionuclide within the stomach may result in a significant error in the measurement of gastric emptying if no attempt is made to correct for gamma-ray attenuation by the patient's tissues. In this study a method of attenuation correction, which uses a single posteriorly located scintillation camera and correction factors derived from a lateral image of the stomach, was compared with a two-camera geometric mean method, both in phantom studies and in five volunteer subjects. A meal of 100 g of ground beef containing 99Tcm-chicken liver, and 150 ml of water, was used in the in vivo studies. In all subjects the geometric mean data showed that solid food emptied in two phases: an initial lag period, followed by a linear emptying phase. Using the geometric mean data as a standard, the anterior camera overestimated the 50% emptying time (T50) by an average of 15% (range 5-18) and the posterior camera underestimated this parameter by 15% (4-22). The posterior data, corrected for attenuation using the lateral image method, underestimated the T50 by 2% (-7 to +7). The difference in the distances of the proximal and distal stomach from the posterior detector was large in all subjects (mean 5.7 cm, range 3.9-7.4). We conclude that attenuation effects may account for large errors in the measurement of gastric emptying with radionuclide methods and that the application of correction factors derived from a lateral image of the stomach reduces these errors.

Adult↗

Characterization of two different Ly-1+ T cell populations that mediate delayed-type hypersensitivity.

This paper describes two functionally different T cell populations that mediate delayed-type hypersensitivity (DTH) reactions in contact-sensitized mice. Both of these T cells are Ly-1+, Qa-2-, and Vicia villosa lectin nonadherent. One of these T cell subpopulations is responsible for the classical 24- to 48-hr component of DTH reactions, is induced 3 to 4 days after immunization, is H-2 restricted, is sensitive to irradiation and to antigen-specific T cell-derived suppressor factors, and is found in nylon wool-nonadherent as well as nylon wool-adherent populations. In contrast, the T cell population that is responsible, via an antigen-specific T cell factor, for a recently described early component of DTH, which is an obligatory initial step for expression of DTH, is induced within 24 hr after immunization, requires much less antigen for immunization, is not H-2 restricted, is not sensitive to irradiation nor to T suppressor factors, and is found exclusively in the nylon wool-nonadherent fraction. These results support a new formulation of DTH. According to this formulation, Ly-1+ T cells produce an antigen-specific, tissue-sensitizing, mast cell-activating factor, and via this factor induce the early component of DTH, which is an obligatory first step in which local antigen challenge induces increased local vascular permeability. This required opening of gaps between endothelial cells is due to T cell factor-dependent release of the vasoactive amine serotonin from cells such as mast cells. This first step allows the second, H-2-restricted, Ly-1+ T cell population to enter the reaction site, and to then be triggered by antigen to release lymphokines that attract the subsequent influx of blood-borne, bone marrow-derived leukocytes to constitute the classical delayed-in-time component of DTH reactions.

Animals↗

Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis.

Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than in controls, with 9 patients being outside the normal range for solid emptying and 7 patients outside the normal range for liquid emptying. Findings from gastric and esophageal emptying tests generally correlated well with symptoms of dysphagia and gastroesophageal reflux. However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux. Delayed gastric emptying may be an important factor in the development of upper gastrointestinal symptoms in patients with progressive systemic sclerosis.

Adult↗

Regional blood flow in ethylnitrosourea-induced brain tumors.

Regional blood flow was measured in experimental brain tumors using iodoantipyrine labeled with carbon 14 and quantitative autoradiography. A total of fifteen oligodendrogliomas, sixteen mixed gliomas, one astrocytoma, one ependymoma, and three malignant schwannomas were studied in 9 rats. The mean tumor blood flows for all glioma classifications were similar, averaging 45 +/- 3 (standard error of the mean) ml . hg-1 . min-1. Flow was fairly uniform within individual oligodendrogliomas and there was no apparent correlation between blood flow and tumor size or location. The mixed gliomas were larger than the oligodendrogliomas and had a wider range of blood flow. Small focal areas of necrosis were observed in 7 mixed gliomas, and low flows were usually measured in these regions; these flows were not always the lowest regional values measured within the mixed gliomas or total group of tumors, however. Small tumor regions with increased vascularity, frequently with endothelial cell proliferation, were observed in oligodendrogliomas and to a greater extent in mixed gliomas; these regions were correlated with small elevations in blood flow (10 to 15 ml . hg-1 . min-1) in comparison with surrounding tumor tissue. Brain adjacent to tumor usually had higher blood flows than that in tumor periphery. Hemispheric differences in blood flow related to the site of primary tumor growth were not observed.

