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Biomedical subjects

J Jacobs

Publications and source records attributed to J Jacobs.

At least 19 recordsLinked to original sources

Specific protein kinase from Saccharomyces cerevisiae cells phosphorylating 60S ribosomal proteins.

A protein kinase, specific for 60S ribosomal proteins, has been isolated from Saccharomyces cerevisiae cells, purified to almost homogeneity and characterized. The isolated enzyme is not related to other known protein kinases. Enzyme purification comprised three chromatography steps; DEAE-cellulose, phosphocellulose and heparin-Sepharose. SDS/PAGE analysis of the purified enzyme, indicated a molecular mass of around 71 kDa for the stained single protein band. The specific activity of the protein kinase was directed towards the 60S ribosomal proteins L44, L44', L45 and a 38 kDa protein. All the proteins are phosphorylated only at the serine residues. None of the 40S ribosomal proteins were phosphorylated in the presence of the kinase. For that reason we have named the enzyme the 60S kinase. An analysis of the phosphopeptide maps of acidic ribosomal proteins, phosphorylated at either the 60S kinase or casein kinase II, showed almost identical patterns. Using the immunoblotting technique, the presence of the kinase has been detected in extracts obtained from intensively growing cells. These findings suggest an important role played by the 60S kinase in the regulation of ribosomal activity during protein synthesis.

Chromatography, Affinity

Chemotherapy and surgery in a murine osteosarcoma.

Surgical and chemotherapeutic effects on pulmonary metastatic disease were evaluated in the MGH-OGS murine osteosarcoma. The tumor responded to three sequential injections of doxorubicin with prolonged growth delay but cisplatin administration (although given in doses sufficient to cause weight loss and significant mortality) was not effective in controlling local disease progression. Using a protocol with three injections of doxorubicin (0.006 mg/g of body weight), it was observed that disease-free survival was enhanced when one of the three doses of doxorubicin was given at the time of surgery (perioperatively). By marginally resecting the primary tumor and permitting its regrowth, a model was developed with recurrent primary and metastatic disease present simultaneously. It was observed in this model that amputation or resection of the recurrent primary lesion resulted in pulmonary metastatic growth acceleration. Using this recurrent primary tumor model, doxorubicin's effect on pulmonary metastatic lesions was enhanced when the drug was given at the time of amputation.

Animals

Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining.

Several studies have reported a suppressed immune function (e.g. blast transformation) during depression. In an attempt to define the cellular basis of the reported immune disorders, the present study investigates the leukocyte cell subset profile of minor, simple major, and melancholic depressives, versus normal controls. We have counted the number of white blood cells (WBC) lymphocytes, monocytes, and granulocytes, while the number of lymphocyte (sub)populations has been identified by phenotype, using monoclonal antibody staining in conjunction with flow cytometry. The following cell surface antigens were determined: CD3+ (pan T), CD19+ (pan B), CD4+ (T helper/inducer), CD8+ (T suppressor/cytotoxic), CD4+CD45RA (T-memory cells), CD4+CD45RA+ (T-virgin cells), surface Ig, class II MHC HLA-DR, and CD25+ (IL-2 receptor). By means of pattern recognition methods, we established distinct immunological changes in minor and simple major depressed and in melancholic patients, setting them apart from the reference population. Depression, per se, is characterized by a higher number of WBC, monocytes, class II MHC HLA-DR, and memory T cells. Minor and simple major depressives exhibited an increased T helper/suppressor ratio. Increased numbers of IL-2 receptor bearing cells are a hallmark for major depression. Melancholics showed an increased number of pan T, pan B and T suppressor/cytotoxic cells. It was concluded that the established immune cell profile of depressed patients may point towards the existence of a systemic immune activation during that illness.

Adjustment Disorders

Clinical performances of ingrowth surfaces.

Since the relatively recent introduction of porous-coated implants for joint replacement applications, considerable experience has been gained concerning the efficacy of these devices. In general, the short- and intermediate-term clinical results have been satisfactory. Based on the authors' experience with retrieved components, bone ingrowth is a consistent finding in well-fixed implants, particularly in areas of rigid fixation and intimate apposition. However, a number of issues have emerged that may jeopardize the long-term success of porous-coated devices. These include femoral component subsidence, porous-surface delamination, endosteal bone loss, and proximal femoral atrophy. Improvements in design, manufacturing processes, and surgical technique can be expected to address some of the current limitations in these implant systems.

Bone Remodeling

Management of refractory peritonitis to maintain the peritoneum for subsequent dialysis.

Peritonitis and its sequelae remain major clinical problems in treating peritoneal dialysis (PD) patients. One of these sequelae is the formation of intra-abdominal adhesions, preventing a patient from returning to peritoneal dialysis after a Tenckhoff catheter is removed for refractory peritonitis. We have recently applied a technique that appears to reduce the incidence of this severe complication. When it is determined that a catheter will be removed for refractory peritonitis, hourly peritoneal dialysis exchanges are performed for 12 hr prior to surgery. Postoperatively, the abdomen is rested for 48 hr, after which a temporary peritoneal dialysis catheter is placed at the bedside and hourly exchanges (with antibiotics) are performed for 2-3 days or until the dialysis fluid white blood cell count improves. Then the temporary catheter is removed and the abdomen is rested until the Tenckhoff catheter is replaced in 10-14 days. We treated 5 consecutive patients with refractory peritonitis (2 Pseudomonas, 1 Proteus, 1 Candida, 1 S. aureus) with this technique. All 5 patients were able to return successfully to peritoneal dialysis. At our institution over the past five years, 9 patients with refractory peritonitis due to the same organisms have had their catheters removed. Only 5 (56%) were able to return to PD. Although preliminary, our technique holds promise for those patients wishing to return to peritoneal dialysis after having a catheter removed for refractory peritonitis.

