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Biomedical subjects

V King

Publications and source records attributed to V King.

52 records · Page 3Linked to original sources

Neglect following unilateral ablation of the caudal but not the rostral portion of medial agranular cortex of the rat and the therapeutic effect of apomorphine.

The medial agranular cortex (AGm) of the rat is often considered analogous to the frontal eye field (FEF) of the monkey. However, recent anatomical, physiological, and behavioral evidence indicates that, while the caudal portion of AGm may indeed be an analog of the primate FEF, the rostral portion of AGm may be more similar to the primate supplementary motor area. The current study examined the effects of unilateral ablation of both the rostral and caudal components of AGm on the ability to orient to unilaterally presented stimuli. As expected, lesions of caudal but not rostral AGm resulted in a severe unilateral neglect of stimuli characteristic of rats with lesions of the entire rostral-caudal extent of AGm and of monkeys with FEF lesions. Caudal AGm operates also had more severe neglect than a group of rats from a previous study with larger AGm lesions which damaged the caudal portion of AGm to varying degrees. In addition, a second study showed the dopamine agonist apomorphine to have an acute dose-dependent therapeutic effect on the neglect resulting from caudal AGm ablation similar to that seen in animals with ablation of the entire rostral-caudal extent of AGm.

Animals↗

Blindness and sexual dimorphism associated with vitamin A deficiency in feedlot cattle.

Clinical, ophthalmoscopic, and histopathologic findings of vitamin A deficiency in a group of 535 feedlot cattle are described. Liver vitamin A content and results of histologic examination of ocular and osseous (optic canal) tissue confirmed the diagnosis. Blindness was the only clinical sign observed. Even though the steers and heifers in this feedlot were approximately the same age and were fed the same ration for an equal period, none of the heifers had overt clinical signs of hypovitaminosis A. Production of vitamin A by the bovine corpus luteum may account for the sexual dimorphism observed in vitamin A-deficient cattle.

Animals↗

Experimental liver metastasis. Implications of clonal proclivity and organ specificity.

"Spontaneous" lung metastases develop in over 50% of the animals bearing subcutaneous isografts of WB-2054, a rat colon carcinoma. A metastatic variant has been developed by "Fidler" type in vivo selection, yielding 100% lung metastasis. In a five-week assay to test the organ specificity of this lung metastatic variant, however, "experimental" liver and lung metastases could be induced in 100% and 60% of animals on portal venous and intravenous injections, respectively. The results demonstrate selection of a metastatic variant from heterogeneous primary tumor, and suggest at least two interacting mechanisms: (1) mechanical (the anatomy of the blood-borne metastatic pathways) and (2) biologic (factors intrinsic to primary tumor subpopulations that can be selected for metastatic proclivity). In addition, liver metastases were successfully established from colon tumors induced by cecal wall injection of tumor cells. Such a spontaneous liver metastasis model will be useful to study the specific mechanisms involved during metastasis of colon cancer to the liver.

1,2-Dimethylhydrazine↗

Production and characterization of neglect in rats with unilateral lesions of ventrolateral orbital cortex.

Neglect is a clinical syndrome characterized by an inability to orient, report, or respond to novel or meaningful stimuli presented to one side of the body or in one hemispace. Neglect in humans and monkeys most often results from damage to one of several interconnected cortical areas, including limbic cortex. In rats damage to only one cortical area, medial agranular cortex (AGm), has been found to produce neglect. Thus, it remains to be determined if there is a cortical circuitry related to neglect in rodents. AGm has extensive bilateral reciprocal connections with the paralimbic area ventrolateral orbital cortex (VLO). The current study was conducted to determine if lesions of VLO also result in neglect in the rat. Male Long-Evans hooded rats with lesions of right VLO (n = 7), left VLO (n = 7), and sham operates (n = 23) were tested for a minimum of 4 weeks on the following: (i) motor asymmetry based on assessment of rotational behavior during a 2-minute period, (ii) neglect based on the degree of orientation to visual, tactile, and auditory stimuli presented in each hemispace, and (iii) tactile extinction based on the tendency to touch the ipsilesional tab first when adhesive tabs were attached to each wrist. Lesions of VLO resulted in no obvious motor asymmetry. Both right and left VLO operates showed significant overall contralesional neglect relative to shams. However, whereas left VLO operates showed significant contralesional neglect relative to shams in the auditory and visual modalities, right VLO operates showed significant neglect in the tactile modality. On the extinction measure only right VLO operates demonstrated an asymmetry, left VLO operates were unimpaired.

