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Biomedical subjects

J Jakubowski

Publications and source records attributed to J Jakubowski.

At least 19 recordsLinked to original sources
PubMed1997

Decrease in kidney calbindin-D 28kDa as a possible mechanism mediating cyclosporine A- and FK-506-induced calciuria and tubular mineralization.

The use of the immunosuppressant cyclosporine A (CsA) is limited by its adverse renal effects. Most recently, we reported that the drug markedly decreases the levels of the calcium-binding protein calbindin-D 28kDa in kidneys of male Wistar rats. In the present study, the potential relationship between drug-induced nephrotoxicity and the decrease in kidney calbindin-D 28kDa was investigated. Four groups of male Wistar rats were treated for 10 or 31 days with either the immunosuppressant CsA (50 mg/kg/day), FK-506 (5 mg/kg/day), rapamycin (5 mg/kg/day) or with the nonimmunosuppressive cyclosporine derivative 3'keto-[Bmt1]-[Val2]-CsA (SDZ PSC-833) (50 mg/kg/day), and the effects on calcium homeostasis, kidney histology and renal calbindin-D 28kDa were examined. Similar effects were found with CsA and FK-506; both drugs strongly reduced kidney calbindin-D 28kDa protein levels, increased urine calcium excretion, caused intratubular calcification, and induced basophilic tubules. In contrast, rapamycin and SDZ PSC-833 caused no decrease in renal calbindin-D 28kDa levels, no noticeable alterations in calcium metabolism, and no renal calcification. The results provide evidence for a link between decreased renal calbindin, increased calcium urine excretion, and intratubular kidney calcification. The present data show no correlation between the decrease in renal calbindin and the induction of basophilic tubules; however, it needs to be investigated if these apparently independent kidney effects may have a common origin upstream of calbindin expression.

Animals↗
PubMed1996

Hemifacial spasm: a prospective long-term follow up of 83 cases treated by microvascular decompression at two neurosurgical centres in the United Kingdom.

OBJECTIVE: To evaluate the use of microvascular decompression (MVD) for the treatment of hemifacial spasm (HFS). METHODS: Eighty three patients with HFS who underwent MVD via a suboccipital craniectomy are presented. RESULTS: Seventy two out of seventy eight patients available for follow up remained free of any spasms at a mean follow up period of eight years. Two patients continued to have minor intermittent muscle twitches and three had recurrence of HFS. One patient's operation was not completed. Twenty had a transient complication and eight were left with permanent postoperative deficits, the commonest being unilateral sensorineural deafness. Seventy one patients declared themselves satisfied with the procedure. A causative vessel was found on the root exit zone of the seventh cranial nerve in 81 patients. CONCLUSION: The procedure seems to provide lasting relief for most patients. The correct operative technique is essential if complications are to be avoided.

Adult↗
PubMed1996

In vitro contractility studies of the rat middle cerebral artery after stereotactic Gamma Knife radiosurgery.

The middle cerebral artery (MCA) was irradiated in 94 rats using the Gamma Knife. The vessels receiving 20, 50, 80 and 200 Gy were removed 24 h later and mounted on a myograph. Contractility responses to potassium and prostaglandin (PG) F2 alpha were tested. After precontraction with PGF2 alpha, the relaxant effects of histamine, papaverine, L-arginine and sodium nitroprusside were examined. Other vessels were preincubated with ouabain or N omega-nitro-L-arginine methyl ester before testing with the relaxant agents. After irradiation, the contractile response to maximal potassium and PGF concentrations was diminished, suggesting dose-dependent radiation damage to the contractile mechanism. The normal MCA shows an initial relaxation in the presence of a low K+ concentration, which is Na+, K(+)-ATPase dependent. According to this study, the endothelium-derived relaxation function was suppressed by radiation, suggesting that there is an early change in irradiated vessels, demonstrable by functional studies, which affects both the smooth muscle and endothelial layers.

Animals↗
PubMed1995

Blood supply, blood flow and autoregulation in the adenohypophysis, and altered patterns in oestrogen-induced adenomatous hyperplasia.

The article addresses the fascinating topic of blood flow in the normal and the adenomatous anterior pituitary gland. This is considered in conjunction with the anatomy and physiology of the area and the neuro secretion. The mechanisms of the control of the development and growth of the prolactinoma and the changes in the microcirculation of the tumour are discussed. It is felt that its altered microvascular pattern and in particular the influx of the systemic low dopamine blood through the supplementary and newly developed blood supply plays an important role in the natural history of these tumours.