Animals↗

Regional blood-to-tissue transport in ethylnitrosourea-induced brain tumors.

Regional blood-to-tissue transport, expressed as a unidirectional transfer rate constant (K), was measured in experimental brain tumors using alpha-aminoisobutyric acid (AIB) labeled with carbon 14 and quantitative autoradiography. A total of sixteen oligodendrogliomas, four mixed gliomas, three astrocytomas, two diffuse gliomatosis, one anaplastic astrocytoma, one ependymoma and four malignant schwannomas were studied in 9 rats. The mean Ks for all glioma classifications were similar, averaging 2.6 +/- 0.4 (standard error of the mean) ml . kg-1 . min-1, and were only slightly higher than those for nontumorous parietal cortex (2.1 ml . kg-1 . min-1), corpus callosum (0.9 ml . kg-1 . min-1), and a comparable region of brain tissue in the contralateral hemisphere (1.3 ml . kg-1 . min-1). Values of K varied minimally in the intracerebral gliomas and were marginally correlated with tumor cell morphology in only two tumors. In some (but not all) of the larger gliomas, increased vascularity, with or without endothelial proliferation, was associated with a 3- to 15-fold increase in K. Regional K values in malignant schwannomas were highly variable (4 to 207 ml . kg-1 . min-1) and generally were not correlated with specific histological features of the tumor, except in some regions with increased vascularity. Estimates of the average fractional extraction of AIB by the intracranial gliomas and malignant schwannomas were 0.01 and 0.2, respectively; average fractional extractions for nontumorous brain were approximately 0.003.

Aminoisobutyric Acids↗

Monoclonal antibody reveals H-2-linked quantitative and qualitative variation in the expression of a Qa-2 region determinant.

We have produced a monoclonal antibody, Y-7, that reacts with a Qa-2 region-controlled determinant. Cellular and strain distribution analyses, coupled with quantitative variation in the amount of Y-7 antigen expressed among strains, provide overwhelming evidence that Y-7 reacts with the Qa-2a determinant. The determinant detected by Y-7 is differentially expressed in T and B lymphocytes in a strain specific manner. Y-7 reacts with the majority of T lymphocytes (greater than 95%) and approximately one-half of B lymphocytes in certain strains (+ + strains), and with the majority of T lymphocytes (greater than 95%) and no B lymphocytes in other strains (+ strains). T lymphocytes in + strains express approximately three fold less of the Y-7 determinant than T lymphocytes from + + strains. In addition, we show that the Y-7 determinant is expressed in approximately one-third to one-half of Lyb-3-, 5- B lymphocytes. Possible mechanisms determining quantitative and qualitative variation in the expression of the Y-7 determinant in T and B lymphocytes are discussed.

Animals↗

Heat-induced changes in the rat parotid gland.

Gland size, amylase activity, total proteins and DNA concentrations were measured in parotid gland during chronic heat exposure (34 degrees C). Subcellular fractionation was performed. Exposure to heat resulted in a decrease in gland size and in DNA concentration; amylase activity/100 mg tissue and amylase specific activity to protein concentration ratio increased. Subcellular fractions, except plasma membrane, decreased significantly. Thus, chronic heat exposure slows down the production of gland constituent proteins, whereas acinar function, e.g. the production and storage of exportable proteins, is not disturbed. The reduced gland size is apparently due to hypoplasia.

Amylases↗

Plasma volume regulation during heat stress: albumin synthesis vs capillary permeability. A comparison between desert and non-desert species.

1. Plasma albumin synthesis was measured in rats and sand rats (Psammomys obesus) during heat acclimation (34 degrees C) and following thermal dehydration (37 degrees C) using 3H 1-leucine as a tracer. 2. In rats, heat acclimation resulted in 48% reduction in albumin synthesis. In sand rats synthesis increased by 160%. Both species achieved a new stabilization of the albumin synthetic system on the 5th day of acclimation. 3. Following thermal dehydration albumin synthesis increased in rats and decreased in sand rats. Acclimation did not alter this response. 4. In our dehydrating system plasma volume was maintained via maintenance of adequate albumin mass. In rats, albumin synthesis apparently contributes to this process. In sand rat, vascular permeability rather than albumin synthesis plays this role.