Animals↗

Hemispheric asymmetry in neglect produced by unilateral lesions of dorsomedial prefrontal cortex in rats.

Unilateral lesions of the medial precentral prefrontal cortex produce severe polymodal neglect which reaches a stable level of recovery over 3 to 4 weeks. Previous research has indicated that neglect is produced by unilateral destruction of this region in either hemisphere, but that the nature of the neglect produced is dependent on the hemisphere damaged. The present study is a further examination of behavioral laterality produced by this unilateral destruction. The results indicated that destruction of medial precentral cortex in the left hemisphere (n = 12) produced severe contralateral multimodal neglect of visual, somatosensory, and auditory stimuli. Identical destruction in the right hemisphere (n = 18) also produced severe neglect, but unlike the left hemisphere operates which always demonstrated contralateral neglect, there were two distinct populations of right hemisphere operates. These subjects demonstrated either ipsilateral neglect or a "switching" response pattern characterized by the initial demonstration of contralateral or ipsilateral neglect and then, during the course of recovery, severe neglect on the opposite body side. Histological analysis indicated that the left and right hemisphere lesions were equivalent, as were the lesions in the two behavioral subcategories of right hemisphere operates. Operated controls (n = 12) did not demonstrate long-standing neglect or this switching pattern. The behavioral laterality observed following unilateral destruction of medial precentral prefrontal cortex is discussed in relationship to the anatomical and neurochemical asymmetries which have been demonstrated in this cortical region.

Acoustic Stimulation↗

Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy.

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.

Adenocarcinoma↗

Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness.

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.

Adenocarcinoma↗

Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.

With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.

1-Butanol↗

The effect of daily low dose gamma irradiation on growth and differentiation of human myeloid leukaemic bone marrow in diffusion chambers.

Bone marrow from each of 8 untreated patients with myeloproliferative disorders was grown in diffusion chambers in 760 rad total body irradiated rats. Rats were then exposed to 11.5, 57.5, or 108.5 rad daily for 14-2l d and cell growth compared to that detected in unirradiated chambers. Cells from acute myelogenous leukaemia patients exposed to 11.5 rad per d grew for 11-21 d and there was no consistent stimulation of differentiation of immature granulocytic cells to mature granulocytes that was attributable to irradiation. Cells from a chronic myeloid leukaemia patient in chronic phase or blast crisis, and a polycythaemia vera patient with myeloid metaplasia showed significant morphologic differentiation from immature to mature granulocytes in control chambers with no additional effect of daily irradiation. Marrow specimens from 2 AML patients exposed to each of 3 daily dose fractions over 14 d revealed a dose-dependent decrease in immature granulocytes with no persistent increase in mature granulocytes. In both irradiated and control chambers, macrophages increased over 21 d. Thus, cells from patients with myeloproliferative disorders may not necessarily differentiate to mature granulocytes following in vivo exposure to ionizing irradiation.

Adult↗

6-Methylpurine-induced inhibition of sclerotia morphogenesis in Sclerotium rolfsii and its reversal by adenosine.

In liquid synthetic medium inoculated with Sclerotium rolfsii (SR), addition of 6-methylpurine (MP, 50microgram/ml) immediately after inoculation led to approximately 100% reduction in sclerotia production. Adenosine, and to a lesser extent guanosine, each at final concentration of 100microgram/ml significantly reduced inhibition of sclerotia formation by SR in presence of 50microgram/ml MP. Uridine and cytidine each at 100microgram/ml had no such effect. The inhibition of sclerotia morphogenesis could be prevented by addition of 800microgram/ml of adenosine together with 50microgram/ml MP. Reversal by adenosine of MP-induced inhibition of sclerotia development was concentration dependent.

Adenosine↗

A study of the mechanism of water transfer across frog skin by a comparison of the permeability of the skin to deuterated and tritiated water.

1. Frog abdominal skins were placed between the two half-cells of a modified version of Ussing's frog skin apparatus.2. The rate of equilibration of deuterated and tritiated water across the skin was followed at pH 5.0, 6.9, and 8.0 with Ringer solution bathing both surfaces of the skin; and at pH 7.0 with sulphate Ringer solution bathing both surfaces of the skin.3. The ratio of the permeability coefficients for the influx of deuterated and tritiated water had a mean value over all the experiments of 0.9954 +/- 0.0207, n = 27, indicating that no isotope effect was observable within the limits of accuracy of the experimental method.4. The thickness of the unstirred layers associated with the frog skin was measured, and, from the data obtained, values of the true permeability coefficients for each isotope were calculated.