Adenoma↗
PubMed1995

The Sheffield model of subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: There is no comprehensive and reliable model available in small animals that is suitable for the study of subarachnoid hemorrhage (SAH). Most of the existing models either require extensive surgery to achieve SAH or neglect the importance of an injury to the vessel and the impact of suddenly raised intracranial pressure (ICP). The presented model is designed to overcome these shortcomings. METHODS: Forty-three male Wistar rats were anesthetized. Regional cerebral blood flow was measured using the H2 clearance method bilaterally in the middle cerebral artery territory. ICP and blood pressure were continuously monitored. Blood gases were kept within physiological limits. SAH was produced by passing a nylon thread up through the right internal carotid artery and piercing a hole in the right anterior cerebral artery. The animals were divided into three experimental groups treated with varied operative techniques. After 3 hours the surviving animals were killed, and SAH was confirmed by postmortem examination. RESULTS: The described method proved to be a reliable way of producing SAH in rats. The onset of SAH was characterized by a sudden increase in ICP. There were some differences in the reduction of regional cerebral blood flow and the survival rate in the experimental groups. This may represent differing degrees of severity of the produced SAH. CONCLUSIONS: We present an inexpensive and reliable model of SAH in the rat that allows the early course of biochemical, physiological, and pathological changes to be studied.

Animals↗
PubMed1994

Reactive airways dysfunction syndrome.

Reactive airways dysfunction syndrome (RADS) is an asthma-like bronchoconstriction state which develops after a short-term exposure to highly irritating volatile substances. Although some of the clinical manifestations can be considered as very similar to those of asthma (e. g. inflammation, hyperresponsiveness and reversibility of the bronchial constriction) the most essential difference lies in the absence of asthma attacks after exposure to small amounts of causative agents few weeks after onset. Thus, the mechanism of RADS cannot be considered to be of an allergic origin. This is supported by the results of the pathomorphologic biopsies taken from bronchi which usually show neutrophilic and lymphocytic infiltrations as well as frequent and severe destruction of the bronchial epithelium. Eosinophilic infiltrations and basement membrane thickness have never been found. The therapy of severe dyspnoea attacks is similar to that of bronchial asthma. Factors that cause RADS comprise a wide range of volatile irritant substances, provided that they occur in high concentrations. Exposure to isocyanates in plumbers heating polyurethane pipes seems to be the major cause of RADS in Poland.

Bronchial Diseases↗
PubMed1993

Middle cerebral artery occlusion without craniectomy in rats. Which method works best?

BACKGROUND AND PURPOSE: Our purpose was to assess the effectiveness of middle cerebral artery occlusion in producing acute focal ischemia in the rat by the use of Koizumi's and Longa's methods, in which occlusion is achieved by passing a nylon thread into the internal carotid artery. METHODS: Cerebral blood flow was measured by using the hydrogen clearance method, and the brains were examined histologically to assess ischemic damage. RESULTS: By Koizumi's method profound reduction in cerebral blood flow was achieved in 28 of 30 rats (93%). The mean cerebral blood flow in the middle cerebral artery territory was 10.7 (95% confidence interval, 9.9-11.5) ml/100 g per minute. By Longa's method reduction in cerebral blood flow was achieved in only 29 of 52 rats (56%), and in these animals mean cerebral blood flow was 33 (95% confidence interval, 28.3-33.7) ml/100 g per minute (p < 0.001 compared with Koizumi's method). Cerebral blood flow was reduced to < 16 ml/100 g per minute in only seven animals (24%). CONCLUSIONS: By Koizumi's method the depth of ischemia is more profound, occlusion is achieved in a much higher proportion of cases, and the incidence of perforation of the intracranial internal carotid is much less frequent than by Longa's method.

Acute Disease↗
PubMed1992

[Computerized tomography in aneurysms of the posterior cranial fossa].

The authors discuss the clinical usefulness of CT scan in patients with ruptured posterior fossa aneurysms. Among 164 patients after SAH, in 17 the bleeding was caused by aneurysms located in posterior fossa. The exact diagnosis of the bleeding during 5 days after SAH was possible in 94% of the patients, that is similar as in supratentorial aneurysms. The characteristic symptoms of SAH in these aneurysms was the symmetric presence of blood in basal cisterns, intraventricular haemorrhage and, in consequence,--hydrocephalus. Aneurysms of bifurcation of BA were characterized by presence of blood in interpeduncular cistern; this phenomenon was not observed in PICA aneurysms. The aneurysms of BA were more often seen in direct CT-Scan.

Basilar Artery↗
PubMed1990

Vasopressin, insulin and peroxide(s) of vanadate (pervanadate) influence Na+ transport mediated by (Na+, K+)ATPase or Na+/H+ exchanger of rat liver plasma membrane vesicles.