Adaptation, Physiological↗

Interrelationships between heat acclimation and salivary cooling mechanism in conscious rats.

1. Adaptation of salivary cooling mechanism during acclimation to heat (34 degrees C) and its role in thermoregulation of the rats was studied on conscious rats with either one submaxillary gland chronically cannulated or both submaxillaries ligated. 2. During heat stress (40 degrees C) acclimated rats showed a decrease both in rectal temperature threshold for salivation (Tre-TS), in salivary flow rate and in Tre (hyperthermic plateau). Animals survived for extended periods and rats with ligated glands survived 40% less than non-ligated rats. 3. For both cannulated and ligated rats short term acclimation (5 days) was the most effective. 4. It is suggested that earlier activation of salivation mechanism is associated with the decreased hyperthermic plateau and that the decreased salivary flow rate allows better control of water balance of the animals. Consequently, survival period during heat stress is extended.

Acclimatization↗

The value of the autopsy in medical audit--a combined clinical and pathological assessment of 100 cases.

We retrospectively reviewed 100 consecutive autopsies performed at the Royal Adelaide Hospital in 1979. The review was made jointly by a clinician, surgical pathologist and forensic pathologist. The mean patient age was 64.5 years. Sixteen percent of premortem anatomical diagnoses were not confirmed at autopsy. Autopsy revealed 171 new anatomical diagnoses. Of these, 33 diagnoses in 27 patients were important in relation to the cause of death and if known premortem would have altered therapy and possibly outcome in two patients. In 11 cases the missed major diagnoses should have been entertained on the basis of available clinical data. Of the 19 sudden deaths, the cause of death was not included in the clinical differential diagnosis in seven cases. Autopsy resulted in a substantial change in the death certification of 43 cases. The data indicate that the autopsy has a great deal to offer in correcting clinical diagnoses and effecting scientific discipline for clinicians.

Adult↗

Gastric emptying in normal subjects--a reproducible technique using a single scintillation camera and computer system.

The gastric emptying of a mixed solid and liquid meal was assessed in 24 normal subjects using a single camera/computer system which allowed continuous monitoring of both solids and liquids. It was shown that variation in tissue attenuation caused by the changing depth of radionuclide within the stomach accounted for large errors in the measurement of gastric emptying (alteration in 50% emptying time of up to 65%). A technique for the correction of attenuation is described which used factors derived from a lateral image of the stomach. In all subjects, solid emptying was slower than liquid emptying and was characterised by a delay (lag period) which was followed by linear emptying. Liquid emptying usually followed a single exponential pattern. The effect of physiological changes induced by increasing the calorie content of the liquid component of the meal was assessed by giving either water, 10% dextrose or 25% dextrose. Liquid emptying was slowed and the lag period of solid was prolonged as the calorie content increased. Reproducibility was assessed in 19 subjects. For the three groups studied (water, 10% dextrose, 25% dextrose) the day-to-day variation in gastric emptying was not significant for any measured parameter, while statistically significant differences were present in solid and liquid emptying between subjects and groups.

Adult↗

Steroid therapy in inappropriate secretion of antidiuretic hormone due to malignant thymoma.

The authors present the case of a 48-year-old female known to have malignant thymoma with metastases for 6 years and treated continuously for 4 years by corticosteroids with marked regression of tumor. The patient ceased medication on her own accord, and was admitted with extensively enlarged tumor and metastases in association with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In view of the previous excellent response of the thymoma to corticosteroids, the same treatment was given again with disappearance of the tumor and the features of SIADH. The authors are unaware of previous use of corticosteroids in SIADH as a consequence of their effect on tumor regressions.

Female↗

Regional blood flow in RT-9 brain tumors.