Adult

Work injuries and exposures in children and young adults: review and recommendations for action.

Child labor, the penultimate form of cheap labor, is endemic in poor countries; it also occurs in affluent countries. Little information has been available on injuries, disease, and effects on growth and development in the tens of millions of children at risk. Preventive and control measures are eliminating the gross abuses, tracing and banning hazardous exposures to toxic agents, eliminating risks of injuries and ergonomic strain, providing health services for working children through the primary health care network, and developing international failsafe design standards for tools and work systems, if these children must work. There is a need to train public health professionals, pediatricians, and maternal and child health care personnel in carrying out simple descriptive epidemiologic studies and setting up interventive programs. Eliminating the worst conditions and controlling hazards where there is no imminent alternative to child labor are suggested as the basis for a two-pronged strategy for protecting children who are forced to work.

Accidents, Occupational

Nitric oxide hemoglobin in mice and rats in endotoxic shock.

Mice given ip bacterial endotoxin (LPS) at 10 mg/kg showed a statistically significant decrease in plasma glucose and an increase in hematocrit at 2 h after injection. Glucose was still decreased at 4 h, but the hematocrit had returned to control values. Nitrosylated hemoglobin (HbNO) was detected at 3, but not at 2 h. By 4 h it had increased 5-fold. When N-monomethylarginine (NMMA) at 100 mg/kg, ip was given 2 h after LPS in mice, the HbNO concentration at 4 h was significantly reduced, but the hypoglycemia was worsened because NMMA itself produced a significant hypoglycemia. Rats given iv LPS, 20 mg/kg, showed a fleeting, transient rise in mean arterial pressure (MAP) lasting only a few min. Thereafter, the MAP tended to drift slowly downward over 4 h, but when the MAP at 30 min intervals was compared to the pre-LPS MAP, there were no significant differences. Plasma glucose in unanesthetized rats was significantly elevated at 1 h, back to control at 2 h, and significantly decreased at 3 h. HbNO was detected as early as 1 h after injection. By 2 h the HbNO concentrations exceeded the highest levels found in mice, and they were still increasing as late as 5 h after injection. Unanesthetized rats showed toxic signs and 3/12 rats died within 4 hours of LPS administration. These results are consistent with a model for endotoxic shock in which LPS stimulates an inducible pathway for NO synthesis.

Animals

Use of standard contraceptive diaphragm in management of stress urinary incontinence.

The management of stress urinary incontinence (SUI) consists of either surgical intervention and/or pharmacologic manipulation. Twelve patients with SUI were evaluated for management by the use of a fitted standard contraceptive diaphragm. Complete resolution of SUI was achieved in 11 of 12 patients (91%). Two of the 12 patients achieved continence but withdrew from the study because of associated discomfort from the diaphragm, therefore, complete resolution of SUI was achieved in 9 of 12 patients (75%).

Adult

The cost of hospitalization for the late complications of diabetes in the United States.

Estimates of the cost of diabetes should take into account the development of complications. Patient records identified from the 1987 National Hospital Discharge Survey were used to evaluate the risk of hospitalization due to late complications. Hospitalization for diabetic nephropathy reached a peak of 6.74/1000 between the ages of 45 and 54 years, compared to 0.14 to 1.80/1000 in controls. Diabetic patients less than or equal to 45 years of age were 46 times more likely to be hospitalized due to neuropathy. The risk of cardiovascular complications is high, with a greater incidence of arterial than venous disorders. Diabetic patients were 22 times more likely to be admitted for skin ulcers/gangrene, 15 times more likely due to peripheral vascular disease, and 10 times due to atherosclerosis. The risk of cerebrovascular accident and heart disease was 6 to 10 times greater in diabetic patients. Seventy-five per cent of diabetic cardiovascular disorders are myocardial infarction or chronic ischaemia. Hospitalization from renal complications occurs at younger ages than in the general population. Ophthalmic complications increase with age. Diabetic complications account for 2% of the total hospital admissions in the US in 1987. The total cost of the treatment of late diabetic complications was estimated at +5091 million (cardiovascular 74%; renal diseases 10%; nephropathy 3.6%; ophthalmic disorders 1.5%; other unspecified diseases 10%).

Age Factors

Neuropathy due to podophyllin intoxication.

A 22-year-old man developed a severe sensorimotor neuropathy following ingestion of podophyllin, which had been prescribed for genital condylomata. The initial toxic symptoms were vomiting and diarrhoea, followed by peripheral neuropathy. The neuropathy was still present 18 months later. Nerve conduction studies and sural nerve biopsy confirmed the presence of axonal degeneration.

Adult

Neonatal sepsis due to Streptococcus pneumoniae.

A 20-year-old primigravida in the 33rd week of gestation was delivered of a girl weighing 1,790 g 23 h after spontaneous rupture of the membranes. 13 h after birth, the child showed signs of shock. Cultures of blood, conjunctiva and nasopharyngeal aspirate grew Streptococcus pneumoniae of serotype 11. Cultures from the mother's cervix and from the placenta and membranes also grew S. pneumoniae of the same serotype. The infant responded well to ampicillin and netilmicin. The early-onset pneumococcal septicemic cases reported over the last 20 years are reviewed.

Adult