Uptake of 22Na+ by liver plasma membrane vesicles, reflecting Na+ transport by (Na+, K+)ATPase or Na+/H+ exchange was studied. Membrane vesicles were isolated from rat liver homogenates or from freshly prepared rat hepatocytes incubated in the presence of [Arg8]vasopressin or pervanadate and insulin. The ATP dependence of (Na+, K+)ATPase-mediated transport was determined from initial velocities of vanadate-sensitive uptake of 22Na+, the Na(+)-dependence of Na+/H+ exchange from initial velocities of amiloride-sensitive uptake. By studying vanadate-sensitive Na+ transport, high-affinity binding sites for ATP with an apparent Km(ATP) of 15 +/- 1 microM were observed at low concentrations of Na+ (1 mM) and K+ (1mM). At 90 mM Na+ and 60 mM K+ the apparent Km(ATP) was 103 +/- 25 microM. Vesiculation of membranes and loading of the vesicles prepared from liver homogenates in the presence of vasopressin increased the maximal velocities of vanadate-sensitive transport by 3.8-fold and 1.9-fold in the presence of low and high concentrations of Na+ and K+, respectively. The apparent Km(ATP) was shifted to 62 +/- 7 microM and 76 +/- 10 microM by vasopressin at low and high ion concentrations, respectively, indicating that the hormone reduced the influence of Na+ and K+ on ATP binding. In vesicles isolated from hepatocytes preincubated with 10 nM vasopression the hormone effect was conserved. Initial velocities of Na+ uptake (at high ion concentrations and 1 mM ATP) were increased 1.6-1.7-fold above control, after incubation of the cells with vasopressin or by affinity labelling of the cells with a photoreactive analogue of the hormone. The velocity of amiloride-sensitive Na+ transport was enhanced by incubating hepatocytes in the presence of 10 nM insulin (1.6-fold) or 0.3 mM pervanadate generated by mixing vanadate plus H2O2 (13-fold). The apparent Km(Na+) of Na+/H+ exchange was increased by pervanadate from 5.9 mM to 17.2 mM. Vesiculation and incubation of isolated membranes in the presence of pervanadate had no effect on the velocity of amiloride-sensitive Na+ transport. The results show that hormone receptor-mediated effects on (Na+, K+)ATPase and Na+/H+ exchange are conserved during the isolation of liver plasma membrane vesicles. Stable modifications of the transport systems or their membrane environment rather than ionic or metabolic responses requiring cell integrity appear to be involved in this regulation.

Adenosine Triphosphate↗
PubMed1989

Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy.

Clinical, electrophysiological and ultrastructural morphometric observations were made in 5 diabetic non-neuropathic patients, 5 diabetic patients with mild neuropathy and 11 diabetic patients with severe neuropathy. Capillary abnormalities were assessed in simultaneous nerve, muscle and skin biopsies and compared with results from 6 age-matched, non-diabetic control subjects. Nerve capillaries demonstrated markedly greater pathology than skin and muscle capillaries. Endoneurial capillary density was significantly reduced in severely neuropathic diabetic patients (p less than 0.01) when compared with control subjects. Capillary basement membrane (p less than 0.002), endothelial cell (p less than 0.003) and total diffusion barrier (endothelial cell, pericyte, basement membrane) (p less than 0.001) thickness were significantly increased, and oxygen diffusing capacity was significantly reduced (p less than 0.001) in the nerves of patients with severe diabetic neuropathy when compared to control subjects. Endothelial cell profile number and luminal perimeter were significantly increased in asymptomatic (p less than 0.01), (p less than 0.05) and severely neuropathic (p less than 0.001), (p less than 0.05) diabetic patients respectively. However, endothelial cell outer perimeter, a measure of capillary size, showed no significant increase in diabetic patients when compared with control subjects. An association was observed between neurophysiological and neuropathological measures of neuropathic severity. There was no significant correlation between the duration of diabetes and HbA1 levels with capillary pathology or with neuropathic severity. Very few abnormalities of muscle and skin correlated with neuropathic severity. However, all measures of nerve capillary pathology correlated significantly with neurophysiological and neuropathological measures of neuropathic severity.

Adult↗
PubMed1989

Intracranial pressure changes following primate subarachnoid haemorrhage.

In 29 anaesthetized baboons avulsion of a small intracranial artery was used to produce a subarachnoid haemorrhage, in a closed-skull situation. Intracranial pressure was measured by extradural transducers, and arterial pressure was also measured continuously, with periodic measurements of cerebral blood flow. After haemorrhage there was an immediate fall in cerebral perfusion pressure in nearly all cases, reaching zero in 9 animals. In 18 there was a significant pressor response in the systemic circulation, but perfusion pressure usually remained low in spite of this response. Perfusion pressure recovered after a few minutes in most cases. In the 19 cases where intracranial pressure was measured on both sides, differences occurred in 11, with the higher pressure always on the same side as the haemorrhage. The difference was evident very soon after haemorrhage in 9 cases, and lasted over half an hour in 5 of them. The mechanism of arrest of bleeding was, in most of this series, not that of a zero perfusion pressure. Explanations for this and for the occurrence of differential pressures are discussed.