Abdomen↗

Sequence requirements for upregulated expression of Drosophila hsp70 transgenes during aging.

hsp70 protein and hsp70:lacZ fusion reporters are upregulated during aging and in response to oxidative stress in the thorax of Drosophila. hsp70 expression was increased during aging in each of seven different Drosophila genetic backgrounds tested, 2.6-4.8-fold. DNA sequence requirements were investigated by analysis of nine distinct hsp70:lacZ fusion reporter constructs in multiple independent transgenic lines. hsp70 sequences -194 to +276 supported an average 2.7-fold increase during aging. This increase was reduced or eliminated by deletion or point mutation of the heat shock response elements, consistent with a transcriptional mechanism. Similar sequence requirements were observed for increased expression in response to catalase null mutation as a model of oxidative stress. hsp70 5'UTR sequences were required for efficient basal expression of transgenes, but were not sufficient to confer detectable upregulation during aging. Inclusion of additional hsp70 coding region sequences from +276 to + 1011 created a larger hsp70:lacZ fusion protein and had two effects: dramatic reduction of the overall expression level of the fusion protein, and an additional three to fourfold upregulation during aging. These results suggest that the coding region sequences reduce fusion protein abundance and that this negative effect decreases as a function of age. The data support a model for increased expression of hsp70 transgenes during aging involving both transcriptional and posttranscriptional components.

Aging↗

Clinical and radiographic evaluation of intertrochanteric osteotomy in dogs: a retrospective study of 18 dogs.

OBJECTIVE: To determine whether intertrochanteric osteotomy (ITO) can prevent the progression of degenerative joint disease (DJD) in dysplastic hip joints. STUDY DESIGN: The results of ITO were assessed retrospectively by using owner questionnaires, physical examination, and radiographic evaluation. ANIMALS: Eighteen client-owned dogs (29 coxofemoral joints were evaluated). METHODS: Lameness was scored according to a grading system. A scoring system was also developed to assess radiographically evident osteoarthritis on a ventrodorsal projection of the coxofemoral joints in extension. RESULTS: Twenty-nine ITO were performed in 18 dogs with varying degrees of hip dysplasia. The dogs were lame on 19 of 29 rear limbs on physical examination before surgery. In 22 of the 29 hip joints, palpation caused signs of pain. The median age at the first and second surgical procedure was 14.5 months and 18 months, respectively. Follow-up evaluation was performed on average at 9.77 (FU I), 22.52 (FU II), and 47.50 months (FU III) after surgery. Based on the owners' evaluation, there was a tendency toward improvement after surgery. The results of the physical examination at the preoperative examination and at the three follow-up examinations did not differ significantly. The follow-up radiographic scores showed significantly worse DJD than the preoperative scores. CONCLUSIONS: ITO does not prevent progression of DJD in the dysplastic hip. CLINICAL RELEVANCE: Knowledge of the long-term effects of ITO is essential for surgeons trying to achieve improvement in dogs with hip dysplasia.

Animals↗

[Anna, Irma and Dora--the key to the mothers in the creation of psychoanalysis].

As a science caught up between the mythical and the rational, psychoanalysis is subject to the pulls of two opposing currents, a creative enlightened one concerned with the investigation of the unconscious, and a conservative counter-current observable in the psychoanalytic theory of femininity. In her analysis of these warning elements the author goes back to the genesis of psychoanalysis and its creator and takes a close look at the primal myth (the legend of Breuer and Anna O.), the primal dream (Irma), and finally the primal analysis (the case of Dora). King's analysis demonstrates that Freud unconsciously appropriated female psychic features and--in unconscious identification with the mother of the Urszene, bound up with adolescent regression and attendant bi-sexual grandeur fantasies--imagined himself as ideal woman and "conceiver". By appropriating female potency for himself and thus making the opposite sex superfluous, Freud's theory of femininity leaves the place of women vacant, relegating them to the role of a defective entity, a castrated man, rather than acknowledging their otherness. In King's view, this phallic monism is inextricably interwoven with adolescent bisexual identifications and fantasies of grandeur about Freud's own gender, while denying gender-difference genuine recognition and integration.

Adolescent↗