Regional blood flow (BF) was measured in RT-9 experimental brain tumors using carbon-14 labeled iodoantipyrine, the Kety tissue-exchange equations, and quantitative autoradiographic techniques. Blood flow was variable within tumor tissue, and the range of BF increased with increasing tumor size; the overall range was 6 to 138 ml/100 gm/min and the maximum range within an individual tumor was 55 ml/100 gm/min. In all but one case, mean tumor BF was less than that in the same anatomic region of the contralateral hemisphere (CBA). The magnitude of BF within individual tumor foci generally could be related to tumor size, location (intraparenchymal versus extraparenchymal), and the presence of necrosis or cysts; it was lower in the geometric centers than in the periphery of medium-sized and large tumors. Brain adjacent to tumor had higher BF's than the tumor periphery; generally, the BF in the brain adjacent to the tumor was less than that in the CBA. A global depression of BF was observed within tumor-free cortex and corpus callosum of the hemisphere ipsilateral to tumor implantation and primary growth, suggesting a hemispheric reduction in metabolic and functional activity.

Animals↗

Regional blood-to-tissue transport in RT-9 brain tumors.

Regional blood-to-tissue transport, expressed as a unidirectional transfer rate constant (K), was measured in experimental RT-9 brain tumors using 14C-alpha-aminoisobutyric acid (AIB) and quantitative autoradiographic techniques. The magnitude of K depends on the permeability, surface area, and blood flow of the tissue capillaries. The transfer rate constant was variable within tumor tissue (range 0.001 to 0.178 ml/gm/min) and depended on tumor size, location (intraparenchymal, meningeal, or choroid plexus associated), and to a lesser extent on necrosis and cyst formation. Brain adjacent to tumor had higher K values, particularly around larger tumors (0.004 to 0.014 ml/gm/min), than corresponding brain regions in the contralateral hemisphere (0.001 to 0.002 ml/gm/min). Estimates of the fractional extraction of AIB by intraparenchymal tumors were between 0.008 and 0.4 ml/gm/min. Values of fractional extraction in this range indicate that tumor capillaries are not freely permeable to this solute. The values of K measured with AIB in this study, for the most part, approximate the permeability-surface area product of tumor and brain capillaries. The experimental data suggest that the permeability-surface area characteristics of the microvasculature in small RT-9 tumors are similar to those of the host tissue, whereas the microvasculature of larger RT-9 tumors is influenced more by intrinsic tumor factors.

Aminoisobutyric Acids↗

Expression of chimeric genes in the early region of SV40.

Chimeric genes have been constructed by inserting foreign gene sequences in the early region of SV40. The genes contained the first exon of the SV40 large T gene with 180 bp of its intron and either the third exon of the rat preproinsulin gene II with 488 bp of its large intron or the third exon of the mouse beta globin gene with 63 bp of its intron. The chimeric genes contained a 5' splicing site (SS) from SV40 and a 3' SS from the inserted gene. Both the preproinsulin and the globin insertions contained a polyadenylation signal. The SV40 early poly(A) addition signal was also retained. High-titer virus stocks were obtained when the recombinants, which contained SV40 origin of replication and the entire late region, were used to transfect a cloned line of COS cells (COS-M6). These stocks typically contained no detectable wild-type virus. RNA mapping demonstrated the following: (a) The SV40-rat preproinsulin chimeric RNA was initiated at the SV40 early promoter, spliced from the SV40 5' SS to the rat preproinsulin 3' SS, and polyadenylated solely at the SV40 poly(A) addition signal. (b) The SV40-mouse beta globin chimeric RNA was initiated at the SV40 early promoter, spliced from the 5' SS to the mouse beta globin 3' SS, and polyadenylated at the mouse beta globin poly(A) site. The chimeric RNAs were overproduced, owing to low levels of T antigen in the COS-M6 cells, which did not completely repress transcription from the early region. Fusion proteins of 15,500 molecular weight resulted from expression in vivo of the SV40-rat preproinsulin chimeric gene and of 11,500 molecular weight for the SV40-mouse beta globin chimeric gene. The molecular weights of the proteins suggested that they were initiated at the early SV40 AUG and that translation continued across the chimeric splice sites. The chimeric proteins were also overproduced.

Animals↗

Abnormalities of gastric emptying in obese patients.

The pattern of gastric emptying in 15 obese patients and 11 control subjects has been assessed using a double isotope technique for measuring solid and liquid emptying with a scintillation camera. In all studies solid emptying was characterized by a lag period (before food enters the duodenum) followed by linear emptying. Liquid emptying was faster than solid and was non-linear. In obese patients solid emptying was delayed due to prolongation of the lag period, and the duration of the lag period correlated with excess body weight. There was no significant change in liquid emptying in obese patients. In control subjects no relationship between gastric emptying rates and body weight was apparent.

Adult↗