Animals↗
PubMed1989

Changes of blood flow in the adenohypophysis of normal and estrogen pretreated Fisher rats by tamoxifen.

Blood flow was measured in the adenohypophysis and in the cerebral cortex of female F344 rats over a period of 90 min using the hydrogen clearance method. Tamoxifen, 1 mg/kg, administered iv reduced the blood flow in the adenohypophysis by 35%, whereas cerebral blood flow and arterial pressure remained unchanged. Seven days sc treatment with tamoxifen (1 mg/kg daily) had no demonstrable effect on blood flow. Anterior pituitary hyperplasia was induced in 15 rats with diethylstilbestrol containing implants. These rats responded to 7 days of sc tamoxifen treatment by 30% increase in adenohypophyseal blood flow. These results suggest that tamoxifen has a different effect on adenohypophysial circulation of the rat depending on whether it is administered in a low- or high-estrogen state.

Animals↗
PubMed1989

Giant epidermoid cysts of the skull.

The authors describe two cases of giant intradiploic epidermoid cysts of the cranial vault and a case of a large epidermoid arising from the frontal sinus and extending intracranially. The aetiology of epithelial cysts is reviewed. The characteristic radiological and CT scan appearances of diploic epidermoid cysts are described, their clinical presentation and surgical management briefly discussed.

Adult↗
PubMed1989

Clinical evaluation of magnetic stimulation in cervical spondylosis.

Conduction in central motor pathways and motor roots was assessed, using the new technique of magnetic stimulation, in 39 patients with cervical spondylosis. Recordings were taken from abductor digiti minimi in all patients and from biceps brachii and abductor hallucis in some. Findings were abnormal ipsilaterally in 27 out of 63 muscles examined in patients with myelopathy, and in 2 out of 38 muscles in patients with radiculopathy. No abnormality was found in 11 muscles examined in patients with negative radiology. There was some correlation between the degree of electrophysiological change and clinical disability. Abnormal conduction was found in some patients with cord compression at the C3/4 or C4/5 interspace but not in a small group with compression at the C5/6 interspace. It seems that magnetic stimulation will provide objective confirmation of upper motor neurone involvement and may provide some measure of its degree, but at present it does not appear to be superior to clinical methods in diagnosing its presence. It may also aid the selection of the correct level for surgical decompression.

Adult↗
PubMed1989

A clinical evaluation of computed tomography in patients with subarachnoid haemorrhage and multiple intracranial aneurysms.

A clinical usefulness of computed tomography was reviewed in 38 consecutive patients with subarachnoid haemorrhage and multiple intracranial aneurysms. CT helped in identification of ruptured aneurysm in more than 70% of cases (it pinpointed source of bleeding in 55% of patients and showed region of haemorrhage in 15% of cases). Its main limitation was inability to detect blood in subarachnoid space (SAS) in patients who were diagnosed later after bleeding (23%). Intracerebral haematoma or localized blood accumulated in SAS showed unequivocally the burst aneurysm. Symmetrical and especially asymmetrical distribution of blood in SAS were also helpful, though the former was misleading in two cases. Moreover, CT detected hypodense lesion of brain in 2 cases, widening of ventricular system in 12 patients and directly visualized aneurysm in 3 cases.

Adult↗
PubMed1988

Primary intracerebral lymphoma: a clinicopathological analysis of 14 patients presenting over a 10-year period in Sheffield.

Intracerebral disease was diagnosed in 14 out of 450 patients who presented with non-Hodgkin's lymphoma between January 1976 and January 1987. Twelve of the 14 presented after June 1980. Age ranged from 31 to 73 years and eight patients were male. Two patients had other tumours, and three had relevant associated immunosuppressive disorders. Radiological assessment of one further patient showed a cavitating bronchial carcinoma. Five patients were untreated, and one died before radiotherapy was complete. Eight patients completed courses of whole-brain irradiation; four of these received higher doses. All entered remission. Three patients are alive, between eight months and seven years after treatment. Of the remaining five, one never recovered intellectual function and died of bronchopneumonia; three died between eight and 30 months after treatment and autopsy showed severe radionecrosis of the brain with no residual tumour. All three had received higher doses of radiation and had undergone burrhole aspiration before treatment. Autopsy was refused on one patient who also appeared to have died from radionecrosis of the brain. Immunohistological examination in eight cases confirms that cerebral non-Hodgkin's lymphoma is a B-cell tumour. As other groups have found, its incidence appears to be rising. Survival rate is poor, and at least some deaths are related to both radiation necrosis and the bulk of residual tumour after diagnostic surgery.

Adult↗